drug.id,drug.ts,drug.title,drug.alias,drug.az_source,drug.alphabet_x_drug_id,drug.property_id 21,"2017-08-31 23:12:57",Ablavar,"Gadofosveset Trisodium Injection",Multum,"{ ""21"": { ""alphabet_x_drug.id"": 21, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""144"": { ""property.id"": 144, ""property.ts"": ""2017-12-04 04:39:11"", ""property.key"": ""Ablavar Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Ablavar Generic Name: gadofosveset trisodium (Pronunciation: GAD oh FOS ve set trye SOE dee um) What is gadofosveset trisodium (Ablavar)? What are the possible side effects of gadofosveset trisodium (Ablavar)? What is the most important information I should know about gadofosveset trisodium (Ablavar)? What should I discuss with my health care provider before receiving gadofosveset trisodium (Ablavar)? How is gadofosveset trisodium given (Ablavar)? What happens if I miss a dose (Ablavar)? What happens if I overdose (Ablavar)? What should I avoid after receiving gadofosveset trisodium (Ablavar)? What other drugs will affect gadofosveset trisodium (Ablavar)? Where can I get more information? What is gadofosveset trisodium (Ablavar)? Gadofosveset trisodium is a contrast agent that produces magnetic effects. It is used in combination with magnetic resonance angiography (MRA) to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on the MRA.Gadofosveset trisodium is used to help diagnose certain disorders of the heart and blood vessels.Gadofosveset trisodium may also be used for purposes not listed in this medication guide. What are the possible side effects of gadofosveset trisodium (Ablavar)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Call your doctor at once if you have a serious side effect such as:urinating less than usual or not at all;drowsiness, confusion, mood changes, increased thirst, loss of appetite;swelling, weight gain, feeling short of breath; orfast, uneven heart rate.Less serious side effects may include:headache, dizziness;nausea;flushing (warmth, redness, or tingly feeling);mild itching;numbness; orredness, cold feeling, warmth, pain, burning, or bruising where the medicine was injected.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about gadofosveset trisodium (Ablavar)? Gadofosveset trisodium can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:burning, itching, swelling, scaling, and tightening or hardening of your skin;muscle weakness;joint stiffness in your arms, hands, legs, or feet;deep bone pain in your ribs or your hips;trouble moving; orskin redness or discoloration.Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadofosveset trisodium. Also tell your doctor if you have recently received any contrast agent similar to gadofosveset trisodium.Also tell your doctor if you have diabetes, high blood pressure, liver disease, a heart rhythm disorder, a personal or family history of Long QT Syndrome, asthma or allergies, if you are over 60 years old, if you have ever had a reaction to a contrast agent, or if you have recently had an injury, surgery, or severe infection.Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions."" }, ""145"": { ""property.id"": 145, ""property.ts"": ""2017-12-04 04:39:11"", ""property.key"": ""Ablavar Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my health care provider before receiving gadofosveset trisodium (Ablavar)? Gadofosveset trisodium can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:burning, itching, swelling, scaling, and tightening or hardening of your skin;muscle weakness;joint stiffness in your arms, hands, legs, or feet;deep bone pain in your ribs or your hips;trouble moving; orskin redness or discoloration.Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadofosveset trisodium. Also tell your doctor if you have recently received any contrast agent similar to gadofosveset trisodium.To make sure you can safely receive this medication, tell your doctor if you have any of these other conditions:diabetes;high blood pressure;liver disease;a heart rhythm disorder;a personal or family history of Long QT Syndrome;asthma, hay fever, or a history of food or drug allergies;if you are over 60 years old;if you have ever had any type of reaction to a contrast agent; orif you have recently had an injury, surgery, or severe infection.FDA pregnancy category C. It is not known whether gadofosveset trisodium will harm an unborn baby. Before you receive this medication, tell your doctor if you are pregnant.It is not known whether gadofosveset trisodium passes into breast milk or if it could harm a nursing baby. Before you receive this medication, tell your doctor if you are breast-feeding a baby. How is gadofosveset trisodium given (Ablavar)? Gadofosveset trisodium is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting during your MRA.Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions."" }, ""146"": { ""property.id"": 146, ""property.ts"": ""2017-12-04 04:39:11"", ""property.key"": ""Ablavar Patient Information including If I Miss a Dose"", ""property.value"": """" } }" 22,"2017-08-31 23:12:57","Abobotulinumtoxin A Injection",Dysport,FDA,"{ ""22"": { ""alphabet_x_drug.id"": 22, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""147"": { ""property.id"": 147, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on DYSPORT® (abobotulinumtoxinA) for Intramuscular Injection WARNING DISTANT SPREAD OF TOXIN EFFECT Postmarketing reports indicate that the effects of DYSPORT® and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including upper limb spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to or lower than the maximum recommended total dose [see WARNINGS AND PRECAUTIONS]. DESCRIPTION Botulinum toxin type A, the active ingredient in DYSPORT® (abobotulinumtoxinA), is a purified neurotoxin type A complex produced by fermentation of the bacterium Clostridium botulinum type A, Hall Strain. It is purified from the culture supernatant by a series of precipitation, dialysis, and chromatography steps. The neurotoxin complex is composed of the neurotoxin, hemagglutinin proteins and non-toxin non-hemagglutinin protein. DYSPORT® is supplied in a single-use, sterile vial for reconstitution intended for intramuscular injection. Each vial contains 300 Units or 500 Units of lyophilized abobotulinumtoxinA, human serum albumin (125 mcg) and lactose (2.5 mg). DYSPORT® may contain trace amounts of cow's milk proteins [see CONTRAINDICATIONS]. One unit of DYSPORT® corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice. The method for performing the assay is specific to Ipsen's product DYSPORT® . Due to differences in specific details such as vehicle, dilution scheme and laboratory protocols for various mouse LD50 assays, Units of biological activity of DYSPORT® are not interchangeable with Units of any other botulinum toxin or any toxin assessed with any other specific assay method [see Dosage Forms and Strengths]."" }, ""148"": { ""property.id"": 148, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Cervical Dystonia DYSPORT® is indicated for the treatment of adults with cervical dystonia. Glabellar Lines DYSPORT® is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adult patients less than 65 years of age. Upper Limb Spasticity DYSPORT® is indicated for the treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors and finger flexors. DOSAGE AND ADMINISTRATION Instructions For Safe Use The potency Units of DYSPORT® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of DYSPORT® cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method [see DESCRIPTION]. Reconstituted DYSPORT® is intended for intramuscular injection only. Reconstitution instructions are specific for each of the 300 Unit vial and the 500 Unit vial. These volumes yield concentrations specific for the use for each indication (Table 1). Table 1: Dilution Instructions for DYSPORT® Vials (500 Units and 300 Units) Diluent* per 500 Unit Vial Resulting Dose Units per 0.1 mL Diluent* per 300 Unit Vial Resulting Dose Units per 0.1 mL 1 mL 50 Units 0.6 mL 50 Units 2.5 mL 20 Units 1.5 mL 20 Units -- -- 2.5 mL 12 Units 5 mL** 10 Units 3 mL 10 Units *Preservative-free 0.9% Sodium Chloride Injection, USP Only Note: These dilutions are calculated for an injection volume of 0.1 mL. A decrease or increase in the DYSPORT® dose is also possible by administering a smaller or larger injection volume (i.e. 0.05 mL (50% decrease in dose), 0.08 mL (20% decrease in dose) or 0.15 mL (50% increase in dose)). ** When using 5 mL of diluent for a 500 Unit vial of DYSPORT®, complete the following steps (see also 2.4 Dosing in Upper Limb Spasticity). 1. Reconstitute a 500 Unit vial of DYSPORT® with 2.5 mL of Preservative-free 0.9% Sodium Chloride Injection, USP, gently mix, and set the vial aside. 2. Withdraw 2.5 mL of Preservative-free 0.9% Sodium Chloride Injection, USP, into a 5 mL syringe. 3. Take the 5 mL syringe with 2.5 mL Preservative-free 0.9% Sodium Chloride Injection, USP, and draw up the DYSPORT® solution from the reconstituted vial without inverting and mix gently. The resulting concentration will be 10 units/0.1 mL. 4. Use immediately after reconstitution in the syringe. Dispose of any unused saline. After reconstitution, DYSPORT® should be used for only one injection session and for only one patient. Once reconstituted, DYSPORT® should be stored in the original container, in a refrigerator at 2 °C to8°C (36 °F to 46°F), protected from light for up to 24 hours. It must be discarded if not used within 24 hours. Do not freeze reconstituted DYSPORT®. Discard the vial and needle in accordance with local regulations. Dosing In Cervical Dystonia The recommended initial dose of DYSPORT® for the treatment of cervical dystonia is 500 Units given intramuscularly as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin. (A description of the average DYSPORT® dose and percentage of total dose injected into specific muscles in the pivotal clinical trials can be found in Table 8 of Section 14.1, Clinical Studies – Cervical Dystonia.) Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia. Clinical studies with DYSPORT® in cervical dystonia suggest that the peak effect occurs between two and four weeks after injection. Simultaneous EMG-guided application of DYSPORT® may be helpful in locating active muscles. Dose Modification Where dose modification is necessary for the treatment of cervical dystonia, uncontrolled open-label studies suggest that dose adjustment can be made in 250 Unit steps according to the individual patient's response, with re-treatment every 12 weeks or longer, as necessary, based on return of clinical symptoms. Uncontrolled open-label studies also suggest that the total dose administered in a single treatment should be between 250 Units and 1000 Units. Re-treatment, if needed, should not occur in intervals of less than 12 weeks. Doses above 1000 Units have not been systematically evaluated. Special Populations Adults and elderly The starting dose of 500 Units recommended for cervical dystonia is applicable to adults of all ages [see Use in Specific Populations]. Pediatric Patients The safety and effectiveness of DYSPORT® in the treatment in pediatric patients less than 18 years of age has not been assessed [see WARNINGS AND PRECAUTIONS]. Instructions for Preparation and Administration for the Treatment of Cervical Dystonia DYSPORT® is supplied as a single-use vial. Only use sterile preservative-free 0.9% Sodium Chloride Injection, USP for reconstitution of DYSPORT®. Each 500 Unit vial of DYSPORT® is to be reconstituted with 1 mL of preservative- free 0.9% Sodium Chloride Injection USP to yield a solution of 50 Units per 0.1 mL. Each 300 Unit vial of DYSPORT® is to be reconstituted with 0.6 mL of preservative-free 0.9% Sodium Chloride Injection USP to yield a solution equivalent to 50 Units per 0.1 mL. Using an appropriately sized sterile syringe, needle and aseptic technique, draw up 1 mL or 0.6 mL of sterile, preservative- free 0.9% Sodium Chloride Injection USP for 500 Unit and 300 Unit vials, respectively. Insert the needle into the DYSPORT® vial. The partial vacuum will begin to pull the saline into the vial. Any remaining required saline should be expressed into the vial manually. Do not use the vial if no vacuum is observed. Swirl gently to dissolve. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Reconstituted DYSPORT® should be a clear, colorless solution, free of particulate matter, otherwise it should not be injected. Expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach an appropriately sized new sterile needle. Discard the vial and needle in accordance with local regulations. Dosing In Glabellar Lines The dose of DYSPORT® for the treatment of glabellar lines is a total of 50 Units given intramuscularly in five equal aliquots of 10 Units each to achieve clinical effect (see Figure 1). Special Populations Adults A total dose of 50 Units of DYSPORT®, in five equal aliquots, should be administered to achieve clinical effect. The clinical effect of DYSPORT® may last up to four months. Repeat dose clinical studies demonstrated continued efficacy with up to four repeated administrations. It should be administered no more frequently than every three months. When used for re-treatment, DYSPORT® should be reconstituted and injected using the same techniques as the initial treatment. Pediatric Patients DYSPORT® for glabellar lines is not recommended for use in pediatric patients less than 18 years of age [see WARNINGS AND PRECAUTIONS]. Instructions for Preparation and Administration for the Treatment of Glabellar Lines DYSPORT® is supplied as a single-use vial. Only use sterile preservative-free 0.9% Sodium Chloride Injection, USP for reconstitution of DYSPORT®. Each 300 Unit vial of DYSPORT® is to be reconstituted with 2.5 mL of preservative-free 0.9% Sodium Chloride Injection USP prior to injection. The concentration of the resulting solution will be 10 Units per 0.08 mL (12 Units per 0.1 mL) to be delivered in five equally divided aliquots of 0.08 mL each. DYSPORT® may also be reconstituted with 1.5 mL of preservative-free 0.9% Sodium Chloride Injection USP for a solution of 10 Units per 0.05 mL (20 Units per 0.1 mL) to be delivered in five equally divided aliquots of 0.05 mL each. Using an appropriately sized sterile syringe, needle and aseptic technique, draw up 2.5 mL or 1.5 mL of preservative- free 0.9% Sodium Chloride Injection USP Insert the needle into the DYSPORT® vial. The partial vacuum will begin to pull the saline into the vial. Any remaining required saline should be expressed into the vial manually. Do not use the vial if no vacuum is observed. Swirl gently to dissolve. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Reconstituted DYSPORT® should be a clear, colorless solution, free of particulate matter otherwise it should not be injected. Draw a single patient dose of DYSPORT® into a sterile syringe. Expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach a 30 gauge needle. Discard the vial and needle in accordance with local regulations. Injection Technique Glabellar facial lines arise from the activity of the lateral corrugator and vertical procerus muscles. These can be readily identified by palpating the tensed muscle mass while having the patient frown. The corrugator depresses the skin creating a “furrowed” vertical line surrounded by tensed muscle (i.e., frown lines). The location, size, and use of the muscles vary markedly among individuals. Physicians administering DYSPORT® must understand the relevant neuromuscular and/or orbital anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures. Risk of ptosis can be mitigated by careful examination of the upper lid for separation or weakness of the levator palpebrae muscle (true ptosis), identification of lash ptosis, and evaluation of the range of lid excursion while manually depressing the frontalis to assess compensation. In order to reduce the complication of ptosis, the following steps should be taken: Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes. Medial corrugator injections should be placed at least 1 centimeter above the bony supraorbital ridge. Ensure the injected volume/dose is accurate and where feasible kept to a minimum. Do not inject toxin closer than 1 centimeter above the central eyebrow. To inject DYSPORT®, advance the needle through the skin into the underlying muscle while applying finger pressure on the superior medial orbital rim. Inject patients with a total of 50 Units in five equally divided aliquots. Using a 30 gauge needle, inject 10 Units of DYSPORT® into each of five sites, two in each corrugator muscle, and one in the procerus muscle (see Figure 1). Figure 1 Dosing In Upper Limb Spasticity Special Populations Adults Dosing in initial and subsequent treatment sessions should be tailored to the individual based on the siz muscles involved, severity of spasticity, the presence of local muscle weakness, the patient's response to adverse event history with DYSPORT®. In the pivotal clinical trial, doses of 500 Units and 1000 Units muscles, Table 2 and Figure 2, at a given treatment session. No more than 1 mL should generally be administered at any single injection site. Table 2: DYSPORT® Dosing by Muscle for Upper Limb Spasticity Muscles Injected Recommended Dose DYSPORT® Recommended Number of Injection(s) per Muscle Flexor carpi radialis (FCR) 100 Units to 200 Units 1 to 2 Flexor carpi ulnaris (FCU) 100 Units to 200 Units 1 to 2 Flexor digitorum profundus (FDP) 100 Units to 200 Units 1 to 2 Flexor digitorum superficialis (FDS) 100 Units to 200 Units 1 to 2 Brachialis 200 Units to 400 Units 1 to 2 Brachioradialis 100 Units to 200 Units 1 to 2 Biceps Brachii (BB) 200 Units to 400 Units 1 to 2 Pronator Teres 100 Units to 200 Units 1 Figure 2: Muscles for Injection for Upper Limb Spasticity Although actual location of the injection sites can be determined by palpation, the use of injection guiding technique e.g. electromyography, electrical stimulation is recommended to target the injection sites. Repeat DYSPORT® treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection. A majority of patients in clinical studies were retreated between 12-16 weeks; however some patients had a longer duration of response, i.e. 20 weeks. The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of DYSPORT® and muscles to be injected. Clinical improvement may be expected one week after administration of DYSPORT®. Pediatric Patients The safety and effectiveness of DYSPORT® in the treatment of upper limb spasticity in pediatric patients less than 18 years of age has not been demonstrated. [see WARNINGS AND PRECAUTIONS] Instructions for Preparation and Administration for the Treatment of Upper Limb Spasticity in Adults DYSPORT® is supplied as a single-use vial. Only use sterile preservative-free 0.9% Sodium Chloride Injection, USP for reconstitution of DYSPORT®. The recommended concentration is 100 Units/mL or 200 Units/mL with preservative-free 0.9% Sodium Chloride Injection USP) (see Table 1). Using an appropriately sized sterile syringe, needle and aseptic technique, draw up the required volume (Table 1) of preservative-free 0.9% Sodium Chloride Injection USP. Insert the needle into the DYSPORT® vial. The partial vacuum will begin to pull the saline into the vial. No more than 2.5 mL of saline should be introduced into the vial (see footnote in Table 1). Do not use the vial if a vacuum is absent. Gently swirl to dissolve. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Reconstituted DYSPORT® should be a clear, colorless solution, free of particulate matter; otherwise it should not be injected. Expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach an appropriately sized new sterile needle. Discard the vial and needle in accordance with local regulations. HOW SUPPLIED Dosage Forms And Strengths For injection: 300 Units or 500 Units of lyophilized powder in a single-use vial for reconstitution with preservative-free 0.9% Sodium Chloride Injection, USP. Storage And Handling DYSPORT® for Injection is supplied in a sterile, single-use, glass vial. DYSPORT® must be stored under refrigeration at 2°to 8°C (36°to 46°F). Protect from light. Do not use after the expiration date on the vial. All vials, including expired vials, or equipment used with DYSPORT® should be disposed of carefully as is done with all medical waste. DYSPORT® contains a unique hologram on the carton. If you do not see the hologram, do not use the product. Instead contact 877- 397-7671. Cervical Dystonia and Adult Upper Limb Spasticity 500 Unit Vial Each vial contains 500 Units of freeze-dried abobotulinumtoxinA. Box containing 1 vial—NDC 15054-0500-1 Box containing 2 vials—NDC 15054-0500-2 300 Unit Vial Each vial contains 300 Units of freeze-dried abobotulinumtoxinA. Box containing 1 vial—NDC 15054-0530-6 Glabellar Lines Each vial contains 300 Units of freeze-dried abobotulinumtoxinA. Box containing 1 vial— NDC 0299-5962-30 Distributed by: Ipsen Biopharmaceuticals, Inc. Basking Ridge, NJ 07920 and Galderma Laboratories, L.P. Fort Worth, TX76177; Manufactured by: Ipsen Biopharmaceuticals, Inc. Wrexham, LL13 9UF, UK. Revised Jul 2015"" }, ""149"": { ""property.id"": 149, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS The following serious adverse reactions are discussed below and elsewhere in labeling: Distant Spread of Toxin Effect [see BOXED WARNING] Lack of Interchangeability between Botulinum Toxin Products [see WARNINGS AND PRECAUTIONS] Spread of Effects from Toxin [see WARNINGS AND PRECAUTIONS] Dysphagia and Breathing Difficulties [see WARNINGS AND PRECAUTIONS] Facial Anatomy in the Treatment of Glabellar Lines [see WARNINGS AND PRECAUTIONS] Pre-existing Neuromuscular Disorders [see WARNINGS AND PRECAUTIONS] Human Albumin [see WARNINGS AND PRECAUTIONS] Intradermal Immune Reaction [see WARNINGS AND PRECAUTIONS] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Cervical Dystonia The data described below reflect exposure to DYSPORT® in 357 cervical dystonia patients in 6 studies. Of these, two studies were randomized, double-blind, single treatment, placebo controlled studies with subsequent optional open label treatment in which dose optimization (250 to 1000 Units per treatment) over the course of 5 treatment cycles was allowed. The population was almost entirely Caucasian (99%) with a median age of 51 years (range 18–82 years). Most patients (87%) were less than 65 years of age; 58.4% were women. Common Adverse Reactions The most commonly reported adverse reactions (occurring in more than 5% of patients who received 500 Units of DYSPORT® in the placebo controlled clinical trials) in cervical dystonia patients were: muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, neck pain, musculoskeletal pain, dysphonia, injection site pain, and eye disorders (consisting of blurred vision, diplopia, and reduced visual acuity and accommodation). Other than injection site reactions, most adverse reactions became noticeable about one week after treatment and lasted several weeks. The rates of adverse reactions were higher in the combined controlled and open-label experience than in the placebo-controlled trials. During the clinical studies, two patients ( < 1%) experienced adverse reactions leading to withdrawal. One patient experienced disturbance in attention, eyelid disorder, feeling abnormal and headache, and one patient experienced dysphagia. Table 3 compares the incidence of the most frequent adverse reactions from a single treatment cycle of 500 Units of DYSPORT® compared to placebo [see Clinical Studies]. Table 3: Most Common Adverse Reactions (>5%) and Greater than Placebo in the Pooled, Double-blind Phase of Clinical Trials in Patients with Cervical Dystonia Adverse Reaction Preferred Term DYSPORT® 500 Units (N=173) % Placebo (N=182) % Any Adverse Reaction 61 51 General disorders and administration site conditions 30 23 Injection site discomfort 13 8 Fatigue 12 10 Injection site pain 5 4 Musculoskeletal and connective tissue disorders 30 18 Muscular weakness 16 4 Musculoskeletal pain 7 3 Gastrointestinal disorders 28 15 Dysphagia 15 4 Dry mouth 13 7 Nervous system disorders 16 13 Headache 11 9 Infections and infestations 13 9 Respiratory, thoracic and mediastinal disorders 12 8 Dysphonia 6 2 Eye Disordersa 7 2 a The following preferred terms were reported: vision blurred, diplopia, visual acuity reduced, eye pain, eyelid disorder, accommodation disorder, dry eye, eye pruritus. Dose-response relationships for common adverse reactions in a randomized multiple fixed-dose study in which the total dose was divided between two muscles (the sternocleidomastoid and splenius capitis) are shown in Table 4. Table 4: Common Adverse Reactions by Dose in Fixed-dose Study in Patients with Cervical Dystonia Adverse Reaction Preferred Term DYSPORT® Dose Placebo 250 Units 500 Units 1000 Units Any Adverse Event 30% 37% 65% 83% Dysphagia 5% 21% 29% 39% Dry Mouth 10% 21% 18% 39% Muscular Weakness 0% 11% 12% 56% Injection Site Discomfort 10% 5% 18% 22% Dysphonia 0% 0% 18% 28% Facial Paresis 0% 5% 0% 11% Eye Disordersa 0% 0% 6% 17% a The following preferred terms were reported: vision blurred, diplopia, visual acuity reduced, eye pain, eyelid disorder, accommodation disorder, dry eye, eye pruritus. Injection Site Reactions Injection site discomfort and injection site pain were common adverse reactions following DYSPORT® administration. Less Common Adverse Reactions The following adverse reactions were reported less frequently ( < 5%). Breathing Difficulty Breathing difficulties were reported by approximately 3% of patients following DYSPORT® administration and in 1% of placebo patients in clinical trials during the double-blind phase. These consisted mainly of dyspnea. The median time to onset from last dose of DYSPORT® was approximately one week, and the median duration was approximately three weeks. Other adverse reactions with incidences of less than 5% in the DYSPORT® 500 Units group in the double-blind phase of clinical trials included dizziness in 3.5% of DYSPORT®-treated patients and 1% of placebo-treated patients, and muscle atrophy in 1% of DYSPORT®-treated patients and in none of the placebo-treated patients. Laboratory Findings Patients treated with DYSPORT® exhibited a small increase from baseline (0.23 mol/L) in mean blood glucose relative to placebo- treated patients. This was not clinically significant among patients in the development program but could be a factor in patients whose diabetes is difficult to control. Electrocardiographic Findings ECG measurements were only recorded in a limited number of patients in an open-label study without a placebo or active control. This study showed a statistically significant reduction in heart rate compared to baseline, averaging about three beats per minute, observed thirty minutes after injection. Glabellar Lines In placebo-controlled clinical trials of DYSPORT®, the most common adverse reactions( ≥ 2%) following injection of DYSPORT® were nasopharyngitis, headache, injection site pain, injection site reaction, upper respiratory tract infection, eyelid edema, eyelid ptosis, sinusitis, and nausea. Table 5 reflects exposure to DYSPORT® in 398 patients 19 to 75 years of age who were evaluated in the randomized, placebo- controlled clinical studies that assessed the use of DYSPORT® for the temporary improvement in the appearance of glabellar lines [see Clinical Studies]. Adverse reactions of any cause occurred in 48% of the DYSPORT®-treated patients and 33% of the placebo- treated patients. Table 5: Most Common Adverse Reactions with > 1% Incidence in Pooled, Placebo-Controlled Trials for Glabellar Lines Adverse Reactions by Body System DYSPORT® n=398 (%)* Placebo n=496 (%)* Any Adverse Reaction 48 33 Eye Disorders Eyelid Edema 2 0 Eyelid Ptosis 2 < 1 Gastrointestinal Disorders Nausea 2 1 General Disorders and Administration Site Conditions Injection Site Pain 3 2 Injection Site Reaction 3 < 1 Infections and Infestations Nasopharyngitis 10 4 Upper Respiratory Tract Infection 3 2 Sinusitis 2 1 Investigations Blood Present in Urine 2 < 1 Nervous System Disorders Headache 9 5 * Patients who received treatment with placebo and DYSPORT® are counted in both treatment columns. In the overall safety database, where some patients received up to twelve treatments with DYSPORT®, adverse reactions were reported for 57% (1425/2491) of patients. The most frequently reported of these adverse reactions were headache, nasopharyngitis, injection site pain, sinusitis, URI, injection site bruising, and injection site reaction (numbness, discomfort, erythema, tenderness, tingling, itching, stinging, warmth, irritation, tightness, swelling). Adverse reactions that occurred after repeated injections in 2–3% of the population included bronchitis, influenza, pharyngolaryngeal pain, cough, contact dermatitis, injection site swelling, and injection site discomfort. The incidence of eyelid ptosis did not increase in the long-term safety studies with multiple re-treatments at intervals ≥ three months. The majority of the reports of eyelid ptosis were mild to moderate in severity and resolved over several weeks. [see DOSAGE AND ADMINISTRATION]. Upper Limb Spasticity Table 6 lists the most frequently reported adverse reactions ( ≥ 2%) in any DYSPORT® dose group and more frequent than placebo in double blind studies evaluating the treatment of upper limb spasticity in adults with DYSPORT®. Table 6: Most Common Adverse Reactions Observed in at Least 2% of Patients Treated in Pooled, Double-Blind Trials of Patients with Upper Limb Spasticity Reported More Frequently than with Placebo Adverse Reaction Preferred Term DYSPORT® Placebo (N=279)% 500 Units (N=197)% 1000 Units (N=194)% Infections and infestations Nasopharyngitis 4 1 1 Urinary tract infection 3 1 2 Influenza 1 2 1 Infection 1 2 1 Musculoskeletal and connective tissue disorders Muscular weakness 2 4 1 Pain in extremity 0 2 1 Musculoskeletal pain 3 2 2 Back pain 1 2 1 Nervous system disorders Headache 1 2 1 Dizziness 3 1 1 Convulsion 2 2 1 Syncope 1 2 0 Hypoaesthesia 0 2 < 1 Partial seizures 0 2 0 General disorders and administration site conditions Fatigue 2 2 0 Asthenia 2 1 < 1 Injury, poisoning and procedural complications Fall 2 3 2 Injury 2 2 1 Contusion 1 2 < 1 Gastrointestinal disorders Diarrhea 1 2 < 1 Nausea 2 1 1 Constipation 0 2 1 Investigation Blood triglycerides increased 2 1 0 Respiratory, thoracic and mediastinal disorders Cough 1 2 1 Vascular disorders Hypertension 1 2 < 1 Psychiatric disorders Depression 2 3 1 Injection Site Reactions Injection site reactions (e.g. pain, bruising, haemorrhage, injection site erythema/haematoma etc.) have occurred following administration of DYSPORT®. Less Common Adverse Reactions In a pooled analysis of clinical studies, adverse reactions with an incidence of less than 2% reported in DYSPORT® treatment groups included dysphagia 0.5%, gait disturbance 0.5%, hypertonia 0.5%, and sensation of heaviness 0.3%. Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post-approval use of DYSPORT®: vertigo, photophobia, influenza-like illness, amyotrophy, burning sensation, facial paresis, hypoesthesia, erythema, and excessive granulation tissue. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of antibody positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies across products in this class may be misleading. Cervical Dystonia About 3% of subjects developed antibodies (binding or neutralizing) over time with DYSPORT® treatment. Glabellar Lines Testing for antibodies to DYSPORT® was performed for 1554 subjects who had up to nine cycles of treatment. Two subjects (0.13%) tested positive for binding antibodies at baseline. Three additional subjects tested positive for binding antibodies after receiving DYSPORT® treatment. None of the subjects tested positive for neutralizing antibodies. Upper Limb Spasticity From 230 subjects treated with DYSPORT® and tested for the presence of binding antibodies, 5 subjects were positive at baseline and 17 developed antibodies after treatment. Among those 17 subjects, 10 subjects developed neutralizing antibodies. An additional 51 subjects from a separate repeat dose study were tested for the presence of neutralizing antibodies only. None of the subjects tested positive. In total, from the 281 subjects treated in the long-term studies and tested for the presence of neutralizing antibodies, 3.6% developed neutralizing antibodies after treatment. In the presence of binding and neutralizing antibodies to DYSPORT® some patients continue to experience clinical benefit. DRUG INTERACTIONS No formal drug interaction studies have been conducted with DYSPORT®. Patients treated concomitantly with botulinum toxins and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents) should be observed closely because the effect of the botulinum toxin may be potentiated. Use of anticholinergic drugs after administration of DYSPORT® may potentiate systemic anticholinergic effects such as blurred vision. The effect of administering different botulinum neurotoxin products at the same time or within several months of each other is unknown. Excessive weakness may be exacerbated by another administration of botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of DYSPORT®."" }, ""150"": { ""property.id"": 150, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Lack Of Interchangeability Between Botulinum Toxin Products The potency Units of DYSPORT® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of DYSPORT® cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method [see DESCRIPTION]. Spread Of Toxin Effect Post-marketing safety data from DYSPORT® and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death related to spread of toxin effects. The risk of the symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than the maximum recommended total dose. Dysphagia And Breathing Difficulties Treatment with DYSPORT® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre- existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant effects occur, additional respiratory muscles may be involved [see Spread of Toxin Effect above]. Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several weeks, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been post-marketing reports of serious breathing difficulties, including respiratory failure. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin [see Spread of Toxin Effect above, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY]. Facial Anatomy In The Treatment Of Glabellar Lines Caution should be exercised when administering DYSPORT® to patients with surgical alterations to the facial anatomy, excessive weakness or atrophy in the target muscle(s), marked facial asymmetry, inflammation at the injection site(s), ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin [see DOSAGE AND ADMINISTRATION] or the inability to substantially lessen glabellar lines by physically spreading them apart [see Clinical Studies]. Do not exceed the recommended dosage and frequency of administration of DYSPORT®. In clinical trials, subjects who received a higher dose of DYSPORT® had an increased incidence of eyelid ptosis. Pre-existing Neuromuscular Disorders Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of DYSPORT® [see ADVERSE REACTIONS]. Human Albumin This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) is also considered extremely remote. No cases of transmission of viral diseases or CJD have ever been reported for albumin. Intradermal Immune Reaction The possibility of an immune reaction when injected intradermally is unknown. The safety of DYSPORT® for the treatment of hyperhidrosis has not been established. DYSPORT® is approved only for intramuscular injection . Patient Counseling Information Advise patients to read the FDA-approved patient labelling (Medication Guide). Advise patients to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with swallowing, speaking or breathing), or if any known symptom persists or worsens. Inform patients that if loss of strength, muscle weakness, blurred vision or drooping eyelids occur, they should avoid driving a car or engaging in other potentially hazardous activities. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis Studies to evaluate the carcinogenic potential of DYSPORT® have not been conducted. Mutagenesis Genotoxicity studies have not been conducted for DYSPORT®. Impairment Of Fertility In a fertility and early embryonic development study in rats in which either males (2.9, 7.2, 14.5 or 29 Units/kg) or females (7.4, 19.7, 39.4 or 78.8 Units/kg) received weekly intramuscular injections prior to and after mating, dose-related increases in pre-implantation loss and reduced numbers of corpora lutea were noted in treated females. Failure to mate was observed in males that received the high dose. The no-effect dose for effects on fertility was 7.4 Units/kg in females and 14.5 Units/kg in males (approximately one-half and equal to, respectively, the maximum recommended human dose of 1000 Units on a body weight basis). Use In Specific Populations Pregnancy Pregnancy Category C DYSPORT® produced embryo-fetal toxicity when given to pregnant rats at doses similar to or greater than the maximum recommended human dose (MRHD) of 1000 Units on a body weight (Units/kg) basis. In an embryo-fetal development study in which pregnant rats received intramuscular injections daily (2.2, 6.6, or 22 Units/kg on gestation days 6 through 17) or intermittently (44 Units/kg on gestation days 6 and 12 only) during organogenesis, increased early embryonic death was observed with both dosing schedules. The no-effect dose for embryo-fetal developmental toxicity was 2.2 Units/kg (one-tenth the MRHD on a body weight basis). Maternal toxicity was seen at 22 and 44 Units/kg. In a pre-and post-natal development study in which female rats received 6 weekly intramuscular injections (4.4, 11.1, 22.2, or 44 Units/kg) beginning on day 6 of gestation and continuing through parturition to weaning, an increase in stillbirths was observed at the highest dose, which was maternally toxic. The no-effect dose for pre- and post-natal developmental toxicity was 22.2 Units/kg (approximately equal to the MRHD on a body weight basis). There are no adequate and well-controlled studies in pregnant women. DYSPORT® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers It is not known whether DYSPORT® is excreted in human milk. Pediatric Use Cervical Dystonia Safety and effectiveness in pediatric patients have not been established [see WARNINGS AND PRECAUTIONS]. Glabellar Lines DYSPORT® is not recommended for use in pediatric patients less than 18 years of age. Upper Limb Spasticity Safety and effectiveness in pediatric patients have not been established [see WARNINGS AND PRECAUTIONS]. Geriatric Use Cervical Dystonia There were insufficient numbers of patients aged 65 and over in the clinical studies to determine whether they respond differently than younger patients. In general, elderly patients should be observed to evaluate their tolerability of DYSPORT®, due to the greater frequency of concomitant disease and other drug therapy [see DOSAGE AND ADMINISTRATION]. Glabellar Lines Of the total number of subjects in the placebo-controlled clinical studies of DYSPORT®, 8 (1%) were 65 and over. Efficacy was not observed in subjects 65 years and over [see Clinical Studies]. For the entire safety database of geriatric subjects, although there was no increase in the incidence of eyelid ptosis, geriatric subjects did have an increase in the number of ocular adverse reactions compared to younger subjects (11% vs. 5%) [see DOSAGE AND ADMINISTRATION]. Upper Limb Spasticity Of the total number of subjects in placebo controlled clinical studies of DYSPORT®, 28.0 percent were 65 and over, while 8.2 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Ethnic Groups Exploratory analyses in trials for glabellar lines in African-American subjects with Fitzpatrick skin types IV, V, or VI and in Hispanic subjects suggested that response rates at Day 30 were comparable to and no worse than the overall population."" }, ""151"": { ""property.id"": 151, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": """" }, ""152"": { ""property.id"": 152, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Mechanism Of Action DYSPORT® inhibits release of the neurotransmitter, acetylcholine, from peripheral cholinergic nerve endings. Toxin activity occurs in the following sequence: Toxin heavy chain mediated binding to specific surface receptors on nerve endings, internalization of the toxin by receptor mediated endocytosis, pH-induced translocation of the toxin light chain to the cell cytosol and cleavage of SNAP25 leading to intracellular blockage of neurotransmitter exocytosis into the neuromuscular junction. This accounts for the therapeutic utility of the toxin in diseases characterized by excessive efferent activity in motor nerves. Recovery of transmission occurs gradually as the neuromuscular junction recovers from SNAP25 cleavage and as new nerve endings are formed. Pharmacodynamics The primary pharmacodynamic effect of DYSPORT® is due to chemical denervation of the treated muscle resulting in a measurable decrease of the compound muscle action potential, causing a localized reduction of muscle activity. Pharmacokinetics Using currently available analytical technology, it is not possible to detect DYSPORT® in the peripheral blood following intramuscular injection at the recommended doses. Clinical Studies Cervical Dystonia The efficacy of DYSPORT® was evaluated in two randomized, double-blind, placebo controlled, single dose, parallel group studies in treatment-naïve cervical dystonia patients. The principal analyses from these trials provide the primary demonstration of efficacy involving 252 patients (121 on DYSPORT®, 131 on placebo) with 36% male and 64% female. Ninety-nine percent of the patients were Caucasian. In both placebo controlled studies (Study 1 and Study 2), a dose of 500 Units DYSPORT® was given by intramuscular injection divided among two to four affected muscles. These studies were followed by long-term open label extensions that allowed titration in 250 Unit steps to doses in a range of 250 to 1000 Units, after the initial dose of 500 Units. In the extension studies, re-treatment was determined by clinical need after a minimum of 12 weeks. The median time to re-treatment was 14 weeks and 18 weeks for the 75th percentile. The primary assessment of efficacy was based on the total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) change from baseline at Week 4 for both studies. The scale evaluates the severity of dystonia, patient perceived disability from dystonia, and pain. The adjusted mean change from baseline in the TWSTRS total score was statistically significantly greater for the DYSPORT® group than the placebo group at Weeks 4 in both studies (see Table 7). Table 7: TWSTRS Total Score Efficacy Outcome from the Phase 3 Cervical Dystonia Studies Intent to Treat Population Study 1 Study 2 DYSPORT® 500 Units N=55 Placebo N=61 DYSPORT® 500 Units N=37 Placebo N=43 Baseline (week 0) Mean (SD) 43.8 (8.0) 45.8 (8.9) 45.1 (8.7) 46.2 (9.4) Week 4 Mean (SD) 30.0 (12.7) 40.2 (11.8) 35.2 (13.8) 42.4 (12.2) Change from Baselinea -15.6 (2.0) -6.7 (2.0) -9.6 (2.0) -3.7 (1.8) Treatment difference 95% confidence interval -8.9* [-12.9 to -4.7] -5.9* [-10.6 to -1.3] Week 8 Mean (SD) 29.3 (11.0) 39.6 (13.5) Change from Baselinea -14.7 (2.0) -5.9 (2.0) Treatment difference 95% confidence interval -8.8* [-12.9 to -4.7] a Change from baseline is expressed as adjusted least squares mean (SE) *Significant at p-value < 0.05 Analyses by gender, weight, geographic region, underlying pain, cervical dystonia severity at baseline and history of treatment with botulinum toxin did not show any meaningful differences between groups. Table 8 indicates the average DYSPORT® dose, and percentage of total dose, injected into specific muscles in the pivotal clinical trials. Table 8: DYSPORT® 500 Units starting dose (units and % of the total dose) by Unilateral Muscle Injected During Double- blind Pivotal Phase 3 studies 2 and 1 Combined Number of patients injected per musclea DYSPORT® Dose Injected Percentage of the total DYSPORT® Dose Injected Median [DYSPORT® Units] (min, max) 75th percentile [DYSPORT® Units] Median [%] (min, max) 75th percentile [%] Sternocleidomastoid 90 125 Units (50, 350) 150 Units 26.5 % (10, 70) 30.0 % Splenius capitis 85 200 Units (75, 450) 250 Units 40.0 % (15, 90) 50.0 % Trapezius 50 102.6 Units (50, 300) 150 Units 20.6 % (10, 60) 30.0 % Levator scapulae 35 105.3 Units (50, 200) 125 Units 21.1 % (10, 40) 25.0 % Scalenus (medius and anterior) 26 115.5 Units (50, 300) 150 Units 23.1 % (10, 60) 30.0 % Semispinalis capitis 21 131.6 Units (50, 250) 175 Units 29.4 % (10, 50) 35.0 % Longissimus 3 150 Units (100, 200) 200 Units 30.0 % (20, 40) 40.0 % a Total number of patients in combined studies 2 and 1 who received initial treatment = 121. Glabellar Lines Three double-blind, randomized, placebo-controlled, clinical studies evaluated the efficacy of DYSPORT® for use in the temporary improvement of the appearance of moderate to severe glabellar lines. These three studies enrolled healthy adults (ages 19-75) with glabellar lines of at least moderate severity at maximum frown. Subjects were excluded if they had marked ptosis, deep dermal scarring, or a substantial inability to lessen glabellar lines, even by physically spreading them apart. The subjects in these studies received either DYSPORT® or placebo. The total dose was delivered in equally divided aliquots to specified injection sites (see Figure 1). Investigators and subjects assessed efficacy at maximum frown by using a 4-point scale (none, mild, moderate, severe). Overall treatment success was defined as post-treatment glabellar line severity of none or mild with at least 2 grade improvement from Baseline for the combined investigator and subject assessments (composite assessment) on Day 30 (see Table 9). Additional endpoints for each of the studies were post-treatment glabellar line severity of none or mild with at least a 1 grade improvement from Baseline for the separate investigator and subject assessments on Day 30. After completion of the randomized studies, subjects were offered participation in a two-year, open-label re-treatment study to assess the safety of multiple treatments. Table 9: Treatment Success at Day 30 (None or Mild with at least 2 Grade Improvement from Baseline at Maximum Frown for the combined Investigator and Subject Assessments (Composite)) Study 2 Grade Improvement DYSPORT® n/N (%) Placebo n/N (%) GL-1 58/105 (55%) 0/53 (0%) GL-2 37/71 (52%) 0/71 (0%) GL-3 120/200 (60%) 0/100 (0%) Treatment with DYSPORT® reduced the severity of glabellar lines for up to four months. Study GL-1 Study GL-1 was a single dose, double-blind, multi-center, randomized, placebo-controlled study in which 158 previously untreated subjects received either placebo or 50 Units of DYSPORT®, administered in five aliquots of 10 Units (see Figure 1). Subjects were followed for 180 days. The mean age was 43 years; most of the subjects were women (85%), and predominantly Caucasian (49%) or Hispanic (47%). At Day 30, 55% of DYSPORT®-treated subjects achieved treatment success: a composite 2 grade improvement of glabellar line severity at maximum frown (Table 9). In study GL-1, the reduction of glabellar line severity at maximum frown was greater at Day 30 in the DYSPORT® group compared to the placebo group as assessed by both Investigators and subjects (Table 10). Table 10: GL-1: Investigator's and Subject's Assessment of Glabellar Line Severity at Maximum Frown Using a 4-point Scale (% and Number of Subjects with Severity of None or Mild) Day Investigator’s Assessment Subject’s Assessment DYSPORT® N=105 Placebo N=53 DYSPORT® N=105 Placebo N=53 14 90% 17% 77% 9% 95 9 81 5 30 88% 4% 74% 9% 92 2 78 5 60 64% 2% 60% 6% 67 1 63 3 90 43% 6% 36% 6% 45 3 38 3 120 23% 4% 19% 6% 24 2 20 3 150 9% 2% 8% 4% 9 1 8 2 180 6% 0% 7% 8% 6 0 7 4 Study GL-2 Study GL-2 was a repeat dose, double-blind, multi-center, placebo-controlled, randomized study. The study was initiated with two or three open-label treatment cycles of 50 Units of DYSPORT® administered in five aliquots of 10 Units DYSPORT® (see Figure 1). After the open-label treatments, subjects were randomized to receive either placebo or 50 Units of DYSPORT®. Subjects could have received up to four treatments through the course of the study. Efficacy was assessed in the final randomized treatment cycle. The study enrolled 311 subjects into the first treatment cycle and 142 subjects were randomized into the final treatment cycle. Overall, the mean age was 47 years; most of the subjects were women (86%) and predominantly Caucasian (80%). At Day 30, 52% of DYSPORT®-treated subjects achieved treatment success: a composite 2 grade improvement of glabellar line severity at maximum frown (see Table 9). The proportion of responders in the final treatment cycle was comparable to the proportion of responders in all prior treatment cycles. After the final repeat treatment with DYSPORT®, the reduction of glabellar line severity at maximum frown was greater at Day 30 in the DYSPORT® group compared to the placebo group as assessed by both Investigators and subjects (Table 12). Table 11: GL-2: Investigator's and Subject's Assessments of Glabellar Line Severity at Maximum Frown Using a 4-point Scale (% and Number of Subjects with Severity of None or Mild) Day Investigator’s Assessment Subject’s Assessment DYSPORT® N=71 Placebo N=71 DYSPORT® N=71 Placebo N=71 30 85% 4% 79% 1% 60 3 56 1 Study GL-3 Study GL-3 was a single dose, double-blind, multi-center, randomized, placebo-controlled study in which 300 previously untreated subjects received either placebo or 50 Units of DYSPORT®, administered in five aliquots of 10 Units (see Figure 1). Subjects were followed for 150 days. The mean age was 44 years; most of the subjects were women (87%), and predominantly Caucasian (75%) or Hispanic (18%). At Day 30, 60% of DYSPORT®-treated subjects achieved treatment success: a composite 2 grade improvement of glabellar line severity at maximum frown (see Table 9). In study GL-3, the reduction of glabellar line severity at maximum frown was greater at Day 30 in the DYSPORT® group compared to the placebo group as assessed by both Investigators and subjects (see Table 12). Table 12: GL-3: Investigator's and Subject's Assessment of Glabellar Line Severity at Maximum Frown Using a 4-point Scale (% and Number of Subjects with Severity of None or Mild) Day Investigator’s Assessment Subject’s Assessment DYSPORT® N=200 Placebo N=100 DYSPORT® N=200 Placebo N=100 14 83% 5% 83% 2% 166 5 165 2 30 86% 0% 82% 2% 171 0 163 2 60 75% 1% 65% 4% 150 1 130 4 90 51% 1% 46% 2% 102 1 91 2 120 29% 1% 31% 3% 58 1 61 3 150 16% 1% 16% 3% 32 1 31 3 Geriatric Subjects In GL1, GL2, and GL3, there were 8 subjects aged 65 and older who were randomized to DYSPORT® 50 Units in 5 equal aliquots of 10 Units (4) or placebo (4). None of the geriatric DYSPORT® subjects were a treatment success at maximum frown at Day 30. Upper Limb Spasticity The efficacy and safety of DYSPORT® for the treatment of upper limb spasticity was evaluated in a randomized, multi-center, double- blind, placebo-controlled study that included 238 patients (159 DYSPORT® and 79 placebo) with upper limb spasticity (Modified Ashworth Scale (MAS) score ≥ 2 in the primary targeted muscle group for toxin naive patients or MAS score ≥ 3 in the primary targeted muscle group for toxin non-naive patients at least 4 months after the last botulinum toxin injection, of any serotype) who were at least 6 months post-stroke or post-traumatic brain injury. DYSPORT® 500 Units (N=80), DYSPORT® 1000 Units (N=79), or placebo (N=79) was injected intramuscularly into the affected upper limb muscles. After injection of the primary targeted muscle groups (PTMG), the remainder of the dose was injected into at least two additional upper limb muscles determined by the patient's individual presentation. Table 13 provides the mean and range of DYSPORT® doses injected and the number of injections into specific muscles of the upper limb. Table 13 :DYSPORT® Dose Injected and Number of Injections per Muscle Muscle DYSPORT® Treatment Group Number of Patients Mean DYSPORT® Units Injected (Min, Max) Number Of Injection Sites Median, [Q1 ; Q3] Flexor digitorum profundus (FDP)* 500 U 54 93.5 Units (50 to 100) 1, [1 ; 2] 1000 U 65 195.5 Units (100 to 300) 2, [1 ; 2] Flexor digitorum superficialis (FDS)* 500 U 63 95.4 Units (50 to 100) 2, [1 ; 2] 1000 U 73 196.8 Units (100 to 300) 2, [1 ; 2] Flexor carpi radialis (FCR)* 500 U 57 92.2 Units (25 to 100) 1, [1 ; 2] 1000 U 57 178.1 Units (80 to 300) 1, [1 ; 2] Flexor carpi ulnaris (FCU)* 500 U 47 89.9 Units (25 to 180) 1, [1 ; 2] 1000 U 49 171.2 Units (80 to 200) 1, [1 ; 2] Brachialis* 500 U 60 148.5 Units (50 to 200) 2, [1 ; 2] 1000 U 43 321.4 Units (100 to 400) 2, [2 ; 2] Brachioradialis* 500 U 42 88.3 Units (50 to 200) 1, [1 ; 2] 1000 U 28 172.1 Units (50 to 200) 1, [1 ; 2] Biceps Brachii (BB) 500 U 28 106.4 Units (50 to 200) 2, [1 ; 2] 1000 U 19 207.4 Units (100 to 400) 2, [1 ; 2] Pronator Teres 500 U 14 81.8 Units (45 to 200) 1, [1 ; 1] 1000 U 30 157.3 Units (80 to 200) 1, [1 ; 1] *PTMG The co-primary efficacy variables were muscle tone assessed by the MAS at the primary targeted muscle group at week 4 and the Physician Global Assessment (PGA) at week 4. Table 14 : Primary Endpoints (PTMG MAS and PGA) and MAS by Muscle Group at Week 4 Placebo (N=79) DYSPORT® (500 units) (N=80) (1000 units) (N=79) LS Mean Change from Baseline in PTMG Muscle Tone on the MAS -0.3 -1.2* -1.4* LS Mean PGA of Response to Treatment 0.7 1.4* 1.8* LS Mean Change from Baseline in Wrist Flexor Muscle Tone on the MAS -0.3 (n=54) -1.4 (n=57) -1.6 (n=58) LS Mean Change from Baseline in Finger Flexor Muscle Tone on the MAS -0.3 (n=70) -0.9 (n=66) -1.2 (n=73) LS Mean Change from Baseline in Elbow Flexor Muscle Tone on the MAS -0.3 (n=56) -1.0 (n=61) -1.2 (n=48) LS= Least Square; *p ≤ 0.05"" }, ""153"": { ""property.id"": 153, ""property.ts"": ""2017-12-04 04:39:16"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION DYSPORT® (DIS-port) (abobotulinumtoxinA) for Injection What is the most important information I should know about DYSPORT®? DYSPORT® may cause serious side effects that can be life threatening including: Problems breathing or swallowing Spread of toxin effects These problems can happen within hours, or days to weeks after an injection of DYSPORT®. Call your doctor or get medical help right away if you have any of these problems after treatment with DYSPORT® 1. Problems swallowing, speaking, or breathing. These problems can happen within hours, or days to weeks after an injection of DYSPORT® usually because the muscles that you use to breathe and swallow can become weak after the injection. Death can happen as a complication if you have severe problems with swallowing or breathing after treatment with DYSPORT®. People with certain breathing problems may need to use muscles in their neck to help them breathe. These patients may be at greater risk for serious breathing problems with DYSPORT®. Swallowing problems may last for several weeks. People who cannot swallow well may need a feeding tube to receive food and water. If swallowing problems are severe, food or liquids may go into your lungs. People who already have swallowing or breathing problems before receiving DYSPORT® have the highest risk of getting these problems. 2. Spread of toxin effects. In some cases, the effect of botulinum toxin may affect areas of the body away from the injection site and cause symptoms of a serious condition called botulism. The symptoms of botulism include: loss of strength and muscle weakness all over the body double vision blurred vision and drooping eyelids hoarseness or change or loss of voice (dysphonia) trouble saying words clearly (dysarthria) loss of bladder control trouble breathing trouble swallowing These symptoms can happen within hours, or days to weeks after you receive an injection of DYSPORT®. These problems could make it unsafe for you to drive a car or do other dangerous activities. See “What should I avoid while receiving DYSPORT®?” What is DYSPORT®? DYSPORT® is a prescription medicine that is injected into muscles and used: to treat cervical dystonia (CD) in adults to improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) in adults younger than 65 years of age for a short period of time (temporary) to treat increased muscle stiffness in, elbow, wrist, and finger muscles in adults with upper limb spasticity. CD is caused by muscle spasms in the neck. These spasms cause abnormal position of the head and often neck pain. After DYSPORT® is injected into muscles; those muscles are weakened for up to 12 to 16 weeks or longer. This may help lessen your symptoms. Frown lines (wrinkles) happen because the muscles that control facial expression are used often (muscle tightening over and over). After DYSPORT® is injected into the muscles that control facial expression, the medicine stops the tightening of these muscles for up to 4 months. It is not known whether DYSPORT® is safe or effective in children under 18 years of age. It is not known whether DYSPORT® is safe or effective for the treatment of other types of muscle spasms. It is not known whether DYSPORT® is safe or effective for the treatment of other wrinkles. Who should not take DYSPORT®? Do not take DYSPORT® if you: are allergic to DYSPORT® or any of the ingredients in DYSPORT®. See the end of this Medication Guide for a list of ingredients in DYSPORT® are allergic to cow's milk protein had an allergic reaction to any other botulinum toxin product such as Myobloc® (rimabotulinumtoxinB), Botox® (onabotulinumtoxinA), or Xeomin® (incobotulinumtoxinA). have a skin infection at the planned injection site What should I tell my doctor before taking DYSPORT®? Tell your doctor about all your medical conditions, including if you: have a disease that affects your muscles and nerves (such as amyotrophic lateral sclerosis [ALS or Lou Gehrig's disease], myasthenia gravis or Lambert-Eaton syndrome). See “What is the most important information I should know about DYSPORT®?” have allergies to any botulinum toxin product had any side effect from any botulinum toxin product in the past have or have had a breathing problem, such as asthma or emphysema have or have had swallowing problems have or have had bleeding problems have diabetes have or have had a slow heart beat or other problem with your heart rate or rhythm have plans to have surgery had surgery on your face have weakness of your forehead muscles (such as trouble raising your eyebrows) have drooping eyelids have any other change in the way your face normally looks are pregnant or plan to become pregnant. It is not known if DYSPORT® can harm your unborn baby are breast-feeding or planning to breast-feed. It is not known if DYSPORT® passes into breast milk Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal products. Using DYSPORT® with certain other medicines may cause serious side effects. Do not start any newmedicines until you have told your doctor that you have received DYSPORT® in the past. Especially tell your doctor if you: have received any other botulinum toxin product in the last four months have received injections of botulinum toxin, such as Myobloc® (rimabotulinumtoxinB), Botox® (onabotulinumtoxinA) or Xeomin® (incobotulinumtoxinA) in the past; be sure your doctor knows exactly which product you received have recently received an antibiotic by injection take muscle relaxants take an allergy or cold medicine take a sleep medicine Ask your doctor if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine. How should I take DYSPORT®? DYSPORT® is an injection that your doctor will give you DYSPORT® is injected into the affected muscles Your doctor may give you another dose of DYSPORT® after 12 weeks or longer, if it is needed If you are being treated for CD or upper limb spasticity, your doctor may change your dose of DYSPORT®, until you andyour doctor find the best dose for you The dose of DYSPORT® is not the same as the dose of any other botulinum toxin product What should I avoid while taking DYSPORT®? DYSPORT® may cause loss of strength or general muscle weakness, blurred vision, or drooping eyelids within hours toweeks of taking DYSPORT®. If this happens, do not drive a car, operate machinery, or do other dangerousactivities. See “What is the most important information I should know about DYSPORT®?” What are the possible side effects of DYSPORT®? DYSPORT®can cause serious side effects. See “What is the most important information I should know about DYSPORT®?” The most common side effects of DYSPORT® in people with cervical dystonia include: muscle weakness neck pain or muscle pain difficulty swallowing dry mouth problems speaking injection site pain feeling of tiredness eye problems headache The most common side effects of DYSPORT® in people with glabellar lines include: stuffy or runny nose and sore throat headache drooping eyelids injection site pain injection site reaction sinus infection upper respiratory infection swelling of eyelids nausea The most common side effects of DYSPORT® in people with upper limb spasticity include: urinary tract infection fall stuffy or runny nose and sore throat muscle weakness depression dizziness musculoskeletal pain Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects DYSPORT®. For more information, ask your doctor pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about DYSPORT®: Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. This Medication Guide summarizes the most important information about DYSPORT®. If you would like more information,talk with your doctor. You can ask your doctor or pharmacist for information about DYSPORT® that is written for healthcareprofessionals. For more information about DYSPORT® call 877-397-7671 or go to www.dysport.com orwww.DysportUSA.com. What are the ingredients in DYSPORT®? Active ingredient: (botulinum toxin Type A) Inactive ingredients: human albumin and lactose. DYSPORT® may contain cow's milk protein."" } }" 23,"2017-08-31 23:12:57","Abobotulinumtoxin A Injection",Dysport,Multum,"{ ""23"": { ""alphabet_x_drug.id"": 23, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""154"": { ""property.id"": 154, ""property.ts"": ""2017-12-04 04:39:24"", ""property.key"": ""Dysport Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Dysport Generic Name: abobotulinumtoxinA (Dysport) (Pronunciation: A boe BOT ue LYE num TOX in A) What is abobotulinumtoxinA (Dysport) (Dysport)? What are the possible side effects of Dysport (Dysport)? What is the most important information I should know about Dysport (Dysport)? What should I discuss with my healthcare provider before I receive Dysport (Dysport)? How is Dysport given (Dysport)? What happens if I miss a dose (Dysport)? What happens if I overdose (Dysport)? What should I avoid after receiving Dysport (Dysport)? What other drugs will affect Dysport (Dysport)? Where can I get more information? What is abobotulinumtoxinA (Dysport) (Dysport)? AbobotulinumtoxinA (Dysport), also called botulinum toxin type A, is made from the bacteria that causes botulism. Botulinum toxin blocks nerve activity in the muscles, causing a temporary reduction in muscle activity.Dysport is used to treat cervical dystonia (severe spasms in the neck muscles).Dysport is also used to temporarily lessen the appearance of facial wrinkles.Dysport may also be used for other purposes not listed in this medication guide. What are the possible side effects of Dysport (Dysport)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.The botulinum toxin contained in Dysport can spread to other body areas beyond where it was injected. This has caused serious life-threatening side effects in some people receiving botulism toxin injections, even for cosmetic purposes.Call your doctor at once if you have any of these serious side effects, some of which can occur up to several weeks after an injection:trouble breathing, talking, or swallowing;hoarse voice, drooping eyelids;problems with vision;unusual or severe muscle weakness (especially in a body area that was not injected with the medication);loss of bladder control;crusting or drainage from your eyes;severe skin rash or itching;fast, slow, or uneven heartbeats; orchest pain or heavy feeling, pain spreading to the arm or shoulder, general ill feeling.Less serious side effects may include:muscle weakness near where the medicine was injected;bruising, bleeding, pain, redness, or swelling where the injection was given;headache, muscle pain or stiffness, neck or back pain;fever, cough, sore throat, runny nose, flu symptoms,dizziness, drowsiness, tired feeling;nausea, diarrhea, stomach pain, loss of appetite;dry mouth, dry eyes, ringing in your ears;increased sweating in areas other than the underarms;itchy or watery eyes, increased sensitivity to light; oreyelid swelling or bruising.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about Dysport (Dysport)? The botulinum toxin contained in this medication can spread to other body areas beyond where it was injected. This has caused serious life-threatening side effects in some people receiving botulism toxin injections, even for cosmetic purposes.Call your doctor at once if you have a hoarse voice, drooping eyelids, vision problems, severe muscle weakness, loss of bladder control, or trouble breathing, talking, or swallowing. Some of these effects can occur up to several weeks after a botulinum toxin injection.Botulinum toxin injections should be given only by a trained medical professional, even when used for cosmetic purposes.Do not seek botulinum toxin injections from more than one medical professional at a time. If you switch healthcare providers, be sure to tell your new provider how long it has been since your last botulinum toxin injection.Using this medication more often than prescribed will not make it more effective and may result in serious side effects.You should not receive this medication if you are allergic to botulinum toxin or cow's milk, or if you have an infection, swelling, or muscle weakness in the area where the medicine will be injected.Before receiving a botulinum toxin injection, tell your doctor if you have ALS ( Lou Gehrig's disease), myasthenia gravis, Lambert-Eaton syndrome, a breathing disorder, trouble swallowing, facial muscle weakness, a change in the appearance of your face, seizures, bleeding problems, heart disease, diabetes, if you have had or will have surgery, or if you have ever received other botulinum toxin injections such as Botox or Myobloc.The effects of a botulinum toxin injection are temporary. Your symptoms may return completely within 3 months after an injection. After repeat injections, it may take less and less time before your symptoms return, especially if your body develops antibodies to the botulinum toxin."" }, ""155"": { ""property.id"": 155, ""property.ts"": ""2017-12-04 04:39:24"", ""property.key"": ""Dysport Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my healthcare provider before I receive Dysport (Dysport)? You should not receive this medication if you are allergic to botulinum toxin or cow's milk, or if you have an infection, swelling, or muscle weakness in the area where the medicine will be injected. Tell your doctor if you have ever had a side effect after receiving a botulinum toxin in the pastIf you have any of these other conditions, you may need a dose adjustment or special tests:amyotrophic lateral sclerosis (ALS, or \"Lou Gehrig's disease\");myasthenia gravis;Lambert-Eaton syndrome;a breathing disorder such as asthma or emphysema;problems with swallowing;facial muscle weakness (droopy eyelids, weak forehead, trouble raising your eyebrows);a change in the normal appearance of your face;a seizure disorder;bleeding problems;heart disease;diabetes;if you have had or plan to have surgery (especially on your face); orif you have ever received other botulinum toxin injections such as Botox or Myobloc (especially in the last 4 months).Dysport is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.FDA pregnancy category C. It is not known whether botulinum toxin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication..It is not known whether botulinum toxin passes into breast milk or if it could harm a nursing baby. Do not receive this medication without telling your doctor if you are breast-feeding a baby. How is Dysport given (Dysport)? This medication is injected into a muscle. A doctor, nurse, or other healthcare provider will give you this injection. Dysport injections should be spaced at least 3 months apart.Botulinum toxin injections should be given only by a trained medical professional, even when used for cosmetic purposes.Your injection may be given into more than one area at a time, depending on the condition being treated.The effects of a Dysport injection are temporary. Your symptoms may return completely within 3 months after an injection. After repeat injections, it may take less and less time before your symptoms return, especially if your body develops antibodies to the botulinum toxin.Do not seek botulinum toxin injections from more than one medical professional at a time. If you switch healthcare providers, be sure to tell your new provider how long it has been since your last botulinum toxin injection.Using this medication more often than prescribed will not make it more effective and may result in serious side effects."" }, ""156"": { ""property.id"": 156, ""property.ts"": ""2017-12-04 04:39:24"", ""property.key"": ""Dysport Patient Information including If I Miss a Dose"", ""property.value"": """" } }" 24,"2017-08-31 23:12:57",Abraxane,"Albumin-bound Paclitaxel for Injectable Suspension",FDA,"{ ""24"": { ""alphabet_x_drug.id"": 24, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""157"": { ""property.id"": 157, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on ABRAXANE® for Injectable Suspension (paclitaxel) Protein-bound Particles for Injectable Suspension WARNING NEUTROPENIA Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1,500 cells/mm³. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. Note: An albumin form of paclitaxel may substantially affect a drug's functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS. DESCRIPTION ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is paclitaxel formulated as albumin-bound nanoparticles with a mean particle size of approximately 130 nanometers. Paclitaxel exists in the particles in a non-crystalline, amorphous state. ABRAXANE is supplied as a white to yellow, sterile, lyophilized powder for reconstitution with 20 mL of 0.9% Sodium Chloride Injection, USP prior to intravenous infusion. Each single-use vial contains 100 mg of paclitaxel (bound to human albumin) and approximately 900 mg of human albumin (containing sodium caprylate and sodium acetyltryptophanate). Each milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel formulated as albumin-bound particles. ABRAXANE is free of solvents. The active agent in ABRAXANE is paclitaxel, a microtubule inhibitor. The chemical name for paclitaxel is 5β,20-Epoxy- 1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine. Paclitaxel has the following structural formula: Paclitaxel is a white to off-white crystalline powder with the empirical formula C47H51NO14 and a molecular weight of 853.91. It is highly lipophilic, insoluble in water, and melts at approximately 216°C to 217°C."" }, ""158"": { ""property.id"": 158, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Metastatic Breast Cancer ABRAXANE is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. Non-Small Cell Lung Cancer ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. Adenocarcinoma Of The Pancreas ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine. DOSAGE AND ADMINISTRATION Metastatic Breast Cancer After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE is 260 mg/m² administered intravenously over 30 minutes every 3 weeks. Non-Small Cell Lung Cancer The recommended dose of ABRAXANE is 100 mg/m² administered as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle. Administer carboplatin on Day 1 of each 21 day cycle immediately after ABRAXANE [see Clinical Studies]. Adenocarcinoma Of The Pancreas The recommended dose of ABRAXANE is 125 mg/m² administered as an intravenous infusion over 30-40 minutes on Days 1, 8 and 15 of each 28-day cycle. Administer gemcitabine immediately after ABRAXANE on Days 1, 8 and 15 of each 28-day cycle [see Clinical Studies]. Dosage In Patients With Hepatic Impairment For patients with mild hepatic impairment (total bilirubin greater than ULN and less than or equal to 1.5 x ULN and aspartate aminotransferase [AST] less than or equal to 10 x ULN), no dose adjustments are required, regardless of indication. Do not administer ABRAXANE to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment. Do not administer ABRAXANE to patients with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN regardless of indication as these patients have not been studied. Recommendations for dosage adjustment for the first course of therapy are shown in Table 1. Table 1: Recommendations for Starting Dose in Patients with Hepatic Impairment SGOT (AST) Levels Bilirubin Levels ABRAXANE Dosea MBC NSCLCc Pancreaticc Adenocarcinoma Mild < 10x ULN AND > ULN to ≤ 1. 5 x ULN 260 mg/m² 100 mg/m² 125 mg/m² Moderate < 10x ULN AND > 1.5 to ≤ 3 x ULN 200 mg/m² b 80 mg/m² b not recommended Severe < 10x ULN AND > 3 to ≤ 5 x ULN 200 mg/m² b 80 mg/m² b not recommended > 10x ULN OR > 5 x ULN not recommended not recommended not recommended MBC = Metastatic Breast Cancer; NSCLC = Non-Small Cell Lung Cancer. a Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance. b A dose increase to 260 mg/m² for patients with metastatic breast cancer or 100 mg/m² for patients with non-small cell lung cancer in subsequent courses should be considered if the patient tolerates the reduced dose for two cycles. c Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic or lung cancer. Dose Reduction/Discontinuation Recommendations Metastatic Breast Cancer Patients who experience severe neutropenia (neutrophils less than 500 cells/mm³ for a week or longer) or severe sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m² for subsequent courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m². For Grade 3 sensory neuropathy hold treatment until resolution to Grade 1 or 2, followed by a dose reduction for all subsequent courses of ABRAXANE [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS  and ADVERSE REACTIONS]. Non-Small Cell Lung Cancer Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm³ and platelet count is at least 100,000 cells/mm³ [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. In patients who develop severe neutropenia or thrombocytopenia withhold treatment until counts recover to an absolute neutrophil count of at least 1500 cells/mm³ and platelet count of at least 100,000 cells/mm³ on Day 1 or to an absolute neutrophil count of at least 500 cells/mm³ and platelet count of at least 50,000 cells/mm³ on Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce ABRAXANE and carboplatin doses as outlined in Table 2. Withhold ABRAXANE for Grade 3-4 peripheral neuropathy. Resume ABRAXANE and carboplatin at reduced doses (see Table 2) when peripheral neuropathy improves to Grade 1 or completely resolves [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. Table 2: Permanent Dose Reductions for Hematologic and Neurologic Adverse Drug Reactions in NSCLC Adverse Drug Reaction Occurrence Weekly ABRAXANE Dose (mg/m²) Every 3-Week Carboplatin Dose (AUC mg«min/mL) Neutropenic Fever (ANC less than 500/mm³ with fever > 38°C) OR Delay of next cycle by more than 7 days for ANC less than 1500/mm³ OR ANC less than 500/mm³ for more than 7 days First 75 4.5 Second 50 3 Third Discontinue Treatment Platelet count less than 50,000/mm³ First 75 4.5 Second Discontinue Treatment Severe sensory Neuropathy - Grade 3 or 4 First 75 4.5 Second 50 3 Third Discontinue Treatment Adenocarcinoma of the Pancreas Dose level reductions for patients with adenocarcinoma of the pancreas, as referenced in Tables 4 and 5, are provided in Table 3. Table 3: Dose Level Reductions for Patients with Adenocarcinoma of the Pancreas Dose Level ABRAXANE (mg/m²) Gemcitabine (mg/m²) Full dose 125 1000 1st dose reduction 100 800 2nd dose reduction 75 600 If additional dose reduction required Discontinue Discontinue Recommended dose modifications for neutropenia and thrombocytopenia for patients with adenocarcinoma of the pancreas are provided in Table 4. Table 4: Dose Recommendation and Modifications for Neutropenia and/or Thrombocytopenia Cycle Day ANC (cells/mm³) Platelet count (cells/mm³) ABRAXANE / Gemcitabine Day 1 < 1500 OR < 100,000 Delay doses until recovery Day 8 500 to < 1000 OR 50,000 to < 75,000 Reduce 1 dose level < 500 OR < 50,000 Withhold doses Day 15: If Day 8 doses were reduced or given without modification: 500 to < 1000 OR 50,000 to < 75,000 Reduce 1 dose level from Day 8 < 500 OR < 50,000 Withhold doses Day 15: If Day 8 doses were withheld: ≥ 1000 OR ≥ 75,000 Reduce 1 dose level from Day 1 500 to < 1000 OR 50,000 to < 75,000 Reduce 2 dose levels from Day 1 < 500 OR < 50,000 Withhold doses ANC = Absolute Neutrophil Count Recommended dose modifications for other adverse drug reactions in patients with adenocarcinoma of the pancreas are provided in Table 5. Table 5: Dose Modifications for Other Adverse Drug Reactions in Patients with Adenocarcinoma of the Pancreas Adverse Drug Reaction ABRAXANE Gemcitabine Febrile Neutropenia: Grade 3 or 4 Withhold until fever resolves and ANC ≥ 1500; resume at next lower dose level Peripheral Neuropathy: Grade 3 or 4 Withhold until improves to ≤ Grade 1; resume at next lower dose level No dose reduction Cutaneous Toxicity: Grade 2 or 3 Reduce to next lower dose level; discontinue treatment if toxicity persists Gastrointestinal Toxicity: Grade 3 mucositis or diarrhea Withhold until improves to ≤ Grade 1; resume at next lower dose level Preparation And Administration Precautions ABRAXANE is a cytotoxic drug and, as with other potentially toxic paclitaxel compounds, caution should be exercised in handling ABRAXANE. The use of gloves is recommended. If ABRAXANE (lyophilized cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure to paclitaxel, events may include tingling, burning and redness. If ABRAXANE contacts mucous membranes, the membranes should be flushed thoroughly with water. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces the likelihood of infusion-related reactions [see ADVERSE REACTIONS]. Premedication to prevent hypersensitivity reactions is generally not needed prior to the administration of ABRAXANE. Premedication may be needed in patients who have had prior hypersensitivity reactions to ABRAXANE. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be re-challenged with this drug [see WARNINGS AND PRECAUTIONS]. Preparation For Intravenous Administration ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION. 1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP. 2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a minimum of 1 minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL. 3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this will result in foaming. 4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder. 5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder occurs. Avoid generation of foam. 6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel. The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. Discard any unused portion. Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient and slowly withdraw the dosing volume of the reconstituted suspension from the vial(s) into a syringe: Dosing volume (mL)=Total dose (mg)/5 (mg/mL). Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile intravenous bag [plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type intravenous bag]. The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of medical devices containing silicone oil as a lubricant (ie, syringes and intravenous bags) to reconstitute and administer ABRAXANE may result in the formation of proteinaceous strands. Visually inspect the reconstituted ABRAXANE suspension in the intravenous bag prior to administration. Discard the reconstituted suspension if proteinaceous strands, particulate matter or discoloration are observed. Stability Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20°C to 25°C (68°F to 77°F) in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Stability of Reconstituted Suspension in the Vial Reconstituted ABRAXANE in the vial should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 24 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion. Stability of Reconstituted Suspension in the Infusion Bag The suspension for infusion when prepared as recommended in an infusion bag should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) and protected from bright light for a maximum of 24 hours. The total combined refrigerated storage time of reconstituted ABRAXANE in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25°C) and lighting conditions for a maximum of 4 hours. Discard any unused portion. HOW SUPPLIED Dosage Forms And Strengths For injectable suspension: lyophilized powder containing 100 mg of paclitaxel formulated as albumin-bound particles in single-use vial for reconstitution. Storage And Handling Product No.: 103450 NDC No.: 68817-134-50 100 mg of paclitaxel in a single-use vial, individually packaged in a carton. Storage Store the vials in original cartons at 20°C to 25°C (68°F to 77°F). Retain in the original package to protect from bright light. Handling And Disposal Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published [see REFERENCES]. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. REFERENCES 1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165. 2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html 3. American Society of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm. 2006;63:1172-1193. 4. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society. Manufactured for: Celgene Corporation, Summit, NJ 07901. Revised: July 2015"" }, ""159"": { ""property.id"": 159, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": """" }, ""160"": { ""property.id"": 160, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Hematologic Effects Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC), 47% of patients with non-small cell lung cancer (NSCLC), and 38% of patients with pancreatic cancer. Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1 (for MBC) and Days 1, 8, and 15 (for NSCLC and for pancreatic cancer). Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm³. In the case of severe neutropenia ( < 500 cells/mm³ for seven days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with either MBC or NSCLC. In patients with MBC, resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level > 1,500 cells/mm³ and platelets recover to a level > 100,000 cells/mm³. In patients with NSCLC, resume treatment if recommended (see DOSAGE AND ADMINISTRATION, Table 2) at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm³ and platelet count of at least 100,000 cells/mm³ on Day 1 or to an ANC of at least 500 cells/mm³ and platelet count of at least 50,000 cells/mm³ on Days 8 or 15 of the cycle [see DOSAGE AND ADMINISTRATION]. In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm³ or platelets are less than 50,000 cells/mm³ and delay initiation of the next cycle if the ANC is less than 1500 cells/mm³ or platelet count is less than 100,000 cells/mm³ on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended [see DOSAGE AND ADMINISTRATION]. Nervous System Sensory neuropathy is dose- and schedule-dependent [see ADVERSE REACTIONS]. The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification. If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to Grade 1 or 2 for metastatic breast cancer or until resolution to ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE [see DOSAGE AND ADMINISTRATION]. Sepsis Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine. Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis. If a patient becomes febrile (regardless of ANC) initiate treatment with broad spectrum antibiotics. For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥ 1500, then resume treatment at reduced dose levels [see DOSAGE AND ADMINISTRATION]. Pneumonitis Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine. Monitor patients for signs and symptoms of pneumonitis and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis. After ruling out infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue treatment with ABRAXANE and gemcitabine. Hypersensitivity Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug. Hepatic Impairment Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution. Patients with hepatic impairment may be at increased risk of toxicity, particularly from myelosuppression; such patients should be closely monitored for development of profound myelosuppression. ABRAXANE is not recommended in patients who have total bilirubin > 5 x ULN or AST > 10 x ULN. In addition, ABRAXANE is not recommended in patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and AST ≤ 10 x ULN). The starting dose should be reduced for patients with moderate or severe hepatic impairment [see DOSAGE AND ADMINISTRATION, Use in Specific Populations and CLINICAL PHARMACOLOGY]. Albumin (Human) ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries a remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin. Use In Pregnancy ABRAXANE can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy at doses lower than the maximum recommended human dose, based on body surface area, caused embryo-fetal toxicities, including intrauterine mortality, increased resorptions, reduced numbers of live fetuses, and malformations. There are no adequate and well-controlled studies in pregnant women receiving ABRAXANE. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE [see Use in Specific Populations]. Use In Men Men should be advised not to father a child while receiving ABRAXANE [see Nonclinical Toxicology]. Patient Counseling Information See FDA-approved patient labeling ABRAXANE injection may cause fetal harm. Advise patients to avoid becoming pregnant while receiving this drug. Women of childbearing potential should use effective contraceptives while receiving ABRAXANE [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. Advise men not to father a child while receiving ABRAXANE [see WARNINGS AND PRECAUTIONS]. Patients must be informed of the risk of low blood cell counts and severe and life-threatening infections and instructed to contact their physician immediately for fever or evidence of infection. [see WARNINGS AND PRECAUTIONS]. Patients should be instructed to contact their physician for persistent vomiting, diarrhea, or signs of dehydration. Patients must be informed that sensory neuropathy occurs frequently with ABRAXANE and patients should advise their physicians of numbness, tingling, pain or weakness involving the extremities [see WARNINGS AND PRECAUTIONS]. Explain to patients that alopecia, fatigue/asthenia, and myalgia/arthralgia occur frequently with ABRAXANE Instruct patients to contact their physician for signs of an allergic reaction, which could be severe and sometimes fatal. [see WARNINGS AND PRECAUTIONS]. Instruct patients to contact their physician immediately for sudden onset of dry persistent cough, or shortness of breath [see WARNINGS AND PRECAUTIONS]. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility The carcinogenic potential of ABRAXANE has not been studied. Paclitaxel was clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay. Administration of paclitaxel formulated as albumin-bound particles to male rats at 42 mg/m² on a weekly basis (approximately 16% of the daily maximum recommended human exposure on a body surface area basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m²/week in this study (approximately 1 to 5% of the daily maximum recommended human exposure on a mg/m² basis). Testicular atrophy/degeneration was observed in single-dose toxicology studies in rodents administered paclitaxel formulated as albumin-bound particles at doses lower than the recommended human dose; doses were 54 mg/m² in rodents and 175 mg/m² in dogs. Use In Specific Populations Pregnancy Pregnancy Category D [see WARNINGS AND PRECAUTIONS]. There are no adequate and well-controlled studies in pregnant women using ABRAXANE. Based on its mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE. Administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy, on gestation days 7 to 17 at doses of 6 mg/m² (approximately 2% of the daily maximum recommended human dose on a mg/m² basis) caused embryofetal toxicities, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m² (approximately 1% of the daily maximum recommended human dose on a mg/m² basis). Nursing Mothers It is not known whether paclitaxel is excreted in human milk. Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated. Geriatric Use Of the 229 patients in the randomized study who received ABRAXANE for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. No toxicities occurred notably more frequently among patients who received ABRAXANE. A subsequent pooled analysis was conducted in 981 patients receiving ABRAXANE monotherapy for metastatic breast cancer, of which 15% were 65 years of age or older and 2% were 75 years of age or older. A higher incidence of epistaxis, diarrhea, dehydration, fatigue and peripheral edema was found in patients 65 years of age or older. Of the 514 patients in the randomized study who received ABRAXANE and carboplatin for the first-line treatment of non-small cell lung cancer, 31% were 65 years or older and 3.5% were 75 years or older. Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients 65 years or older compared to patients younger than 65 years old. No overall difference in effectiveness, as measured by response rates, was observed between patients 65 years or older compared to patients younger than 65 years old. Of the 431 patients in the randomized study who received ABRAXANE and gemcitabine for the first-line treatment of pancreatic adenocarcinoma, 41% were 65 years or older and 10% were 75 years or older. No overall differences in effectiveness were observed between patients who were 65 years of age or older and younger patients. Diarrhea, decreased appetite, dehydration and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old. Clinical studies of ABRAXANE did not include sufficient number of patients with pancreatic cancer who were 75 years and older to determine whether they respond differently from younger patients. Patients With Hepatic Impairment The exposure to paclitaxel may be higher in patients with hepatic impairment than in patients with normal hepatic function. Reduce  ABRAXANE starting dose in patients with moderate to severe hepatic impairment. Do not administer ABRAXANE to patients with total bilirubin > 5 x ULN or AST > 10 x ULN [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Do not administer to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment [see DOSAGE AND ADMINISTRATION]. Patients With Renal Impairment Adjustment of the starting ABRAXANE dose is not required for patients with mild to moderate renal impairment (estimated creatinine clearance ≥ 30 to < 90 mL/min) [see CLINICAL PHARMACOLOGY]. There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)."" }, ""161"": { ""property.id"": 161, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": """" }, ""162"": { ""property.id"": 162, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Mechanism Of Action ABRAXANE is a microtubule inhibitor that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Pharmacokinetics Absorption The pharmacokinetics of total paclitaxel following 30 and 180-minute infusions of ABRAXANE at dose levels of 80 to 375 mg/m² were determined in clinical studies. Dose levels of mg/m² refer to mg of paclitaxel in ABRAXANE. Following intravenous administration of ABRAXANE, paclitaxel plasma concentrations declined in a biphasic manner, the initial rapid decline representing distribution to the peripheral compartment and the slower second phase representing drug elimination. The drug exposure (AUCs) was dose proportional over 80 to 300 mg/m² and the pharmacokinetics of paclitaxel for ABRAXANE were independent of the duration of intravenous administration. The pharmacokinetic data of 260 mg/m² ABRAXANE administered over a 30-minute infusion was compared to the pharmacokinetics of 175 mg/m² paclitaxel injection over a 3-hour infusion. Clearance was larger (43%) and the volume of distribution was higher (53%) for ABRAXANE than for paclitaxel injection. There were no differences in terminal half-lives. Distribution Following ABRAXANE administration to patients with solid tumors, paclitaxel is evenly distributed into blood cells and plasma and is highly bound to plasma proteins (94%). In a within-patient comparison study, the fraction of unbound paclitaxel in plasma was significantly higher with ABRAXANE (6.2%) than with solvent-based paclitaxel (2.3%). This contributes to significantly higher exposure to unbound paclitaxel with ABRAXANE compared with solvent-based paclitaxel, when the total exposure is comparable. In vitro studies of binding to human serum proteins, using paclitaxel concentrations ranging from 0.1 to 50 μg/mL, indicated that the presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. The total volume of distribution is approximately 1741 L; the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of paclitaxel. Metabolism In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6α- hydroxypaclitaxel by CYP2C8; and to two minor metabolites, 3'-p-hydroxypaclitaxel and 6α, 3'-p-dihydroxypaclitaxel, by CYP3A4. In vitro, the metabolism of paclitaxel to 6α-hydroxypaclitaxel was inhibited by a number of agents (ketoconazole, verapamil, diazepam, quinidine, dexamethasone, cyclosporin, teniposide, etoposide, and vincristine), but the concentrations used exceeded those found in vivo following normal therapeutic doses. Testosterone, 17α-ethinyl estradiol, retinoic acid, and quercetin, a specific inhibitor of CYP2C8, also inhibited the formation of 6α-hydroxypaclitaxel in vitro. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with compounds that are substrates, inducers, or inhibitors of CYP2C8 and/or CYP3A4 [see DRUG INTERACTIONS]. Elimination At the clinical dose range of 80 to 300 mg/m², the mean total clearance of paclitaxel ranges from 13 to 30 L/h/m², and the mean terminal half-life ranges from 13 to 27 hours. After a 30-minute infusion of 260 mg/m² doses of ABRAXANE, the mean values for cumulative urinary recovery of unchanged drug (4%) indicated extensive non-renal clearance. Less than 1% of the total administered dose was excreted in urine as the metabolites 6α-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel. Fecal excretion was approximately 20% of the total dose administered. Specific Populations Pharmacokinetics in Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of paclitaxel following ABRAXANE administration was studied in patients with advanced solid tumors. The results showed that mild hepatic impairment (total bilirubin > 1 to ≤ 1.5 x ULN, AST ≤ 10 x ULN, n=8) had no clinically important effect on pharmacokinetics of paclitaxel. Patients with moderate (total bilirubin > 1.5 to ≤ 3 x ULN, AST ≤ 10 x ULN, n=7) or severe (total bilirubin > 3 to ≤ 5 x ULN, n=5) hepatic impairment had a 22% to 26% decrease in the maximum elimination rate of paclitaxel and approximately 20% increase in mean paclitaxel AUC compared with patients with normal hepatic function (total bilirubin ≤ ULN, AST ≤ ULN, n=130). [see DOSAGE AND ADMINISTRATION and Use In Specific Populations]. Elimination of paclitaxel shows an inverse correlation with total bilirubin and a positive correlation with serum albumin. Pharmacokinetic/pharmacodynamic modeling indicates that there is no correlation between hepatic function (as indicated by the baseline albumin or total bilirubin level) and neutropenia after adjusting for ABRAXANE exposure. Pharmacokinetic data are not available for patients with total bilirubin > 5 x ULN or for patients with metastatic adenocarcinoma of the pancreas [see DOSAGE AND ADMINISTRATION and Use in Specific Populations]. Pharmacokinetics in Renal Impairment The effect of pre-existing mild (creatinine clearance ≥ 60 to < 90 mL/min, n=61) or moderate (creatinine clearance ≥ 30 to < 60 mL/min, n=23) renal impairment on the pharmacokinetics of paclitaxel following ABRAXANE administration was studied in patients with advanced solid tumors. Mild to moderate renal impairment had no clinically important effect on the maximum elimination rate and systemic exposure (AUC and Cmax) of paclitaxel [see Use In Specific Populations]. Other Intrinsic Factors Population pharmacokinetic analyses for ABRAXANE show that body weight (40 to 143 kg), body surface area (1.3 to 2.4 m²), gender, race (Asian vs. White), age (24 to 85 years) and type of solid tumors do not have a clinically important effect on the maximum elimination rate and systemic exposure (AUC and Cmax) of paclitaxel. Pharmacokinetic Interactions between ABRAXANE and Carboplatin Administration of carboplatin immediately after the completion of the ABRAXANE infusion to patients with NSCLC did not cause clinically meaningful changes in paclitaxel exposure. The observed mean AUCinf of free carboplatin was approximately 23% higher than the targeted value (6 min*mg/mL), but its mean half-life and clearance were consistent with those reported in the absence of paclitaxel. Pharmacokinetic Interactions between ABRAXANE and Gemcitabine Pharmacokinetic interactions between ABRAXANE and gemcitabine have not been studied in humans. Clinical Studies Metastatic Breast Cancer Data from 106 patients accrued in two single arm open label studies and from 460 patients enrolled in a randomized comparative study were available to support the use of ABRAXANE in metastatic breast cancer. Single Arm Open Label Studies In one study, ABRAXANE was administered as a 30-minute infusion at a dose of 175 mg/m² to 43 patients with metastatic breast cancer. The second trial utilized a dose of 300 mg/m² as a 30-minute infusion in 63 patients with metastatic breast cancer. Cycles were administered at 3-week intervals. Objective responses were observed in both studies. Randomized Comparative Study This multicenter trial was conducted in 460 patients with metastatic breast cancer. Patients were randomized to receive ABRAXANE at a dose of 260 mg/m² given as a 30-minute infusion, or paclitaxel injection at 175 mg/m² given as a 3-hour infusion. Sixty-four percent of patients had impaired performance status (ECOG 1 or 2) at study entry; 79% had visceral metastases; and 76% had > 3 sites of metastases. Fourteen percent of the patients had not received prior chemotherapy; 27% had received chemotherapy in the adjuvant setting, 40% in the metastatic setting and 19% in both metastatic and adjuvant settings. Fifty-nine percent received study drug as second or greater than second-line therapy. Seventy-seven percent of the patients had been previously exposed to anthracyclines. In this trial, patients in the ABRAXANE treatment arm had a statistically significantly higher reconciled target lesion response rate (the trial primary endpoint) of 21.5% (95% CI: 16.2% to 26.7%), compared to 11.1% (95% CI: 6.9% to 15.1%) for patients in the paclitaxel injection treatment arm. See Table 11. There was no statistically significant difference in overall survival between the two study arms. Table 11: Efficacy Results from Randomized Metastatic Breast Cancer Trial ABRAXANE 260 mg/m² Paclitaxel Injection 175 mg/m² Reconciled Target Lesion Response Rate (primary endpoint)a All randomized patients Response Rate [95% CI] 50/233 (21.5%) [16.19% - 26.73%] 25/227 (11.1%) [6.94% - 15.09%] p-valueb 0.003 Patients who had failed combination chemotherapy or relapsed within 6 months of adjuvant chemotherapyc Response Rate [95% CI] 20/129 (15.5%) [9.26% - 21.75%] 12/143 (8.4%) [3.85% - 12.94%] a Reconciled Target Lesion Response Rate (TLRR) was the prospectively defined protocol specific endpoint, based on independent radiologic assessment of tumor responses reconciled with investigator responses (which also included clinical information) for the first 6 cycles of therapy. The reconciled TLRR was lower than the investigator Reported Response Rates, which are based on all cycles of therapy. b From Cochran-Mantel-Haenszel test stratified by 1st line vs. > 1st line therapy. c Prior therapy included an anthracycline unless clinically contraindicated. Non-Small Cell Lung Cancer A multicenter, randomized, open-label study was conducted in 1052 chemonaive patients with Stage IIIb/IV non-small cell lung cancer to compare ABRAXANE in combination with carboplatin to paclitaxel injection in combination with carboplatin as first-line treatment in patients with advanced non-small cell lung cancer. ABRAXANE was administered as an intravenous infusion over 30 minutes at a dose of 100 mg/m² on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as an intravenous infusion over 3 hours at a dose of 200 mg/m², following premedication. In both treatment arms carboplatin at a dose of AUC =6 mg•min/mL was administered intravenously on Day 1 of each 21-day cycle after completion of ABRAXANE/paclitaxel infusion. Treatment was administered until disease progression or development of an unacceptable toxicity. The major efficacy outcome measure was overall response rate as determined by a central independent review committee using RECIST guidelines (Version 1.0). In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 81% were White, 49% had adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1, and 73% were current or former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients in the ABRAXANE/carboplatin arm had a statistically significantly higher overall response rate compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%) see Table 12]. There was no statistically significant difference in overall survival between the two study arms. Table 12: Efficacy Results from Randomized Non-Small Cell Lung Cancer Trial (Intent-to-Treat Population) ABRAXANE (100 mg/m² weekly) + carboplatin (N=521) Paclitaxel Injection (200 mg/m² every 3 weeks) + carboplatin (N=531) Overall Response Rate (ORR) Confirmed complete or partial overall response, n (%) 170 (33%) 132 (25%) 95% CI 28.6, 36.7 21.2, 28.5 P-value (Chi-Square test) 0.005 Median DoR in months (95% CI) 6.9 (5.6, 8.0) 6.0 (5.6, 7.1) Overall Response Rate by Histology Carcinoma/Adenocarcinoma 66/254 (26%) 71/264 (27%) Squamous Cell Carcinoma 94/229 (41%) 54/221 (24%) Large Cell Carcinoma 3/9 (33%) 2/13 (15%) Other 7/29 (24%) 5/33 (15%) CI = confidence interval; DoR= Duration of response Adenocarcinoma Of The Pancreas A multicenter, multinational, randomized, open-label study was conducted in 861 patients comparing ABRAXANE plus gemcitabine versus gemcitabine monotherapy as first-line treatment of metastatic adenocarcinoma of the pancreas. Key eligibility criteria were Karnofsky Performance Status (KPS) ≥ 70, normal bilirubin level, transaminase levels ≤ 2.5 times the upper limit of normal (ULN) or ≤ 5 times the ULN for patients with liver metastasis, no prior cytotoxic chemotherapy in the adjuvant setting or for metastatic disease, no ongoing active infection requiring systemic therapy, and no history of interstitial lung disease. Patients with rapid decline in KPS ( ≥ 10%) or serum albumin ( ≥ 20%) during the 14 day screening period prior to study randomization were ineligible. A total of 861 patients were randomized (1:1) to the ABRAXANE/gemcitabine arm (N=431) or to the gemcitabine arm (N=430). Randomization was stratified by geographic region (Australia, Western Europe, Eastern Europe, or North America), KPS (70 to 80 versus 90 to 100), and presence of liver metastasis (yes versus no). Patients randomized to ABRAXANE/gemcitabine received ABRAXANE 125 mg/m² as an intravenous infusion over 30-40 minutes followed by gemcitabine 1000 mg/m² as an intravenous infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Patients randomized to gemcitabine received 1000 mg/m² as an intravenous infusion over 30-40 minutes weekly for 7 weeks followed by a 1-week rest period in Cycle 1 then as 1000 mg/m² on Days 1, 8 and 15 of each subsequent 28-day cycle. Patients in both arms received treatment until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS). Additional outcome measures were progression-free survival (PFS) and overall response rate (ORR), both assessed by independent, central, blinded radiological review using RECIST (version 1.0). In the intent to treat (all randomized) population, the median age was 63 years (range 27-88 years) with 42% ≥ 65 years of age; 58% were men; 93% were White and KPS was 90-100 in 60%. Disease characteristics included 46% of patients with 3 or more metastatic sites; 84% of patients had liver metastasis; and the location of the primary pancreatic lesion was in the head of pancreas (43%), body (31%), or tail (25%). Results for overall survival, progression-free survival, and overall response rate are shown in Table 13. Table 13: Efficacy Results from Randomized Study in Patients with Adenocarcinoma of the Pancreas (ITT Population) ABRAXANE(125 mg/m²) and gemcitabine (N = 431) Gemcitabine (N = 430) Overall Survival Number of deaths, n (%) 333 (77) 359 (83) Median Overall Survival (months) 8.5 6.7 95% CI 7.9, 9.5 6.0, 7.2 HR (95% CI) a 0.72 (0.62, 0.83) P-valueb < 0.0001 Progression-free Survivalc Death or progression, n (%) 277 (64) 265 (62) Median Progression-free Survival (months) 5.5 3.7 95% CI 4.5, 5.9 3.6, 4.0 HR (95% CI) a 0.69 (0.58, 0.82) P-valueb < 0.0001 Overall Response Ratec Confirmed complete or partial overall response, n (%) 99 (23) 31 (7) 95% CI 19.1, 27.2 5.0, 10.1 P-value d < 0.0001 CI = confidence interval, HR= hazard ratio of ABRAXANE plus gemcitabine / gemcitabine, ITT = intent-to-treat population. a Stratified Cox proportional hazard model. b Stratified log-rank test stratified by geographic region (North America versus Others), Karnofsky performance score (70 to 80 versus 90 to 100), and presence of liver metastasis (yes versus no). c Based on Independent Radiological Reviewer Assessment. d Chi-square test. In exploratory analyses conducted in clinically relevant subgroups with a sufficient number of subjects, the treatment effects on overall survival were similar to that observed in the overall study population. Figure 1: Kaplan-Meier Curve of Overall Survival (Intent-to-treat Population)"" }, ""163"": { ""property.id"": 163, ""property.ts"": ""2017-12-04 04:39:35"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION ABRAXANE® (ah-BRAKS-ane) (paclitaxel) Protein-bound Particles for Injectable Suspension Read this Patient Information before you start receiving ABRAXANE and before each infusion. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is ABRAXANE? ABRAXANE is a prescription medicine used to treat: advanced breast cancer in people who have already received certain other medicines for their cancer. advanced non-small cell lung cancer, in combination with carboplatin in people who cannot be treated with surgery or radiation. and advanced pancreatic cancer, when used in combination with gemcitabine as the first medicine for advanced pancreatic cancer. It is not known if ABRAXANE is safe or effective in children. Who should not receive ABRAXANE? Do not receive ABRAXANE if: your white blood cell count is below 1,500 cells/ mm³. you have had a severe allergic reaction to ABRAXANE. What should I tell my doctor before receiving ABRAXANE? Before you receive ABRAXANE, tell your doctor if you: have liver or kidney problems. have any other medical conditions. are a man planning to father a child. You should not father a child during your treatment with ABRAXANE. ABRAXANE can harm the unborn baby of your partner. Talk to your doctor if this is a concern to you. are pregnant or plan to become pregnant. ABRAXANE can harm your unborn baby. You should not become pregnant while receiving ABRAXANE. Women who may become pregnant should use effective birth control (contraception). Talk to your doctor about the best way to prevent pregnancy while receiving ABRAXANE. are breastfeeding or plan to breastfeed. It is not known if ABRAXANE passes into your breast milk. You and your doctor should decide if you will receive ABRAXANE or breastfeed. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list to show your doctor and pharmacist when you get a new medicine. How will I receive ABRAXANE? Your doctor will prescribe ABRAXANE in an amount that is right for you. Premedication to prevent allergic reactions is generally not needed to receive ABRAXANE. Premedication may be needed if you have had an allergic reaction to ABRAXANE. In case of severe allergic reaction, ABRAXANE should not be used again. ABRAXANE will be given to you by intravenous infusion into your vein. Your doctor should do regular blood tests while you receive ABRAXANE. What are the possible side effects of ABRAXANE? ABRAXANE may cause serious side effects, including: decreased blood cell counts. ABRAXANE can cause a severe decrease in neutrophils (a type of white blood cells important in fighting against bacterial infections) and platelets (important for clotting and to control bleeding). Your doctor will check your blood cell count during your treatment with ABRAXANE and after you have stopped your treatment. numbness, tingling, pain, or weakness in your hands or feet (neuropathy). severe infection (sepsis). If you receive ABRAXANE in combination with gemcitabine, infections can be severe and lead to death. Tell your doctor right away if you have a fever (temperature of greater than 100.4° F) or develop signs of infection. lung or breathing problems. If you receive ABRAXANE in combination with gemcitabine, lung or breathing problems may be severe and can lead to death. Tell your doctor right away if you have a sudden onset of persistent dry cough or shortness of breath. allergic reactions. Allergic reactions to ABRAXANE may be severe and can lead to death. The most common side effects of ABRAXANE include: hair loss numbness, tingling, pain, or weakness in the hands or feet abnormal heart beat tiredness joint and muscle pain changes in your liver function tests rash low red blood cell count (anemia). Red blood cells carry oxygen to your body tissues. Tell your doctor if you feel weak, tired or short of breath. nausea and vomiting infections. If you have a fever (temperature of greater than 100.4° F) or other signs of infection, tell your doctor right away. Diarrhea Loss of body fluid (dehydration) Swelling in the hands or feet These are not all the possible side effects of ABRAXANE. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of ABRAXANE. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. This Patient Information leaflet summarizes the important information about ABRAXANE. If you would like more information, talk to your doctor. You can ask your doctor or pharmacist for information about ABRAXANE that is written for health professionals. For more information, call 1-888-423-5436. What are the ingredients in ABRAXANE? Active ingredient: paclitaxel (bound to human albumin). Other ingredient: human albumin (containing sodium caprylate and sodium acetyltryptophanate)."" } }" 25,"2017-08-31 23:12:57",Abraxane,"Albumin-bound Paclitaxel for Injectable Suspension",Multum,"{ ""25"": { ""alphabet_x_drug.id"": 25, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""164"": { ""property.id"": 164, ""property.ts"": ""2017-12-04 04:39:45"", ""property.key"": ""Abraxane Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Abraxane Generic Name: paclitaxel protein-bound (Pronunciation: PAK li TAX el PRO teen-bound) What is paclitaxel protein-bound (Abraxane)? What are the possible side effects of paclitaxel protein-bound (Abraxane)? What is the most important information I should know about paclitaxel protein-bound (Abraxane)? What should I discuss with my healthcare provider before receiving paclitaxel protein-bound (Abraxane)? How is paclitaxel protein-bound given (Abraxane)? What happens if I miss a dose (Abraxane)? What happens if I overdose (Abraxane)? What should I avoid while using paclitaxel protein-bound (Abraxane)? What other drugs will affect paclitaxel protein-bound (Abraxane)? Where can I get more information? What is paclitaxel protein-bound (Abraxane)? Paclitaxel protein-bound is a cancer medication that interferes with the growth and spread of cancer cells in the body.Paclitaxel protein-bound is used in the treatment of breast cancer.Paclitaxel protein-bound is usually given after other cancer medicines have been tried without successful treatment.Paclitaxel protein-bound may also be used for purposes not listed in this medication guide. What are the possible side effects of paclitaxel protein-bound (Abraxane)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.Call your doctor at once if you have a serious side effect such as:fever, chills, body aches, flu symptoms, sores in your mouth and throat;feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;feeling like you might pass out;feeling short of breath (even with mild exertion), swelling, rapid weight gain;chest pain, sudden cough, wheezing, trouble breathing, fast heart rate; orsevere skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.Less serious side effects may include:numbness or tingly feeling;muscle or joint pain;nausea, vomiting;diarrhea; orhair loss.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about paclitaxel protein-bound (Abraxane)? Do not use paclitaxel protein-bound if you are pregnant. It could harm the unborn baby.Use birth control to prevent pregnancy while you are receiving paclitaxel protein-bound, whether you are a man or a woman. Paclitaxel protein-bound use by either parent may cause birth defects.You should not use paclitaxel protein-bound if you are allergic to it, or if you have a low white blood cell count.Before you receive this medication, tell your doctor if you have kidney disease, liver disease, heart disease, or bone marrow suppression.To make sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow-up visits to your doctor.Call your doctor at once if you have a serious side effect such as fever, chills, flu symptoms, mouth sores, easy bruising or bleeding, pale skin, feeling light-headed or short of breath, swelling or rapid weight gain, chest pain, sudden cough, rapid heart rate, or trouble breathing."" }, ""165"": { ""property.id"": 165, ""property.ts"": ""2017-12-04 04:39:45"", ""property.key"": ""Abraxane Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my healthcare provider before receiving paclitaxel protein-bound (Abraxane)? You should not use paclitaxel protein-bound if you are allergic to it, or if you have a low white blood cell count.To make sure you can safely receive paclitaxel protein-bound, tell your doctor if you have any of these other conditions:kidney disease;liver disease;heart disease, heart rhythm disorder; orbone marrow suppression.FDA pregnancy category D. Do not use paclitaxel protein-bound if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.Use birth control to prevent pregnancy while you are receiving paclitaxel protein-bound, whether you are a man or a woman. Paclitaxel protein-bound use by either parent may cause birth defects.It is not known whether paclitaxel protein-bound passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are receiving paclitaxel protein-bound. How is paclitaxel protein-bound given (Abraxane)? Paclitaxel protein-bound is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Paclitaxel protein-bound must be given slowly, and the IV infusion can take at least 30 minutes to complete.Paclitaxel protein-bound is usually given once every 3 weeks. Follow your doctor's dosing instructions very carefully.Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when paclitaxel protein-bound is injected.To make sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow-up visits to your doctor."" }, ""166"": { ""property.id"": 166, ""property.ts"": ""2017-12-04 04:39:45"", ""property.key"": ""Abraxane Patient Information including If I Miss a Dose"", ""property.value"": """" } }" 26,"2017-08-31 23:12:57","Absorbable Gelatin Compressed Sponge, USP","Gelfoam Compressed Sponge",FDA,"{ ""26"": { ""alphabet_x_drug.id"": 26, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""167"": { ""property.id"": 167, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Drug Description"", ""property.value"": ""Gelfoam® absorbable gelatin compressed sponge, USP DESCRIPTION GELFOAM Sterile Compressed Sponge is a medical device intended for application to bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product prepared from purified porcine skin, Gelatin USP Granules and Water for Injection, USP. It may be cut without fraying and is able to absorb and hold within its interstices, many times its weight of blood and other fluids."" }, ""168"": { ""property.id"": 168, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS HEMOSTASIS: GELFOAM Sterile Compressed Sponge, used dry or saturated with sterile sodium chloride solution, is indicated in surgical procedures as a hemostatic device, when control of capillary, venous, and arteriolar bleeding by pressure, ligature, and other conventional procedures is either ineffective or impractical. Although not necessary, GELFOAM can be used either with or without thrombin to obtain hemostasis. Directions For Use Sterile technique should always be used to remove GELFOAM Sterile Compressed Sponge from its packaging. Cut to the desired size, a piece of GELFOAM, either dry or saturated with sterile, isotonic sodium chloride solution (sterile saline), can be applied with pressure directly to the bleeding site. When applied dry, a single piece of GELFOAM should be manually applied to the bleeding site, and held in place with moderate pressure until hemostasis results. When used with sterile saline, GELFOAM should be first immersed in the solution and then withdrawn, squeezed between gloved fingers to expel air bubbles, and then replaced in saline until needed. The GELFOAM sponge should promptly return to its original size, with slight expansion in thickness and shape in the solution. If it does not, it should be removed again and kneaded vigorously until all air is expelled and it does expand to its original size, with slight increases in thickness and shape when returned to the sterile saline. GELFOAM if used wet it may be blotted to dampness on gauze before application to the bleeding site. It should be held in place with moderate pressure, using a pledget of cotton or small gauze sponge until hemostasis results. Removal of the pledget or gauze is made easier by wetting it with a few drops of sterile saline, to prevent pulling up the GELFOAM, which by then should enclose a firm clot. Use of suction applied over the pledget of cotton or gauze to draw blood into the GELFOAM is unnecessary, as GELFOAM will draw up sufficient blood by capillary action. The first application of GELFOAM will usually control bleeding, but if not, additional applications may be made. For additional applications, fresh pieces should be used and prepared as previously described. Use only the minimum amount of GELFOAM, cut to appropriate size, necessary to produce hemostasis. The GELFOAM may be left in place at the bleeding site, when necessary. Since GELFOAM causes little more cellular reaction than does the blood clot, the wound may be closed over it. GELFOAM may be left in place when applied to mucosal surfaces until it liquefies. For use with thrombin, consult the thrombin insert for complete prescribing information and proper sample preparation. DOSAGE AND ADMINISTRATION Sterile technique should always be used in removing the inner envelope containing the GELFOAM Sterile Sponge from the outer printed sealed envelope. The minimum amount of GELFOAM of appropriate size and shape should be applied (dry or wet, see Directions for Use) to the bleeding site and held firmly in place until hemostasis is observed. Opened envelopes of unused GELFOAM should always be discarded. HOW SUPPLIED GELFOAM Sterile Compressed Sponge is supplied in an individual sterile envelope enclosed in an outer peelable envelope. Sterility of the product is assured unless the outer envelope has been damaged or opened. It is available as follows Sponge-Size 100 Box of 6 GTIN 00300090353018 (0009-0353-01) (100 sq cm (8X12.5 cm), 15 5/8 sq in (3 1/8 X 5 in) Storage And Handling GELFOAM Sterile Compressed Sponge should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the package is opened, contents are subject to contamination. It is recommended that GELFOAM be used as soon as the package is opened and unused contents discarded. This product is prepackaged sterile and intended only for single use. Reuse can result in transmission of bloodborne pathogens (including HIV and hepatitis), potentially endangering patients and health care providers. Adherence to the principles of aseptic technique when using this product is essential. Caution Federal law restricts this device to sale by or on the order of a physician. Manufactured by: Pharmacia and Upjohn Company, 7000 Portage Road, Kalamazoo, Michigan 49001, USA, 1-800-253-8600. Distributed by: Pharmacia & Upjohn Co., Division of Pfizer Inc., New York, NY 10017. Revised December 2014"" }, ""169"": { ""property.id"": 169, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS There have been reports of fever associated with the use of GELFOAM, without demonstrable infection. GELFOAM Sterile Compressed Sponge may form a nidus of infection and abscess formation1, and has been reported to potentiate bacterial growth. Giant-cell granuloma has been reported at the implantation site of absorbable gelatin product in the brain2, and compression of the brain and spinal cord resulting from an accumulation of sterile fluid3 has been reported following use of absorbable gelatin sponge in closed space. Foreign body reactions, “encapsulation” of fluid and hematoma have also been reported. When GELFOAM was used in laminectomy operations, multiple neurologic events were reported, including but not limited to cauda equina syndrome, spinal stenosis, meningitis, arachnoiditis, headaches, paresthesias, pain, bladder and bowel dysfunction, and impotence. Excessive fibrosis and prolonged fixation of a tendon have been reported when absorbable gelatin products were used in severed tendon repair. Toxic shock syndrome has been reported in association with the use of GELFOAM in nasal surgery. Fever, failure of absorption, and hearing loss have been reported in association with the use of GELFOAM during tympanoplasty. Adverse Reactions Reported From Unapproved Use GELFOAM is not recommended for use other than as an adjunct for hemostasis. While some adverse medical events following the unapproved use of GELFOAM have been reported (see ADVERSE REACTIONS), other hazards associated with such use may not have been reported. When GELFOAM has been used during intravascular catheterization for the purpose of producing vessel occlusion, the following adverse events have been reported; fever, duodenal and pancreatic infarct, embolization of lower extremity vessels, pulmonary embolization, splenic abscess, necrosis of specific anatomic areas, asterixis, and death. These adverse medical events have been associated with the use of GELFOAM for repair of dural defects encountered during laminectomy and craniotomy operations: fever, infection, leg paresthesias, neck and back pain, bladder and bowel incontinence, cauda equina syndrome, neurogenic bladder, impotence, and paresis. DRUG INTERACTIONS No information provided. REFERENCES 1. Lindstrom PA: Complications from the use of absorbable hemostatic sponges. AMA Arch Surg 1956; 73:133-141. 2. Knowlson GTG: Gelfoam granuloma in the brain. J Neuro Neurosurg Psychiatry 1974; 37:971-973. 3. Herndon JH, Grillo HC, Riseborough EJ, et al: Compression of the brain and spinal cord following use of GELFOAM. Arch Surg 1972; 104:107."" }, ""170"": { ""property.id"": 170, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS GELFOAM Sterile Compressed Sponge is not intended as a substitute for meticulous surgical technique and the proper application of ligatures, or other conventional procedures for hemostasis. GELFOAM is supplied as a sterile product and cannot be resterilized. Unused, opened envelopes of GELFOAM should be discarded. WARNING: To prevent contamination, employ aseptic procedure in opening envelope and withdrawing GELFOAM. If the envelope is torn or punctured, the contained GELFOAM should not be used. Only the minimum amount of GELFOAM necessary to achieve hemostasis should be used. Once hemostasis is attained, excess GELFOAM should be carefully removed. The use of GELFOAM is not recommended in the presence of infection. GELFOAM should be used with caution in contaminated areas of the body. If signs of infection or abscess develop where GELFOAM has been positioned, reoperation may be necessary in order to remove the infected material and allow drainage. Although the safety and efficacy of the combined use of GELFOAM with other agents such as topical thrombin has not been evaluated in controlled clinical trials, if in the physician's judgment concurrent use of other agents is medically advisable, the product literature for that agent should be consulted for complete prescribing information. While packing a cavity for hemostasis is sometimes surgically indicated, GELFOAM should not be used in this manner unless excess product not needed to maintain hemostasis is removed. Whenever possible, it should be removed after use in laminectomy procedures and from foramina in bone, once hemostasis is achieved. This is because GELFOAM may swell to its original size on absorbing fluids, and produce nerve damage by pressure within confined bony spaces. The packing or wadding of GELFOAM, particularly within bony cavities, should be avoided, since swelling to original size may interfere with normal function and/or possibly result in compression necrosis of surrounding tissues. PRECAUTIONS Use only the minimum amount of GELFOAM Sterile Compressed Sponge needed for hemostasis, holding it at the site until bleeding stops, then removing the excess. GELFOAM should not be used for controlling postpartum bleeding or menorrhagia. It has been demonstrated that fragments of another hemostatic agent, microfibrillar collagen, pass through the 40μ transfusion filters of blood scavenging systems. GELFOAM should not be used in conjunction with autologous blood salvage circuits since the safety of this use has not been evaluated in controlled clinical trials. Microfibrillar collagen has been reported to reduce the strength of methylmethacrylate adhesives used to attach prosthetic devices to bone surfaces. As a precaution, GELFOAM should not be used in conjunction with such adhesives. GELFOAM is not recommended for the primary treatment of coagulation disorders. It is not recommended that GELFOAM be saturated with an antibiotic solution or dusted with antibiotic powder. Positioning of the patient resulting in negative peripheral venous pressure during a procedure has been reported to be a contributing factor resulting in life-threatening thromboembolic events."" }, ""171"": { ""property.id"": 171, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS GELFOAM Sterile Compressed Sponge should not be used in closure of skin incisions because it may interfere with the healing of skin edges. This is due to mechanical interposition of gelatin and is not secondary to intrinsic interference with wound healing. GELFOAM should not be placed in intravascular compartments, because of the risk of embolization. Do not use GELFOAM Sterile Compressed Sponge in patients with known allergies to porcine collagen."" }, ""172"": { ""property.id"": 172, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Actions GELFOAM Sterile Compressed Sponge has hemostatic properties. While its mode of action is not fully understood, its effect appears to be more physical than the result of altering the blood clotting mechanism. When not used in excessive amounts, GELFOAM is absorbed completely, with little tissue reaction. This absorption is dependent on several factors, including the amount used, degree of saturation with blood or other fluids, and the site of use. When placed in soft tissues, GELFOAM is usually absorbed completely within four to six weeks, without inducing excessive scar tissue. When applied to bleeding nasal, rectal, or vaginal mucosa, it liquefies within two to five days. Clinical Studies GELFOAM Sterile Compressed Sponge is a water-insoluble, hemostatic device prepared from purified porcine skin gelatin, and capable of absorbing up to 45 times its weight of whole blood.4 The absorptive capacity of GELFOAM is a function of its physical size, increasing as the size of the gelatin sponge increases.5 The mechanism of action of surface-mediated hemostatic devices is supportive and mechanical.5 Surface-acting devices, when applied directly to bleeding surfaces, arrest bleeding by the formation of an artificial clot and by producing a mechanical matrix that facilitates clotting.6 Jenkins et al7 have theorized that the clotting effect of GELFOAM may be due to release of thromboplastin from platelets, occurring when platelets entering the sponge become damaged by contact with the walls of its myriad of interstices. Thromboplastin interacts with prothrombin and calcium to produce thrombin, and this sequence of events initiates the clotting reaction. The authors suggest that the physiologic formation of thrombin in the sponge is sufficient to produce formation of a clot, by its action on the fibrinogen in blood.7 The spongy physical properties of the gelatin sponge hasten clot formation and provide structural support for the forming clot.6,8 Several investigators have reported that GELFOAM becomes liquefied within a week or less and is completely absorbed in four to six weeks, without inducing excessive scar formation.4,7,9,10,11 Barnes10 reviewed experiences with GELFOAM in gynecologic surgery. No excessive scar tissue, attributable to the absorption of GELFOAM, could be palpated at postoperative examination. Animal Pharmacology Surface-acting hemostatic devices, when applied directly to bleeding surfaces, arrest bleeding by providing a mechanical matrix that facilitates clotting.6,8,13,14 Due to their bulk, surface-acting hemostatic agents slow the flow of blood, protect the forming clot, and offer a framework for deposition of the cellular elements of blood.6,7,8,13 MacDonald and Mathews12 studied GELFOAM implants in canine kidneys and reported that it assisted in healing, with no marked inflammatory or foreign-body reactions. Jenkins and Janda13 studied the use of GELFOAM in canine liver resections and noted that the gelatin sponge appeared to offer a protective cover and provide structural support for the reparative process. Correll et al14 studied the histology of GELFOAM Sterile Compressed Sponge when implanted in rat muscle and reported no significant tissue reaction. REFERENCES 4. Council on Pharmacy and Chemistry: Absorbable Gelatin sponge — new and nonofficial remedies. JAMA 1947; 135:921. 5. Goodman LS, Gilman A: Surface-acting drugs, in The Pharmacologic Basis of Therapeutics, ed 6. New York, MacMillan Publishing Co. 1980, p 955. 6. Guralnick W, Berg L: GELFOAM in oral surgery. Oral Surg 1948; 1:629-632. 7. Jenkins HP, Senz EH, Owen H, et al: Present status of gelatin sponge for control of hemorrhage. JAMA 1946; 132:614-619. 8. Jenkins HP, Janda R, Clarke J: Clinical and experimental observations on the use of gelatin sponge or foam. Surg 1946; 20:124-132. 9. Treves N: Prophylaxis of post mammectomy lymphedema by the use of GELFOAM laminated rolls. Cancer 1952; 5:73-83. 10. Barnes AC: The use of gelatin foam sponges in obstetrics and gynecology. Am J Obstet Gynecol 1963; 86:105-107. 11. Rarig HR: Successful use of gelatin foam sponge in surgical restoration of fertility. Am J Obstet Gynecol 1963; 86:136. 12. MacDonald SA, Mathews WH: Fibrin foam and GELFOAM in experimental kidney wounds. Annual American Urological Association, July 1946. 13. Jenkins HP, Janda R: Studies on the use of gelatin sponge or foam as a hemostatic agent in experimental liver resections and injuries to large veins. Ann Surg 1946; 124:952-961. 14. Correll JT, Prentice HR, Wise EC: Biologic investigations of a new absorbable sponge. Surg Gynecol Obstet 1945; 181:585-589."" }, ""173"": { ""property.id"": 173, ""property.ts"": ""2017-12-04 04:39:51"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections."" } }" 27,"2017-08-31 23:12:57","Absorbable Gelatin Dental Sponge","Gelfoam Dental Sponge",FDA,"{ ""27"": { ""alphabet_x_drug.id"": 27, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""174"": { ""property.id"": 174, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Drug Description"", ""property.value"": ""Gelfoam® absorbable gelatin sponge, USP DESCRIPTION GELFOAM Dental Sponges are small, sterile, surgical sponges prepared from specially treated and purified gelatin solution which is beaten to desired porosity, dried, sectioned, packaged, sealed, and sterilized by dry heat. GELFOAM is pliable, and is capable of absorbing and holding within its meshes many times its weight in whole blood. It is used as a hemostatic device."" }, ""175"": { ""property.id"": 175, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Hemostasis In oral and dental surgery, GELFOAM Dental Sponges are an aid in providing hemostasis. GELFOAM may be used either dry or moistened, depending upon conditions present at operation and preference of the surgeon. Isotonic saline is suitable for use with GELFOAM. Although not necessary, GELFOAM can be used either with or without thrombin to obtain hemostasis. DOSAGE AND ADMINISTRATION Directions For Use When used dry, GELFOAM Dental Sponges, cut to desired size, are rolled between the fingers and lightly compressed to the approximate diameter of the cavity or socket to be filled. Following insertion of the rolled pack, light finger pressure should be applied for one or two minutes. When used moistened, GELFOAM, cut to desired size, is immersed in the solution of sodium chloride. The piece is then removed from the solution, squeezed thoroughly to remove air bubbles present in the meshes, and replaced in the solution where it will swell to its original size. It is then taken from the solution, blotted on sterile gauze to remove excess fluid, and placed in the cavity or wound. For use with thrombin, consult the thrombin insert for complete prescribing information and proper sample preparation. HOW SUPPLIED GELFOAM Dental Sponges are available in Size 4 (2 x 2 cm) envelopes of 2 sponges GTIN 00300090396053 (0009-0396-05) Storage And Handling GELFOAM Dental Sponges should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the package is opened, contents are subject to contamination. It is recommended that GELFOAM be used as soon as the package is opened and unused contents discarded. This product is prepackaged sterile and intended only for single use. Reuse can result in transmission of bloodborne pathogens (including HIV and hepatitis), potentially endangering patients and health care providers. Adherence to the principles of aseptic technique when using this product is essential. Caution Federal law restricts this device to sale by or on the order of a dentist or physician. Manufactured by: Pharmacia and Upjohn Company, 7000 Portage Road, Kalamazoo, Michigan 49001, USA, 1-800-253-8600. Distributed by: Pharmacia & Upjohn Co., Division of Pfizer Inc., New York, NY 10017. Revised December 2014"" }, ""176"": { ""property.id"": 176, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS Although sterile, GELFOAM Dental Sponges may form a nidus of infection and abscess. DRUG INTERACTIONS No information provided."" }, ""177"": { ""property.id"": 177, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS This product should not be resterilized by heat, because heating may change absorption time. Ethylene oxide is not recommended for resterilization because it may be trapped in the interstices of the foam. Although not reported for GELFOAM Dental Sponges, the gas is toxic to tissue and in trace amounts may cause burns or irritation. Although the safety and efficacy of the combined use of GELFOAM with other agents such as topical thrombin has not been evaluated in controlled clinical trials, if in the physician's judgment concurrent use of other agents is medically advisable, the product literature for that agent should be consulted for complete prescribing information. GELFOAM is supplied as a sterile product and cannot be resterilized. Unused, opened envelopes of GELFOAM should be discarded. WARNING: To prevent contamination, employ aseptic procedure in opening envelope and withdrawing GELFOAM. If the envelope is torn or punctured, the contained GELFOAM should not be used. PRECAUTIONS Use of GELFOAM Dental Sponges is not recommended in presence of frank infection. If signs of infection or abscess develop in an area where GELFOAM has been placed, reoperation may be necessary to remove infected material and allow drainage. By absorbing fluid, GELFOAM may expand and impinge on neighboring structures. Therefore, when placed into cavities or closed tissue spaces, minimal preliminary compression is advised and care should be exercised to avoid over packing. Positioning of the patient resulting in negative peripheral venous pressure during a procedure has been reported to be a contributing factor resulting in life-threatening thromboembolic events."" }, ""178"": { ""property.id"": 178, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS GELFOAM Dental Sponges should not be used in closure of skin incisions because they may interfere with the healing of skin edges. Do not use GELFOAM Dental Sponges in patients with known allergies to porcine collagen."" }, ""179"": { ""property.id"": 179, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Actions When implanted in tissues, GELFOAM Dental Sponges are completely absorbed within four to six weeks without inducing excessive scar tissue."" }, ""180"": { ""property.id"": 180, ""property.ts"": ""2017-12-04 04:40:01"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections."" } }" 28,"2017-08-31 23:12:57","Absorbable Gelatin Powder",Gelfoam,FDA,"{ ""28"": { ""alphabet_x_drug.id"": 28, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""181"": { ""property.id"": 181, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on Gelfoam® absorbable gelatin powder (absorbable gelatin powder from absorbable gelatin sponge, USP) DESCRIPTION GELFOAM is a medical device intended for application to bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product prepared from purified pork Skin Gelatin USP Granules and Water for Injection, USPand is able to absorb and hold within its interstices, many times its weight of blood and other fluids. GELFOAM Sterile Powder is a fine, dry, heat-sterilized light powder prepared by milling absorbable gelatin sponge."" }, ""182"": { ""property.id"": 182, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Hemostasis GELFOAM Sterile Powder, saturated with sterile sodium chloride solution, is indicated in surgical procedures, including those involving cancellous bone bleeding, as a hemostatic device, when control of capillary, venous, and arteriolar bleeding by pressure, ligature, and other conventional procedures is either ineffective or impractical. Although not necessary, GELFOAM can be used either with or without thrombin to obtain hemostasis. Directions For Use GELFOAM Sterile Powder can be saturated with sterile, isotonic sodium chloride solution (sterile saline) or a solution of thrombin1, before use as an adjunct to hemostasis. The envelope of GELFOAM Sterile Powder should be opened and the contents (1 gram) poured carefully into a sterile beaker, avoiding contamination. Using sterile technique, a puttylike paste is prepared by adding a total of approximately 3-4 mL of sterile saline or thrombin solution1 to the GELFOAM. If a mixture of less viscosity is desired, 7-10 mL of sterile saline or thrombin solution may be utilized. Dispersion of the powder can be avoided by initially compressing it with the gloved fingers into the bottom of the beaker and then kneading it into the desired consistency. The resulting doughy paste may be smeared or pressed against the bleeding surface to control bleeding. When bleeding stops the excess should be removed. Use only the minimum amount of GELFOAM, necessary to produce hemostasis. The GELFOAM may be left in place at the bleeding site, when necessary. Since GELFOAM causes little more cellular reaction than does the blood clot, the wound may be closed over it. GELFOAM may be left in place when applied to mucosal surfaces until it liquefies. For use with thrombin, consult the thrombin insert for complete prescribing information and proper sample preparation. DOSAGE AND ADMINISTRATION Sterile technique should always be used. The minimum amount of GELFOAM should be applied to the bleeding site (see Directions For Use) with pressure until hemostasis is observed. Opened envelopes of unused GELFOAM should always be discarded. HOW SUPPLIED GELFOAM Sterile Powder (absorbable gelatin powder) is supplied in envelopes containing 1 gram: GTIN 00300090433048 (0009-0433-04). Storage And Handling GELFOAM Sterile Powder should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the envelope is opened, contents are subject to contamination. It is recommended that GELFOAM be used as soon as the envelope is opened and unused contents discarded.This product is prepackaged sterile and intended only for single use. Reuse can result in transmission of bloodborne pathogens (including HIV and hepatitis), potentially endangering patients and health care providers. Adherence to the principles of aseptic technique when using this product is essential. Caution Federal law restricts this device to sale by or on the order of a physician. REFERENCES 1 Prepared as per label recommendations. Manufactured by: Pharmacia and Upjohn Company, 7000 Portage Road, Kalamazoo, Michigan 49001, USA 1-800-253-8600, LAB-0307-6.0. Distributed by: Pharmacia & Upjohn Co., Division of Pfizer Inc., New York, NY 10017. Revised December 2014."" }, ""183"": { ""property.id"": 183, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS There have been reports of fever associated with the use of GELFOAM, without demonstrable infection. GELFOAM may serve as a nidus for infection and abscess formation1, and has been reported to potentiate bacterial growth. Giant-cell granuloma has been reported at the implantation site of absorbable gelatin product in the brain2, as has compression of the brain and spinal cord resulting from the accumulation of sterile fluid.3 Foreign body reactions, “encapsulation” of fluid and hematoma have also been reported. When GELFOAM was used in laminectomy operations, multiple neurologic events were reported, including but not limited to cauda equina syndrome, spinal stenosis, meningitis, arachnoiditis, headaches, paresthesias, pain, bladder and bowel dysfunction, and impotence. Excessive fibrosis and prolonged fixation of a tendon have been reported when absorbable gelatin products were used in severed tendon repair. Toxic shock syndrome has been reported in association with the use of GELFOAM in nasal surgery. Fever, failure of absorption, and hearing loss have been reported in association with the use of GELFOAM during tympanoplasty. Adverse Reactions Reported From Unapproved Uses GELFOAM is not recommended for use other than as an adjunct for hemostasis. While some adverse medical events following the unapproved use of GELFOAM have been reported to Pharmacia & Upjohn Company (see ADVERSE REACTIONS above), other hazards associated with such use may not have been reported. When GELFOAM has been used during intravascular catheterization for the purpose of producing vessel occlusion, the following adverse events have been reported; fever, duodenal and pancreatic infarct, embolization of lower extremity vessels, pulmonary embolization, splenic abscess, necrosis of specific anatomic areas, asterixis, and death. These adverse medical events have been associated with the use of GELFOAM for repair of dural defects encountered during laminectomy and craniotomy operations: fever, infection, leg paresthesias, neck and back pain, bladder and bowel incontinence, cauda equina syndrome, neurogenic bladder, impotence, and paresis. Adverse Events Associated With Bone Hemostasis In a clinical study, 108 patients received GELFOAM Sterile Powder on the cut surface of the sternum during cardiopulmonary bypass surgery, while 107 patients received no treatment on the cut surface of the bone. Table 1 is a summary of medical events reported by at least 1.0% of patients in a treatment group. The most frequently reported events were atrial fibrillation, perioperative event, and wound infection. Events occurring in less than 1.0% of the patients were as follows: anaphylaxis, cardiogenic shock, delirium tremens, infection at the vascular catheter site, unevaluable reaction, sepsis, angina pectoris, atrial arrhythmia, nodal arrhythmia, arteriosclerosis, cardiac insufficiency, cardiac tamponade, cardiomyopathy, deep vein thrombosis, mitral valve disorder, endocarditis, ventricular extrasystoles, heart arrest, hypotension, mesenteric occlusion, superventricular tachycardia, thrombophlebitis, thrombosis, gastrointestinal disorder, gastrointestinal bleeding, increased serum creatinine, dehydration, anemia, thrombocytopenia, abnormal healing, hypovolemia, hypoxia, metabolic acidosis, cerebral infarction, visual hallucinations, stupor, aspiration pneumonia, chest congestion, pleural effusion, pulmonary infiltration, retinal artery occlusion, anuria, UG disorder, abnormal kidney function and menorrhagia. Table 1: Summary of Medical Events for GELFOAM Sterile Powder when used as a Bone Hemostatic Agent During Cardiopulmonary Bypass Surgery Medical Event GELFOAM N=108 Control N=107 Total N=215 n % n % n % Atrial Fibrillation 14 (13) 12 (11) 26 (12) Wound Infection 6 (6) 1 (0.9) 7 (3.3) Perioperative Event 4 (4) 5 (4.7) 9 (4.2) Congestive Heart Failure 4 (4) 0 (0) 4 (1.9) Ventricular Tachycardia 2 (2) 3 (2.8) 5 (2.3) Atrial Flutter 2 (2) 0 (0) 2 (0.9) Peripheral Vascular Disorder 2 (2) 0 (0) 2 (0.9) Pneumothorax 2 (2) 3 (2.8) 5 (2.3) Respiratory Failure 2 (2) 2 (1.9) 4 (1.9) Respiratory Arrest 2 (2) 1 (0.9) 3 (1.4) Fever 1 (1) 2 (1.9) 3 (1.4) Heart Block 1 (1) 2 (1.9) 3 (1.4) Prolonged Wound Drainage 0 (0) 1 (0.9) 1 (0.5) Cellulitis 0 (0) 2 (1.9) 2 (0.9) Dyspnea 0 (0) 2 (1.9) 2 (0.9) Pneumonia 0 (0) 2 (1.9) 2 (0.9) In general, the following adverse events have been reported with the use of absorbable porcine gelatin-based hemostatic agents: Gelatin-based hemostatic agents may serve as a nidus for infection and abscess formation and have been reported to potentiate bacterial growth. Giant cell granulomas have been observed at implant sites when used in the brain. Compression of the brain and spinal cord resulting from the accumulation of sterile fluid has been observed. Multiple neurologic events were reported when absorbable gelatin-based hemostatic agents were used in laminectomy operations, including cauda equina syndrome, spinal stenosis, meningitis, arachnoiditis, headaches, paresthesias, pain, bladder and bowel dysfunction, and impotence and paresis. The use of absorbable gelatin-based hemostatic agents have been associated with paralysis, due to device migration into foramina in the bone around the spinal cord, and blindness due to device migration in the orbit of the eye, during lobectomy, laminectomy and repair of a frontal skull fracture and lacerated lobe. Foreign body reactions, “encapsulation” of fluid, and hemotoma have been observed at implant sites. Excessive fibrosis and prolonged fixation of a tendon have been reported when absorbable gelatin-based sponges were used in severed tendon repair. Toxic shock syndrome was reported in association with the use of absorbable gelatin-based hemostats in nasal surgery. Fever, failure of absorption, and hearing loss have been observed when absorbable hemostatic agents were used during tympanoplasty. DRUG INTERACTIONS No information provided."" }, ""184"": { ""property.id"": 184, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS GELFOAM is not intended as a substitute for meticulous surgical technique and the proper application of ligatures, or other conventional procedures for hemostasis. GELFOAM is supplied as a sterile product and cannot be resterilized. Unused, opened envelopes of GELFOAM should be discarded. To prevent contamination, employ aseptic procedure in opening envelope and withdrawing GELFOAM. If the envelope is torn or punctured, the contained GELFOAM should not be used. Only the minimum amount of GELFOAM necessary to achieve hemostasis should be used. Once hemostasis is attained, excess GELFOAM should be carefully removed. The use of GELFOAM is not recommended in the presence of infection. GELFOAM should be used with caution in contaminated areas of the body. If signs of infection or abscess develop where GELFOAM has been positioned, reoperation may be necessary in order to remove the infected material and allow drainage. Although the safety and efficacy of the combined use of GELFOAM with other agents such as topical thrombin has not been evaluated in controlled clinical trials, if in the physician's judgment concurrent use of other agents is medically advisable, the product literature for that agent should be consulted for complete prescribing information. While packing a cavity for hemostasis is sometimes surgically indicated, GELFOAM should not be used in this manner unless excess product not needed to maintain hemostasis is removed. Whenever possible, it should be removed after use in laminectomy procedures and from foramina in bone, once hemostasis is achieved. This is because GELFOAM may swell on absorbing fluids, and produce nerve damage by pressure within confined bony spaces. The packing of GELFOAM, particularly within bony cavities, should be avoided, since swelling may interfere with normal function and/or possibly result in compression necrosis of surrounding tissues. PRECAUTIONS The minimum amount of GELFOAM Sterile Powder needed for hemostasis should be applied together with pressure until the bleeding stops. The excess should then be removed. GELFOAM should not be used for controlling postpartum hemorrhage or menorrhagia. It has been demonstrated that fragments of another hemostatic agent, microfibrillar collagen, pass through the 40μ transfusion filters of blood scavenging systems. GELFOAM should not be used in conjunction with autologous blood salvage circuits since the safety of this use has not been evaluated in controlled clinical trials. Microfibrillar collagen has been reported to reduce the strength of methylmethacrylate adhesives used to attach prosthetic devices to bone surfaces. As a precaution, GELFOAM should not be used in conjunction with such adhesives. GELFOAM is not recommended for the primary treatment of coagulation disorders. It is not recommended that GELFOAM be saturated with an antibiotic solution or dusted with antibiotic powder. Positioning of the patient resulting in negative peripheral venous pressure during a procedure has been reported to be a contributing factor resulting in life-threatening thromboembolic events."" }, ""185"": { ""property.id"": 185, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS GELFOAM should not be used in closure of skin incisions because it may interfere with healing of the skin edges. This is due to mechanical interposition of gelatin and is not secondary to intrinsic interference with wound healing. GELFOAM should not be placed in intravascular compartments, because of the risk of embolization. Do not use GELFOAM Sterile Powder in patients with known allergies to porcine collagen."" }, ""186"": { ""property.id"": 186, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Action GELFOAM has hemostatic properties. While its mode of action is not fully understood, its effect appears to be more physical than the result of altering the blood clotting mechanism. When not used in excessive amounts, GELFOAM is absorbed completely, with little tissue reaction. This absorption is dependent on several factors, including the amount used, degree of saturation with blood or other fluids, and the site of use. When placed in soft tissues, GELFOAM is usually absorbed completely in from four to six weeks, without inducing excessive scar tissue. When applied to bleeding nasal, rectal or vaginal mucosa, it liquefies within two to five days. Animal Pharmacology Surface-acting hemostatic devices, when applied directly to bleeding surfaces, arrest bleeding by providing a mechanical matrix that facilitates clotting.6,8,13,14 Due to their bulk, surface-acting hemostatic agents slow the flow of blood, protect the forming clot, and offer a framework for deposition of the cellular elements of blood.6,7,8,13 MacDonald and Mathews12 studied GELFOAM implants in canine kidneys and reported that it assisted in healing, with no marked inflammatory or foreign-body reactions. Jenkins and Janda13 studied the use of GELFOAM in canine liver resections and noted that the gelatin sponge appeared to offer a protective cover and provide structural support for the reparative process. Correll et all14 studied the histology of GELFOAM Sterile Sponge when implanted in rat muscle and reported no significant tissue reaction. Clinical Studies GELFOAM Sterile Powder is a water-insoluble, hemostatic device prepared from purified skin gelatin, and capable of absorbing up to 45 times its weight of whole blood.4 The absorptive capacity of GELFOAM is a function of its physical size, increasing as the amount of the gelatin powder increases.5 The mechanism of action of surface-mediated hemostatic devices is supportive and mechanical.5 Surface acting devices, when applied directly to bleeding surfaces, arrest bleeding by the formation of an artificial clot and by producing a mechanical matrix that facilitates clotting.6 Jenkins et al7 have theorized that the clotting effect of GELFOAM may be due to release of thromboplastin from platelets, occurring when platelets entering the sponge become damaged by contact with the walls of its myriad of interstices. Thromboplastin interacts with prothrombin and calcium to produce thrombin, and this sequence of events initiates the clotting reaction. The authors suggest that the physiologic formation of thrombin in the sponge is sufficient to produce formation of a clot, by its action on the fibrinogen in blood.7 The spongy physical properties of the gelatin sponge hasten clot formation and provide structural support for the forming clot.6,8 Several investigators have claimed that GELFOAM becomes liquefied within a week or less and is completely absorbed in four to six weeks, without inducing excessive scar formation.4,7,9,10,11 Barnes10 reviewed experiences with GELFOAM in gynecologic surgery. No excessive scar tissue, attributable to the absorption of GELFOAM, could be palpated at postoperative examination. Bone Hemostasis Study The efficacy of GELFOAM Sterile Powder as a bone hemostatic agent during cardiopulmonary bypass surgery was evaluated. Study Design Two randomized open-label clinical studies were conducted at separate investigative sites. The objectives were as follows: To evaluate the effectiveness of GELFOAM Sterile Powder as a hemostatic agent in the treatment of sternal bone bleeding during cardiopulmonary bypass surgery. To identify any deleterious effects of GELFOAM Sterile Powder on interference with bone healing. To determine any systemic or local wound side effects from leaving GELFOAM Sterile Powder in situ. Patients between the ages of 18 to 74 years old undergoing cardiopulmonary bypass surgery were randomly assigned to either a GELFOAM group or a Control group. The GELFOAM group (composed of 108 patients) had a paste made up of sterile saline solution and GELFOAM Sterile Powder applied to the cut sternal surface immediately following sternotomy. The Control group (composed of 107 patients received no treatment applied to the cut surface. Blood loss was monitored both during surgery and postoperatively. Blood loss during surgery was determined by measuring the weight of the powder before and after application to the cut edge of the sternum. Postoperative blood loss was collected from the mediastinal drainage tubes. The total blood loss (in milligrams) over 72 hours was determined for each patient. Study Endpoints Patients were evaluated upon admission (preoperative), during surgery (intraoperative), after surgery (postoperative), upon hospital discharge (7 to 10 days after surgery), and at the 3-month follow-up visit. An additional poststudy follow-up was required if a patient reported an ongoing medical event at the 3-month follow-up visit. Study Results In both studies, the amount of blood loss was significantly less in the GELFOAM group than in the Control group. In Study 001, the mean blood loss in the GELFOAM group was 13727.7 mg while the mean blood loss in the Control group was more than double at 27712.0 mg. Similar results were found in Study 002, where the mean blood loss in the GELFOAM group was 9514.8 mg while the mean blood loss in the Control group was 22687.5 mg. Table 2: Blood Loss in Sternotomy Patients Site 001 Site 002 GELFOAM Control GELFOAM Control Mean Blood Loss (mg) 13727.7 27712.0 9514.8 22687.5 Median Blood Loss (mg) 11561.0 24798.0 6950.0 16900.0 Minimum Blood Loss (mg) 2922.0 10748.0 800.0 900.0 Maximum Blood Loss (mg) 87448.0 61535.0 46000.0 89800.0 Patients in the GELFOAM and Control groups were similar with regard to sterna bone healing. At hospital discharge, normal bone healing was reported for 105 patients (97%) in the GELFOAM group and 104 patients (97%) in the Control group. At the 3-month follow-up, 103 patients (95%) in the GELFOAM group and 100 patients (93%) in the Control group were healed. Few patients in either treatment group had sternotomy infection or other postoperative infection complications related to sternotomy. At hospital discharge, two patients treated with GELFOAM had mediastinitis. No Control patients had any infections at hospital discharge. One patient treated with GELFOAM had a non-infection related complication. At the 3-month follow-up, one of the original patients treated with GELFOAM who had mediastinitis still showed signs of infection. In addition, two additional patients treated with GELFOAM developed mediastinitis at the 3-month follow-up. One patient in the Control group experienced sternal osteomyelitis at the 3-month follow-up but recovered with no residual effects. No patients from the GELFOAM arm of the study had reported complications of sternal osteomyelitis. There was a total of four Control patients who had non-infection-related complications. One Control patient had serous/sanguineous wound drainage from the left leg and sternum incisions at hospital discharge. This complication was non-infectious and the patient recovered with no residual side effects. Three Control patients all experienced chronic pain syndrome, a symptom which can occur following thoracic/cardiac surgery. Evaluation sternal bone healing at the 3-month follow-up for these patients showed no evidence of non-union of the sternum. In all three cases, bone healing at the 3-month follow-up was reported as being normal. A summary of sternotomy infection information is located in Table 3. Table 3: Summary of Postoperative Infection Complications Hospital Discharge 3-Month Follow-up GELFOAM Control GELFOAM Control N % N % N % N % Any Infection yes 1 (1) 0 (0) 5 (5) 0 (0) no 104 (99) 106 (100) 95 (95) 105 (100) Superficial Wound yes 0 (0) 0 (0) 2 (2) 0 (0) no 105 (100) 106 (100) 98 (98) 105 (100) Sternal Osteomyelitis yes 0 (0) 0 (0) 1 (1) 1 (1) no 105 (100) 106 (100) 99 (99) 105 (99) Mediastinitis yes 1 (1) 0 (0) 2 (2) 0 (0) no 104 (99) 106 (100) 98 (98) 105 (100) Complication Related to Sternotomy yes 0 (0) 0 (0) 1 (1) 3 (3) no 105 (100) 106 (100) 99 (99) 102 (97) Study Conclusions These studies demonstrate that a paste made from GELFOAM Sterile Powder is safe and effective in treating intraoperative bleeding when applied to the cut surface of cancellous bone and has shown superior hemostasis versus no treatment at all to the cut bone surface. The benefit to patients is that a reduction in bleeding will make surgery easier to perform by reducing the time the surgeon needs to revisit cut bone surfaces to clean up the bleeding. This study also demonstrated that GELFOAM Sterile Powder could be left in situ without increased risk of bone infection or nonunion of the sternum. REFERENCES 1. Lindstrom PA: Complications from the use of absorbable hemostatic sponges. AMA Arch Surg 1956;73:133-141. 2. Knowlson GTG: Gelfoam granuloma in the brain. J Neuro Neurosurg Psychiatry 1974;37:971-973. 3. Herndon JH, Grillo HC, Riseborough EJ, et al: Compression of the brain and spinal cord following use of GELFOAM. Arch Surg 1972;104:107. 4. Council on Pharmacy and Chemistry: Absorbable Gelatin sponge – new and nonofficial remedies. JAMA 1947;135:921. 5. Goodman LS, Gilman A: Surface-acting drugs, in The Pharmacologic Basis of Therapeutics, ed 6. New York, MacMillan Publishing Co. 1980, p 955. 6. Guralnick W, Berg L: GELFOAM in oral surgery. Oral Surg 1948;1:629-632. 7. Jenkins HP, Senz EH, Owen H, et al: Present status of gelatin sponge for control of hemorrhage. JAMA 1946;132:614-619. 8. Jenkins HP, Janda R, Clarke J: Clinical and experimental observations on the use of gelatin sponge or foam. Surg 1946;20:124-132. 9. Treves N: Prophylaxis of post mammectomy lymphedema by the use of GELFOAM laminated rolls. Cancer 1952;5:73-83. 10. Barnes AC: The use of gelatin foam sponges in obstetrics and gynecology. Am J Obstet Gynecol 1963;86:105-107. 11. Rarig HR: Successful use of gelatin foam sponge in surgical restoration of fertility. Am J Obstet Gynecol 1963;86:136. 12. MacDonald SA, Mathews WH: Fibrin foam and GELFOAM in experimental kidney wounds. Annual American Urological Association, July 1946. 13. Jenkins HP, Janda R: Studies on the use of gelatin sponge or foam as a hemostatic agent in experimental liver resections and injuries to large veins. Ann Surg 1946;124:952-961. 14. Correll JT, Prentice HR, Wise EC: Biologic investigations of a new absorbable sponge. Surg Gynecol Obstet 1945;181:585-589."" }, ""187"": { ""property.id"": 187, ""property.ts"": ""2017-12-04 04:40:04"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION No information provided. Please refer to the WARNINGS AND PRECAUTIONS sections."" } }" 29,"2017-08-31 23:12:57","Absorbable Gelatin Sponge, USP","Gelfoam Sponge",FDA,"{ ""29"": { ""alphabet_x_drug.id"": 29, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""188"": { ""property.id"": 188, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Drug Description"", ""property.value"": ""Gelfoam® absorbable gelatin sponge, USP DESCRIPTION GELFOAM Sterile Sponge is a medical device intended for application to bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product prepared from purified pork Skin Gelatin USP Granules and Water for Injection, USP. It may be cut without fraying and is able to absorb and hold within its interstices, many times its weight of blood and other fluids."" }, ""189"": { ""property.id"": 189, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Directions For Use Sterile technique should always be used to remove GELFOAM Sterile Sponge from its packaging. Cut to the desired size, a piece of GELFOAM, either dry or saturated with sterile, isotonic sodium chloride solution (sterile saline), can be applied with pressure directly to the bleeding site. When applied dry, a single piece of GELFOAM should be manually compressed before application to the bleeding site, and then held in place with moderate pressure until hemostasis results. When used with sterile saline, GELFOAM should be first immersed in the solution and then withdrawn, squeezed between gloved fingers to expel air bubbles, and then replaced in saline until needed. The GELFOAM sponge should promptly return to its original size and shape in the solution. If it does not, it should be removed again and kneaded vigorously until all air is expelled and it does expand to its original size and shape when returned to the sterile saline. GELFOAM is used wet or blotted to dampness on gauze before application to the bleeding site. It should be held in place with moderate pressure, using a pledget of cotton or small gauze sponge until hemostasis results. Removal of the pledget or gauze is made easier by wetting it with a few drops of sterile saline, to prevent pulling up the GELFOAM which by then should enclose a firm clot. Use of suction applied over the pledget of cotton or gauze to draw blood into the GELFOAM is unnecessary, as the GELFOAM will draw up sufficient blood by capillary action. The first application of GELFOAM will usually control bleeding, but if not, additional applications may be made using fresh pieces, prepared as described above. Use only the minimum amount of GELFOAM, cut to appropriate size, necessary to produce hemostasis. The GELFOAM may be left in place at the bleeding site, when necessary. Since GELFOAM causes little more cellular reaction than does the blood clot, the wound may be closed over it. GELFOAM may be left in place when applied to mucosal surfaces until it liquefies. For use with thrombin, consult the thrombin insert for complete prescribing information and proper sample preparation. DOSAGE AND ADMINISTRATION Sterile technique should always be used in removing the inner envelope containing the GELFOAM Sterile Sponge from the outer printed sealed envelope. The minimum amount of GELFOAM of appropriate size and shape should be applied dry or wet (see INDICATIONS AND USAGE, Directions for Use) to the bleeding site and held firmly in place until hemostasis is observed. Opened envelopes of unused GELFOAM should always be discarded. HOW SUPPLIED GELFOAM Sterile Sponge is supplied in a sterile envelope enclosed in an outer peelable envelope. Sterility of the product is assured unless the outer envelope has been damaged or opened. It is available in the following sizes: Sponge-Size 12—7 mm Box of 12 GTIN 00300090315085 (0009-0315-08) Sponge-Size 50 Box of 4 GTIN 00300090323011 (0009-0323-01) Sponge-Size 100 Box of 6 GTIN 00300090342012 (0009-0342-01) Sponge-Size 200 Box of 6 GTIN 00300090349035 (0009-0349-03) Storage And Handling GELFOAM Sterile Sponge should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the package is opened, contents are subject to contamination. It is recommended that GELFOAM be used as soon as the package is opened and unused contents discarded. This product is prepackaged sterile and intended only for single use. Reuse can result in transmission of bloodborne pathogens (including HIV and hepatitis), potentially endangering patients and health care providers. Adherence to the principles of aseptic technique when using this product is essential. Caution Federal law restricts this device to sale by or on the order of a physician. Manufactured by: Pharmacia and Upjohn Company, 7000 Portage Road, Kalamazoo, Michigan 49001, USA, 1-800-253-8600, LAB-0309-4.0. Revised December 2014. Distributed by: Pharmacia & Upjohn Co., Division of Pfizer Inc., New York, NY 10017. Revised: Dec 2014"" }, ""190"": { ""property.id"": 190, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS There have been reports of fever associated with the use of GELFOAM, without demonstrable infection. GELFOAM Sterile Sponge may serve as a nidus of infection and abscess formation1, and has been reported to potentiate bacterial growth. Giantcell granuloma has been reported at the implantation site of absorbable gelatin product in the brain,2 as has compression of the brain and spinal cord resulting from the accumulation of sterile fluid.3 Foreign body reactions, encapsulation of fluid and hematoma have also been reported. When GELFOAM was used in laminectomy operations, multiple neurologic events were reported, including but not limited to cauda equina syndrome, spinal stenosis, meningitis, arachnoiditis, headaches, paresthesias, pain, bladder and bowel dysfunction, and impotence. Excessive fibrosis and prolonged fixation of a tendon have been reported when absorbable gelatin products were used in severed tendon repair. Toxic shock syndrome has been reported in association with the use of GELFOAM in nasal surgery. Fever, failure of absorption, and hearing loss have been reported in association with the use of GELFOAM during tympanoplasty. Adverse Reactions Reported From Unapproved Uses GELFOAM is not recommended for use other than as an adjunct for hemostasis. While some adverse medical events following the unapproved use of GELFOAM have been reported to Pharmacia & Upjohn Company (see ADVERSE REACTIONS above), other hazards associated with such use may not have been reported. When GELFOAM has been used during intravascular catheterization for the purpose of producing vessel occlusion, the following adverse events have been reported; fever, duodenal and pancreatic infarct, embolization of lower extremity vessels, pulmonary embolization, splenic abscess, necrosis of specific anatomic areas, asterixis, and death. The following adverse medical events have been associated with the use of GELFOAM for repair of dural defects encountered during laminectomy and craniotomy operations: fever, infection, leg paresthesias, neck and back pain, bladder and bowel incontinence, cauda equine syndrome, neurogenic bladder, impotence, and paresis. DRUG INTERACTIONS No information provided. REFERENCES 1. Lindstrom PA: Complications from the use of absorbable hemostatic sponges. AMA Arch Surg. 1956; 73(1):133-141. 2. Knowlson GTG. Gelfoam granuloma in the brain. J Neurol Neurosurg Psychiatry 1974; 37:971-973. 3. Herndon JH, Grillo HC, Riseborough EJ, et al: Compression of the brain and spinal cord following use of GELFOAM. Arch Surg. 1972;104:107."" }, ""191"": { ""property.id"": 191, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS GELFOAM Sterile Sponge is not intended as a substitute for meticulous surgical technique and the proper application of ligatures, or other conventional procedures for hemostasis. GELFOAM is supplied as a sterile product and cannot be resterilized. Unused, opened envelopes of GELFOAM should be discarded. WARNING: To prevent contamination, employ aseptic procedure in opening envelope and withdrawing GELFOAM. If the envelope is torn or punctured, the contained GELFOAM should not be used. Only the minimum amount of GELFOAM necessary to achieve hemostasis should be used.  Once hemostasis is attained, excess GELFOAM should be carefully removed. The use of GELFOAM is not recommended in the presence of infection. GELFOAM should be used with caution in contaminated areas of the body. If signs of infection or abscess develop where GELFOAM has been positioned, reoperation may be necessary in order to remove the infected material and allow drainage. Although the safety and efficacy of the combined use of GELFOAM with other agents such as topical thrombin has not been evaluated in controlled clinical trials, if in the physician's judgment concurrent use of other agents is medically advisable, the product literature for that agent should be consulted for complete prescribing information. While packing a cavity for hemostasis is sometimes surgically indicated, GELFOAM should not be used in this manner unless excess product not needed to maintain hemostasis is removed. Whenever possible, it should be removed after use in laminectomy procedures and from foramina in bone, once hemostasis is achieved. This is because GELFOAM may swell to its original size on absorbing fluids, and produce nerve damage by pressure within confined bony spaces. The packing or wadding of GELFOAM, particularly within bony cavities, should be avoided, since swelling to original size may interfere with normal function and/or possibly result in compression necrosis of surrounding tissues. PRECAUTIONS Use only the minimum amount of GELFOAM Sterile Sponge needed for hemostasis, holding it at the site until bleeding stops and then removing the excess. GELFOAM should not be used for controlling postpartum hemorrhage or menorrhagia. It has been demonstrated that fragments of another hemostatic agent, microfibrillar collagen, pass through the 40μ transfusion filters of blood scavenging systems. GELFOAM should not be used in conjunction with autologous blood salvage circuits since the safety of this use has not been evaluated in controlled clinical trials. Microfibrillar collagen has been reported to reduce the strength of methyl-methacrylate adhesives used to attach prosthetic devices to bone surfaces. As a precaution, GELFOAM should not be used in conjunction with such adhesives. GELFOAM is not recommended for the primary treatment of coagulation disorders. It is not recommended that GELFOAM be saturated with an antibiotic solution or dusted with antibiotic powder. Positioning of the patient resulting in negative peripheral venous pressure during a procedure has been reported to be a contributing factor resulting in life-threatening thromboembolic events."" }, ""192"": { ""property.id"": 192, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS GELFOAM Sterile Sponge should not be used in closure of skin incisions because it may interfere with healing of the skin edges. This is due to mechanical interposition of gelatin and is not secondary to intrinsic interference with wound healing. GELFOAM should not be placed in intravascular compartments, because of the risk of embolization. Do not use GELFOAM Sterile Sponge in patients with known allergies to porcine collagen."" }, ""193"": { ""property.id"": 193, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Action GELFOAM Sterile Sponge has hemostatic properties. While its mode of action is not fully understood, its effect appears to be more physical than the result of altering the blood clotting mechanism. When not used in excessive amounts, GELFOAM is absorbed completely, with little tissue reaction. This absorption is dependent upon several factors, including the amount used, degree of saturation with blood or other fluids, and the site of use. When placed in soft tissues, GELFOAM is usually absorbed completely within four to six weeks, without inducing excessive scar tissue. When applied to bleeding nasal, rectal, or vaginal mucosa, it liquefies within two to five days. HEMOSTASIS: GELFOAM Sterile Sponge, used dry or saturated with sterile sodium chloride solution, is indicated in surgical procedures as a hemostatic device, when control of capillary, venous, and arteriolar bleeding by pressure, ligature, and other conventional procedures is either ineffective or impractical. Although not necessary, GELFOAM can be used either with or without thrombin to obtain hemostasis. Clinical Studies GELFOAM Sterile Sponge is a water-insoluble, hemostatic device prepared from purified skin gelatin, and capable of absorbing up to 45 times its weight of whole blood.10 The absorptive capacity of GELFOAM is a function of its physical size, increasing as the size of the gelatin sponge increases.11 The mechanism of action of surface-mediated hemostatic devices is supportive and mechanical.11 Surface-acting devices, when applied directly to bleeding surfaces, arrest bleeding by the formation of an artificial clot and by producing a mechanical matrix that facilitates clotting.4 Jenkins et-al 8 have theorized that the clotting effect of GELFOAM may be due to release of thromboplastin from platelets, occurring when platelets entering the sponge become damaged by contact with the walls of its myriad interstices. Thromboplastin interacts with prothrombin and calcium to produce thrombin, and this sequence of events initiates the clotting reaction. The authors suggest that the physiologic formation of thrombin in the sponge is sufficient to produce formation of a clot, by its action on the fibrinogen in blood.8 The spongy physical properties of the gelatin sponge hasten clot formation and provide structural support for the forming clot.4,5 Several investigators have claimed that GELFOAM becomes liquefied within a week or less and is completely absorbed in four to six weeks, without inducing excessive scar formation.7,10,12,13,14 Barnes13 reviewed experiences with GELFOAM in gynecologic surgery. No excessive scar tissue, attributable to the absorption of GELFOAM, could be palpated at postoperative examination. Animal Pharmacology Surface-acting hemostatic devices, when applied directly to bleeding surfaces, arrest bleeding by providing a mechanical matrix that facilitates clotting.4,5,6,7 Due to their bulk, surfaceacting hemostatic agents slow the flow of blood, protect the forming clot, and offer a framework for deposition of the cellular elements of blood.4,5,6,8 MacDonald and Mathews9 studied GELFOAM implants in canine kidneys and reported that it assisted in healing, with no marked inflammatory or foreign-body reactions. Jenkins and Janda5 studied the use of GELFOAM in canine liver resections and noted that the gelatin sponge appeared to offer a protective cover and provide structural support for the reparative process. Correll et al7 studied the histology of GELFOAM Sterile Sponge when implanted in rat muscle and reported no significant tissue reaction. REFERENCES 4. Guralnick W, Berg L: GELFOAM in oral surgery. Oral Surg 1948; 1:629-632. 5. Jenkins HP, Janda R, Clarke J: Clinical and experimental observations on the use of gelatin sponge or foam. Surg 1946; 20:124-132. 6. Jenkins HP, Janda R: Studies on the use of gelatin sponge or foam as a hemostatic agent in experimental liver resections and injuries to large veins. Ann Surg. 1946;124:952-961. 7. Correll JT, Prentice HR, Wise EC: Biologic investigations of a new absorbable sponge. Surg Gynecol Obstet. 1945; 181:585-589. 8. Jenkins HP, Senz EH, Owen H, et al: Present status of gelatin sponge for control of hemorrhage. JAMA 1946; 132:614-619. 9. MacDonald SA, Mathews WH: Fibrin foam and GELFOAM in experimental kidney wounds. Annual American Urological Association, July 1946. 10. Council on Pharmacy and Chemistry: Absorbable Gelatin sponge - new and nonofficial remedies. JAMA. 1947; 135:921. 11. Goodman LS, Gilman A: Surface-acting drugs, in The Pharmacologic Basis of Therapeutics, ed 6. New York, MacMillan Publishing Co. 1980, p 955. 12. Treves N: Prophylaxis of postmammectomy lymphedema by the use of GELFOAM laminated rolls. Cancer 1952; 5:73-83. 13. Barnes AC: The use of gelatin foam sponges in obstetrics and gynecology. Am J Obstet Gynecol 1963; 86:105-107. 14. Rarig HR: Successful use of gelatin foam sponge in surgical restoration of fertility. Am J Obstet Gynecol. 1963; 86:136."" }, ""194"": { ""property.id"": 194, ""property.ts"": ""2017-12-04 04:40:07"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections."" } }" 30,"2017-08-31 23:12:57","Absorbable Gelatin Sterile Ophthalmic Film",Gelfilm,FDA,"{ ""30"": { ""alphabet_x_drug.id"": 30, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""195"": { ""property.id"": 195, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on Gelfilm® absorbable gelatin film, USP DESCRIPTION GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film are absorbable gelatin film approximately 0.075 mm in thickness, designed for use as an absorbable gelatin implant in neurosurgery and thoracic and ocular surgery. In the dry state absorbable gelatin film has the appearance and texture of cellophane of equivalent thickness; when moistened, it assumes a rubbery consistency and can be cut to desired size and shape and fitted to rounded or irregular surfaces."" }, ""196"": { ""property.id"": 196, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Neurosurgery Nonconducive to undue inflammatory reaction and absorbable at a rate sufficiently slow to permit dural regeneration and healing of the arachnoid layer, GELFILM Sterile Film favorably meets requisites for a dural substitute. Use in patients undergoing craniotomies has been reported to prevent development of meningocerebral adhesions and thereby reduce risk of postoperative sequelae. Thoracic Surgery In repair of pleural defects in connection with thoracotomies, thoracoplasties, and extrapleural procedures, implantation of GELFILM Sterile Film has been observed to be followed by minimal tissue reaction and closure of the defect by ingrowth of regenerating pleural and fibrous tissue across the gradually resorbed GELFILM implant. Ocular Surgery Various ocular surgical procedures in which GELFILM Sterile Ophthalmic Film has been used include glaucoma filtration operations (i.e., iridencleisis and trephination), extraocular muscle surgery, and diathermy or sclera “buckling” operations for retinal detachment. Experimental studies in rabbits and clinical trials in patients have shown a remarkable lack of cellular reaction to GELFILM implanted subconjunctivally or used as a seton into the anterior chamber. Objective evidence that GELFILM implants aid in preventing formation of adhesionsbetween contiguous ocular structures has been reported as follows: in iridencleisis in which GELFILM was employed as a seton, the resultant filtrating areas were large and there was no postoperative rise in intraocular tension; in extraocular muscle surgery and operations for retinal detachment, insertion of GELFILM implants between contiguous tissue layers was found to enhance the ease of secondary operations. DOSAGE AND ADMINISTRATION Directions For Use To prepare for use, immerse absorbable gelatin film in sterile saline solution and allow it to soak until it becomes quite pliable; it may then be cut to desired size and shape without difficulty and applied as follows: For covering dural defects, GELFILM Sterile Film is placed over the surface of the brain, the edges of the implant tucked beneath the dura and the wound then closed in the usual manner. If desired, the GELFILM can be sutured loosely to the dura. Care must be exercised, however, because moist film tears easily. For covering pleural defects, GELFILM Sterile Film is placed over the defect and anchored in place by small interrupted sutures. For use as a seton in iridencleisis, a small piece of GELFILM Sterile Ophthalmic Film (approximately 4 x 10 mm) is placed over the prolapsed iris pillar parallel to the limbus; Tenon's capsule and the conjunctiva are then closed with continuous absorbable sutures spaced to insure tight closure. In diathermy or scleral “buckling” operations, GELFILM Sterile Ophthalmic Film may be placed over the sclera, the muscle and the conjunctiva then sutured over the underlying GELFILM. In extraocular muscle surgery, GELFILM Sterile Ophthalmic Film may be placed over and beneath the muscle before Tenon's capsule and the conjunctiva are closed in layers. HOW SUPPLIED GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film are supplied in the following packages: GELFILM Sterile Film, for use in neurosurgery and thoracic surgery, sterile envelopes, one per carton, GTIN 00300090283018 (0009-0283-01). GELFILM Sterile Ophthalmic Film, for use in ocular surgery, sterile envelopes, six per carton, GTIN 00300090297039 (0009-0297-03). Storage And Handling GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the envelopes have been opened, contents are subject to contamination. To insure sterility, it is recommended that absorbable gelatin film be used immediately after withdrawal from the envelope. This product is prepackaged sterile and intended only for single use. Reuse can result in transmission of bloodborne pathogens (including HIV and hepatitis), potentially endangering patients and health care providers. Adherence to the principles of aseptic technique when using this product is essential. Warning: To prevent contamination, employ aseptic procedure in opening envelope and withdrawing GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film. If the envelope is torn or punctured, the contained GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film should not be used. Caution Federal law restricts this device to sale by or on the order of a physician. Manufactured by: Pharmacia and Upjohn Company, 7000 Portage Road, Kalamazoo, Michigan 49001, USA, 1-800-253-8600, Revised: December 2014. Distributed by: Pharmacia & Upjohn Co., Division of Pfizer Inc., New York, NY 10017"" }, ""197"": { ""property.id"": 197, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS No information provided. DRUG INTERACTIONS No information provided."" }, ""198"": { ""property.id"": 198, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS No information provided. PRECAUTIONS Because the rate of absorption of GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film is likely to be increased in presence of purulent exudation, it is recommended that absorbable gelatin film not be implanted in grossly contaminated or infected surgical wounds."" }, ""199"": { ""property.id"": 199, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS Do not use GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film in patients with known allergies to porcine collagen."" }, ""200"": { ""property.id"": 200, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Actions Rate of absorption of GELFILM Sterile Film and GELFILM Sterile Ophthalmic Film after implantation ranges from one to six months depending on size of the implant and site of implantation. Pleural and muscle implants have been reported to be completely absorbed in eight to 14 days, whereas dural and ocular implants usually require at least two to five months for absorption. Absence of undue tissue reaction incident to implantation and absorption of absorbable gelatin film, with consequent decreased likelihood of developing adhesions, has been found to be of particular value in dural and ocular implants."" }, ""201"": { ""property.id"": 201, ""property.ts"": ""2017-12-04 04:40:17"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION No information provided. Please refer to the WARNINGS AND PRECAUTIONS sections."" } }" 31,"2017-08-31 23:12:57",Absorica,Isotretinoin,FDA,"{ ""31"": { ""alphabet_x_drug.id"": 31, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""202"": { ""property.id"": 202, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on ABSORICA® (isotretinoin) Capsules WARNING CAUSES BIRTH DEFECTS Pregnancy Category X ABSORICA must not be used by female patients who are or may become pregnant [see WARNINGS AND PRECAUTIONS and Use in Specific Populations]. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking ABSORICA in any amount, even for short periods of time [see WARNINGS AND PRECAUTIONS and Use in Specific Populations]. Potentially any fetus exposed during pregnancy can be affected [see Use in Specific Populations]. There are no accurate means of determining whether an exposed fetus has been affected [see WARNING AND PRECAUTIONS and Use in Specific Populations]. Birth defects which have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion and premature births have been reported [see Use in Specific Populations]. Documented external abnormalities include: skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia; facial dysmorphia; cleft palate). Documented internal abnormalities include: CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases death has occurred with certain abnormalities previously noted [see Use in Specific Populations]. If pregnancy does occur during the treatment of a female patient who is taking ABSORICA, ABSORICA must be discontinued immediately and she should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling [see Use in Specific Populations]. Special Prescribing Requirements Because of the risk of teratogenicity and to minimize fetal exposure, ABSORICA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called iPLEDGE™. Under the ABSORICA REMS, prescribers, patients, pharmacies, and distributors must enroll and be registered in the program [see WARNINGS AND PRECAUTIONS]. DESCRIPTION ABSORICA (isotretinoin) Capsules contain 10 mg, 20 mg, 25 mg, 30 mg, 35 mg or 40 mg of isotretinoin (a retinoid) in hard gelatin capsules for oral administration. In addition to the active ingredient, isotretinoin, each capsule contains the following inactive ingredients: propyl gallate, sorbitan monooleate, soybean oil and stearoyl polyoxylglycerides. The gelatin capsules contain the following dye systems: 10 mg – iron oxide (yellow) and titanium dioxide; 20 mg – iron oxide (red), and titanium dioxide; 25 mg – FD&C Blue #1, FD&C Yellow #5, FD&C Yellow #6 and titanium dioxide; 30 mg – iron oxide (black, red and yellow) and titanium dioxide; 35 mg – FD&C Blue #2, iron oxide (black, red and yellow) and titanium dioxide; 40 mg – iron oxide (black, red and yellow) and titanium dioxide. Chemically, isotretinoin is 13-cis-retinoic acid and is related to both retinoic acid and retinol (vitamin A). It is a yellow to orange crystalline powder with a molecular weight of 300.44. It is practically insoluble in water, soluble in chloroform and sparingly soluble in alcohol and in isopropyl alcohol. The structural formula is: Meets USP Dissolution Test 3"" }, ""203"": { ""property.id"": 203, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS ABSORICA is a retinoid indicated for the treatment of severe recalcitrant nodular acne in patients 12 years of age and older. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse reactions associated with its use, ABSORICA should be reserved for patients with multiple severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, ABSORICA is indicated only for those female patients who are not pregnant, because ABSORICA can cause severe birth defects [see CONTRAINDICATIONS]. Limitations of Use A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience with isotretinoin has shown that patients may continue to improve following treatment with isotretinoin. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth [see WARNINGS AND PRECAUTIONS]. As a part of the iPLEDGE program, ABSORICA may only be administered to patients enrolled in the program [see WARNINGS AND PRECAUTIONS]. DOSAGE AND ADMINISTRATION Healthcare professionals who prescribe ABSORICA must be certified in the iPLEDGE program and must comply with the required monitoring to ensure safe use of ABSORICA [see WARNINGS AND PRECAUTIONS]. The required laboratory testing must be completed prior to dosing ABSORICA [see Laboratory Testing below]. Pregnancy Testing, and Contraceptive measures must be followed prior to dosing ABSORICA [see Use in Specific Populations]. Recommended Dosage The recommended dosage range for ABSORICA is 0.5 to 1 mg/kg/day given in two divided doses without regard to meals for 15 to 20 weeks (see Table 1). To decrease the risk of esophageal irritation, patients should swallow the capsules with a full glass of liquid [see PATIENT INFORMATION]. The safety of once daily dosing with ABSORICA has not been established. Once daily dosing is not recommended. Table 1: ABSORICA Dosing by Body Weight (Based on Administration With or Without Food) Body Weight Total Daily (mg) Kilograms Pounds 0.5 mg/kg 1 mg/kg 2 mg/kg 40 88 20 40 80 50 110 25 50 100 60 132 30 60 120 70 154 35 70 140 80 176 40 80 160 90 198 45 90 180 100 220 50 100 200 Dosage Range In trials comparing 0.1, 0.5, and 1 mg/kg/day, it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects, some of which may be dose-related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated. Duration Of Use A normal course of treatment is 15 – 20 weeks. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of ABSORICA, even in low doses, has not been studied, and is not recommended. It is important that ABSORICA be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of ABSORICA on bone loss is unknown [see WARNINGS AND PRECAUTIONS]. Laboratory Testing Pregnancy Testing [See Use in Specific Populations] Lipid Profile Perform a fasting lipid profile including triglycerides prior to use of ABSORICA [see WARNINGS AND PRECAUTIONS]. Liver Function Test Perform liver function tests prior to use of ABSORICA [see WARNINGS AND PRECAUTIONS]. HOW SUPPLIED Dosage Forms And Strengths ABSORICA is available in 10 mg, 20 mg, 25 mg, 30 mg, 35 mg and 40 mg capsules. 10 mg: Dark yellow, opaque, capsule imprinted with black ink “G 240” on cap and “10” on the body 20 mg: Red, opaque, capsule imprinted with black ink “G 241” on cap and “20” on the body 25 mg: Green, opaque, capsule imprinted with white ink “G 342” on cap and “25” on the body 30 mg: Brown, opaque, capsule imprinted with white ink “G 242” on cap and “30” on the body 35 mg: Dark blue, opaque, capsule imprinted with white ink “G 343” on cap and “35” on the body 40 mg: Brown and red, capsule imprinted with white ink “G 325” on cap and “40” on the body ABSORICA (isotretinoin) Capsules are supplied as follows: 10 mg: Dark yellow, opaque, capsule imprinted with black ink “G 240” on cap and “10” on the body Box of 30 capsules (3 x 10 Prescription Packs): NDC 10631-115-31 20 mg: Red, opaque, capsule imprinted with black ink “G 241” on cap and “20” on the body Box of 30 capsules (3 x 10 Prescription Packs): NDC 10631-116-31 25 mg: Green, opaque, capsule imprinted with white ink “G 342” on cap and “25” on the body Box of 30 capsules (3 x 10 Prescription Packs): NDC 10631-133-31 30 mg: Brown, opaque, capsule imprinted with white ink “G 242” on cap and “30” on the body Box of 30 capsules (3 x 10 Prescription Packs): NDC 10631-117-31 35 mg: Dark blue, opaque, capsule imprinted with white ink “G 343” on cap and “35” on the body Box of 30 capsules (3 x 10 Prescription Packs): NDC 10631-134-31 40 mg: Brown and red, capsule imprinted with white ink “G 325” on cap and “40” on the body Box of 30 capsules (3 x 10 Prescription Packs): NDC 10631-118-31 Storage And Handling Store at 20° C -25° C (68° F -77° F), excursion permitted between 15° C 30° C (59° F -86° F) [see USP controlled room temperature]. Protect from light. Manufactured for: Ranbaxy Laboratories Inc., Jacksonville, FL 32257 USA GK-244. Revised: September 2015."" }, ""204"": { ""property.id"": 204, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS The following adverse reactions with ABSORICA or other isotretinoin products are described in more detail in other sections of the labeling: Embryofetal Toxicity [see WARNINGS AND PRECAUTIONS] Psychiatric Disorders [see WARNINGS AND PRECAUTIONS] Pseudotumor Cerebri [see WARNINGS AND PRECAUTIONS] Serious Skin Reactions [see WARNINGS AND PRECAUTIONS] Pancreatitis [see WARNINGS AND PRECAUTIONS] Lipid Abnormalities [see WARNINGS AND PRECAUTIONS] Hearing Impairment [see WARNINGS AND PRECAUTIONS] Hepatotoxicity [see WARNINGS AND PRECAUTIONS] Inflammatory Bowel Disease [see WARNINGS AND PRECAUTIONS] Skeletal Abnormalities [see WARNINGS AND PRECAUTIONS] Ocular Abnormalities [see WARNINGS AND PRECAUTIONS] Hypersensitivity [see WARNINGS AND PRECAUTIONS] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of ABSORICA cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice. The adverse reactions listed below reflect both clinical experience with ABSORICA, and consider other adverse reactions that are known from clinical trials and the post-marketing surveillance with oral isotretinoin. The relationship of some of these events to isotretinoin therapy is unknown. Many of the side effects and adverse events seen in patients receiving isotretinoin are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, e.g., of the lips, nasal passage, and eyes). Dose Relationship Cheilitis and hypertriglyceridemia are adverse reactions that are usually dose related. Most adverse reactions reported in clinical trials with isotretinoin were reversible when therapy was discontinued; however, some persisted after cessation of therapy. Body as a Whole The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): fatigue, irritability, pain. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: allergic reactions, including vasculitis, systemic hypersensitivity, edema, lymphadenopathy, weight loss. Cardiovascular The following adverse reactions have been reported with isotretinoin: vascular thrombotic disease, stroke, palpitation, tachycardia. Endocrine/Metabolism and Nutritional The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): decreased appetite, weight fluctuation, hyperlipidaemia. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: hypertriglyceridemia, alterations in blood sugar. Gastrointestinal The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): lip dry, chapped lips, cheilitis, nausea, constipation, diarrhea, abdominal pain, vomiting. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: inflammatory bowel disease, hepatitis, pancreatitis, bleeding and inflammation of the gums, colitis, esophagitis/esophageal ulceration, ileitis, and other nonspecific gastrointestinal symptoms. Hematologic The following adverse reactions have been reported with isotretinoin: allergic reactions, anemia, thrombocytopenia, neutropenia, rare reports of agranulocytosis. Infections and infestations The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): nasopharyngitis, hordeolum, upper respiratory tract infection. In addition to the above adverse reactions, the following adverse reaction has been reported with isotretinoin: infections (including disseminated herpes simplex). Laboratory Abnormalities The following changes in laboratory tests have been noted in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): blood creatine phosphokinase (CPK) increased, blood triglycerides increased, alanine aminotransferase (SGPT) increased, aspartate aminotransferase (SGOT) increased, gamma-glutamyltransferase (GGTP) increased, blood cholesterol increased, low density lipoprotein (LDL) increased, white blood cell count decreased, blood alkaline phosphatase increased, blood bilirubin increased, blood glucose increased, high density lipopoprotein (HDL) decreased, bone mineral density decreased. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: increased LDH, elevation of fasting blood sugar, hyperuricemia, decreases in red blood cell parameters, decreases in white blood cell counts (including severe neutropenia and rare reports of agranulocytosis), elevated sedimentation rates, elevated platelet counts, thrombocytopenia, white cells in the urine, proteinuria, microscopic or gross hematuria. Musculoskeletal and Connective Tissue The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): decreases in bone mineral density, musculoskeletal symptoms (sometimes severe) including back pain, athralgia, musculoskeletal discomfort, musculoskeletal pain, neck pain, pain in extremity, myalgia, musculoskeletal stiffness [see WARNINGS AND PRECAUTIONS]. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, tendonitis, arthritis, transient pain in the chest, and rare reports of rhabdomyolysis. Neurological The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): headache, syncope. In addition to the above adverse reactions, other adverse reactions reported with isotretinoin include: pseudotumor cerebri, dizziness, drowsiness, lethargy, malaise, nervousness, paresthesias, seizures, stroke, weakness. Psychiatric The following adverse reactions have been reported in clinical trials conducted with ABSORICA and a generic product of Accutane® (isotretinoin): suicidal ideation, insomnia, anxiety, depression, irritability, panic attack, anger, euphoria, violent behaviors, emotional instability. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: suicide attempts, suicide, aggression, psychosis and hallucination auditory. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy. Reproductive System The following adverse reaction has been reported with isotretinoin: abnormal menses. Respiratory The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): epistaxis, nasal dryness. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: bronchospasms (with or without a history of asthma), respiratory infection, voice alteration. Skin and Subcutaneous Tissue The following adverse reactions have been reported in a clinical trial conducted with ABSORICA and a generic product of Accutane® (isotretinoin): dry skin, dermatitis, eczema, rash, dermatitis contact, alopecia, pruritus, sunburn, erythema. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: acne fulminans, alopecia (which in some cases persists), bruising, dry nose, eruptive xanthomas, erythema multiforme, flushing, fragility of skin, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, nail dystrophy, paronychia, peeling of palms and soles, photoallergic/photosensitizing reactions, pruritus, pyogenic granuloma, rash (including facial erythema, seborrhea, and eczema), Stevens-Johnson syndrome, sunburn susceptibility increased, sweating, toxic epidermal necrolysis, urticaria, vasculitis (including Wegener's granulomatosis), abnormal wound healing (delayed healing or exuberant granulation tissue with crusting). Special Senses Hearing: The following adverse reactions have been reported with isotretinoin: tinnitus and hearing impairment. Ocular: The following adverse reactions have been reported in clinical trials conducted with ABSORICA and a generic product of Accutane® (isotretinoin): dry eye, visual acuity reduced, vision blurred, eye pruritis, eye irritation, asthenopia, decreased night vision, ocular hyperemia, increased lacrimation, and conjunctivitis. In addition to the above adverse reactions, the following adverse reactions have been reported with isotretinoin: corneal opacities, decreased night vision which may persist, cataracts, color vision disorder, conjunctivitis, eyelid inflammation, keratitis, optic neuritis, photobia, visual disturbances. Renal and Urinary The following adverse reactions have been reported in clinical trials conducted with isotretinoin: glomerulonephritis, nonspecific urogenital findings. DRUG INTERACTIONS Vitamin A ABSORICA is closely related to vitamin A. Therefore, the use of both vitamin A and ABSORICA at the same time may lead to vitamin A side effects. Patients should be advised against taking vitamin supplements containing Vitamin A to avoid additive toxic effects. Tetracyclines Concomitant treatment with ABSORICA and tetracyclines should be avoided because isotretinoin use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Phenytoin Isotretinoin has not been shown to alter the pharmacokinetics of phenytoin in a trial in seven healthy volunteers. These results are consistent with the in vitro finding that neither isotretinoin nor its metabolites induce or inhibit the activity of the CYP2C9 human hepatic P450 enzyme. Phenytoin is known to cause osteomalacia. No formal clinical trials have been conducted to assess if there is an interactive effect on bone loss between phenytoin and isotretinoin. Therefore, caution should be exercised when using these drugs together. St. John's Wort Isotretinoin use is associated with depression in some patients. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John's Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's Wort. Systemic Corticosteroids Systemic corticosteroids are known to cause osteoporosis. No formal clinical trials have been conducted to assess if there is an interactive effect on bone loss between systemic corticosteroids and isotretinoin. Therefore, caution should be exercised when using these drugs together. Norethindrone/Ethinyl Estradiol In a trial of 31 premenopausal female patients with severe recalcitrant nodular acne receiving Norethindrone/ethinyl estradiol as an oral contraceptive agent, isotretinoin at the recommended dose of 1 mg/kg/day, did not induce clinically relevant changes in the pharmacokinetics of ethinyl estradiol and norethindrone and in the serum levels of progesterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prescribers are advised to consult the package insert of medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products."" }, ""205"": { ""property.id"": 205, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS ABSORICA must not be used by female patients who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking ABSORICA in any amount, even for short periods of time. ABSORICA 25 mg contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No.5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Embryofetal Toxicity Teratogenicity Major congenital malformations, spontaneous abortions, and premature births have been documented following pregnancy exposure to isotretinoin [see Use In Specific Populations]. Females of Reproductive Potential must comply with the pregnancy testing and contraception requirements described in the iPLEDGE program [see iPLEDGE Program and Use In Specific Populations]. There are no accurate means of determining whether an exposed fetus has been affected. No Blood Donation Patients must be informed not to donate blood during isotretinoin therapy and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to isotretinoin. iPLEDGE Program Because of the risk of teratogenicity and to minimize fetal exposure, ABSORICA is available only through a restricted program under a REMS called iPLEDGE. Under the ABSORICA REMS, prescribers, patients, pharmacies, and distributors must enroll and be registered in the program. ABSORICA must not be prescribed, dispensed or otherwise obtained through the internet or any other means outside of the iPLEDGE program. Only FDA-approved isotretinoin products must be distributed, prescribed, dispensed, and used. Required components of the iPLEDGE Program are: ABSORICA must only be prescribed by prescribers who are registered and activated with the iPLEDGE program and agree to comply with the REMS requirements described in the booklets entitled The Guide to Best Practices for the iPLEDGE Program, The iPLEDGE Program Prescriber Contraception Counseling Guide, and Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Isotretinoin. Male patients and Females of non-reproductive potential: To obtain ABSORICA, these patients must understand the risks and benefits of ABSORICA, comply with the REMS requirements described in the booklet entitled The iPLEDGE Program Guide to Isotretinoin for Male Patients and Female Patients Who Cannot Get Pregnant, and sign a Patient Information/Informed Consent form. Females of reproductive potential: ABSORICA is contraindicated in female patients who are or may become pregnant [see CONTRAINDICATIONS]. Females of reproductive potential who are not pregnant must understand the risks and benefits, comply with the REMS requirements described in the booklet entitled The iPLEDGE Program Guide to Isotretinoin for Female Patients Who Can Get Pregnant and The iPLEDGE Program Birth Control Workbook (including the pregnancy testing and contraception requirements [see Use In Specific Populations and PATIENT INFORMATION]), and sign a Patient Information/Informed Consent form and Patient Information/Informed Consent About Birth Defects form. Additionally, the patient must answer questions about the iPLEDGE program and pregnancy prevention monthly. Pharmacies that dispense ABSORICA must be registered and activated with iPLEDGE, must only dispense to patients who are authorized to receive ABSORICA, and agree to comply with the REMS requirements described in the booklet entitled The Pharmacist Guide for the iPLEDGE Program. Females of reproductive potential must obtain the prescription within 7 days of the specimen collection for the pregnancy test; male patients and females of non-reproductive potential must obtain the prescription within 30 days of the office visit. ABSORICA must only be dispensed in no more than a 30-day supply with a Medication Guide. Refills require a new prescription and a new authorization from the iPLEDGE system. Wholesalers and distributors that distribute ABSORICA must be registered with iPLEDGE and agree to comply with the REMS requirements. If a pregnancy does occur during ABSORICA treatment, ABSORICA must be discontinued immediately. The patient should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure during or 1 month after ABSORICA therapy must be reported immediately to the FDA via the MedWatch telephone number 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com). Further information, including a list of qualified pharmacies, is available at www.ipledgeprogram.com or 1-866-495-0654. Unacceptable Contraception Micro-dosed Progesterone Preparations Micro-dosed progesterone preparations (“minipills” that do not contain an estrogen) are an inadequate method of contraception during ABSORICA therapy. Psychiatric Disorders Isotretinoin may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action has been established for these reactions [see ADVERSE REACTIONS]. Prescribers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Isotretinoin. Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of ABSORICA therapy, patients and family members should be asked about any history of psychiatric disorder, and at each visit during therapy patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Signs and symptoms of depression, as described in the brochure (Recognizing Psychiatric Disorders in Adolescents and Young Adults), include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interest in activities, fatigue, difficulty concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impulses, and persistent physical symptoms unresponsive to treatment. Patients should stop ABSORICA and the patient or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit. Discontinuation of ABSORICA therapy may be insufficient; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. Patients may report mental health problems or family history of psychiatric disorders. These reports should be discussed with the patient and/or the patient's family. A referral to a mental health professional may be necessary. The physician should consider whether ABSORICA therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of ABSORICA therapy. Pseudotumor Cerebri Isotretinoin use has been associated with cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Concomitant treatment with tetracyclines should therefore be avoided. Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, they should be told to discontinue ABSORICA immediately and be referred to a neurologist for further diagnosis and care [see ADVERSE REACTIONS]. Serious Skin Reactions There have been post-marketing reports of erythema multiforme and severe skin reactions [e.g., Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)] associated with isotretinoin use. These reactions may be serious and result in death, life-threatening events, hospitalization, or disability. Patients should be monitored closely for severe skin reactions, and discontinuation of ABSORICA should be considered if warranted. Pancreatitis Acute pancreatitis has been reported in isotretinoin-treated patients with either elevated or normal serum triglyceride levels. In rare instances, fatal hemorrhagic pancreatitis has been reported. ABSORICA should be stopped if hypertriglyceridemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur. Lipid Abnormalities Elevations of serum triglycerides in excess of 800 mg/dL have been reported in patients treated with isotretinoin. Marked elevations of serum triglycerides were reported in approximately 25% of patients receiving isotretinoin in clinical trials. In addition, approximately 15% developed a decrease in high-density lipoproteins and about 7% showed an increase in cholesterol levels. In clinical trials, the effects of triglycerides, HDL and cholesterol were reversible upon cessation of isotretinoin therapy. Some patients have been able to reverse triglyceride elevation by reduction in weight, restriction of dietary fat and alcohol, and reduction in the dose while continuing isotretinoin. Blood lipid determinations should be performed before ABSORICA is given and then at intervals until the lipid response to ABSORICA is established, which usually occurs within 4 weeks. Especially careful consideration must be given to risk/benefit for patients who may be at high risk of triglyceridemia during ABSORICA therapy (patients with diabetes, obesity, increased alcohol intake, lipid metabolism disorder or familial history of lipid metabolism disorder). If ABSORICA therapy is instituted, more frequent checks of serum values for lipids and/or blood sugar are recommended [see Laboratory Monitoring for Adverse Reactions]. The cardiovascular consequences of hypertriglyceridemia associated with isotretinoin are unknown. Hearing Impairment Impaired hearing has been reported in patients taking isotretinoin; in some cases, the hearing impairment has been reported to persist after therapy has been discontinued. Mechanism(s) and causality for this reaction have not been established. Patients who experience tinnitus or hearing impairment should discontinue ABSORICA treatment and be referred for specialized care for further evaluation [see ADVERSE REACTIONS]. Hepatotoxicity Clinical hepatitis considered to be possibly or probably related to isotretinoin therapy has been reported. Additionally, mild to moderate elevations of liver enzymes have been observed in approximately 15% of individuals treated during clinical trials with isotretinoin, some of which normalized with dosage reduction or continued administration of the drug. If normalization does not readily occur or if hepatitis is suspected during treatment with ABSORICA, the drug should be discontinued and the etiology further investigated. Inflammatory Bowel Disease Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. In some instances, symptoms have been reported to persist after isotretinoin treatment has been stopped. Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue ABSORICA immediately [see ADVERSE REACTIONS]. Skeletal Abnormalities Bone Mineral Density Changes Isotretinoin may have a negative effect on bone mineral density (BMD) in some patients. In a clinical trial of ABSORICA and a generic product of Accutane® (isotretinoin), 27/306 (8.8%) of adolescents had BMD declines, defined as ≥ 4% lumbar spine or total hip, or ≥ 5% femoral neck, during the 20 week treatment period. Repeat scans conducted within 2-3 months after the post-treatment scan showed no recovery of BMD. Longer term data at 4-11 months showed that 3 out of 7 patients had total hip and femoral neck BMD below pre-treatment baseline, and 2 others did not show the increase in BMD above baseline expected in this adolescent population. Therefore, physicians should use caution when prescribing ABSORICA to patients with a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsant [see Use in Specific Populations]. Musculoskeletal Abnormalities Approximately 16% of patients treated with isotretinoin in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of the drug. In a trial of pediatric patients treated with isotretinoin, approximately 29% (104/358) developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female patients than male patients. Arthralgias were experienced in 22% (79/358) of pediatric patients. Arthralgias were severe in 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should be done in patients who present with these symptoms during or after a course of ABSORICA. Consideration should be given to discontinuation of ABSORICA if any significant abnormality is found. There have been spontaneous reports of osteoporosis, osteopenia, bone fractures and/or delayed healing of bone fractures in patients while on therapy with isotretinoin or following cessation of therapy with isotretinoin. While causality to isotretinoin has not been established, an effect cannot be ruled out. Patients may be at an increased risk when participating in sports with repetitive impact where the risks of spondylolisthesis with and without pars fractures and hip growth plate injures in early and late adolescence are known. Effects of multiple courses of isotretinoin on the developing musculoskeletal system are unknown. There is some evidence that long-term, high-dose, or multiple courses of therapy with isotretinoin have more of an effect than a single course of therapy on the musculoskeletal system. Longer term effects have not been studied. It is important that ABSORICA be given at the recommended doses for no longer than the recommended duration. Hyperostosis A high prevalence of skeletal hyperostosis was noted in clinical trials for disorders of keratinization with a mean dose of 2.24 mg/kg/day of isotretinoin. Additionally, skeletal hyperostosis was noted in 6 of 8 patients in a prospective trial of disorders of keratinization. Minimal skeletal hyperostosis and calcification of ligaments and tendons have also been observed by x-ray in prospective trials of nodular acne patients treated with a single course of therapy at recommended doses. The skeletal effects of multiple isotretinoin treatment courses for acne are unknown. In a clinical trial of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, hyperostosis was not observed after 16 to 20 weeks of treatment with approximately 1 mg/kg/day of isotretinoin given in two divided doses. Hyperostosis may require a longer time frame to appear. The clinical course and significance remain unknown. Premature Epiphyseal Closure There are spontaneous literature reports of premature epiphyseal closure in acne patients receiving recommended doses of isotretinoin. The effect of multiple courses of isotretinoin on epiphyseal closure is unknown. In a 20-week clinical trial that included 289 adolescents on ABSORICA or a generic product of Accutane® (isotretinoin) who had hand radiographs taken to assess bone age, a total of 9 (3.11%) patients had bone age changes that were clinically significant and for which a drug-related effect cannot be excluded. Ocular Abnormalities Visual problems should be carefully monitored. All ABSORICA patients experiencing visual difficulties should discontinue ABSORICA treatment and have an ophthalmological examination [see ADVERSE REACTIONS]. Corneal Opacities Corneal opacities have occurred in patients receiving isotretinoin for acne and more frequently when higher drug dosages were used in patients with disorders of keratinization. The corneal opacities that have been observed in clinical trial patients treated with isotretinoin have either completely resolved or were resolving at follow-up 6 to 7 weeks after discontinuation of the drug [see ADVERSE REACTIONS]. Decreased Night Vision Decreased night vision has been reported during isotretinoin therapy and in some instances the event has persisted after therapy was discontinued. Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. Dry Eye Dry eye has been reported in subjects during isotretinoin therapy. Patients who wear contact lenses may have trouble wearing them while on ABSORICA treatment and afterwards. Hypersensitivity Anaphylactic reactions and other allergic reactions have been reported in isotretinoin-treated patients. Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement (including renal) have been reported. Severe allergic reaction necessitates discontinuation of therapy and appropriate medical management. Laboratory Monitoring For Adverse Reactions Lipids Test Pretreatment and follow-up blood lipids should be obtained under fasting conditions. After consumption of alcohol, at least 36 hours should elapse before these determinations are made. It is recommended that these tests be performed at weekly or biweekly intervals until the lipid response to ABSORICA is established. The incidence of hypertriglyceridemia is 1 patient in 4 on isotretinoin [see Lipid Abnormalities]. Liver Function Test Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported in patients on isotretinoin, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to ABSORICA has been established [see Hepatotoxicity]. Glucose Some patients receiving isotretinoin have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during isotretinoin therapy, although no causal relationship has been established. CPK Some patients undergoing vigorous physical activity while on isotretinoin therapy have experienced elevated CPK levels; however, the clinical significance is unknown. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity. In an isotretinoin clinical trial of 924 patients, marked elevations in CPK ( ≥ 350 U/L) were observed in approximately 24% of patients. In another clinical trial of 217 pediatric patients (12 – 17 years) elevations in CPK were observed in 12% of patients, including those undergoing strenuous physical activity in association with reported musculoskeletal adverse events such as back pain, arthralgia, limb injury, or muscle sprain. In these patients, approximately half of the CPK elevations returned to normal within 2 weeks and half returned to normal within 4 weeks. No cases of rhabdomyolysis were reported in this clinical trial. Patient Counseling Information See FDA-Approved Patient Labeling (Medication Guide) Advise the patient that ABSORICA is only available through a restricted program called iPLEDGE. As a component of the iPLEDGE program, prescribers must instruct patients to read the Medication Guide, the iPLEDGE program patient educational booklets, and watch the video with the following videos — “Be Prepared, Be Protected” and “Be Aware: The Risk of Pregnancy While on Isotretinoin”. The video includes information about contraception, the most common reasons that contraception fails, and the importance of using 2 forms of effective contraception when taking teratogenic drugs and comprehensive information about types of potential birth defects which could occur if a female patient who is pregnant takes ABSORICA at any time during pregnancy. Male patients and Females of non-reproductive potential must understand the risks and benefits of ABSORICA, comply with the REMS requirements described in the booklet entitled The iPLEDGE Program Guide to Isotretinoin for Male Patients and Female Patients Who Cannot Get Pregnant, and sign a Patient Information/Informed Consent form. Females of reproductive potential must be instructed that they must not be pregnant when ABSORICA therapy is initiated or plan to become pregnant while receiving ABSORICA therapy. Additionally, they must use 2 forms of effective contraception simultaneously for 1 month before starting ABSORICA, while taking ABSORICA, and for 1 month after ABSORICA has been stopped, unless they commit to continuous abstinence from heterosexual intercourse. They should also sign a Patient Information/Informed Consent form and Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form prior to beginning ABSORICA therapy. Female patients should be seen by their prescribers monthly and have a urine or serum pregnancy test, in a CLIA-certified laboratory, performed each month during treatment to confirm negative pregnancy status before another ABSORICA prescription is written. Additionally, a pregnancy test must be completed at the end of the entire course of ABSORICA therapy and 1 month after discontinuation of therapy. Advise the patient that isotretinoin is found in the semen of male patients taking isotretinoin, but the amount delivered to a female partner would be about one million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin induced embryopathy is unknown, 20 years of post-marketing reports include four with isolated defects compatible with features of retinoid exposed fetuses; however two of these reports were incomplete and two had other possible explanations for the defects observed. Advise the patient that ABSORICA is available only from pharmacies that are certified in the iPLEDGE program, and provide them with the telephone number (1-866-495-0654) and website (www.ipledgeprogram.com) for information on how to obtain. Advise patients that they may be requested to participate in a survey to evaluate the effectiveness of the iPLEDGE program. Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of ABSORICA treatment, patients and family members should be asked about any history of psychiatric disorder, and at each visit during treatment patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Inform patients that symptoms of depression include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interest in activities, fatigue, difficulty concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impulses, and persistent physical symptoms unresponsive to treatment. Patients should stop treatment and the patient or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit. Discontinuation of ABSORICA treatment may be insufficient; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. Patients may report mental health problems or family history of psychiatric disorders. These reports should be discussed with the patient and/or the patient's family. A referral to a mental health professional may be necessary. The physician should consider whether ABSORICA therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of ABSORICA therapy. Patients must be informed that some patients, while taking isotretinoin or soon after stopping isotretinoin, have become depressed or developed other serious mental problems. Symptoms of depression include sad, “anxious” or empty mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down, or trouble concentrating. Some patients taking isotretinoin have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts), some have tried to end their own lives, and some have ended their own lives. There were reports that some of these people did not appear depressed. There have been reports of patients on isotretinoin becoming aggressive or violent. There have also been reports of psychotic symptoms, which indicate a loss of contact with reality. Psychotic symptoms include feelings of suspiciousness toward others, strange beliefs, hearing voices or other noises without an obvious source, and seeing unusual objects or people with no explanation. No one knows if isotretinoin caused these behaviors and symptoms or if they would have happened even if the person did not take isotretinoin. If any of these behaviors or symptoms occur, the patient should stop treatment and the patient or family member should contact the prescriber promptly without waiting until the next visit [see WARNINGS AND PRECAUTIONS]. Some people have had other signs of depression while taking isotretinoin. Patients must be informed that they must not share ABSORICA with anyone else because of the risk of birth defects and other serious adverse reactions. Patients must be informed not to donate blood during therapy and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to ABSORICA. ABSORICA may be taken without regard to meals [see DOSAGE AND ADMINISTRATION]. To decrease the risk of esophageal irritation, patients should swallow the capsules with a full glass of liquid. Patients should be informed that inflammatory bowel disease (including regional ileitis) may occur without a prior history of intestinal disorders. In rare instances, symptoms have been reported to persist after treatment has stopped. Patients should be informed that if they experience abdominal pain, rectal bleeding or severe diarrhea, they should discontinue ABSORICA immediately. Patients should be informed that transient exacerbation (flare) of acne has been seen, generally during the initial period of therapy. Wax epilation and skin resurfacing procedures (such as dermabrasion, laser) should be avoided during ABSORICA therapy and for at least 6 months thereafter due to the possibility of scarring. Patients should be advised to avoid prolonged exposure to UV rays or sunlight. Patients should be informed that they may experience dry eye, corneal opacities, and decreased night vision. Contact lens wearers may experience decreased tolerance to contact lenses during and after therapy. Patients should be informed that 16% of patients treated with isotretinoin in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of the drug. Transient pain in the chest has been reported less frequently. In the clinical trial, these symptoms generally cleared rapidly after discontinuation of therapy, but in some cases persisted. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity. Pediatric patients and their caregivers should be informed that approximately 17% to 29% of pediatric patients treated with isotretinoin developed back pain. In a clinical trial, back pain was severe in 13.5% of the cases and occurred at a higher frequency in female patients than male patients. Arthralgias were experienced in 22% (79/358) of pediatric patients. Arthralgias were severe in 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should be done in patients who present with these symptoms during or after a course of treatment. Consideration should be given to discontinuation of isotretinoin if any significant abnormality is found. Neutropenia and rare cases of agranulocytosis have been reported in patients treated with isotretinoin. ABSORICA should be discontinued if clinically significant decreases in white cell counts occur. Patients should be advised that severe skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported in post marketing data in patients treated with isotretinoin. Treatment with ABSORICA should be discontinued if clinically significant skin reactions occur. Adolescent patients who participate in sports with repetitive impact should be informed that isotretinoin use may increase their risk of spondylolisthesis or hip growth plate injuries. There are spontaneous reports of fractures and/or delayed healing in patients while on therapy with isotretinoin or following cessation of therapy with isotretinoin while involved in these activities [see WARNINGS AND PRECAUTIONS]. Nonclinical Toxicology Carcinogenesis, Mutagenesis and Impairment Of Fertility In male and female Fischer 344 rats given oral isotretinoin at dosages of 8 or 32 mg/kg/day (1.3 to 5.3 times the recommended clinical dose of 1 mg/kg/day, respectively, after normalization for total body surface area) for greater than 18 months, there was a dose-related increased incidence of pheochromocytoma relative to controls. The incidence of adrenal medullary hyperplasia was also increased at the higher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor; therefore, the relevance of this tumor to the human population is uncertain. The Ames test was conducted with isotretinoin in two laboratories. The results of the tests in one laboratory were negative while in the second laboratory a weakly positive response (less than 1.6 x background) was noted in S. typhimurium TA100 when the assay was conducted with metabolic activation. No dose response effect was seen and all other strains were negative. Additionally, other tests designed to assess genotoxicity (Chinese hamster cell assay, mouse micronucleus test, S. cerevisiae D7 assay, in vitro clastogenesis assay with human-derived lymphocytes, and unscheduled DNA synthesis assay) were all negative. In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition were observed at oral dosages of isotretinoin of 2, 8, or 32 mg/kg/day (0.3, 1.3, or 5.3 times the recommended clinical dose of 1 mg/kg/day, respectively, after normalization for total body surface area). In dogs, testicular atrophy was noted after treatment with oral isotretinoin for approximately 30 weeks at dosages of 20 or 60 mg/kg/day (10 or 30 times the recommended clinical dose of 1 mg/kg/day, respectively, after normalization for total body surface area). In general, there was microscopic evidence for appreciable depression of spermatogenesis but some sperm were observed in all testes examined and in no instance were completely atrophic tubules seen. In trials of 66 men, 30 of whom were patients with nodular acne under treatment with oral isotretinoin, no significant changes were noted in the count or motility of spermatozoa in the ejaculate. In a study of 50 men (ages 17 to 32 years) receiving isotretinoin therapy for nodular acne, no significant effects were seen on ejaculate volume, sperm count, total sperm motility, morphology or seminal plasma fructose. Use In Specific Populations Pregnancy Pregnancy Category X [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Risk Summary ABSORICA is contraindicated during pregnancy because isotretinoin can cause can cause fetal harm when administered to a pregnant woman. There is an increased risk of major congenital malformations, spontaneous abortions, and premature births following isotretinoin exposure during pregnancy in humans. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to a fetus. Clinical Considerations If pregnancy does occur during treatment of a female patient who is taking ABSORICA, ABSORICA must be discontinued immediately and she should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Human Data Major congenital malformations that have been documented following isotretinoin exposure include malformations of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. External malformations include: skull; ear (including anotia, micropinna, small or absent external auditory canals); eye (including microphthalmia); facial dysmorphia and cleft palate. Internal abnormalities include: CNS (including cerebral and cerebellar malformations, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular; thymus gland; parathyroid hormone deficiency. In some cases death has occurred as a result of the malformations. Isotretinoin is found in the semen of male patients taking isotretinoin, but the amount delivered to a female partner would be about one million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin induced embryopathy is unknown and 20 years of post-marketing reports include four reports with isolated defects compatible with features of retinoid exposed fetuses, two of these reports were incomplete and two had other possible explanations for the defects observed. Cases of IQ scores less than 85 with or without other abnormalities have been reported. An increased risk of spontaneous abortion and premature births have been documented with isotretinoin exposure during pregnancy. Nursing Mothers It is not known whether this drug is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from ABSORICA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The use of ABSORICA in pediatric patients less than 12 years of age has not been studied. The use of ABSORICA for the treatment of severe recalcitrant nodular acne in pediatric patients ages 12 to 17 years should be given careful consideration, especially for those patients where a known metabolic or structural bone disease exists [see WARNINGS AND PRECAUTIONS]. Use of ABSORICA in this age group for severe recalcitrant nodular acne is supported by evidence from a clinical trial of ABSORICA compared to a generic product of Accutane® (isotretinoin) in 397 pediatric patients (12 to 17 years). Results from this trial demonstrated that both ABSORICA and the other isotretinoin drug product, at a dose of 1 mg/kg/day given in two divided doses, was effective in treating severe recalcitrant nodular acne in pediatric patients. In trials with isotretinoin, adverse reactions reported in pediatric patients were similar to those described in adults except for the increased incidence of back pain and arthralgia (both of which were sometimes severe) and myalgia in pediatric patients. In a trial of pediatric patients treated with isotretinoin, approximately 29% (104/358) developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female patients than male patients. Arthralgias were experienced in 22% (79/358) of pediatric patients. Arthralgias were severe in 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should be done in patients who present with these symptoms during or after a course of ABSORICA. Consideration should be given to discontinuation of ABSORICA if any significant abnormality is found. The effect on bone mineral density (BMD) of a 20-week course of therapy with ABSORICA or a generic product of Accutane® (isotretinoin) was evaluated in a double-blind, randomized clinical trial involving 396 adolescents with severe recalcitrant nodular acne (mean age 15.4, range 1217, 80% males). Following 20 weeks of treatment, there were no statistically significant differences between the treatment groups. The mean changes in BMD from baseline for the overall trial population were 1.8% for lumbar spine, -0.1% for total hip and -0.3% for femoral neck. Mean BMD Z-scores declined from baseline at each of these sites (-0.053, -0.109 and -0.104 respectively). Out of 306 adolescents, 27 (8.8%) had clinically significant BMD declines defined as ≥ 4% lumbar spine or total hip, or ≥ 5% femoral neck, including 2 subjects for lumbar spine, 17 for total hip and 20 for femoral neck. Repeat DXA scans within 2-3 months after the post treatment scan showed no recovery of BMD. Longer-term follow up at 4-11 months showed that 3 out of 7 patients had total hip and femoral neck BMD below pretreatment baseline, and 2 others did not show the increase in BMD above baseline expected in this adolescent population. The significance of these changes in regard to long-term bone health and future fracture risk is unknown [see WARNINGS AND PRECAUTIONS]. In an open-label clinical trial (N=217) of a single course of therapy with isotretinoin for adolescents with severe recalcitrant nodular acne, bone density measurements at several skeletal sites were not significantly decreased (lumbar spine change > -4% and total hip change > -5%) or were increased in the majority of patients. One patient had a decrease in lumbar spine bone mineral density > 4% based on unadjusted data. Sixteen (7.9%) patients had decreases in lumbar spine bone mineral density > 4%, and all the other patients (92%) did not have significant decreases or had increases (adjusted for body mass index). Nine patients (4.5%) had a decrease in total hip bone mineral density > 5% based on unadjusted data. Twenty-one (10.6%) patients had decreases in total hip bone mineral density > 5%, and all the other patients (89%) did not have significant decreases or had increases (adjusted for body mass index). Follow-up trials performed in 8 of the patients with decreased bone mineral density for up to 11 months thereafter demonstrated increasing bone density in 5 patients at the lumbar spine, while the other 3 patients had lumbar spine bone density measurements below baseline values. Total hip bone mineral densities remained below baseline (range -1.6% to -7.6%) in 5 of 8 patients (62.5%). In a separate open-label extension trial of 10 patients, ages 13 to 18 years, who started a second course of isotretinoin 4 months after the first course, two patients showed a decrease in mean lumbar spine bone mineral density up to 3.25%. There are spontaneous literature reports of premature epiphyseal closure in acne patients receiving recommended doses of isotretinoin. The effect of multiple courses of isotretinoin on epiphyseal closure is unknown. In a 20week clinical trial that included 289 adolescents who had hand radiographs taken to assess bone age, a total of 9 patients had bone age changes that were clinically significant and for which a drug-related effect cannot be excluded [see WARNINGS AND PRECAUTIONS]. Geriatric Use Clinical trials of ABSORICA did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Although reported clinical experience has not identified differences in responses between elderly and younger patients, effects of aging might be expected to increase some risks associated with ABSORICA therapy. Females Of Reproductive Potential All females of reproductive potential must comply with the iPLEDGE program requirements [see WARNINGS AND PRECAUTIONS]. Pregnancy Testing ABSORICA must only be prescribed to female patients who are known not to be pregnant as confirmed by a negative CLIA-certified laboratory conducted pregnancy test. Females of reproductive potential must have had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial ABSORICA prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for ABSORICA. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the two tests must be at least 19 days. For patients with regular menstrual cycles, perform the second pregnancy test during the first 5 days of the menstrual period immediately preceding the beginning of ABSORICA therapy and after the patient has used 2 forms of contraception for 1 month. For patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, perform the second pregnancy test immediately preceding the beginning of ABSORICA therapy and after the patient has used 2 forms of contraception for 1 month. Each month of continued ABSORICA therapy, patients must have a negative result from a urine or serum pregnancy test. A pregnancy test must be repeated each month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription. A pregnancy test must also be completed at the end of the entire course of isotretinoin therapy and 1 month after the discontinuation of isotretinoin. Contraception Females of reproductive potential must use 2 forms of effective contraception simultaneously, at least 1 of which must be a primary form, unless the patient commits to continuous abstinence from heterosexual contact, or the patient has undergone a hysterectomy or bilateral oophorectomy, or has been medically confirmed to be post-menopausal. Patients must use 2 forms of effective contraception for at least 1 month prior to initiation of ABSORICA therapy, during ABSORICA therapy, and for 1 month after discontinuing ABSORICA therapy. Micro-dosed progesterone preparations (“minipills” that do not contain an estrogen) are an inadequate method of contraception during isotretinoin therapy [see WARNINGS AND PRECAUTIONS]. Effective forms of contraception include both primary and secondary forms of contraception: Primary forms Secondary forms Tubal sterilization Partner’s vasectomy Intrauterine device Hormonal (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring) Barrier: male latex condom with or without spermicide diaphragm with spermicide cervical cap with spermicide Other: Vaginal sponge (contains spermicide) Any birth control method can fail. There have been reports of pregnancy from female patients who have used combination oral contraceptives, as well as transdermal patch/ injectable/ implantable/ vaginal ring hormonal birth control products; these pregnancies occurred while taking isotretinoin. These reports are more frequent for female patients who use only a single method of contraception. Therefore, it is critically important for females of reproductive potential use 2 effective forms of contraception simultaneously. Using two forms of contraception simultaneously substantially reduces the chances that a female will become pregnant over the risk of pregnancy with either form alone. A drug interaction that decreases effectiveness of hormonal contraceptives has not been entirely ruled out for isotretinoin. Although hormonal contraceptives are highly effective, prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John's Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's Wort [see DRUG INTERACTIONS]. If the patient has unprotected heterosexual intercourse at any time 1 month before, during, or 1 month after therapy, she must: Stop taking ABSORICA immediately, if on therapy Have a pregnancy test at least 19 days after the last act of unprotected heterosexual intercourse Start using 2 forms of effective contraception simultaneously again for 1 month before resuming ABSORICA therapy Have a second pregnancy test after using 2 forms of effective contraception for 1 month as described above depending on whether she has regular menses or not. If a pregnancy does occur during ABSORICA treatment, ABSORICA must be discontinued immediately. The patient should be referred to an Obstetrician- Gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure during or 1 month after ABSORICA therapy must be reported immediately to the FDA via the MedWatch number 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-4950654 or via the internet (www.ipledgeprogram.com) [see WARNINGS AND PRECAUTIONS]."" }, ""206"": { ""property.id"": 206, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms quickly resolve without apparent residual effects. ABSORICA causes serious birth defects at any dosage (see BOXED CONTRAINDICATIONS AND WARNINGS). Females of reproductive potential who present with ABSORICA overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the BOXED CONTRAINDICATIONS AND WARNINGS. Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in WARNINGS AND PRECAUTIONS. Educational materials for such patients can be obtained by calling the manufacturer. Because an overdose would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a female patient who is or might become pregnant, for 1 month after the overdose. All patients with ABSORICA overdose should not donate blood for at least 1 month. CONTRAINDICATIONS Pregnancy ABSORICA can cause fetal harm when administered to a pregnant woman. Major congenital malformations, spontaneous abortions, and premature births have been documented following pregnancy exposure to isotretinoin in any amount and even for short periods of time. ABSORICA is contraindicated in females who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations]. Hypersensitivity Hypersensitivity to this product (or Vitamin A, given the chemical similarity to isotretinoin) or to any of its components [see WARNINGS AND PRECAUTIONS]."" }, ""207"": { ""property.id"": 207, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Mechanism Of Action ABSORICA is a retinoid, which when administered in pharmacologic dosages of 0.5 to 1 mg/kg/day, inhibits sebaceous gland function and keratinization. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and is related to the dose and duration of treatment with isotretinoin and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation. The exact mechanism of action of ABSORICA is unknown. Pharmacodynamics The pharmacodynamics of ABSORICA are unknown. Pharmacokinetics Absorption Due to its high lipophilicity, oral absorption of isotretinoin is enhanced when given with a high-fat meal. ABSORICA is bioequivalent to Accutane® (isotretinoin) capsule when both drugs are taken with a high-fat meal. ABSORICA is more bioavailable than Accutane® (isotretinoin) capsules when both drugs are taken fasted; the AUC0-t of ABSORICA is approximately 83% greater than that of Accutane® . ABSORICA is therefore not interchangeable with generic products of Accutane® . A single dose two-way crossover pharmacokinetic trial was conducted in 14 healthy adult male subjects comparing ABSORICA 40 mg (1 x 40 mg capsules), dosed under fasted and fed conditions. Under fed conditions after a high-fat meal, it was observed that the mean AUC0-t and Cmax were approximately 50% and 26% higher, than that observed under fasting conditions (Table 2). The observed elimination half-life (T½) was slightly lower in the fed state versus fasted. The time to peak concentration (Tmax) increased with food and this may be related to a longer absorption phase. Table 2: Pharmacokinetic parameters of ABSORICA mean (%CV) following administration of 40 mg strength, N=14 ABSORICA (1 x 40 mg capsules) AUC0-t (ng x hr/mL) Cmax (ng/mL) Tmax (hr) T½ (hr) Fed 6095 (26 %) 395 (39 %) 6.4 (47 %) 22 (25 %) Fasted 4055 (20 %) 314 (26 %) 2.9 (34 %) 24 (28 %) Published clinical literature has shown that there is no difference in the pharmacokinetics of isotretinoin between patients with nodular acne and healthy subjects with normal skin. Distribution Isotretinoin is more than 99.9% bound to plasma proteins, primarily albumin. Metabolism Following oral administration of isotretinoin, at least three metabolites have been identified in human plasma: 4-oxo-isotretinoin, retinoic acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin). Retinoic acid and 13-cis-retinoic acid are geometric isomers and show reversible interconversion. The administration of one isomer will give rise to the other. Isotretinoin is also irreversibly oxidized to 4-oxo-isotretinoin, which forms its geometric isomer 4-oxo-tretinoin. After a single 40 mg oral dose of ABSORICA to 57 healthy adult subjects, concurrent administration of food increased the extent of formation of all metabolites in plasma when compared to the extent of formation under fasted conditions. All of these metabolites possess retinoid activity that is in some in vitro models more than that of the parent isotretinoin. However, the clinical significance of these models is unknown. In vitro studies indicate that the primary P450 isoforms involved in isotretinoin metabolism are 2C8, 2C9, 3A4, and 2B6. Isotretinoin and its metabolites are further metabolized into conjugates, which are then excreted in urine and feces. Elimination Following oral administration of an 80 mg dose of 14C-isotretinoin as a liquid suspension, 14C-activity in blood declined with a half-life of 90 hours. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%). After a single 40 mg (2 x 20 mg) oral dose of ABSORICA to 57 healthy adult subjects under fed conditions, the mean ± SD elimination half-lives (T½) of isotretinoin and 4-oxo-isotretinoin under fed states were 18 hours and 38 hours, respectively. Special Patient Populations The pharmacokinetics of isotretinoin were evaluated after single and multiple doses in 38 pediatric patients (12 to 15 years) and 19 adult patients ( ≥ 18 years) who received isotretinoin for the treatment of severe recalcitrant nodular acne. In both age groups, 4-oxo-isotretinoin was the major metabolite; tretinoin and 4-oxo-tretinoin were also observed. There were no statistically significant differences in the pharmacokinetics of isotretinoin between pediatric and adult patients. Animal Toxicology In rats given 8 or 32 mg/kg/day of isotretinoin (1.3 to 5.3 times the recommended clinical dose of 1 mg/kg/day after normalization for total body surface area) for 18 months or longer, the incidences of focal calcification, fibrosis and inflammation of the myocardium, calcification of coronary, pulmonary and mesenteric arteries, and metastatic calcification of the gastric mucosa were greater than in control rats of similar age. Focal endocardial and myocardial calcifications associated with calcification of the coronary arteries were observed in two dogs after approximately 6 to 7 months of treatment with isotretinoin at a dosage of 60 to 120 mg/kg/day (30 to 60 times the recommended clinical dose of 1 mg/kg/day, respectively, after normalization for total body surface area). Clinical Studies A double-blind, randomized, parallel group trial (Study 1) was conducted in patients with severe recalcitrant nodular acne to evaluate the efficacy and safety of ABSORICA compared to a generic product of Accutane® under fed conditions. Enrolled patients had a weight of 40 to 110 kg with at least 10 nodular lesions on the face and/or trunk. A total of 925 patients were randomized 1:1 to receive ABSORICA or a generic product of Accutane® (isotretinoin). Study patients ranged from 12 to 54 years of age, were approximately 60% male, 40% female, and were 87% White, 4% Black, 6% Asian, and 3% Other. Patients were treated an initial dose of 0.5 mg/kg/day in two divided doses for the first 4 weeks followed by 1 mg/kg/day in two divided doses for the following 16 weeks. Change from Baseline to Week 20 in total nodular lesion count and proportion of patients with at least a 90% reduction in total nodular lesion count from Baseline to Week 20 are presented in Table 3. Total nodular lesion counts by visit are presented in Figure 1. Table 3: Efficacy Results at Week 20 (Study 1) ABSORICA N=464 Isotretinoin* N=461 Nodular Lesions Mean Baseline Count 18.4 17.7 Mean Reduction -15.68 -15.62 Patients Achieving 90% Reduction 324 (70%) 344 (75%) *A generic product of Accutane® Figure 1: Total Nodular (Facial and Truncal) Lesion Count by Visit in Study 1"" }, ""208"": { ""property.id"": 208, ""property.ts"": ""2017-12-04 04:40:19"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION ABSORICA® (AB-SORE-I-KAH) (isotretinoin) Capsules Read the Medication Guide that comes with ABSORICA before you start taking it and each time you get a prescription. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is the most important information I should know about ABSORICA? ABSORICA is used to treat a type of severe acne (nodular acne) that has not been helped by other treatments, including antibiotics. Because ABSORICA can cause birth defects, ABSORICA is only for patients who can understand and agree to carry out all of the instructions in the iPLEDGE program. ABSORICA may cause serious mental health problems. 1. Birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby, and early (premature) births. Females who are pregnant or who plan to become pregnant must not take ABSORICA. Females must not get pregnant: for 1 month before starting ABSORICA while taking ABSORICA for 1 month after stopping ABSORICA If you get pregnant while taking ABSORICA, stop taking it right away and call your doctor. Doctors and patients should report all cases of pregnancy to: FDA MedWatch at 1-800-FDA-1088, and the iPLEDGE pregnancy registry at 1-866-495-0654 2. Serious mental health problems. ABSORICA may cause: depression psychosis (seeing or hearing things that are not real) suicide. Some patients taking ABSORICA have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. And some people have ended their own lives. Stop ABSORICA and call your doctor right away if you or a family member notices that you have any of the following signs and symptoms of depression or psychosis: start to feel sad or have crying spells lose interest in activities you once enjoyed sleep too much or have trouble sleeping become more irritable, angry, or aggressive than usual (for example, temper outbursts, thoughts of violence) have a change in your appetite or body weight have trouble concentrating withdraw from your friends or family feel like you have no energy have feelings of worthlessness or guilt start having thoughts about hurting yourself or taking your own life (suicidal thoughts) start acting on dangerous impulses start seeing or hearing things that are not real After stopping ABSORICA, you may also need follow-up mental health care if you had any of these symptoms. What is ABSORICA? ABSORICA is a medicine taken by mouth to treat the most severe form of acne (nodular acne) that cannot be cleared up by any other acne treatments, including antibiotics. ABSORICA can cause serious side effects (see “What is the most important information I should know about ABSORICA?”). ABSORICA can only be: prescribed by doctors that are registered in the iPLEDGE program dispensed by a pharmacy that is registered with the iPLEDGE program given to patients who are registered in the iPLEDGE program and agree to do everything required in the program What is severe nodular acne? Severe nodular acne is when many red, swollen, tender lumps form in the skin. These can be the size of pencil erasers or larger. If untreated, nodular acne can lead to permanent scars. Who should not take ABSORICA? Do not take ABSORICA if you are pregnant, plan to become pregnant, or become pregnant during ABSORICA treatment. ABSORICA causes severe birth defects. See “What is the most important information I should know about ABSORICA?” Do not take ABSORICA if you are allergic to anything in it. See the end of this Medication Guide for a complete list of ingredients in ABSORICA. What should I tell my doctor before taking ABSORICA? Tell your doctor if you or a family member has any of the following health conditions: mental problems asthma liver disease diabetes heart disease bone loss (osteoporosis) or weak bones an eating problem called anorexia nervosa (where people eat too little) food or medicine allergies Tell your doctor if you are pregnant or breastfeeding. ABSORICA must not be used by females who are pregnant or breastfeeding. Tell your doctor about all of the medicines you take including prescription and over-thecounter medicines, vitamins and herbal supplements. ABSORICA and certain other medicines can interact with each other, sometimes causing serious side effects. Especially tell your doctor if you take: Vitamin A supplements. Vitamin A in high doses has many of the same side effects as ABSORICA. Taking both together may increase your chance of getting side effects. Tetracycline antibiotics. Tetracycline antibiotics taken with ABSORICA can increase the chances of getting increased pressure in the brain. Progestin-only birth control pills (mini-pills). They may not work while you take ABSORICA. Ask your doctor or pharmacist if you are not sure what type you are using. Dilantin (phenytoin). This medicine taken with ABSORICA may weaken your bones. Corticosteroid medicines. These medicines taken with ABSORICA may weaken your bones. St. John's Wort. This herbal supplement may make birth control pills work less effectively. These medicines should not be used with ABSORICA unless your doctor tells you it is okay. Know the medicines you take. Keep a list of them to show to your doctor and pharmacist. Do not take any new medicine without talking with your doctor. How should I take ABSORICA? You must take ABSORICA exactly as prescribed. You must also follow all the instructions of the iPLEDGE program. Before prescribing ABSORICA, your doctor will: explain the iPLEDGE program to you have you sign the Patient Information/Informed Consent form (for all patients). Females who can get pregnant must also sign another consent form. You will not be prescribed ABSORICA if you cannot agree to or follow all the instructions of the iPLEDGE program. You will get no more than a 30-day supply of ABSORICA at a time. This is to make sure you are following the ABSORICA iPLEDGE program. You should talk with your doctor each month about side effects. The amount of ABSORICA you take has been specially chosen for you. It is based on your body weight, and may change during treatment. Take ABSORICA 2 times a day without regard to meals, unless your doctor tells you otherwise. Swallow your ABSORICA capsules whole with a full glass of liquid. Do not chew or suck on the capsule. ABSORICA can hurt the tube that connects your mouth to your stomach (esophagus) if it is not swallowed whole. If you miss a dose, just skip that dose. Do not take two doses at the same time. If you take too much ABSORICA or overdose, call your doctor or poison control center right away. Your acne may get worse when you first start taking ABSORICA. This should last only a short while. Talk with your doctor if this is a problem for you. You must return to your doctor as directed to make sure you don't have signs of serious side effects. Your doctor may do blood tests to check for serious side effects from ABSORICA. Females who can get pregnant will get a pregnancy test each month. Females who can get pregnant must agree to use two separate forms of effective birth control at the same time one month before, while taking, and for one month after taking ABSORICA. You must access the iPLEDGE system to answer questions about the program requirements and to enter your two chosen forms of birth control. To access the iPLEDGE system, go to www.ipledgeprogram.com or call 1-866-495-0654. You must talk about effective birth control methods with your doctor or go for a free visit to talk about birth control with another doctor or family planning expert. Your doctor can arrange this free visit, which will be paid for by the company that makes ABSORICA. If you have sex at any time without using two forms of effective birth control, get pregnant, or miss your expected period, stop using ABSORICA and call your doctor right away. What should I avoid while taking ABSORICA? Do not get pregnant while taking ABSORICA and for one month after stopping ABSORICA. See “What is the most important information I should know about ABSORICA?” Do not breastfeed while taking ABSORICA and for one month after stopping ABSORICA. We do not know if ABSORICA can pass through your milk and harm the baby. Do not give blood while you take ABSORICA and for one month after stopping ABSORICA. If someone who is pregnant gets your donated blood, her baby may be exposed to ABSORICA and may be born with birth defects. Do not take other medicines or herbal products with ABSORICA unless you talk to your doctor. See “What should I tell my doctor before taking ABSORICA?” Do not drive at night until you know if ABSORICA has affected your vision. ABSORICA may decrease your ability to see in the dark. Do not have cosmetic procedures to smooth your skin, including waxing, dermabrasion, or laser procedures, while you are using ABSORICA and for at least 6 months after you stop. ABSORICA can increase your chance of scarring from these procedures. Check with your doctor for advice about when you can have cosmetic procedures. Avoid sunlight and ultraviolet lights as much as possible. Tanning machines use ultraviolet lights. ABSORICA may make your skin more sensitive to light. Do not share ABSORICA with other people. It can cause birth defects and other serious health problems. What are the possible side effects of ABSORICA? ABSORICA can cause birth defects (deformed babies), loss of a baby before birth (miscarriage), death of the baby, and early (premature) births. See “What is the most important information I should know about ABSORICA?” ABSORICA may cause serious mental health problems. See “What is the most important information I should know about ABSORICA?” serious brain problems. ABSORICA can increase the pressure in your brain. This can lead to permanent loss of eyesight and, in rare cases, death. Stop taking ABSORICA and call your doctor right away if you get any of these signs of increased brain pressure: bad headache blurred vision dizziness nausea or vomiting seizures (convulsions) stroke skin problems. Skin rash can occur in patients taking ABSORICA. In some patients a rash can be serious. Stop using ABSORICA and call your doctor right away if you develop conjunctivitis (red or inflamed eyes, like “pink eye”), a rash with a fever, blisters on legs, arms or face and/or sores in your mouth, throat, nose, eyes, or if your skin begins to peel. stomach area (abdomen) problems. Certain symptoms may mean that your internal organs are being damaged. These organs include the liver, pancreas, bowel (intestines), and esophagus (connection between mouth and stomach). If your organs are damaged, they may not get better even after you stop taking ABSORICA. Stop taking ABSORICA and call your doctor if you get: severe stomach, chest or bowel pain trouble swallowing or painful new or worsening heartburn diarrhea rectal bleeding yellowing of your skin or eyes dark urine bone and muscle problems. ABSORICA may affect bones, muscles, and ligaments and cause pain in your joints or muscles. Tell your doctor if you plan hard physical activity during treatment with ABSORICA. Tell your doctor if you get: back pain joint pain broken bone. Tell all healthcare providers that you take ABSORICA if you break a bone. Stop ABSORICA and call your doctor right away if you have muscle weakness. Muscle weakness with or without pain can be a sign of serious muscle damage. ABSORICA may stop long bone growth in teenagers who are still growing. hearing problems. Stop using ABSORICA and call your doctor if your hearing gets worse or if you have ringing in your ears. Your hearing loss may be permanent. vision problems. ABSORICA may affect your ability to see in the dark. This condition usually clears up after you stop taking ABSORICA, but it may be permanent. Other serious eye effects can occur. Stop taking ABSORICA and call your doctor right away if you have any problems with your vision or dryness of the eyes that is painful or constant. If you wear contact lenses, you may have trouble wearing them while taking ABSORICA and after treatment. lipid (fats and cholesterol in blood) problems. ABSORICA can raise the level of fats and cholesterol in your blood. This can be a serious problem. Return to your doctor for blood tests to check your lipids and to get any needed treatment. These problems usually go away when ABSORICA treatment is finished. serious allergic reactions. Stop taking ABSORICA and get emergency care right away if you develop hives, a swollen face or mouth, or have trouble breathing. Stop taking ABSORICA and call your doctor if you get a fever, rash, or red patches or bruises on your legs. blood sugar problems. ABSORICA may cause blood sugar problems including diabetes. Tell your doctor if you are very thirsty or urinate a lot. decreased red and white blood cells. Call your doctor if you have trouble breathing, faint, or feel weak. The common, less serious side effects of ABSORICA are dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds. ABSORICA contains the color additive FD&C Yellow No. 5 (tartrazine) which may cause allergic type reactions, including asthma in some people. The overall occurrence of allergic reaction is low. This reaction is most often seen in people who also have an allergy to aspirin. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Ranbaxy Inc., the manufacturer of ABSORICA at 1800-406-7984. How should I store ABSORICA? Store ABSORICA at room temperature, 68° to 77° F (20° to 25° C). Protect from light. Keep ABSORICA and all medicines out of the reach of children. General Information about ABSORICA Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use ABSORICA for a condition for which it was not prescribed. Do not give ABSORICA to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about ABSORICA. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about ABSORICA that is written for health care professionals. You can also call iPLEDGE program at 1-866-495-0654 or visit www.ipledgeprogram.com. What are the ingredients in ABSORICA? Active ingredient: Isotretinoin, USP Inactive ingredients: Propyl gallate, sorbitan monooleate, soybean oil and stearoyl polyoxylglycerides. Gelatin capsules contain the following dye systems: 10 mg – iron oxide (yellow) and titanium dioxide; 20 mg – iron oxide (red) and titanium dioxide; 25 mg – FD&C Blue #1, FD&C Yellow #5 (tartrazine), FD&C Yellow #6 and titanium dioxide; 30 mg – iron oxide (black, red and yellow) and titanium dioxide; 35 mg – FD&C Blue #2, iron oxide (black, red and yellow) and titanium dioxide; and 40 mg – iron oxide (black, red and yellow) and titanium dioxide."" } }" 32,"2017-08-31 23:12:57",Abstral,"Fentanyl Sublingual Tablets",FDA,"{ ""32"": { ""alphabet_x_drug.id"": 32, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""209"": { ""property.id"": 209, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on ABSTRAL® (fentanyl) Sublingual Tablet WARNING RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL Respiratory Depression Fatal respiratory depression has occurred in patients treated with immediate-release transmucosal fentanyl, including following use in opioid non-tolerant patients and improper dosing. The substitution of ABSTRAL for any other fentanyl product may result in fatal overdose. Due to the risk of respiratory depression, ABSTRAL is contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients. [see CONTRAINDICATIONS] ABSTRAL must be kept out of reach of children. [see Patient Counseling Information and HOW SUPPLIED/Storage and Handling] The concomitant use of ABSTRAL with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression. [see DRUG INTERACTIONS] Medication Errors Substantial differences exist in the pharmacokinetic profile of ABSTRAL compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose. When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to ABSTRAL.   When dispensing, do not substitute an ABSTRAL prescription for other fentanyl products. Abuse Potential ABSTRAL contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. ABSTRAL can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ABSTRAL in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Because of the risk for misuse, abuse, addiction, and overdose, ABSTRAL is available only through a restricted program, required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the TIRF (Transmucosal Immediate Release Fentanyl) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program [see WARNINGS AND PRECAUTIONS]. Further information is available at www.TIRFREMSAccess.com or by calling1-866-822-1483. DESCRIPTION ABSTRAL (fentanyl) sublingual tablet is a solid formulation of fentanyl citrate, a potent opioid analgesic intended for oral sublingual administration. ABSTRAL is formulated as a white tablet available in six strengths, distinguishable by the shape of the tablet and by de-bossing on the tablet surface. Active Ingredient: Fentanyl citrate, USP is N-(1-Phenethyl-4-piperidyl) propionanilide citrate (1:1). Fentanyl is a highly lipophilic compound (octanol-water partition coefficient at pH 7.4 is 816:1) that is freely soluble in organic solvents and sparingly soluble in water (1:40). The molecular weight of the free base is 336.5 (the citrate salt is 528.6). The pKa of the tertiary nitrogens are 7.3 and 8.4. The compound has the following structural formula: All tablet strengths are expressed as the amount of fentanyl free base, e.g., the 100 mcg strength tablet contains 100 mcg of fentanyl free base. Inactive Ingredients: Croscarmellose sodium, magnesium stearate, mannitol, and silicified microcrystalline cellulose."" }, ""210"": { ""property.id"": 210, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS ABSTRAL (fentanyl) sublingual tablets are indicated for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking around-theclock medicine consisting of at least 60 mg of oral morphine daily, or at least 25 mcg of transdermal fentanyl/hour, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or at least 25 mg oral oxymorphone daily, or an equianalgesic dose of another opioid medication daily for a week or longer. Patients must remain on around-the-clock opioids when taking ABSTRAL. ABSTRAL is contraindicated for patients who are not already tolerant to opioids because life-threatening respiratory depression and death could result at any dose in patients not on a chronic regimen of opioids. For this reason, ABSTRAL is contraindicated in the management of acute or postoperative pain, including headache/migraine, dental pain, or use in the emergency room. ABSTRAL is intended to be prescribed only by healthcare professionals who are knowledgeable of, and skilled in, the use of Schedule II opioids to treat cancer pain. Limitations of Use As a part of the TIRF REMS Access program, ABSTRAL may be dispensed only to outpatients enrolled in the program [see WARNINGS AND PRECAUTIONS]. For inpatient administration of ABSTRAL (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use), patient and prescriber enrollment is not required. DOSAGE AND ADMINISTRATION Healthcare professionals who prescribe ABSTRAL on an outpatient basis must enroll in the TIRF REMS Access program and comply with the requirements of the REMS to ensure safe use of ABSTRAL [See WARNINGS AND PRECAUTIONS]. As with all opioids, the safety of patients using such products is dependent on health care professionals prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use. Dose Titration The objective of dose titration is to identify an effective and tolerable maintenance dose for ongoing management of breakthrough cancer pain episodes. The effective and tolerable dose of ABSTRAL will be determined by dose titration in individual patients. Carefully supervise patients until a dose that provides adequate analgesia with tolerable side effects is reached for breakthrough pain control. Starting Dose: Individually titrate ABSTRAL to a dose that provides adequate analgesia with tolerable side effects. Begin titration of all patients with an initial dose of ABSTRAL of 100 mcg. Due to differences in the pharmacokinetic properties and individual variability, even patients switching from other fentanyl containing products to ABSTRAL must start with the 100 mcg dose. However, for patients converting from Actiq, see Table 1: Initial Dosing Recommendations for Patients on ACTIQ. ABSTRAL is not equivalent on a mcg per mcg basis with all other fentanyl products, therefore, do not switch patients on a mcg per mcg basis from any other fentanyl product. ABSTRAL is NOT a generic version of any other fentanyl product. Start all patients with a single 100 mcg tablet. If adequate analgesia is obtained within 30 minutes of administration of the 100 mcg tablet, continue to treat subsequent episodes of breakthrough pain with this dose. If adequate analgesia is not obtained after ABSTRAL, the patient may use a second ABSTRAL dose (after 30 minutes) as directed by their health care provider. No more than two doses of ABSTRAL may be used to treat an episode of breakthrough pain. Patients must wait at least 2 hours before treating another episode of breakthrough pain with ABSTRAL. Titration Steps: If adequate analgesia was not obtained with the first 100 mcg dose, continue dose escalation in a stepwise manner over consecutive breakthrough episodes until adequate analgesia with tolerable side effects is achieved. Increase the dose by 100 mcg multiples up to 400 mcg as needed. If adequate analgesia is not obtained with a 400 mcg dose, the next titration step is 600 mcg. If adequate analgesia is not obtained with a 600 mcg dose, the next titration step is 800 mcg. During titration, patients can be instructed to use multiples of 100 mcg tablets and/or 200 mcg tablets for any single dose. Instruct patients not to use more than 4 tablets at one time. If adequate analgesia is not obtained 30 minutes after the use of ABSTRAL, the patient may repeat the same dose of ABSTRAL. No more than two doses of ABSTRAL may be used to treat an episode of breakthrough pain. Rescue medication as directed by the health care provider can be used if adequate analgesia is not achieved after use of ABSTRAL. The efficacy and safety of doses higher than 800 mcg have not been evaluated in clinical studies in patients. ABSTRAL Titration Process ABSTRAL dosing for a subsequent episode should be separated by at least 2 hours ABSTRAL dose Using 200 mcg 2 x 100 mcg tablets, or 1 x 200 mcg tablets 300 mcg 3 x 100 mcg tablets, or 1 x 300 mcg tablets 400 mcg 4 x 100 mcg tablets, or 2 x 200 mcg tablets, or 1 x 400 mcg tablets 600 mcg 3 x 200 mcg tablets, or 1 x 600 mcg tablets 800 mcg 4 x 200 mcg tablets, or 1 x 800 mcg tablets In order to minimize the risk of ABSTRAL-related adverse reactions and to identify the appropriate dose, it is imperative that patients be supervised closely by health professionals during the titration process. Conversion From Actiq The initial dose of Abstral is always 100 mcg with the only exception being patients already using Actiq. a. For patients being converted from Actiq, prescribers must use the Initial Dosing Recommendations for Patients on Actiq. See Table 1 for initial dosing recommendations. Patients must be instructed to stop the use of Actiq and dispose of any remaining units. Table 1: Initial Dosing Recommendations for Patients on ACTIQ Current ACTIQ Dose (mcg) Initial Abstral Dose (mcg) 200 100 mcg 400 200 mcg 600 200 mcg 800 200 mcg 1200 200 mcg 1600 400 mcg b. For patients converting from Actiq doses 400 mcg and below, initiate titration with 100 mcg Abstral and proceed using multiples of this strength. c. For patients converting from Actiq doses of 600 and 800 mcg, initiate titration with 200 mcg and 200 mcg Abstral, respectively and proceed using multiples of this strength. d. For patients converting from Actiq doses of 1200 and 1600 mcg, initiate titration with 200 mcg and 400 mcg Abstral, respectively and proceed using multiples of this strength. Maintenance Therapy Once an appropriate dose for pain management has been established, instruct patients to use only one ABSTRAL tablet of the appropriate strength per dose. Maintain patients on this dose. If adequate analgesia is not obtained after use of ABSTRAL, the patient may use a second ABSTRAL dose (after 30 minutes) as directed by their health care provider. No more than two doses of ABSTRAL may be used to treat an episode of breakthrough pain. Patients must wait at least 2 hours before treating another episode of breakthrough pain with ABSTRAL. Dose Re-adjustment If the response (analgesia or adverse reactions) to the titrated ABSTRAL dose markedly changes, an adjustment of dose may be necessary to ensure that an appropriate dose is maintained. If more than four episodes of breakthrough pain are experienced per day, re-evaluate the dose of the long-acting opioid used for persistent underlying cancer pain. If the long-acting opioid or dose of long-acting opioid is changed, re-evaluate and re-titrate the ABSTRAL dose as necessary to ensure the patient is on an appropriate dose. Limit the use of ABSTRAL to treat four or fewer episodes of breakthrough pain per day. It is imperative that any dose re-titration is monitored carefully by a healthcare professional. Administration Of ABSTRAL Place ABSTRAL tablets on the floor of the mouth directly under the tongue immediately after removal from the blister unit. Do not chew, suck, or swallow ABSTRAL tablets. Allow ABSTRAL tablets to completely dissolve in the sublingual cavity. Advise patients not to eat or drink anything until the tablet is completely dissolved. In patients who have a dry mouth, water may be used to moisten the buccal mucosa before taking ABSTRAL. Discontinuation Of Therapy For patients no longer requiring opioid therapy, consider discontinuing ABSTRAL along with a gradual downward titration of other opioids to minimize possible withdrawal effects. In patients who continue to take their chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain, ABSTRAL therapy can usually be discontinued immediately. HOW SUPPLIED Dosage Forms And Strengths ABSTRAL is formulated as a sublingual tablet and is available in six strengths, distinguishable by the shape of the tablet and by de- bossing on the tablet surface. All tablets are white: 100 microgram tablet is a round tablet marked with the number “1” 200 microgram tablet is an oval-shaped tablet marked with the number “2” 300 microgram tablet is a triangle-shaped tablet marked with the number “3” 400 microgram tablet is a diamond-shaped tablet marked with the number “4” 600 microgram tablet is a “D”-shaped tablet marked with the number “6” 800 microgram tablet is a capsule-shaped tablet marked with the number “8” [see HOW SUPPLIED/Storage and Handling]. Storage And Handling ABSTRAL is supplied in individually sealed child-resistant blister packages contained in a cardboard outer carton, in pack sizes of 12 (100 mcg, 200 mcg, 300 mcg and 400 mcg strengths) or 32 (all strengths) tablets. The packaging is color-coded for each ABSTRAL tablet strength. The amount of fentanyl contained in ABSTRAL can be fatal to a child, individual for whom it is not prescribed or non-opioid tolerant adult. Patients and their caregivers must be instructed to keep ABSTRAL out of the reach of children [see BOXED WARNING - WARNINGS: Potential For Abuse and Importance Of Proper Patient Selection and WARNINGS AND PRECAUTIONS, and PATIENT INFORMATION]. Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture. Disposal Of ABSTRAL Patients and their household members must be advised to dispose of any tablets remaining from a prescription as soon as they are no longer needed. Instructions are included in Patient Counseling Information and in the Medication Guide. To dispose of any unused ABSTRAL tablets, remove them from the blister cards and flush down the toilet. Do Page 18 of 21 not dispose of the ABSTRAL blister cards or cartons down the toilet. If additional assistance is required, call Galena Biopharma, Inc. at 1-888-227-8725. How Supplied ABSTRAL is supplied in six dosage strengths. Tablets are supplied in child-resistant, protective blister cards with peelable foil. Each blister card contains 4 tablets, in pack sizes of 12 (100 mcg, 200 mcg, 300 mcg and 400 mcg strengths) or 32 (all strengths) tablets. Each tablet is white in color, with the strength distinguishable by the shape of the dosage unit and by de-bossing on the tablet surface: Dosage Strength (fentanyl base) Tablet Shape Tablet Markings Carton/Blister Package Color Pack size NDC Number 100 mcg Round “1” Light blue 12 32 57881-331-12 57881-331-32 200 mcg Oval “2” Dark orange 12 32 57881-332-12 57881-332-32 300 mcg Triangle “3” Brown 12 32 57881-333-12 57881-333-32 400 mcg Diamond “4” Violet 12 32 57881-334-12 57881-334-32 600 mcg “D” “6” Turquoise 32 57881-336-32 800 mcg Capsule “8” Indigo 32 57881-338-32 Note: Colors and shapes are a secondary aid in product identification. Please be sure to confirm the printed dosage before dispensing. Manufactured by: Pharmaceutics International, Inc., Hunt Valley, MD 21031. Manufactured for: Galena Biopharma, Inc. Portland, OR 97239. Issued: July 2014"" }, ""211"": { ""property.id"": 211, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ABSTRAL has been evaluated in 311 opioid-tolerant cancer patients with breakthrough pain. Two hundred and seventy (270) of these patients were treated in multiple-dose studies. The duration of therapy for patients in multiple-dose studies ranged from 1-405 days with an average duration of 131 days and with 44 patients treated for at least 12 months. The most commonly observed adverse reactions with ABSTRAL include typical opioid adverse reactions, such as nausea, constipation, somnolence and headache. Expect opioid side effects and manage them accordingly. The clinical trials of ABSTRAL were designed to evaluate safety and efficacy in treating patients with cancer and breakthrough pain; all patients were taking concomitant opioids, such as sustained-release morphine, sustained-release oxycodone or transdermal fentanyl, for their persistent pain. The adverse reaction data presented in Table 2 reflect the actual percentage of patients experiencing reactions among patients who received ABSTRAL for breakthrough pain along with concomitant opioid use for persistent pain. There has been no attempt to correct for concomitant use of other opioids, duration of ABSTRAL therapy or cancer-related symptoms. Table 2 lists adverse reactions with an overall frequency of 5% or greater within the total population that occurred during titration by maximum dose received. The ability to assign ABSTRAL a dose-response relationship to these adverse reactions is limited by the titration schemes used in these studies. Table2: Adverse Reactions Which Occurred During Titration at a Frequency of ≥ 5% System Organ Class Preferred term N (%) 100 mcg (n=22) 200 mcg (n=23) 300 mcg (n=55) 400 mcg (n=38) 600 mcg (n=52) 800 mcg (n=80) Total (n=270) Gastrointestinal disorders Nausea 1 (4.5) 4 (17.4) 5 (9.1) 1 (2.6) 2 (3.8) 2 (2.5) 15 (5.6) Nervous system disorders Somnolence 0 2 (8.7) 4 (7.3) 2 (5.3) 2 (3.8) 2 (2.5) 12 (4.4) Dizziness 0 0 3 (5.5) 2 (5.3) 0 1 (1.3) 6 (2.2) Headache 0 0 0 1 (2.6) 3 (5.8) 1 (1.3) 5 (1.9) Table 3 lists, by successful dose, adverse reactions with an overall frequency of ≥ 5% within the total population that occurred after a successful dose had been determined. Table3: Adverse Reactions Which Occurred During Maintenance Therapy at a Frequency of ≥ 5% System Organ Class Preferred term N (%) 100 mcg (n=7) 200 mcg (n=12) 300 mcg (n=22) 400 mcg (n=20) 600 mcg (n=35) 800 mcg (n=72) Total (n=168) Gastrointestinal disorders Nausea 1 (14.3) 0 2 (9.1) 0 1 (2.9) 6 (8.3) 10 (6.0) Stomatitis 0 1 (8.3) 1 (4.5) 0 0 1 (1.4) 3 (1.8) Constipation 0 0 1 (4.5) 2 (10.0) 1 (2.9) 4 (5.6) 8 (4.8) Dry mouth 0 0 0 1 (5.0) 2 (5.7) 0 3 (1.8) Nervous system disorders Headache 0 0 0 2 (10.0) 1 (2.9) 2 (2.8) 5 (3.0) Dysgeusia 1 (14.3) 0 0 0 0 1 (1.4) 2 (1.2) General disorders and administration site conditions Fatigue 0 0 0 1 (5.0) 2 (5.7) 0 3 (1.8) Injury, poisoning and procedural complications Accidental overdose 1 (14.3) 0 0 0 0 0 1 (0.6) Respiratory, thoracic and mediastinal disorders Dyspnoea 0 1 (8.3) 0 0 0 0 1 (0.6) Skin and subcutaneous disorders Hyperhidrosis 1 (14.3) 0 0 0 0 1 (1.4) 2 (1.2) The frequencies listed below represent adverse reactions that occurred in ≥ 1% of patients from two clinical trials who experienced that reaction while receiving ABSTRAL. Reactions are classified by system organ class. Adverse Reactions ( ≥ 1%) Cardiac disorders: bradycardia, tachycardia. Eye disorders: vision blurred. Gastrointestinal disorders: abdominal pain, abdominal pain upper, aphthous stomatitis, constipation, dry mouth, dyspepsia, gingival ulceration, impaired gastric emptying, lip ulceration, mouth ulceration, nausea, stomach discomfort, stomatitis, tongue disorder, vomiting. General disorders and administration site conditions: asthenia, drug withdrawal syndrome, fatigue, malaise. Immune system disorders: drug hypersensitivity. Injury, poisoning and procedural complications: accidental overdose. Metabolism and nutrition disorders: anorexia, decreased appetite. Nervous system disorders: amnesia, disturbance in attention, dizziness, dysgeusia, headache, hypoesthesia, lethargy, parosmia, somnolence, tremor. Psychiatric disorders: affect lability, anxiety, confusional state, depression, disorientation, dysphoria, euphoric mood, insomnia, mental status changes, paranoia, sleep disorder. Reproductive system and breast disorders: erectile dysfunction. Respiratory, thoracic and mediastinal disorder: dyspnea, oropharyngeal pain, throat tightness. Skin and subcutaneous disorders: hyperhidrosis, night sweats, pruritus, rash, skin lesion. Vascular disorders: hypotension. DRUG INTERACTIONS Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4); therefore potential interactions may occur when ABSTRAL is given concurrently with agents that affect CYP3A4 activity. The concomitant use of ABSTRAL with CYP3A4 inhibitors (e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, diltiazem, erythromycin, fluconazole, grapefruit juice, verapamil, or cimetidine) may result in a potentially dangerous increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Patients receiving ABSTRAL who begin therapy with, or increase the dose of, CYP3A4 inhibitors need to be carefully monitored for signs of opioid toxicity over an extended period of time. Increase dosage conservatively. The concomitant use of ABSTRAL with CYP3A4 inducers (e.g., barbiturates, carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, or troglitazone) may result in a decrease in fentanyl plasma concentrations, which could decrease the efficacy of ABSTRAL. Patients receiving ABSTRAL who stop therapy with, or decrease the dose of, CYP3A4 inducers need to be monitored for signs of increased ABSTRAL activity and the dose of ABSTRAL must be adjusted accordingly. Drug Abuse And Dependence Controlled Substance ABSTRAL contains fentanyl, a Schedule II substance. Schedule II opioid substances such as fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone have a high potential for abuse and addiction. ABSTRAL is also subject to misuse and criminal diversion. Abuse And Addiction Manage the handling of ABSTRAL to minimize the risk of misuse, including the restriction of access and accounting procedures as appropriate to the clinical setting and as required by law [see HOW SUPPLIED/Storage and Handling]. Concerns about abuse, addiction, and diversion must not prevent the proper management of pain. However, all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common. “Drug-seeking” behavior is very common in addicts and drug abusers. Abuse and addiction are separate and distinct from physical dependence and tolerance. Be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Since ABSTRAL may be diverted for nonmedical use, careful record keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised. Proper patient assessment, safe prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Contact your State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. Dependence Physical dependence is not ordinarily a concern in the treatment of patients with chronic cancer pain, and fear of tolerance and physical dependence must not deter using opiate doses that adequately relieve the pain. Guide the administration of Abstral by the response of the patient. Opioid analgesics may cause physical dependence that can result in withdrawal symptoms in patients who abruptly discontinue the drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene) or mixed agonist/antagonist analgesics (pentazocine, butorphanol, buprenorphine, nalbuphine). Physical dependence usually does not occur to a clinically significant degree until after several weeks of continued opioid usage. Tolerance, in which increasingly larger doses are required in order to produce the same degree of analgesia, is initially manifested by a shortened duration of analgesic effect, and subsequently, by decreases in the intensity of analgesia."" }, ""212"": { ""property.id"": 212, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS See BOXED WARNING - WARNINGS: IMPORTANCE OF PROPER PATIENT SELECTION and POTENTIAL FOR ABUSE Hypoventilation (Respiratory Depression) Serious or fatal respiratory depression can occur even at recommended doses in patients using ABSTRAL. Respiratory depression is more likely to occur in patients with underlying respiratory disorders and elderly or debilitated patients, usually following large initial doses, including ABSTRAL, in opioid non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with the “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid- induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous. ABSTRAL And Other Fentanyl Products ABSTRAL is NOT equivalent to all other fentanyl products used to treat breakthrough pain on a mcg per mcg basis. There are differences in the pharmacokinetics of ABSTRAL relative to other fentanyl products which could potentially result in clinically important differences in the amount of fentanyl absorbed and could result in a fatal overdose. When prescribing ABSTRAL to a patient, DO NOT convert on a mcg to mcg basis from other fentanyl products. Directions for safely converting patients to ABSTRAL from other fentanyl products are not currently available except for Actiq [see Conversion from Actiq ]. This includes oral, transdermal, or parenteral formulations of fentanyl. Therefore, for opioid-tolerant patients starting treatment for breakthrough pain, the initial dose of ABSTRAL is 100 mcg. Individually titrate each patient's dose to provide adequate analgesia while minimizing side effects. [See DOSAGE AND ADMINISTRATION] When dispensing ABSTRAL to a patient, DO NOT substitute it for any other fentanyl product prescription. Patient/Caregiver Instructions Patients and their caregivers must be instructed that ABSTRAL contains a medicine in an amount which can be fatal to a child. Even though ABSTRAL is provided in child-resistant packaging, patients and their caregivers must be instructed to keep tablets out of the reach of children. [see HOW SUPPLIED/Storage and Handling, and PATIENT INFORMATION]. Taking ABSTRAL could be fatal in individuals for whom it is not prescribed and for those who are not opioid-tolerant. Physicians and dispensing pharmacists must specifically question patients or caregivers about the presence of children in the home (on a full time or visiting basis) and counsel them regarding the dangers to children from inadvertent exposure. Additive CNS Depressant Effects The concomitant use of ABSTRAL with other CNS depressants, including other opioids, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcoholic beverages may produce increased depressant effects (e.g., hypoventilation, hypotension, and profound sedation). Concomitant use with potent inhibitors of cytochrome P450 3A4 isoform (e.g., erythromycin, ketoconazole, and certain protease inhibitors) may increase fentanyl levels, resulting in increased depressant effects [see DRUG INTERACTIONS]. Patients on concomitant CNS depressants must be monitored for a change in opioid effects and the dose of ABSTRAL adjusted, if warranted. Effects On Ability To Drive And Use Machines Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). Warn patients taking ABSTRAL of these dangers and counsel them accordingly. Chronic Pulmonary Disease Because potent opioids can cause hypoventilation, titrate ABSTRAL with caution in patients with chronic obstructive pulmonary disease or pre-existing medical conditions predisposing them to hypoventilation. In such patients, even normal therapeutic doses of ABSTRAL may further decrease respiratory drive to the point of respiratory failure. Head Injuries And Increased Intracranial Pressure Administer ABSTRAL with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury; use only if clinically warranted. Cardiac Disease Intravenous administration of fentanyl may produce bradycardia. Therefore, use ABSTRAL with caution in patients with bradyarrhythmias. MAO Inhibitors ABSTRAL is not recommended for use in patients who have received MAO inhibitors within the past 14 days. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Transmucosal Immediate Release Fentanyl (TIRF) Risk Evaluation And Mitigation Strategy (REMS) Access Program Because of the risk for misuse, abuse, addiction, and overdose [see Drug Abuse and Dependence], ABSTRAL is available only through a restricted program called the TIRF REMS Access program. Under the TIRF REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program. For inpatient administration (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of ABSTRAL, patient and prescriber enrollment is not required. Required components of the TIRF REMS Access program are: Healthcare professionals who prescribe ABSTRAL must review the prescriber educational materials for the TIRF REMS Access program, enroll in the program, and comply with the REMS requirements. To receive ABSTRAL, outpatients must understand the risks and benefits and sign a Patient-Prescriber Agreement. Pharmacies that dispense ABSTRAL must enroll in the program and agree to comply with the REMS requirements. Wholesalers and distributors that distribute ABSTRAL must enroll in the program and distribute only to authorized pharmacies. Further information, including a list of qualified pharmacies/distributors, is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483. Patient Counseling Information See FDA-approved patient labeling (Medication Guide) Patient/Caregiver Instructions Before initiating treatment with Abstral, explain the statements below to patients and/or caregivers. Instruct patients to read the Medication Guide each time Abstral is dispensed because new information may be available. TIRF REMS Access Program Outpatients must be enrolled in the TIRF REMS Access program before they can receive Abstral. Allow patients the opportunity to ask questions and discuss any concerns regarding Abstral or the TIRF REMS Access program. As a component of the TIRF REMS Access program, prescribers must review the contents of the Abstral Medication Guide with every patient before initiating treatment with Abstral. Advise the patient that Abstral is available only from pharmacies that are enrolled in the TIRF REMS Access program, and provide them with the telephone number and website for information on how to obtain the drug. Advise the outpatient that only enrolled health care providers may prescribe Abstral. Patient must sign the Patient-Prescriber Agreement to acknowledge that they understand the risks of Abstral. Advise patients that they may be requested to participate in a survey to evaluate the effectiveness of the TIRF REMS Access program. Instruct patients and their caregivers that ABSTRAL contains medicine in an amount that could be fatal in children, in individuals for whom ABSTRAL is not prescribed, and in those who are not opioid tolerant. Patients and their caregivers must be instructed to keep ABSTRAL, both used and unused dosage units, out of the reach of children. Patients and their caregivers must be instructed to dispose of any unneeded tablets remaining from a prescription as soon as possible [see HOW SUPPLIED/Storage and Handling, and WARNINGS AND PRECAUTIONS] Instruct patients and their caregivers to read the Medication Guide each time ABSTRAL is dispensed because new information may be available. Instruct patients not to take Abstral for acute pain, postoperative pain, pain from injuries, headache, migraine, or any other short- term pain, even if they have taken other opioid analgesics for these conditions. Instruct patients on the meaning of opioid tolerance and Abstral is only to be used as a supplemental pain medication for patients with pain requiring regular opioids, who have developed tolerance to the opioid medication and who need additional opioid treatment of breakthrough pain episodes. Instruct that if they are not taking an opioid medication on a regular around-the-clock basis, they must not take Abstral. You must not take more than 2 doses of ABSTRAL for each episode of breakthrough cancer pain. You must wait two hours before treating a new episode of breakthrough pain with ABSTRAL. Instruct patients NOT to share Abstral and that sharing Abstral with anyone else could result in the other individual's death due to overdose. Advise patients that Abstral contains fentanyl, which is a pain medication similar to hydromorphone, methadone, morphine, oxycodone, and oxymorphone. Advise patients that the active ingredient in Abstral, fentanyl, is a drug that some people abuse. Abstral is to be taken only by the patient for whom it was prescribed, and protected from theft or misuse in the work or home environments. Instruct patients to talk to their doctor if breakthrough pain is not alleviated or worsens after taking Abstral. Instruct patients to use Abstral exactly as prescribed by their doctor and not to take Abstral more often than prescribed. Caution patients that Abstral can affect a person's ability to perform activities that require a high level of attention (such as driving or using heavy machinery). Warn patients taking Abstral of these dangers and counsel accordingly. Warn patients not to combine Abstral with alcohol, sleep aids, or tranquilizers except by order of the prescribing physician, because dangerous additive effects may occur resulting in serious injury or death. Inform female patients that if they become pregnant or plan to become pregnant during treatment with Abstral to ask their doctor about the effects that Abstral (or any medicine) may have on them and their unborn child. Disposal of Unopened ABSTRAL Blister Packages When No Longer Needed Advise patients and their household members to dispose of any unopened packs remaining from a prescription as soon as they are no longer needed. Instruct patients that, to dispose of any unused ABSTRAL tablets, remove them from the blister cards and flush them down the toilet. Do not dispose of the ABSTRAL blister cards or cartons down the toilet. Detailed instructions for the proper storage, administration, disposal, and important instructions for managing an overdose of ABSTRAL are provided in the ABSTRAL Medication Guide. Ensure patients read this information in its entirety and give them an opportunity to have their questions answered. In the event that a caregiver requires additional assistance in disposing of excess units that remain in the home after the drug is no longer needed, instruct them to call the toll-free number for Galena Biopharma, Inc. 1-888-227-8725 or seek assistance from their local DEA office. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential of fentanyl. Fentanyl citrate was not mutagenic in the in vitro Ames reverse mutation assay in S. typhimurium or E. coli, or the mouse lymphoma mutagenesis assay, and was not clastogenic in the in vivo mouse micronucleus assay. Fentanyl has been shown to impair fertility in rats at doses of 30 mcg/kg intravenously and 160 mcg/kg subcutaneously. Conversion to the human equivalent doses indicates that this is within the range of the human recommended dosing for ABSTRAL. Use In Specific Populations Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Use ABSTRAL during pregnancy only if the potential benefit justifies the potential risk to the fetus. No epidemiological studies of congenital anomalies in infants born to women treated with fentanyl during pregnancy have been reported. Chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures in newborn infants characteristic of neonatal abstinence syndrome. In women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers. Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. Fentanyl is embryocidal in rats as evidenced by increased resorptions in pregnant rats at doses of 30 mcg/kg intravenously or 160 mcg/kg subcutaneously. Conversion to human equivalent doses indicates this is within the range of the human recommended dosing for ABSTRAL. Fentanyl citrate was not teratogenic when administered to pregnant animals. Published studies demonstrated that administration of fentanyl (10, 100, or 500 mcg/kg/day) to pregnant rats from day 7 to 21, of their 21 day gestation, via implanted microosmotic minipumps, was not teratogenic (the high dose was approximately 6times the human dose of 800 mcg per pain episode on a mcg/m² basis). Intravenous administration of fentanyl (10 mcg/kg or 30 mcg/kg) to pregnant female rats from gestation day 6 to 18, was embryo- or feto-toxic, and caused a slightly increased mean delivery time in the 30 mcg/kg/day group, but was not teratogenic. Labor And Delivery Fentanyl readily crosses the placenta. Therefore do not use ABSTRAL during labor and delivery (including caesarean section) since it may cause respiratory depression in the fetus or in the newborn infant. Nursing Mothers Fentanyl is excreted in human milk; therefore, do not use ABSTRAL in women who are nursing because of the possibility of sedation and/or respiratory depression in their infants. Symptoms of opioid withdrawal may occur in infants at the cessation of nursing by women using ABSTRAL. Pediatric Use The safety and efficacy of ABSTRAL have not been established in patients below 18 years of age. Geriatric Use Of the 270 opioid tolerant patients with breakthrough cancer pain in the Phase 3 clinical studies of Abstral, 58 (21%) were 65 years of age and older. There was no difference in the median titrated dose in patients aged 65 years and older compared to those < 65 years. No clinically meaningful difference was noted in the safety profile of the group 65 years of age and older as compared to younger patients in ABSTRAL clinical trials. Elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously, compared with the younger adult population. Therefore, exercise caution when individually titrating ABSTRAL in elderly patients to provide adequate efficacy while minimizing risk. Patients With Renal And Hepatic Impairment Insufficient information exists to make recommendations regarding the use of ABSTRAL in patients with impaired renal or hepatic function. Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and the inactive metabolite is mostly eliminated in urine. If the drug is used in these patients, use the drug with caution because of the reduced hepatic metabolism and renal excretion capacity in such patients. Gender Both male and female opioid-tolerant cancer patients were studied for the treatment of breakthrough cancer pain. No clinically relevant gender differences were noted either in efficacy or in observed adverse reactions."" }, ""213"": { ""property.id"": 213, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE Clinical Presentation The manifestations of ABSTRAL overdosage are expected to be similar in nature to intravenous fentanyl and other opioids, and are an extension of its pharmacological actions with the most serious significant effect being hypoventilation [see CLINICAL PHARMACOLOGY]. Immediate Management Immediate management of opioid overdose includes removal of the ABSTRAL tablet, if still in the mouth, ensuring a patent airway, physical and verbal stimulation of the patient, and assessment of level of consciousness, ventilatory and circulatory status. Treatment Of Overdosage (Accidental Ingestion) In The Opioid NON-Tolerant Person Provide ventilatory support, obtain intravenous access, and administer naloxone or other opioid antagonists as clinically indicated. The duration of respiratory depression following overdose may be longer than the effects of the opioid antagonist's action (e.g., the half-life of naloxone ranges from 30 to 81 minutes) and repeated administration may be necessary. Consult the package insert of the individual opioid antagonist for details. Treatment Of Overdosage In Opioid-Tolerant Patients Provide ventilatory support and obtain intravenous access as clinically indicated. Judicious use of naloxone or another opioid antagonist may be warranted in some instances, but at the risk of precipitating an acute withdrawal syndrome. General Considerations For Overdose Management of severe ABSTRAL overdose includes: securing a patent airway, assisting or controlling ventilation and establishing intravenous access. In the presence of hypoventilation or apnea, assist or control ventilation, and administer oxygen as indicated. Carefully observe and appropriately manage patients with overdose until their clinical condition is well controlled. Although muscle rigidity interfering with respiration has not been seen following the use of ABSTRAL, this is possible with fentanyl and other opioids. If it occurs, manage it by using assisted or controlled ventilation, by an opioid antagonist, and as a final alternative, by a neuromuscular blocking agent. CONTRAINDICATIONS ABSTRAL is contraindicated in the management of pain in opioid non-tolerant patients, because life-threatening hypoventilation could occur at any dose in patients not already taking around-the-clock opioid therapy. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, or at least 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for a week or longer. ABSTRAL is contraindicated in the management of acute or postoperative pain, including headache/migraine, dental pain, or use in the emergency room. ABSTRAL is contraindicated in patients with known intolerance or hypersensitivity to any of its components or the drug fentanyl. Anaphylaxis and hypersensitivity have been reported in association with the use of other oral transmucosal fentanyl products."" }, ""214"": { ""property.id"": 214, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Mechanism Of Action Fentanyl is a pure opioid agonist whose principal therapeutic action is analgesia. Other members of the class known as opioid agonists include substances such as morphine, oxycodone, hydromorphone, codeine, and hydrocodone. Pharmacodynamics Pharmacological effects of opioid agonists include anxiolysis, euphoria, feelings of relaxation, respiratory depression, constipation, miosis, cough suppression, and analgesia. Like all pure opioid agonist analgesics, with increasing doses there is increasing analgesia, unlike with mixed agonist/antagonists or non-opioid analgesics, where there is a limit to the analgesic effect with increasing doses. With pure opioid agonist analgesics, there is no defined maximum dose; the ceiling to analgesic effectiveness is imposed only by side effects, the more serious of which may include somnolence and respiratory depression. Analgesia In general, the effective concentration and the concentration at which toxicity occurs increase with increasing tolerance with any and all opioids. The rate of development of tolerance varies widely among individuals. As a result, individually titrate the dose of ABSTRAL to achieve the desired effect [see DOSAGE AND ADMINISTRATION]. Central Nervous System The precise mechanism of the analgesic action is unknown although fentanyl is known to be a μ-opioid receptor agonist. Specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and play a role in the analgesic effects of this drug. Fentanyl produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves both a reduction in the responsiveness of the brain stem to increases in carbon dioxide and to electrical stimulation. Fentanyl causes miosis even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Gastrointestinal System Fentanyl causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and in the duodenum. Digestion of food is delayed in the small intestine and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid induced-effects may include a reduction in gastric, biliary and pancreatic secretions, spasm of the sphincter of Oddi, and transient elevations in serum amylase. Cardiovascular System Fentanyl may produce release of histamine with or without associated peripheral vasodilation. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Endocrine System Opioid agonists have been shown to have a variety of effects on the secretion of hormones. Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin secretion, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon in humans and other species (e.g., rats and dogs). Thyroid stimulating hormone (TSH) has been shown to be both inhibited and stimulated by opioids. Respiratory System All opioid mu-receptor agonists, including fentanyl, produce dose-dependent respiratory depression. The risk of respiratory depression is less in patients receiving chronic opioid therapy who develop tolerance to these effects. Peak respiratory depressive effects may be seen as early as 15 to 30 minutes from the start of oral transmucosal fentanyl citrate administration and may persist for several hours. Serious or fatal respiratory depression can occur even at recommended doses. Fentanyl depresses the cough reflex as a result of its CNS activity. Although not observed with oral transmucosal fentanyl products in clinical trials, fentanyl given rapidly by intravenous injection in large doses may cause rigidity in the muscles of respiration resulting in respiratory difficulties. Therefore, be aware of this potential complication [see BOXED WARNING - WARNINGS: Importance Of Proper Patient Selection and Potential for Abuse, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and OVERDOSAGE]. Pharmacokinetics Absorption Fentanyl is a highly lipophilic drug. Orally administered fentanyl undergoes pronounced hepatic and intestinal first pass effects. Absorption of fentanyl from ABSTRAL sublingual tablets is mainly through the oral mucosa. The bioavailability of ABSTRAL sublingual tablets has been calculated to be 54%. Dose proportionality across the 100 mcg to 800 mcg ABSTRAL dose range has been demonstrated (Table4). Mean plasma fentanyl levels following single doses of ABSTRAL are shown in Figure 1. The median time to maximum plasma concentration (Tmax) across these four doses of ABSTRAL varied from 30 to 60 minutes (range of 15 - 240 minutes). Figure 1: Mean (+/- SD) Plasma Fentanyl Concentration versus Time after Administration of Single Doses of 100 mcg, 200 mcg, 400 mcg and 800 mcg ABSTRAL to Healthy Subjects Pharmacokinetic parameters are presented in Table 4. Table 4: Mean (CV%) Fentanyl Pharmacokinetic Parameters after Single-Dose Administration of 100, 200, 400 and 800 mcg Doses of ABSTRAL to Healthy Subjects (n=12 per Dose Level) Parameter Unit Abstral dose 100 mcg 200 mcg 400 mcg 800 mcg Cmax (ng/mL) 0.187 (33) 0.302 (31) 0.765 (38) 1.42 (33) Tmax a (min) 30 [19-120] 52 [16-240] 60 [30-120] 30 [15-60] AUC0-inf (ng•h/mL) 0.974 (34) 1.92 (27) 5.49 (35) 8.95 (33) T½ (h) 5.02 (51) 6.67 (30) 13.5 (37) 10.1 (34) a median (range) In another study, dose proportionality between 800 mcg and 1600 mcg in Cmax and AUC has also been demonstrated. Pharmacokinetic studies have shown that multiple tablets are bioequivalent to single tablets of the equivalent dose. Distribution Fentanyl is highly lipophilic. Animal data showed that following absorption, fentanyl is rapidly distributed to the brain, heart, lungs, kidneys and spleen followed by a slower redistribution to muscles and fat. The plasma protein binding of fentanyl is 80-85%. The main binding protein is alpha-1-acid glycoprotein, but both albumin and lipoproteins contribute to some extent. The free fraction of fentanyl increases with acidosis. The mean volume of distribution at steady state (Vss) was 4 L/kg. Metabolism Fentanyl is metabolized in the liver and in the intestinal mucosa to norfentanyl by cytochrome P450 3A4 isoform. Norfentanyl was not found to be pharmacologically active in animal studies [see DRUG INTERACTIONS]. Elimination Fentanyl is more than 90% eliminated by biotransformation to N-dealkylated and hydroxylated inactive metabolites. Less than 7% of the dose is excreted unchanged in the urine, and only about 1% is excreted unchanged in the feces. The metabolites are mainly excreted in the urine, while fecal excretion is less important. The total plasma clearance of fentanyl was 0.5 L/hr/kg (range 0.3 - 0.7 L/ hr/kg). Clinical Studies The efficacy of ABSTRAL was investigated in a clinical trial in opioid tolerant adult patients experiencing breakthrough cancer pain. Breakthrough cancer pain was defined as a transient flare of moderate-to-severe pain occurring in patients with cancer experiencing persistent cancer pain otherwise controlled with maintenance doses of opioid medications including at least 60 mg morphine/day, 50 mcg transdermal fentanyl/hour, or an equianalgesic dose of another opioid for 1 week or longer. All patients were on stable doses of either long-acting oral opioids or transdermal fentanyl for their persistent cancer pain. A double-blind, placebo-controlled, crossover study was performed in patients with cancer to evaluate the effectiveness of ABSTRAL for the treatment of breakthrough cancer pain. Open-label titration identified a dose of ABSTRAL in which a patient obtained adequate analgesia with tolerable side effects, within the range of 100 mcg to 800 mcg. In the double-blind efficacy study, patients who identified a successful dose were randomized to a sequence of 10 treatments; seven with ABSTRAL and three with placebo. Of the 131 patients who entered the titration phase of the study, 78 (60%) achieved a successful dose during the titration phase. Sixty- six patients entered the double-blind phase and 60 completed the study. The dose of ABSTRAL was determined by titration starting at 100 mcg. The final titrated dose of ABSTRAL for breakthrough cancer pain was not predicted from the daily maintenance dose of opioid used to manage the persistent cancer pain. In a second open-label safety study using an identical titration regimen, 96 of 139 patients (69%) who entered the study titrated to a dose in which the patient obtained adequate analgesia with tolerable side effects during the titration phase. Table 5 presents the final titrated dose for both the double-blind efficacy and open-label safety studies. Table 5: Final dose of ABSTRAL following initial titration in all clinical efficacy and safety studies ABSTRAL Dose N=174 n (%) 100 mcg 11 (6) 200 mcg 15 (9) 300 mcg 35 (20) 400 mcg 25 (14) 600 mcg 40 (23) 800 mcg 48 (28) The primary outcome measure, the mean sum of pain intensity difference at 30 minutes (SPID30) for ABSTRAL-treated episodes was statistically significantly higher than for placebo-treated episodes. Figure 2: Mean Pain Intensity Difference (±SE) for ABSTRAL Compared to Placebo"" }, ""215"": { ""property.id"": 215, ""property.ts"": ""2017-12-04 04:40:24"", ""property.key"": ""Medication Guide"", ""property.value"": """" } }" 33,"2017-08-31 23:12:57",Abstral,"Fentanyl Sublingual Tablets",Multum,"{ ""33"": { ""alphabet_x_drug.id"": 33, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""216"": { ""property.id"": 216, ""property.ts"": ""2017-12-04 04:40:35"", ""property.key"": ""Abstral Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Abstral, Subsys Generic Name: fentanyl (sublingual) (Pronunciation: FEN tan il sub LIN gwal) What is fentanyl sublingual (Abstral, Subsys)? What are the possible side effects of fentanyl (Abstral, Subsys)? What is the most important information I should know about fentanyl (Abstral, Subsys)? What should I discuss with my healthcare provider before taking fentanyl (Abstral, Subsys)? How should I take fentanyl sublingual (Abstral, Subsys)? What happens if I miss a dose (Abstral, Subsys)? What happens if I overdose (Abstral, Subsys)? What should I avoid while taking fentanyl (Abstral, Subsys)? What other drugs will affect fentanyl (Abstral, Subsys)? Where can I get more information? What is fentanyl sublingual (Abstral, Subsys)? Fentanyl sublingual (under the tongue) is an opioid pain medication. An opioid is sometimes called a narcotic.Fentanyl sublingual tablets (Abstral) and sublingual spray (Subsys) are used to treat \"breakthrough\" cancer pain. Fentanyl sublingual is taken together with other non-fentanyl narcotic pain medicine that is used around the clock. This medication is not for treating pain that is not cancer-related, such as pain from surgery or dental work, migraine headaches, or back pain.Fentanyl sublingual may also be used for purposes not listed in this medication guide. What are the possible side effects of fentanyl (Abstral, Subsys)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Stop using fentanyl and call your doctor at once if you have a serious side effect such as:slow heart rate, weak or shallow breathing, sighing, severe drowsiness;confusion, extreme fear, unusual thoughts or behavior; orfeeling like you might pass out.Less serious side effects may include:dry mouth, nausea, vomiting, constipation;headache, drowsiness, tired feeling; orwhite patches or sores inside your mouth or on your lips.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about fentanyl (Abstral, Subsys)? Do not use this medication to replace any other form of fentanyl, such as Actiq, Fentora, Onsolis, Duragesic, Lazanda, or generic brands of fentanyl (injection, skin patch, dissolving film, or \"lollipop\" device). Before taking fentanyl, tell your doctor if you have a breathing disorder (asthma, wheezing, COPD), slow heartbeats, seizures, mental illness, low blood pressure, liver or kidney disease, a debilitating condition, or a history of head injury, brain tumor, or addiction to drugs or alcohol.Tell your doctor if there are children living in the home where you will store this medicine. Keep fentanyl out of the reach of children. The amount of fentanyl in each Abstral tablet or Subsys spray unit can be fatal to a child.Never share fentanyl with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it."" }, ""217"": { ""property.id"": 217, ""property.ts"": ""2017-12-04 04:40:35"", ""property.key"": ""Abstral Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my healthcare provider before taking fentanyl (Abstral, Subsys)? Do not take fentanyl unless you are already being treated with a similar opioid pain medicine and your body is tolerant to it. Talk with your doctor if you are not sure you are opioid-tolerant.Do not take fentanyl if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. Tell your doctor if there are children living in the home where you will store this medicine. Keep fentanyl out of the reach of children. The amount of fentanyl in each Abstral tablet or Subsys spray unit can be fatal to a child.To make sure you can safely take fentanyl sublingual, tell your doctor if you have any of these other conditions:a breathing disorder such as wheezing, asthma, or chronic obstructive pulmonary disease (COPD);seizures, epilepsy, or a history of head injury or brain tumor;low blood pressure, slow heartbeats or other heart rhythm disorder;mental illness such as depression, schizophrenia, or hallucinations;liver or kidney disease; ora personal or family history of drug or alcohol addiction.Fentanyl may be habit-forming and should be used only by the person it was prescribed for. Never share fentanyl with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.FDA pregnancy category C. It is not known whether fentanyl will harm an unborn baby. Fentanyl may cause breathing problems, seizure, or addiction and withdrawal symptoms in a newborn if the mother takes the medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant while using fentanyl sublingual.Fentanyl may also cause drowsiness, breathing problems, or addiction and withdrawal symptoms in a nursing infant. Do not breast-feed while you are taking fentanyl sublingual. How should I take fentanyl sublingual (Abstral, Subsys)? Use exactly as prescribed. Never use fentanyl in larger amounts, or for longer than recommended by your doctor. Keep using your around-the-clock narcotic pain medicine but never take Abstral or Subsys together with a second form of fentanyl.Do not use Abstral or Subsys to replace any other form of fentanyl, such as Actiq, Fentora, Onsolis, Duragesic, Lazanda, or generic brands of fentanyl (injection, skin patch, dissolving film, or \"lollipop\" device). If you switch to Abstral or Subsys from another form of fentanyl, you will not use the same dose. You must start with the lowest dose (100 micrograms). Your doctor may change your dose to make sure you get the best results.Place the Abstral tablet under your tongue, as far back as you can. Do not break, chew, suck, or swallow the tablet whole. Allow it to dissolve in your mouth without chewing. Do not drink or eat anything during this time.You may use a second Abstral tablet 30 minutes after the first. Use only the same strength and amount you used for the first dose. Call your doctor if you still have pain after taking the second tablet. Do not take more than 2 tablets for each episode of breakthrough cancer pain. You must wait at least 2 hours after your last dose of Abstral before you can treat a new pain episode. Point the Subsys spray nozzle into your mouth, lift your tongue, and spray the medicine under your tongue. Hold the liquid under the tongue for 30 to 60 seconds. Do not spit, swallow, or rinse your mouth during this time. You may use a second Subsys spray unit 30 minutes after the first. Use only the same strength and amount you used for the first dose. Call your doctor if you still have pain after using the second spray. Do not use more than 2 sprays for each episode of breakthrough cancer pain.You must wait at least 4 hours after your last dose of Subsys before you can treat a new pain episode. Do not treat more than 4 pain episodes per day with fentanyl sublingual. Call your doctor if you have breakthrough pain more than 4 times in one day.Do not stop taking fentanyl or your other narcotic pain medicine without your doctor's advice. Ask your doctor how to avoid withdrawal symptoms when you stop using pain medication.Store in the original carton at room temperature, away from heat and moisture. Keep track of the amount of medicine used from each carton. Fentanyl is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.Keep out of the reach of children. The amount of fentanyl in each Abstral tablet or Subsys spray unit can be fatal to a child.Carefully follow the instructions for disposing of this medicine when it is no longer needed. Throw away any unused Abstral tablets by removing them from the blister pack and flushing them down a toilet. Dispose of used Subsys spray units in the disposal bags provided with this medication. Empty any unused spray units into the disposal bottle provided."" }, ""218"": { ""property.id"": 218, ""property.ts"": ""2017-12-04 04:40:35"", ""property.key"": ""Abstral Patient Information including If I Miss a Dose"", ""property.value"": """" } }" 34,"2017-08-31 23:12:57",ACAM2000,"Smallpox (Vaccinia) Vaccine, Live",FDA,"{ ""34"": { ""alphabet_x_drug.id"": 34, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""219"": { ""property.id"": 219, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Drug Description"", ""property.value"": ""ACAM2000 (Smallpox (Vaccinia) Vaccine, Live,) WARNING Suspected cases of myocarditis and/or pericarditis have been observed in healthy adult primary vaccinees (at an approximate rate of 5.7 per 1000, 95% CI: 1.9-13.3) receiving ACAM2000 [see WARNINGS AND PRECAUTIONS]. Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including STEVENS-JOHNSON SYNDROME), eczema vaccinatum resulting in permanent sequelae or death, ocular complications, blindness, and fetal death have occurred following either primary vaccination or revaccination with live vaccinia virus smallpox vaccines [see WARNINGS AND PRECAUTIONS]. These risks are increased in vaccinees with the following conditions and may result in severe disability, permanent neurological sequelae and/or death: Cardiac disease or a history of cardiac disease Eye disease treated with topical steroids Congenital or acquired immune deficiency disorders, including those taking immunosuppressive medications Eczema and persons with a history of eczema or other acute or chronic exfoliative skin conditions Infants less than 12 months of age Pregnancy ACAM2000 is a live vaccinia virus that can be transmitted to persons who have close contact with the vaccinee and the risks in contacts are the same as those for the vaccinee. The risk for experiencing serious vaccination complications must be weighed against the risks for experiencing a potentially fatal smallpox infection. DESCRIPTION ACAM2000, Smallpox (Vaccinia) Vaccine, Live, is a live vaccinia virus derived from plaque purification cloning from Dryvax® (Wyeth Laboratories, Marietta, PA, calf lymph vaccine, New York City Board of Health Strain) and grown in African Green Monkey kidney (Vero) cells and tested to be free of adventitious agents. ACAM2000 is provided as a lyophilized preparation of purified live virus containing the following non-active excipients: 6-8 mM HEPES (pH 6.5-7.5), 2% human serum albumin USP, 0.5 – 0.7% sodium chloride USP, 5% mannitol USP, and trace amounts of neomycin and polymyxin B. Diluent for ACAM2000 contains 50% (v/v) Glycerin USP, 0.25% (v/v) Phenol USP in Water for Injection USP, supplied in 3 mL clear glass vials containing 0.6 mL of diluent. After reconstitution, each vial of ACAM2000 vaccine contains approximately 100 doses (0.0025 mL/dose). The concentration of vaccinia virus is 1.0-5.0 x 108 plaque-forming units (PFU)/mL or 2.5-12.5 x 105 PFU/dose determined by plaque assay in Vero cells. ACAM2000 is administered by the percutaneous route (scarification) using 15 jabs of a stainless steel bifurcated needle that has been dipped into the vaccine."" }, ""220"": { ""property.id"": 220, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS ACAM2000® is indicated for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection. DOSAGE AND ADMINISTRATION ACAM2000 must be administered only by vaccine providers with training to safely and effectively administer the vaccine by the percutaneous route (scarification). ACAM2000 should not be injected by the intradermal, subcutaneous, intramuscular, or intravenous route. Instructions For Vaccine Preparation Reconstitution ACAM2000 is reconstituted by addition of 0.3 mL of diluent to the vial containing lyophilized vaccine. Note: this 0.3 mL of diluent is not the entire content of the diluent vial. ACAM2000 should only be reconstituted with 0.3 mL of the diluent provided. The vaccine vial should be removed from cold storage and brought to room temperature before reconstitution. The flip cap seals of the vaccine and diluent vials are removed, and each rubber stopper is wiped with an isopropyl alcohol swab and allowed to dry thoroughly. Using aseptic technique and a sterile 1 mL syringe fitted with a 25 gauge x 5/8” needle (provided), draw up 0.3 mL of diluent and transfer the entire content of the syringe to the vaccine vial. Gently swirl to mix but try not to get product on the rubber stopper. The reconstituted vaccine should be a clear to slightly hazy, colorless to straw-colored liquid free from extraneous matter. Reconstituted vaccine should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is observed, the vaccine should not be used and the vial should be disposed safely. [See Preparation / Handling Precautions and Instructions for Disposal] Storage following Reconstitution After reconstitution, ACAM2000 vaccine may be administered within 6 to 8 hours if kept at room temperature (20-25°C, 68-77°F). Unused, reconstituted ACAM2000 vaccine may be stored in a refrigerator (2-8°C, 36-46°F) up to 30 days, after which it should be discarded as a biohazardous material. [See Preparation / Handling Precautions and Instructions for Disposal] Exposure of reconstituted vaccine to room temperature during vaccination sessions should be minimized by placing it in refrigerator or on ice between patient administrations. Preparation / Handling Precautions And Instructions For Disposal Personnel preparing and administering the vaccine should wear surgical or protective gloves and avoid contact of vaccine with skin, eyes or mucous membranes. The vaccine vial, its stopper, the diluent syringe, the vented needle used for reconstitution, the bifurcated needle used for administration, and any gauze or cotton that came in contact with the vaccine should be discarded in leak-proof, puncture-proof biohazard containers. These containers should then be disposed of appropriately. Vaccination Instructions All vaccine providers must receive education on the proper administration as required by the U.S. Food and Drug Administration. All vaccine providers also receive a Medication Guide to distribute to each vaccinee prior to administering the vaccine. In the event of an actual smallpox emergency, declared by the Secretary of the U.S. Department of Health and Human Services, vaccine providers may follow educational instructions they receive from the manufacturer, such as how to educate vaccinees without a Medication Guide. The site of vaccination is the upper arm over the insertion of the deltoid muscle. No skin preparation should be performed unless the skin at the intended site of vaccination is obviously dirty, in which case an alcohol swab(s) may be used to clean the area. If alcohol is used, the skin must be allowed to dry thoroughly to prevent inactivation of the live vaccine virus by the alcohol. Remove the vaccine vial cap. Remove bifurcated needle from individual wrapping. Submerge bifurcated end of needle in reconstituted vaccine solution. The needle will pick up a droplet of vaccine (0.0025 mL) within the fork of the bifurcation. Use aseptic technique, i.e., do not insert the upper part of the needle that has been in contact with fingers into the vaccine vial, and never re-dip the needle into the vaccine vial if the needle has touched skin. Deposit the droplet of vaccine onto clean, dry skin of the arm prepared for vaccination. The needle is held between thumb and first finger perpendicular to the skin. The wrist of the hand holding the needle of the vaccinator rests against the patient's arm. Rapidly make 15 jabs of the needle perpendicular to the skin through the vaccine droplet to puncture the skin, within a diameter of about 5 mm. The jabs should be vigorous enough so that a drop of blood appears at the vaccination site. Any excess droplets of vaccine and blood should be wiped off the skin using a dry gauze pad and discarded in a biohazard container. Discard the needle in a biohazard sharps container. Close the vaccine vial by reinserting the rubber cap and return to a refrigerator or place on ice unless it will be used immediately to vaccinate another subject. [See Storage Following Reconstitution] Cover the vaccination site loosely with a gauze bandage, using first aid adhesive tape to keep it in place. This bandage provides a barrier to protect against spread of the vaccinia virus. If the vaccinee is involved in direct patient care, the gauze should be covered with a semipermeable (semiocclusive) dressing as an additional barrier. A semipermeable dressing is one that allows for the passage of air but does not allow for the passage of fluids. Wash hands with soap and warm water or with alcohol-based hand rubs such as gels or foams after direct contact with the vaccination site, the bandage or clothes, towels or sheets that might be contaminated with virus from the vaccination site. This is vital in order to remove any virus from your hands and prevent contact spread. Put the contaminated bandages in a sealed plastic bag and throw them away in the trash. Wash separately clothing, towels, bedding or other items that may have come in direct contact with the vaccination site or drainage from the site, using hot water with detergent and/or bleach. Wash hands afterwards. Don't use a bandage that blocks air from the vaccination site. This may cause the skin at the vaccination site to soften and wear away. Use loose gauze secured with medical tape to cover the site. Don't put salves or ointments on the vaccination site. Instructions For Interpreting Vaccination Response Primary Vaccinees In an individual vaccinated for the first time (primary vaccination), the expected response to vaccination is the development of a major cutaneous reaction (characterized by a pustule) at the site of inoculation. The lesion evolves gradually, with appearance of a papule at the site of vaccination after 2-5 days. The papule becomes vesicular, then pustular, and reaches its maximum size at 8-10 days after vaccination. The pustule dries and forms a scab, which usually separates within 14-21 days, leaving a pitted scar. (See Figure 1) Formation of a major cutaneous reaction by day 6-8 is evidence of a successful 'take' and acquisition of protective immunity. An equivocal reaction is any reaction that is not a major reaction, and indicates a non-take (vaccination failure) due to impotent vaccine or inadequate vaccination technique. Previously Vaccinated Individuals (Revaccination) Successful vaccination in an individual previously exposed to vaccine is confirmed when a major cutaneous reaction [See Primary Vaccinees and Figure 1] is observed 6 to 8 days post-vaccination. However any prior vaccination may modify (reduce) the cutaneous response upon revaccination (Figure 2) such that the absence of a cutaneous response does not necessarily indicate vaccination failure. Previously vaccinated individuals who do not have a cutaneous response on revaccination do not require revaccination to try to elicit a cutaneous response. Vaccination Failures Individuals who are not successfully vaccinated (i.e., vaccination failures) after primary vaccination may be revaccinated again in an attempt to achieve a satisfactory take. The vaccination procedures should be checked, and vaccination repeated with vaccine from another vial or vaccine lot, employing the same technique described above [See Vaccination Instructions]. If a repeat vaccination is conducted using vaccine from another vial or vaccine lot fails to produce a major reaction, healthcare providers should consult the Centers for Disease Control and Prevention (CDC) at (404) 639-3670 or their state or local health department before giving another vaccination. Figure 1: Progression of major cutaneous reaction after primary vaccination1 Figure 2: Progression of major cutaneous reaction after revaccination1 Booster Schedule Persons at continued high risk of exposure to smallpox (e.g., research laboratory workers handling variola virus) should receive repeat ACAM2000 vaccination every three years. Smallpox Vaccination Recommendations From US Government Agencies Additional information may be obtained from U.S. Department of Defense (http://www.dtic.mil/whs/directives/corres/html/620503.htm) and U.S. Centers for Disease Control and Prevention (CDC) about smallpox vaccination (http://www.bt.cdc/gov/agent/smallpox/vaccination). HOW SUPPLIED Dosage Forms And Strengths After reconstitution of the lyophilized preparation, each vial has approximately 100 doses of 0.0025 mL of vaccinia virus (live) containing 2.5-12.5x105 plaque forming units / dose. ACAM2000, Smallpox (Vaccinia) Vaccine, Live, is supplied in multiple-dose 3 mL clear glass vials containing lyophilized powder (freeze-dried vaccine). After reconstitution with 0.3 mL of diluent, the vial contains approximately 100 nominal doses of 0.0025 mL of vaccinia virus (live), 1.0 - 5.0x108 PFU/mL or 2.5-12.5x105 PFU/dose. Diluent for ACAM2000, 50% (v/v) Glycerin USP, 0.25% (v/v) Phenol USP in Water for Injection USP, is supplied in 3 mL clear glass vials containing 0.6 mL of diluent. Bifurcated needles are supplied in boxes (5 x 5 x 1 in) containing 100 needles. 1 mL tuberculin syringes with 25 gauge x 5/8” needles are supplied for vaccine reconstitution. Storage And Handling ACAM2000 should be stored in a freezer with an average temperature of -15°C to -25°C (+5°F to -13°F). Prior to reconstitution, ACAM2000 vaccine retains a potency of 1.0x108 PFU or higher per dose for at least 18 months when stored at refrigerated temperatures of +2-8°C (36-46°F). During shipment, ACAM2000 should be maintained at a temperature of -10°C or colder. After reconstitution, ACAM2000 vaccine may be administered during a 6 to 8 hour workday at room temperature (20-25°C, 68-77°F). Reconstituted ACAM2000 vaccine may be stored in a refrigerator (2-8°C, 36-46°F) no longer than 30 days, after which it should be discarded [See Vaccination Instructions]. Diluent for Smallpox Vaccine, (Vero Cells) Lyophilized, ACAM2000 should be stored at room temperature (15-30°C, 59-86°F). ACAM2000 contains live vaccinia virus that is transmissible, and should be handled as an infectious agent once vials are open. See [Instructions for Vaccine Preparation] and [Preparation / Handling Precautions and Instructions for Disposal] for details on handling and disposal. REFERENCES 1 Fulginiti VA, Papier A, Lane JM, Neff JM, Henderson, DA. Smallpox vaccination: a review, part 1. background, vaccination technique, normal vaccination and revaccination, and expected normal reactions. Clin Infect Dis. 2003;37:241-250. Sanofi Pasteur Biologics Co., 38 Sidney Street, Cambridge, MA 02139. Revised: October 2009"" }, ""221"": { ""property.id"": 221, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS The following adverse reactions are discussed in greater detail in other sections of the labeling: Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome) and eczema vaccinatum. Severe disability, permanent neurological sequelae, and/or death may occur. Death of unvaccinated individuals who have contact with vaccinated individuals. [See WARNINGS AND PRECAUTIONS]. Myocarditis and/or pericarditis, ischemic heart disease and non-ischemic, dilated cardiomyopathy [See WARNINGS AND PRECAUTIONS]. Ocular complications and blindness [See WARNINGS AND PRECAUTIONS]. Overall Adverse Reaction Profile Information regarding the safety of ACAM2000 has been derived from three sources: 1) ACAM2000 clinical trial experience (Phase 1, 2 and 3 clinical trials), 2) data compiled during the era of routine smallpox vaccination using other NYCBH vaccinia vaccines and 3) adverse event data obtained during military and civilian smallpox vaccination programs (2002-2005) that used Dryvax®, a licensed live vaccinia virus smallpox vaccine. General Disorders and Administrative Site Conditions: In the ACAM2000 clinical studies 97% and 92% of vaccinia-naïve and previously vaccinated subjects, respectively, experienced one or more adverse event. Common events included injection site reactions (erythema, pruritus, pain and swelling) and constitutional symptoms (fatigue, malaise, feeling hot, rigors and exercise tolerance decreased). Across all ACAM2000 studies 10% of vaccinia-naïve and 3% of previously vaccinated subjects experienced at least one severe adverse event (defined as interfering with normal daily activities). Nervous System Disorder: Overall, 50% and 34% of vaccinia-naïve subjects and previously vaccinated subjects, respectively, reported headaches in ACAM2000 studies. There have been reports of headache following smallpox vaccination which required hospitalization. Although < 1% of the subjects in the ACAM2000 program experienced severe headaches, none required hospitalization. Neurological adverse events assessed among the 2002 - 2005 military (n=590,400) and DHHS (n=64,600) programs temporally associated with smallpox vaccination included headache (95 cases), non-serious limb paresthesias (17 cases) or pain (13 cases) and dizziness or vertigo (13 cases). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 9 seizures (including 1 death), and 3 cases of Guillain-Barre syndrome. Among these 39 events, 27 (69%) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination. There have also been cases of photophobia following smallpox vaccination, some of which required hospitalization. Musculoskeletal and Connective Tissue Disorders: Across all ACAM2000 studies, severe, vaccine-related myalgia was seen in 1% of vaccinia-naïve subjects and < 1% of previously vaccinated subjects. Other adverse events included back pain, arthralgia and pain in extremity and none occurred with a frequency of more than 2% in either the vaccinia-naïve or previously vaccinated populations. Blood and Lymphatic System Disorders: The only adverse event occurring at ≥ 5% in the ACAM2000 studies were lymph node pain and lymphadenopathy. The incidence of severe lymph node pain and lymphadenopathy was < 1%. Gastrointestinal (GI) Disorders: Commonly reported GI disorders among ACAM2000-treated subjects included nausea and diarrhea (14%), constipation (6%), and vomiting (4%). Severe abdominal pain, nausea, vomiting, constipation diarrhea and toothache accounted for all the severe adverse events reported and occurred in < 1% of subjects. Skin and Subcutaneous Tissue Disorders: Erythema and rash were noted in 18% and 8% of subjects respectively. In ACAM2000 subjects 1% of vaccinia-naïve and < 1% of previously vaccinated subjects experienced at least one severe adverse event. With the exception of one case of contact dermatitis and one case of urticaria, erythema and rash accounted for all severe events. Generalized rashes (erythematous, papulovesicular, urticarial, folliculitis, nonspecific) are not uncommon following smallpox vaccination and are presumed to be hypersensitivity reactions occurring among persons without underlying illnesses. These rashes are generally self-limited and require little or no therapy, except among patients whose conditions appear to be toxic or who have serious underlying illnesses. Inadvertent inoculation at other body sites is the most frequent complication of vaccinia vaccination, usually resulting from autoinoculation of the vaccine virus transferred from the site of vaccination. The most common sites involved are the face, nose, mouth, lips, genitalia and anus. Accidental infection of the eye (ocular vaccinia) may result in ocular complications including, but not limited to, keratitis, corneal scarring and blindness. Major cutaneous reactions at the site of inoculation, characterized by large area of erythema and induration and streaking inflammation of draining lymphatics may resemble cellulitis. Benign and malignant lesions have been reported to occur at the smallpox vaccination site. ACAM2000 Clinical Trial Experience Two randomized, controlled, multi-center Phase 3 trials enrolled 2244 subjects that received ACAM2000 and 737 that received a comparison licensed live vaccinia virus vaccine, Dryvax®. Study 1 was conducted in male (66% and 63% for ACAM2000 and Dryvax®, respectively) and female (34% and 37% for ACAM2000 and Dryvax®, respectively) subjects who previously had not been vaccinated with smallpox vaccine (i.e., vaccinia-naïve subjects). The majority of subjects were Caucasian (76% and 71% for ACAM2000 and Dryvax®, respectively) and the mean age was 23 in both groups with an age range from 18-30 years. Study 2 was conducted in male (50% and 48% for ACAM2000 and Dryvax®, respectively) and female (50% and 52% for ACAM2000 and Dryvax®, respectively) subjects who had been vaccinated with smallpox vaccine > 10 years previously (i.e., previously vaccinated subjects). The majority of subjects were Caucasian (78% for both groups) and the mean age was 49 years in both groups with an age range of 31 to 84 years. Common Adverse Events Reported In ACAM2000 Clinical Program Adverse events reported by ≥ 5% of subjects in either the ACAM2000 or the comparison treatment group during Phase 3 studies are presented by type of adverse events, by baseline vaccination status (vaccinia-naïve versus previously vaccinated) and by treatment group. Severe vaccine-related adverse events, defined as interfering with normal daily activities, in vaccinia-naïve subjects were reported by 10% of subjects in the ACAM2000 group and 13% in the comparison group. In the previously vaccinated subjects, the incidence of severe vaccine-related adverse events was 4% for the ACAM2000 groups and 6% for the comparison group. Table 3 : Adverse Events Reported by ≥ 5% of Subjects in ACAM2000 or Dryvax® Study 1 Vaccinia-Naive Subjects Study 2 Previously Vaccinated Subjects ACAM2000 N=873 n (%) Dryvax® N=289 n (%) ACAM2000 N=1371 n (%) Dryvax® N=448 n (%) At least 1 adverse event 864 (99) 288 (100) 1325 (97) 443 (99) Blood and lymphatic system disorders 515 (59) 204 (71) 302 (22) 133 (30) Lymph node paina* 494 (57) 199 (69) 261 (19) 119 (27) Lymphadenopathy 72 (8) 35 (12) 78 (6) 29 (6) Gastrointestinal disorders 273 (31) 91 (31) 314 (23) 137 (31) Nauseaa 170 (19) 65 (22) 142 (10) 63 (14) Diarrheaa 144 (16) 34 (12) 158 (12) 77 (17) Constipationa 49 (6) 9 (3) 88 (6) 31 (7) Vomitinga 42 (5) 10 (3) 40 (3) 18 (4) General disorders and administration site conditions 850 (97) 288 (100) 1280 (93) 434 (97) Injection site pruritusa 804 (92) 277 (96) 1130 (82) 416 (93) Injection site erythemaa 649 (74) 229 (79) 841(61) 324 (72) Injection site paina 582 (67) 208 (72) 505 (37) 209 (47) Fatiguea 423 (48) 161 (56) 468 (34) 184 (41) Injection site swelling 422 (48) 165 (57) 384 (28) 188 (42) Malaisea 327 (37) 122 (42) 381 (28) 147 (33) Feeling hota 276 (32) 97 (34) 271 (20) 114 (25) Rigorsa 185 (21) 66 (23) 171 (12) 76 (17) Exercise tolerance decreaseda 98 (11) 35 (12) 105 (8) 50 (11) Musculoskeletal and connective tissue disorders 418 (48) 153 (53) 418 (30) 160 (36) Myalgiaa 404 (46) 147 (51) 374 (27) 148 (33) Nervous system disorders 444 (51) 151 (52) 453 (33) 174 (39) Headachea 433 (50) 150 (52) 437 (32) 166 (37) Respiratory, thoracic, and mediastinal disorders 134 (15) 40 (14) 127 (9) 42 (9) Dyspneaa 39 (4) 16 (6) 41 (3) 18 (4) Skin and subcutaneous tissue disorders 288 (33) 103 (36) 425 (31) 139 (31) Erythemaa 190 (22) 69 (24) 329 (24) 107 (24) Rasha 94 (11) 30 (10) 80 (6) 29 (6) a Event was listed on a checklist included in subject diaries; therefore should be considered solicited. In addition to events listed above the following were also included as part of the checklist: chest pain and heart palpitations, but these events did not occur in ≥ 5% of subjects. DRUG INTERACTIONS Simultaneous Administration With Other Vaccines There are no data evaluating the simultaneous administration of ACAM2000 with other vaccines. Interference With Laboratory Tests ACAM2000 may induce false-positive tests for syphilis. Positive RPR tests results should be confirmed using a more specific test, such as the FTA assay. ACAM2000 may induce temporary false-negative results for the tuberculin skin test (purified protein derivative [PPD]) and possibly, blood tests for tuberculosis. Tuberculin testing should be delayed if possible for 1 month following smallpox vaccination."" }, ""222"": { ""property.id"": 222, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Persons at greatest risk of experiencing serious vaccination complications are often those at greatest risk for death from smallpox. The risk for experiencing serious vaccination complications must be weighed against the risks for experiencing a potentially fatal smallpox infection. Serious Complications And Death Serious complications that may follow either primary live vaccinia smallpox vaccination or revaccination include: myocarditis and/or pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome), eczema vaccinatum, blindness, and fetal death in pregnant women. These complications may rarely lead to severe disability, permanent neurological sequelea and death. Based on clinical trials, symptoms of suspected myocarditis or pericarditis (such as chest pain, raised troponin/cardiac enzymes, or ECG abnormalities) occur in 5.7 per 1000 primary vaccinations. This finding includes cases of acute symptomatic or asymptomatic myocarditis or pericarditits or both. Historically, death following vaccination with live vaccinia virus is a rare event; approximately 1 death per million primary vaccinations and 1 death per 4 million revaccinations have occurred after vaccination with live vaccinia virus. Death is most often the result of sudden cardiac death, postvaccinial encephalitis, progressive vaccinia, or eczema vaccinatum. Death has also been reported in unvaccinated contacts accidentally infected by individuals who have been vaccinated. Incidence Of Serious Complications In 1968 US Surveillance Studies Estimates of the risks of occurrence of serious complications after primary vaccination and revaccination, based on safety surveillance studies conducted when live vaccinia virus smallpox vaccine (i.e., New York City Board of Health strain, Dryvax®) was routinely recommended, are as follows: Table 1A : Rates of reported complicationsa associated with primary vaccinia vaccinations (cases/million vaccinations)b Age (yrs) < 1 1-4 5-19 ≥ 20 Overall ratesh Inadvertent inoculationc § 507.0 577.3 371.2 606.1 529.2 Generalized vaccinia 394.4 233.4 139.7 212.1 241.5 Eczema vaccinatum 14.1 44.2 34.9 30.3 38.5 Progressive vacciniad --g 3.2 --g --g 1.5 Post-vaccinial encephalitis 42.3 9.5 8.7 --g 12.3 Deathe 5 0.5 0.5 unknown -- Totalf 1549.3 1261.8 855.9 1515.2 1253.8 a See article for descriptions of complications. b Adapted from Lane JM, Ruber FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis. 1970; 122:303-309. c Referenced as accidental implantation. d Referenced as vaccinia necrosum. e Death from all complications. f Rates of overall complications by age group include complications not provided in this table, including severe local reactions, bacterial superinfection of the vaccination site, and erythema multiforme. g No instances of this complication were identified during the 1968 10-state survey. h Overall rates for each complication include persons of unknown age. Table 1B : Rates of reported serious complicationsa associated with vaccinia revaccinations (cases/million vaccinations)b Age (yrs) < 1 1-4 5- 19 ≥ 20 Overall ratesb Inadvertent inoculationc g 109.1 47.7 25.0 42.1 Generalized vaccinia g g 9.9 9.1 9.0 Eczema vaccinatum g g 2.0 4.5 3.0 Progressive vacciniad g g g 6.8 3.0 Post-vaccinial encephalitis g g g 4.5 2.0 Deathe -- -- -- -- -- Totalf g 200.0 85.5 113.6 108.2 See Table 1A for explanation of footnotes. Incidence Of Serious Complications And Emergence Of Myocarditis And/Or Pericarditis In 2002-2005 Data on the incidence of adverse events among U.S. military personnel and civilian first responders vaccinated with Dryvax®, a licensed live vaccinia virus smallpox vaccine, during vaccination programs initiated in December 2002 are shown below in Table 2. The incidence of preventable adverse events (eczema vaccinatum, contact transmission, and auto-inoculation) were notably lower in these programs when compared with data collected in the 1960s; presumably because of better vaccination screening procedures and routine use of protective bandages over the inoculation site. Myocarditis and pericarditis were not commonly reported following smallpox vaccination in the 1960s, but emerged as a more frequent event based on more active surveillance in the military and civilian programs. Table 2 : Serious adverse events in 2002-20055 Adverse event Department of Defense program (n=730,580a) as of Jan05 Department of Health and Human Services program (n=40, 422) as of Jan04b N Incidence/ million N Incidence /million Myo/pericarditis Post-vaccinal 86 117.71 21 519.52 encephalitis 1 1.37 1 24.74 Eczema vaccinatum 0 0.00 0 0.00 Generalized vaccinia 43 58.86 3 74.22 Progressive vaccinia 0 0.00 0 0.00 Fetal vaccinia 0 0.00 0 0.00 Contact transmission 52 71.18 0 0.00 Auto-inoculation (nonocular) 62 84.86 20 494.78 Ocular vaccinia 16 21.90 3 74.22 a 71% primary vaccination; 89% male; median age 28.5 yr b 36% primary vaccination; 36% male; median age 47.1 yr Myocarditis And Pericarditis In The ACAM2000 Clinical Trial Experience In clinical trials involving 2983 subjects who received ACAM2000 and 868 subjects who received Dryvax®, ten (10) cases of suspected myocarditis [0.2% (7 of 2983) ACAM2000 subjects and 0.3% (3 of 868) Dryvax® subjects] were identified. The mean time to onset of suspected myocarditis and/or pericarditis from vaccination was 11 days, with a range of 9 to 20 days. All subjects who experienced these cardiac events were naïve to vaccinia. Of the 10 subjects, 2 were hospitalized. None of the remaining 8 cases required hospitalization or treatment with medication. Of the 10 cases, 8 were sub-clinical and were detected only by ECG abnormalities with or without associated elevations of cardiac troponin I. All cases resolved by 9 months, with the exception of one female subject in the Dryvax® group, who had persistent borderline abnormal left ventricular ejection fraction on echocardiogram. The best estimate of risk for myocarditis and pericarditis is derived from the Phase 3 ACAM2000 clinical trials where there was active monitoring for potential of myocarditis and pericarditis. Among vaccinees naïve to vaccinia, 8 cases of suspected myocarditis and pericarditis were identified across both treatment groups, for a total incidence rate of 6.9 per 1000 vaccinees (8 of 1,162). The rate for the ACAM2000 treatment group were similar: 5.7 (95% CI: 1.9-13.3) per 1000 vaccinees (5 of 873 vaccinees) and for the Dryvax® group 10.4 (95% CI: 2.1-30.0) per 1000 vaccinees (3 of 289 vaccinees). No cases of myocarditis and/or pericarditis were identified in 1819 previously vaccinated subjects. The long-term outcome of myocarditis and pericarditis following ACAM2000 vaccination is currently unknown. Cardiac Disease Ischemic cardiac events, including fatalities, have been reported following smallpox vaccination; the relationship of these events, if any, to vaccination has not been established. In addition, cases of non-ischemic, dilated cardiomyopathy have been reported following smallpox vaccination; the relationship of these cases to smallpox vaccination is unknown. There may be increased risks of adverse events with ACAM2000 in persons with known cardiac disease, including those diagnosed with previous myocardial infarction, angina, congestive heart failure, cardiomyopathy, chest pain or shortness of breath with activity, stroke or transient ischemic attack, or other heart conditions. In addition, subjects who have been diagnosed with 3 or more of the following risk factors for ischemic coronary disease: 1) high blood pressure; 2) elevated blood cholesterol; 3) diabetes mellitus or high blood sugar; 4) first degree relative (for example mother, father, brother, or sister) who had a heart condition before the age of 50; or 5) smoke cigarettes may have increased risks. Ocular Complications And Blindness Accidental infection of the eye (ocular vaccinia) may result in ocular complications including keratitis, corneal scarring and blindness. Patients who are using corticosteroid eye drops may be at increased risk of ocular complications with ACAM2000. Presence Of Congenital Or Acquired Immune Deficiency Disorders Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems, including patients with leukemia, lymphoma, organ transplantation, generalized malignancy, HIV/AIDS, cellular or humoral immune deficiency, radiation therapy, or treatment with antimetabolites, alkylating agents, or high-dose corticosteroids ( > 10 mg prednisone/day or equivalent for ≥ 2 weeks). The vaccine is contraindicated in individuals with severe immunodeficiency [See CONTRAINDICATIONS]. Vaccinees with close contacts who have these conditions may be at increased risk because live vaccinia virus can be shed and be transmitted to close contacts. History Or Presence Of Eczema And Other Skin Conditions Persons with eczema of any description such as, atopic dermatitis, neurodermatitis, and other eczematous conditions, regardless of severity of the condition, or persons who have a history of these conditions at any time in the past, are at higher risk of developing eczema vaccinatum. Vaccinees with close contacts who have eczematous conditions, may be at increased risk because live vaccinia virus can shed and be transmitted to these close contacts. Vaccinees with other active acute, chronic or exfoliative skin disorders (including burns, impetigo, varicella zoster, acne vulgaris with open lesions, Darier's disease, psoriasis, seborrheic dermatitis, erythroderma, pustular dermatitis, etc.), or vaccinees with household contacts having such skin disorders might also be at higher risk for eczema vaccinatum. Infants ( < 12 Months Of Age) And Children ACAM2000 has not been studied in infants or children. The risk of serious adverse events following vaccination with live vaccinia virus is higher in infants. Vaccinated persons who have close contact with infants, e.g., breastfeeding, must take precautions to avoid inadvertent transmission of ACAM2000 live vaccinia virus to infants. Pregnancy ACAM2000 has not been studied in pregnant women. Live vaccinia virus vaccines can cause fetal vaccinia and fetal death. If ACAM2000 is administered during pregnancy, the vaccinee should be apprised of the potential hazard to the fetus [See Use in Specific Populations]. Vaccinees with close contacts who are pregnant may be at increased risk because live vaccinia virus can shed and be transmitted to close contacts. Allergy To ACAM2000 Smallpox Vaccine Or Its Components ACAM2000 contains neomycin and polymyxin B. Persons allergic to these components may be at higher risk for adverse events after vaccination. Both the vaccine and diluent vial stoppers do not contain latex material. Management Of Smallpox Vaccine Complications The CDC can assist physicians in the diagnosis and management of patients with suspected complications of vaccinia (smallpox) vaccination. Vaccinia Immune Globulin (VIG) is indicated for certain complications of vaccination live vaccinia virus smallpox vaccine. If VIG is needed or additional information is required, physicians should contact the CDC at (404) 639-3670, Monday through Friday 8 AM to 4:30 PM Eastern Standard Time; at other times call (404) 639-2888. Prevention Of Transmission Of Live Vaccinia Virus The most important measure to prevent inadvertent auto-inoculation and contact transmission from vaccinia vaccination is thorough hand washing after changing the bandage or after any other contact with the vaccination site. Individuals susceptible to adverse effects of vaccinia virus, i.e., those with cardiac disease, eye disease, immunodeficiency states, including HIV infection, eczema, pregnant women and infants, should be identified and measures should be taken to avoid contact between those individuals and persons with active vaccination lesions. Recently vaccinated healthcare workers should avoid contact with patients, particularly those with immunodeficiencies, until the scab has separated from the skin at the vaccination site. However, if continued contact with patients is unavoidable, vaccinated healthcare workers should ensure the vaccination site is well covered and follow good hand-washing technique. In this setting, a more occlusive dressing may be used. Semipermeable polyurethane dressings are effective barriers to shedding of vaccinia. However, exudate may accumulate beneath the dressing, and care must be taken to prevent viral spread when the dressing is changed. In addition, accumulation of fluid beneath the dressing may increase skin maceration at the vaccination site. Accumulation of exudate may be decreased by first covering the vaccination with dry gauze, then applying the dressing over the gauze. The dressing should be changed every 1-3 days [See Self Inoculation and Spread to Close Contacts and Care of the Vaccination Site and Potentially Contaminated Materials]. Blood And Organ Donation Blood and organ donation should be avoided for at least 30 days following vaccination with ACAM2000. Limitations Of Vaccine Effectiveness ACAM2000 smallpox vaccine may not protect all persons exposed to smallpox. Patient Counseling Information Please refer patient to the Medication Guide prepared for ACAM2000 Smallpox Vaccine. Serious Complications Of Vaccination Patients must be informed of the major serious adverse events associated with vaccination, including myocarditis and/or pericarditis, progressive vaccinia in immunocompromised persons, eczema vaccinatum in persons with skin disorders, auto- and accidental inoculation, generalized vaccinia, urticaria, erythema multiforme major (including Stevens-Johnson syndrome) and fetal vaccinia in pregnant women. Protecting Contacts At Highest Risk For Adverse Events Patients must be informed that they should avoid contact with individuals at high risk of serious adverse effects of vaccinia virus, for instance, those with past or present eczema, immunodeficiency states including HIV infection, pregnancy, or infants less than 12 months of age. Self-inoculation And Spread To Close Contacts Patients must be advised that virus is shed from the cutaneous lesion at the site of inoculation from approximately Day 3 until scabbing occurs, typically between Days 14-21 after primary vaccination. Vaccinia virus may be transmitted by direct physical contact. Accidental infection of skin at sites other than the site of intentional vaccination (self-inoculation) may occur by trauma or scratching. Contact spread may also result in accidental inoculation of household members or other close contacts. The result of accidental infection is a pock lesion(s) at an unwanted site(s) in the vaccinee or contact, and resembles the vaccination site. Self-inoculation occurs most often on the face, eyelid, nose, and mouth, but lesions at any site of traumatic inoculation can occur. Self-inoculation of the eye may result in ocular vaccinia, a potentially serious complication. Care Of The Vaccination Site And Potentially Contaminated Materials Patients must be given the following instructions: The vaccination site must be completely covered with a semipermeable bandage. Keep site covered until the scab falls off on its own. The vaccination site must be kept dry. Normal bathing may continue, but cover the vaccination site with waterproof bandage when bathing. The site should not be scrubbed. Cover the vaccination site with loose gauze bandage after bathing. Don't scratch the vaccination site. Don't scratch or pick at the scab. Do not touch the lesion or soiled bandage and subsequently touch other parts of the body particularly the eyes, anal and genital areas that are susceptible to accidental (auto-) inoculation. After changing the bandage or touching the site, wash hands thoroughly with soap and water or > 60% alcohol-based hand-rub solutions. To prevent transmission to contacts, physical contact of objects that have come into contact with the lesion (e.g. soiled bandages, clothing, fingers) must be avoided. Wash separately clothing, towels, bedding or other items that may have come in direct contact with the vaccination site or drainage from the site, using hot water with detergent and/or bleach. Wash hands afterwards. Soiled and contaminated bandages must be placed in plastic bags for disposal. The vaccinee must wear a shirt with sleeves that covers the vaccination site as an extra precaution to prevent spread of the vaccinia virus. This is particularly important in situations of close physical contact. The vaccinee must change the bandage every 1 to 3 days. This will keep skin at the vaccination site intact and minimize softening. Don't put salves or ointments on the vaccination site. When the scab fall off, throw it away in a sealed plastic bag and wash hands afterwards. Use In Specific Populations Pregnancy Pregnancy Category D ACAM2000 has not been studied in pregnant women. Live vaccinia virus vaccines can cause fetal harm when administered to a pregnant woman. Congenital infection, principally occurring during the first trimester, has been observed after vaccination with live vaccinia smallpox vaccines, although the risk may be low. Generalized vaccinia of the fetus, early delivery of a stillborn infant, or a high risk of perinatal death has been reported. The only setting in which vaccination of pregnant women should be considered is when exposure to smallpox is considered likely. If this vaccine is used during pregnancy, or if the vaccinee lives in the same household with or has close contact with a pregnant women, the vaccinee should be apprised of the potential hazard to the fetus. Healthcare providers, state health departments, and other public health staff should report to the National Smallpox Vaccine in Pregnancy Registry all cases in which persons who received ACAM2000, or were exposed to a woman who received ACAM2000 within 28 days after vaccination, during pregnancy, or within 42 days prior to conception. Civilian women should contact their healthcare provider or state health department for help enrolling in the registry. Clinicians or public health staff should report civilian cases through their state health department or to CDC, telephone 404-639-8253 or 877 554 4625. Military cases should be reported to the DoD, telephone 619 553-9255, Defense Switched Network (DSN) 553-9255, fax 619 767-4806 or e-mail NHRC-BirthRegistry@med.navy.mil. Nursing Mothers ACAM2000 has not been studied in lactating women. It is not known whether vaccine virus or antibodies are secreted in human milk. Live vaccinia virus can be inadvertently transmitted from a lactating mother to her infant. Infants are at high risk of developing serious complications from live vaccinia smallpox vaccination. Pediatric Use The safety and effectiveness of ACAM2000 have not been established in the age groups from birth to age 16. The use of ACAM2000 in all pediatric age groups is supported by evidence from the adequate and well-controlled studies of ACAM2000 in adults and with additional historical data with use of live vaccinia virus smallpox vaccine in pediatrics. Before the eradication of smallpox disease, live vaccinia virus smallpox vaccine was administered routinely in all pediatric age groups, including neonates and infants, and was effective in preventing smallpox disease. During that time, live vaccinia virus was occasionally associated with serious complications in children, the highest risk being in infants younger than 12 months of age. [See WARNINGS AND PRECAUTIONS]. Geriatric Use Clinical studies of ACAM2000 did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. There are no published data to support the use of this vaccine in geriatric (persons > 65 years) populations. 5 Poland GA, Grabenstein JD, Neff JM. The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation program. Vaccine. 2005;23:2078-2081."" }, ""223"": { ""property.id"": 223, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS There are very few absolute contraindications to this vaccine for those who are at high risk for smallpox. The risk for experiencing serious vaccination complications must be weighed against the risks for experiencing a potentially fatal smallpox infection. See WARNINGS AND PRECAUTIONS for persons who are at higher risk of experiencing serious vaccination complications. Severe Immune Deficiency Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems. Individuals with severe immunodeficiency who are not expected to benefit from the vaccine should not receive ACAM2000. These individuals may include individuals who are undergoing bone marrow transplantation or individuals with primary or acquired immunodeficiency who require isolation."" }, ""224"": { ""property.id"": 224, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Smallpox vaccine does not contain smallpox virus (variola) and cannot spread or cause smallpox. Mechanism Of Action Vaccinia virus is a member of the same taxonomic group (the Orthopox genus) as smallpox (variola) virus, and immunity induced by vaccinia virus cross-protects against variola virus. Vaccinia virus causes a localized virus infection of the epidermis at the site of inoculation, surrounding dermal and subcutaneous tissues, and draining lymph nodes. Virus may be transiently present in blood and infects reticuloendothelial and other tissues. Langerhans cells in the epidermis are specific targets for the early stage of virus replication. The formation of a pustule ('pock' or 'take') at the site of inoculation provides evidence of protective immunity. The virus replicates within cells and viral antigens are presented to the immune system. Neutralizing antibodies and B and T cells provide long-term memory. The level of neutralizing antibody that protects against smallpox is unknown but > 95% of persons undergoing primary vaccination develop neutralizing or hemagglutination inhibiting antibodies to vaccinia. Pharmacodynamics Cutaneous Response The cutaneous responses following smallpox vaccination are dependent on the immune status of the individual, potency of the vaccine, and vaccination technique. Two types of responses have been defined by the WHO Expert Committee on Smallpox, and described by the Advisory Committee on Immunization Practices (ACIP). The responses include: a) major cutaneous reaction, which indicates that virus replication has taken place and vaccination was successful; or b) equivocal reaction. Equivocal reactions may be a consequence of pre-existing immunity adequate to suppress viral multiplication, vaccination technique failure, or use of inactive vaccine or vaccine that has lost potency. Successful vaccination in persons who are naïve to smallpox vaccination, termed primary vaccination, is represented by a major cutaneous reaction, defined as a vesicular or pustular lesion or an area of definite palpable induration or congestion surrounding a central lesion that might be a crust or an ulcer. Subjects who have been previously vaccinated and are revaccinated may manifest a reduced cutaneous response compared to vaccinia-naïve subjects, but still exhibit an immune response to the vaccine. [See DOSAGE AND ADMINISTRATION] Neutralizing Antibody and Cellular Immune Responses Neutralizing antibodies are known to mediate protection against smallpox. Neutralizing antibodies against vaccinia develop in > 95% of individuals following primary vaccination, rise rapidly (by day 15-20 after vaccination) and may be boosted on revaccination. Antibody titers are highly variable. Titers may remain high for longer periods following two or more vaccinations than after a primary vaccination. The level of the neutralizing antibody response following primary vaccination is generally in proportion to the intensity of the cutaneous reaction. The level of neutralizing antibody that is required to protect against smallpox has not been clearly established, although some studies indicate that persons with antibody titers > 1:32 are protected. Cellular immune responses are also elicited by vaccination and may contribute to protection and immunological memory. Virus Shedding Virus is shed from the vaccination site during the period starting with the development of a papule (day 2-5); shedding ceases when the scab separates and the lesion is re-epithelialized, about 14-21 days after vaccination. Steps should be taken in clinical use to reduce the risk of accidental infection of other sites in the vaccinated patient or of contact spread to other individuals [See Vaccination Instructions]. Clinical Studies Vaccine efficacy was assessed by comparing the immunologic response of ACAM2000 to another US-licensed live vaccinia virus smallpox vaccine, Dryvax®, in two randomized, multi-center active-controlled clinical trials; one study in subjects who previously had not been vaccinated with smallpox vaccine (i.e., vaccinia-naïve subjects) and one study in subjects who had been vaccinated with smallpox vaccine > 10 years previously (i.e., previously vaccinated subjects). In both trials, the co-primary efficacy endpoints were the proportion of subjects with a successful vaccination/revaccination and the geometric mean neutralizing antibody titer (GMT) on Day 30. Successful primary vaccination was defined as a major cutaneous reaction on Day 7 or 10 (Days 6 to 11, with allowable visit window). Successful revaccination was defined as development of any cutaneous lesion on Day 7 (± 1 day) of a measurable size. Successful revaccination was determined by a panel of experts who reviewed digital photographs of the cutaneous lesions. The statistical method used to compare the proportion of subjects who were successfully vaccinated in the two treatment groups was a test of non-inferiority of ACAM2000 to the active comparator intended to rule out a greater than 5% margin of superiority of the comparator for successful primary vaccination (Study 1) and a 10% margin of superiority of the comparator for successful revaccination (Study 2). Non-inferiority was to be declared if the lower bound of the 1-sided 97.5% confidence interval (CI) for the percent difference between ACAM2000 and the comparator exceeded -5% in naïve subjects and -10% in previously vaccinated subjects. Analysis of the GMT was performed using a test of non-inferiority of neutralizing antibody titer between ACAM2000 and the comparator, intended to ensure that the ratio of the GMTs of ACAM2000: comparator vaccine was at least 0.5 (equivalent to the difference of the log10 (GMT) being at least -0.301). In Study 1, a total of 1037 male and female vaccinia-naïve subjects, aged 18 to 30 years inclusive, primarily Caucasian (76%) were randomized in a 3:1 ratio to receive ACAM2000 (780 subjects) or comparator (257 subjects). The ACAM2000 subjects were further stratified to receive one of three lots (Lots A, B and C) at a 1:1:1 ratio (258, 264, and 258 subjects, respectively). All subjects were to be evaluated for their cutaneous response and a random subset was selected for evaluation of neutralizing antibody response. In Study 2, a total of 1647 male and female previously-vaccinated subjects, aged 31 to 84 years inclusive, primarily Caucasian (81%) were randomized in a 3:1 ratio to receive ACAM2000 (1242 subjects) or the comparator (405 subjects). The ACAM2000 subjects were further stratified to receive one of three lots (Lots A, B and C) at a 1:1:1 ratio (411, 417, and 414 subjects, respectively). All subjects were evaluated for their cutaneous response and a random subset was to be selected for evaluation of neutralizing antibody response. Table 4 presents the results of the primary efficacy analyses for both studies. Table 4 : Cutaneous Response (Vaccination Success) and Neutralizing Antibody Response in Subjects Given ACAM2000 Vs. Comparator Vaccine Study Population / Treatment Group Study 1 Vaccinia-Naive Subjects Study 2 Previously Vaccinated Subjects ACAM 2000 Comparator ACAM 2000 Comparator Cutaneous Response (Vaccination Success) Size of Evaluable Populationa 776 257 1189 388 Number of Vaccination Successes (%) 747 (96)b 255 (99) 998 (84)h 381 (98) 97.5% 1-sided CI by normal approx. on percent difference between ACAM2000-Comparator -4.67%c -17%i Non-Inferiority to Comparator Yes No Neutralizing Antibody Response ( based on PRNT50d Titer on Day 30) Size of Evaluable Populatione 565 190 734 376 GMTf 166 255 286 445 Log10 mean 2.2 2.4 2.5 2.6 97.5% 1-sided CI by ANOVA on difference between ACAM2000-Comparator -0.307g -0.275j Meets NonInferiority to Comparator No Yes a Subjects who received study vaccine and were evaluated for a local cutaneous reaction within the protocol-designated timeframe were included in the efficacy evaluable (EE) population. b Results for vaccine lots, A, B and C were 95%, 98% and 96%. c Since the critical value for the evaluation was declared to be -5%, ACAM2000 is considered to be non-inferior to Comparator for this parameter. d PRNT50 – Vaccinia 50% plaque reduction neutralization test. e A randomly selected sample of subjects who received study vaccine and had samples collected for neutralizing antibody response at Baseline and at the designated time-point post-treatment were included in the antibody evaluable (AnE) population. f GMT – Geometric mean neutralizing antibody titer. g Since the critical value for the evaluation was declared to be -0.301, ACAM2000 is not considered to be non-inferior to Comparator for this parameter. h Results for vaccine lots, A, B and C were 79%, 87% and 86%. i Since the critical value for the evaluation was declared to be -10%, ACAM2000 is not considered to be non-inferior to Comparator for this parameter. j Since the critical value for the evaluation was declared to be -0.301, ACAM2000 is considered to be non-inferior to Comparator for this parameter. The primary determinant for an effective immune response in those naïve to vaccine is a major cutaneous reaction. ACAM2000 was non-inferior to comparator in this population with regard to eliciting a major cutaneous reaction. The measure of the strength of the generated antibody response was similar but did not meet the predefined criterion for non-inferiority. Among subjects who were previously vaccinated, development of a major cutaneous response after revaccination with vaccinia-based smallpox vaccines may not provide an accurate measure of the strength of the immune response because the pre-existing immunity modifies the scope of the cutaneous response. In previously vaccinated subjects, ACAM2000 was non-inferior to the comparator with regard to the strength of the neutralizing antibody immune response. Therefore, ACAM2000 was non-inferior to the comparator in the rate of major cutaneous reaction in those naïve to the vaccine, and the strength of the neutralizing antibody immune response in those previously exposed to vaccinia-based smallpox vaccines. REFERENCES 2 Centers for Disease Control and Prevention. Notice to readers: Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2003;52(13):282-284. 3 Lane J, Millar J. Risks of smallpox vaccination complications in the United States. Am J Epidemiol. 1971;93:238-240. 4 Lane, JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis. 1970;122(4):303-309. 6 Casey GC, Iskander JK, Roper MH, Mast EE, Wen X-J, Torok TJ, et al..Adverse events associated with smallpox vaccination in the United States, January-October 2003. JAMA. 005;94(21):2734-2743. 7 Centers for Disease Control and Prevention.Update: Cardiac and other adverse events following civilian smallpox vaccination – United States, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(27):639-42. 8 Centers for Disease Control and Prevention. Cardiac adverse events following smallpox vaccination – United States, 2003. MMWR Morb Mortal Wkly Rep. 2003; 52(12):248-50. 9 Centers for Disease Control and Prevention. Update: adverse events following smallpox vaccination – United States, 2003. MMWR Morb Mortal Wkly Rep. 2003; 52(13):278-282. 10 Neff JM, Lane JM, Pert JH, Moore R, Millar JD, Henderson DA. Complications of smallpox vaccination. National survey in the United States, 1963. N Engl J Med. 1967;276:125-132. 11 Centers for Disease Control and Prevention. Recommendations for Using Smallpox Vaccine in a Pre-event vaccination Program. Supplemental Recommendation of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR 2003;52 (No. RR-7). 12 Centers for Disease Control and Prevention.Notice to Readers. National smallpox vaccine in pregnancy registry. MMWR Morb Mortal Wkly Rep. 2003;52(12):256. 13 Centers for Disease Control and Prevention. Vaccinia (smallpox) vaccine recommendation of the Advisory Committee in Immunization Practices (ACIP). 2001. MMWR Morb Mortal Wkly Rep. 2001;50 (RR10):1-25. 14 Sejvar J, Labutta RJ, Chapman LE, Grabenstein JD, Iskander J. Lane JM. Neurological adverse events associated with smallpox vaccination in the United States, 2002-2004. JAMA. 2005;294(24):2744-50. 15 Nagao S, Inaba S, Iijima S. Langerhans cells at the sites of vaccinia virus inoculation. Arch Dermatol Res. 1976;256(1):23-31. 16 Cole, G. Blanden R. Immunology of poxviruses. In. Nahmias AJ, O'Reilly RJ, eds Comprehensive Immunology, Immunology of Human Infection, Part II, Viruses and Parasites. Vol 9 New York, NY: Plenum; 1982:1-19. 17 Mack TM, Noble J, Thomas DB. A Prospective Study of Serum Antibody and Protection Against Smallpox. Am. J Trop Med & Hygiene. 1972: 21(2):214-218. 18 Department of Defense Directive. Number 6205.3 DoD immunization program for biological warfare defense. 1993. Available from http://www.dtic.mil/whs/directives/corres/html/620503.htm. Accessed July 17, 2007. 19 Centers for Disease Control and Prevention. Recommendations for use of smallpox vaccine for bioterrorism preparedness and response. Available from http://www.bt.cdc/gov/agent/smallpox/vaccination. Accessed July 17, 2007."" }, ""225"": { ""property.id"": 225, ""property.ts"": ""2017-12-04 04:40:47"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION Smallpox (Vaccinia) Vaccine, Live ACAM2000® Please read this Medication Guide before you receive a vaccination with ACAM2000. This Guide does not take the place of talking to your healthcare provider about ACAM2000 and the smallpox disease. What is the most important information I should know about the ACAM2000 smallpox vaccine? If you are at a high risk for being exposed to smallpox, you should be vaccinated even if you have health problems, unless you have certain problems with your immune system. People who have health problems may have a higher chance of getting serious side effects from vaccination but are also those who have a higher chance of dying from the smallpox disease. ACAM2000 may cause serious heart problems called myocarditis and pericarditis, or swelling of the heart tissues. In studies, about 1 in every 175 persons who got the vaccine for the first time may have experienced myocarditis and/or pericarditis. On rare occasions these conditions can result in an irregular heart beat and death. Your chances of getting heart problems from the vaccine are lower if you have already had this vaccine before. You can have myocarditis and/or pericarditis even if you have no symptoms. Call your healthcare provider or get emergency help right away if you have: chest pain or pressure fast or irregular heartbeat breathing problems See “What are the possible side effects of ACAM2000?” Because the vaccine has a live virus, it can spread to other parts of your body or to other people if you touch the vaccination site and then touch other parts of your body or other people. The vaccine virus can spread until the vaccination scab falls off (2 to 4 weeks after vaccination). If the virus is spread to a person who should not get the vaccine, the side effects can be very serious and life-threatening. See “How do I care for the smallpox vaccination site?” What is the ACAM2000 smallpox vaccine? ACAM2000 is a prescription vaccine used to protect people against smallpox disease. It is for use in people who have a high chance of getting the disease. ACAM2000 contains live vaccinia virus (a “pox”-type virus) to protect against smallpox disease. Who should not get the ACAM2000 smallpox vaccine? In an emergency, you should be vaccinated if you are at high risk for getting smallpox disease even if you have health problems (except if you have certain problems with your immune system as discussed below). Your healthcare provider may not give you ACAM2000 if you have problems with your immune system. You may have immune system problems if you: have leukemia have lymphoma have had a bone marrow or organ transplant have cancer that has spread have HIV, AIDS have cellular or humoral immune deficiency are being treated with radiation are being treated with steroids, prednisone, or cancer drugs How do I receive ACAM2000? ACAM2000 smallpox vaccine is not a shot like other vaccines. Your healthcare provider will make 15 pokes in the skin of your upper arm with a needle containing ACAM2000. The pokes are not deep, but will cause a drop of blood to form. This is called the vaccination site. It is important to care for the vaccination site properly so that the virus doesn't spread to other parts of your body or to other people. You can infect another part of your body or other people until the scab falls off. How do I care for the ACAM2000 vaccination site? It is important to ALWAYS: Wear bandages to cover the entire vaccination site. Wear sleeves to cover the site. Wash your hands, wash your hands, wash your hands. When changing bandages or caring for your vaccination site, wear gloves. Use an absorbent bandage to completely cover your vaccination site. Change your bandage when it begins to soak through (at least every 1 to 3 days). Throw away gloves and used bandages in sealed or double plastic bags. A small amount of bleach can be added to the bag to kill the virus. Wear clothes with sleeves to cover the site and prevent scratching the vaccination site. It is especially important to wear a bandage and sleeves to bed to avoid scratching. Wash your hands frequently with alcohol-based cleansers or soap and water. Be sure to wash your hands each time you change your bandage or if you touch the vaccination site. Do not use creams or ointments on the vaccination site because they will delay healing and can spread the virus. Do not scratch or pick at the vaccination site. You can take a bath or shower, but don't touch or scrub the vaccination site. It is best to cover the vaccination site with a waterproof bandage. If the vaccination site gets wet, dry the site with toilet paper and flush it. (Do not use a cloth towel because it can spread the virus.) Cover the vaccination site with a loose gauze bandage after bathing to allow it to dry out. Do not use a bandage that blocks air from the vaccination site. This could cause the skin at the vaccination site to soften and wear away. If you exercise enough to cause sweat to drip, use a waterproof bandage on the vaccination site when exercising. Wash clothing, towels, bedding or other items that may have come in contact with the vaccination site separately from other wash. Use hot water with detergent and bleach. When the scab falls off, throw it away in a sealed plastic bag with a small amount of bleach. Wash your hands afterwards. What should I expect at the vaccination site and in the weeks following vaccination? If vaccination is successful, a red and itchy bump forms at the vaccination site in 2 to 5 days. Over the next few days, the bump becomes a blister and fills with pus. During the second week, the blister dries up and a scab forms. The scab falls off after 2 to 4 weeks, leaving a scar. People vaccinated for the first time may have a larger reaction than those being revaccinated. See expected responses below: Smallpox Vaccination Site: expected response after vaccination Note: After 6 to 8 days, check to be sure that your vaccination site looks like one of the pictures above. If it does not look like this, see your healthcare provider because you may need to be revaccinated. If you need medical care in the month after your vaccination, tell your healthcare provider you just got a smallpox vaccination. Certain people, such as laboratory workers who work with smallpox, are at risk of being exposed to smallpox over a long period of time. These people may need a booster vaccination every 3 years to maintain protection against smallpox. What should I avoid after getting vaccinated with the ACAM2000 smallpox vaccine? For 4 weeks after vaccination AND until the vaccination site has healed, you should avoid: getting pregnant. Smallpox vaccine may rarely cause infection in an unborn baby if the mother is vaccinated during pregnancy. This infection usually results in stillbirth or death. handling babies or breastfeeding. swimming or hot tub use. donating blood. Tuberculin (TB) testing. Smallpox vaccine may cause the TB test to give the wrong result. Avoid rubbing, scratching or touching the vaccination site. Until the vaccination scab falls off, do NOT: have contact with people who cannot get the vaccine to prevent accidental spread of the vaccine virus. This includes physical contact and household contact. If there is someone in your household who should not get the vaccine, such as a pregnant woman, an infant, or someone who has an illness, you should not stay in the house until the vaccination scab falls off. share a bed, clothes, towels, linen, or toiletries with unvaccinated people. We don't know if the vaccine virus can be spread to cats, dogs, or other household pets, or whether pets can spread the virus to other people in the household. Try to keep the vaccine virus from reaching your pet. See “How do I care for the smallpox vaccination site?” What are the possible side effects of ACAM2000? ACAM2000 may cause serious heart problems, including myocarditis and pericarditis. This can happen within 3 to 4 weeks after you get the vaccine. Call your healthcare provider or get emergency help right away if you have: chest pain or pressure fast or irregular heartbeat breathing problems Most people who get myocarditis and/or pericarditis seem to get better after a few weeks. But heart problems may last longer in some people, and in rare cases, could lead to death. Other serious side effects include: swelling of the brain or spinal cord problems with the vaccination site blister, such as it becoming infected spreading of the vaccine virus to other parts of your body or to another person severe allergic reaction after vaccination accidental infection of the eye (which may cause swelling of the cornea causing watery painful eyes and blurred vision, scarring of the cornea, and blindness) Common side effects include: itching headache swollen lymph nodes body ache sore arm mild rash fever fatigue The risks for serious vaccine side effects are greater for people who: have skin problems called eczema or atopic dermatitis have skin problems, such as burns, impetigo, contact dermatitis, chickenpox, shingles, psoriasis, or uncontrolled acne have had heart problems have serious heart or blood vessel problems including angina, previous heart attack, artery disease, congestive heart failure, stroke, or other cardiac problems smoke or have high blood pressure, high cholesterol, diabetes, high blood sugar, or a family history of heart problems are breastfeeding are pregnant, could be pregnant, or plan to become pregnant are less than 1 year old are taking steroid eye drops or ointment have had problems after previous doses or are allergic to ACAM2000 or any part of ACAM2000 such as antibiotics neomycin or polymyxin B Tell your healthcare provider if you have any of the above conditions. The virus from your vaccination can spread to other people and cause serious side effects. It is important to tell your healthcare provider if you: live or work with a person who has skin problems (like eczema, dermatitis, burns, psoriasis, bad acne) or is suffering from impetigo, chickenpox or shingles live or have close contact with a baby, or a person who is pregnant or breastfeeding live or have close contact with a person who has an immune deficiency or cardiac disease See “How do I care for the ACAM2000 vaccination site?” Tell your healthcare provider about any side effect that bothers you or that does not go away. To report SUSPECTED SIDE EFFECTS (ADVERSE REACTIONS), contact sanofi pasteur Inc. at 1-800-822-2463 (1-800-VACCINE) or VAERS at 800-822-7967 and https://vaers.hhs.gov General information about the safe and effective use of ACAM2000 This Medication Guide provides a summary of the most important information about ACAM2000. Medicines are sometimes prescribed for purposes other than those listed in the Medication Guide. If you would like more information or have any questions, talk to your healthcare provider. You can ask your healthcare provider for information about ACAM2000 that is written for healthcare professionals. You can also visit http:www.sanofipasteur.us/acam2000. The vaccine should not be used for a condition other than that for which it is prescribed. What are the ingredients in ACAM2000? ACAM2000: live vaccinia virus derived from plaque purification cloning from Dryvax (Wyeth Laboratories, Marietta, PA, calf lymph vaccine, New York City Board of Health Strain) and grown in African Green Monkey kidney (Vero) cells Inactive ingredients: 6-8 mM HEPES (pH 6.5-7.5), 2% human serum albumin USP, 0.5 - 0.7% sodium chloride USP, 5% mannitol USP, and trace amounts of the antibiotics neomycin and polymyxin B Diluent for ACAM2000: 50% (v/v) Glycerin USP, 0.25% (v/v) Phenol USP in Water for Injection USP This Medication Guide has been approved by the U.S. Food and Drug Administration."" } }" 35,"2017-08-31 23:12:57","Acamprosate Calcium",Campral,FDA,"{ ""35"": { ""alphabet_x_drug.id"": 35, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""226"": { ""property.id"": 226, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on CAMPRAL® (acamprosate calcium) Tablets DESCRIPTION Campral® (acamprosate calcium) is supplied in an enteric-coated tablet for oral administration. Acamprosate calcium is a synthetic compound with a chemical structure similar to that of the endogenous amino acid homotaurine, which is a structural analogue of the amino acid neurotransmitter γ-aminobutyric acid and the amino acid neuromodulator taurine. Its chemical name is calcium acetylaminopropane sulfonate. Its chemical formula is C H N O S Ca and molecular weight is 400.48. Its structural formula is: Acamprosate calcium is a white, odorless or nearly odorless powder. It is freely soluble in water, and practically insoluble in absolute ethanol and dichloromethane. Each Campral® tablet contains acamprosate calcium 333 mg, equivalent to 300 mg of acamprosate. Inactive ingredients in Campral tablets include: crospovidone, microcrystalline cellulose, magnesium silicate, sodium starch glycolate, colloidal anhydrous silica, magnesium stearate, talc, propylene glycol and Eudragit L 30 D or equivalent. Sulfites were used in the synthesis of the drug substance and traces of residual sulfites may be present in the drug product."" }, ""227"": { ""property.id"": 227, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS Campral® is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Treatment with Campral should be part of a comprehensive management program that includes psychosocial support. The efficacy of Campral in promoting abstinence has not been demonstrated in subjects who have not undergone detoxification and not achieved alcohol abstinence prior to beginning Campral treatment. The efficacy of Campral in promoting abstinence from alcohol in polysubstance abusers has not been adequately assessed. DOSAGE AND ADMINISTRATION The recommended dose of Campral is two 333 mg tablets (each dose should total 666 mg) taken three Sections or subsections omitted from the full prescribing information are not listed. times daily. A lower dose may be effective in some patients. Although dosing may be done without regard to meals, dosing with meals was employed during clinical trials and is suggested in those patients who regularly eat three meals daily. Treatment with Campral should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence, and should be maintained if the patient relapses. Campral should be used as part of a comprehensive psychosocial treatment program. Dosage In Renal Impairment For patients with moderate renal impairment (creatinine clearance of 30-50 mL/min), a starting dose of one 333 mg tablet taken three times daily is recommended. Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min). [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, Use in Specific Populations, and CLINICAL PHARMACOLOGY] HOW SUPPLIED Dosage Forms And Strengths Campral 333 mg tablets are enteric-coated, white, round, biconvex tablets, identified with “333” debossed on one side. NDC:68151-4760-0 in a PACKAGE of 1 TABLET, DELAYED RELEASES Storage And Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Manufactured by: Merck Santé s.a.s. Subsidiary of Merck KGaA, Darmstadt, Germany 37, rue Saint- Romain 69008 LYON FRANCE. Manufactured for: Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO, 63045. Revised: Aug 2014"" }, ""228"": { ""property.id"": 228, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinically significant serious adverse reactions associated with Campral described elsewhere in labeling include suicidality and depression and acute kidney failure [see WARNINGS AND PRECAUTIONS] The adverse event data described below reflect the safety experience in over 7000 patients exposed to Campral for up to one year, including over 2000 Campral-exposed patients who participated in placebocontrolled trials. Adverse Events Leading To Discontinuation In placebo-controlled trials of 6 months or less, 8% of Campral-treated patients discontinued treatment due to an adverse event, as compared to 6% of patients treated with placebo. In studies longer than 6 months, the discontinuation rate due to adverse events was 7% in both the placebo-treated and the Campral-treated patients. Only diarrhea was associated with the discontinuation of more than 1% of patients (2% of Campral-treated vs. 0.7% of placebo-treated patients). Other events, including nausea, depression, and anxiety, while accounting for discontinuation in less than 1% of patients, were nevertheless more commonly cited in association with discontinuation in Campral-treated patients than in placebo-treated patients. Common Adverse Events Reported In Controlled Trials Common adverse events were collected spontaneously in some controlled studies and using a checklist in other studies. The overall profile of adverse events was similar using either method. shows those events that occurred in any Campral treatment group at a rate of 3% or greater and greater than the placebo group in controlled clinical trials with spontaneously reported adverse events. The reported frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed, without regard to the causal relationship of the events to the drug. Table 1: Events Occurring at a Rate of at Least 3% and Greater than Placebo in any Campral Treatment Group in Controlled Clinical Trials with Spontaneously Reported Adverse Events Body System/ Preferred Term Number of Patients (%) with Events Campral 1332 mg/day Campral 1998 mg/day 1 Campral Pooled 2 Placebo Number of patients in Treatment Group 397 1539 2019 1706 Number (%) of patients with an AE 248 (62%) 910 (59%) 1231 (61%) 955 (56%) Body as a Whole 121 (30%) 513 (33%) 685 (34%) 517 (30%) Accidental Injury*† 17 ( 4%) 44 ( 3%) 70 ( 3%) 52 ( 3%) Asthenia 29 ( 7%) 79 ( 5%) 114 ( 6%) 93 ( 5%) Pain 6 ( 2%) 56 ( 4%) 65 ( 3%) 55 ( 3%) Digestive System 85 (21%) 440 (29%) 574 (28%) 344 (20%) Anorexia 20 ( 5%) 35 ( 2%) 57 ( 3%) 44 ( 3%) Diarrhea 39 (10%) 257 (17%) 329 (16%) 166 (10%) Flatulence 4 ( 1%) 55 ( 4%) 63 ( 3%) 28 ( 2%) Nausea 11 ( 3%) 69 ( 4%) 87 ( 4%) 58 ( 3%) Nervous System 150 (38%) 417 (27%) 598 (30%) 500 (29%) Anxiety††** 32 ( 8%) 80 ( 5%) 118 ( 6%) 98 ( 6%) Depression 33 ( 8%) 63 ( 4%) 102 ( 5%) 87 ( 5%) Dizziness 15 ( 4%) 49 ( 3%) 67 ( 3%) 44 ( 3%) Dry mouth 13 ( 3%) 23 ( 1%) 36 ( 2%) 28 ( 2%) Insomnia 34 ( 9%) 94 ( 6%) 137 ( 7%) 121 ( 7%) Paresthesia 11 ( 3%) 29 ( 2%) 40 ( 2%) 34 ( 2%) Skin and Appendages 26 ( 7%) 150 (10%) 187 ( 9%) 169 (10%) Pruritus 12 ( 3%) 68 ( 4%) 82 ( 4%) 58 ( 3%) Sweating 11 ( 3%) 27 ( 2%) 40 ( 2%) 39 ( 2%) †*includes events coded as &ldquolfracture” by sponsor; ††**includes events coded as &ldquolnervousness” by sponsor includes 258 patients treated with acamprosate calcium 2000 mg/day, using a different dosage strength and regimen.1 includes all patients in the first two columns as well as 83 patients treated with acamprosate calcium 3000 mg/day, using a different dosage strength and regimen.2 Concomitant Therapies In clinical trials, the safety profile in subjects treated with Campral concomitantly with anxiolytics, hypnotics and sedatives (including benzodiazepines), or non-opioid analgesics was similar to that of subjects taking placebo with these concomitant medications. Patients taking Campral concomitantly with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone. Other Events Observed During The Premarketing Evaluation Of Campral Following is a list of terms that reflect treatment-emergent adverse events reported by patients treated with Campral in 20 clinical trials (4461 patients treated with Campral, 3526 of whom received the maximum recommended dose of 1998 mg/day for up to one year in duration). This listing does not include those events already listed above; events for which a drug cause was considered remote; event terms which were so general as to be uninformative; and events reported only once which were not likely to be acutely life-threatening. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the summary of adverse events in controlled trials appear in this listing); Infrequent adverse events are those occurring in 1/100 to 1/1000 patients; Rare events are those occurring in fewer than 1/1000 patients. Body as a Whole -Frequent: headache, abdominal pain, back pain, infection, flu syndrome, chest pain, chills, suicide attempt; Infrequent: fever, intentional overdose, malaise, allergic reaction, abscess, neck pain, hernia, intentional injury; Rare: ascites, face edema, photosensitivity reaction, abdomen enlarged, sudden death. Cardiovascular System -Frequent: palpitation, syncope; Infrequent: hypotension, tachycardia, hemorrhage, angina pectoris, migraine, varicose vein, myocardial infarct, phlebitis, postural hypotension; Rare: heart failure, mesenteric arterial occlusion, cardiomyopathy, deep thrombophlebitis, shock. Digestive System - Frequent : vomiting, dyspepsia, constipation, increased appetite; Infrequent: liver function tests abnormal, gastroenteritis, gastritis, dysphagia, eructation, gastrointestinal hemorrhage, pancreatitis, rectal hemorrhage, liver cirrhosis, esophagitis, hematemesis, nausea and vomiting, hepatitis; Rare: melena, stomach ulcer, cholecystitis, colitis, duodenal ulcer, mouth ulceration, carcinoma of liver.   Endocrine System -Rare: goiter, hypothyroidism. Hemic and Lymphatic System -Infrequent: anemia, ecchymosis, eosinophilia, lymphocytosis, thrombocytopenia; Rare: leukopenia, lymphadenopathy, monocytosis. Metabolic and Nutritional Disorders -Frequent - peripheral edema, weight gain; Infrequent: weight loss, hyperglycemia, SGOT increased, SGPT increased, gout, thirst, hyperuricemia, diabetes mellitus, avitaminosis, bilirubinemia; Rare:alkaline phosphatase increased, creatinine increased, hyponatremia, lactic dehydrogenase increased. Musculoskeletal System -Frequent - myalgia, arthralgia; Infrequent: leg cramps; Rare: rheumatoid arthritis, myopathy. Nervous System -Frequent -somnolence, libido decreased, amnesia, thinking abnormal, tremor, vasodilatation, hypertension; Infrequent: convulsion, confusion, libido increased, vertigo, withdrawal syndrome, apathy, suicidal ideation, neuralgia, hostility, agitation, neurosis, abnormal dreams, hallucinations, hypesthesia; Rare: alcohol craving, psychosis, hyperkinesia, twitching, depersonalization, increased salivation, paranoid reaction, torticollis, encephalopathy, manic reaction. Respiratory System -Frequent: rhinitis, cough increased, dyspnea, pharyngitis, bronchitis; Infrequent: asthma, epistaxis, pneumonia; Rare: laryngismus, pulmonary embolus. Skin and Appendages -Frequent: rash; Infrequent: acne, eczema, alopecia, maculopapular rash, dry skin, urticaria, exfoliative dermatitis, vesiculobullous rash; Rare: psoriasis. Special Senses -Frequent : abnormal vision, taste perversion; Infrequent: tinnitus, amblyopia, deafness; Rare: ophthalmitis, diplopia, photophobia. Urogenital System -Frequent : impotence; Infrequent - metrorrhagia, urinary frequency, urinary tract infection, sexual function abnormal, urinary incontinence, vaginitis; Rare: kidney calculus, abnormal ejaculation, hematuria, menorrhagia, nocturia, polyuria, urinary urgency. Postmarketing Experience The following adverse reactions have been identified during post approval use of Campral. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious Adverse Events Observed During the Non-US Postmarketing Evaluation Of Campral (acampros ate calcium) The serious adverse event of acute kidney failure has been reported to be temporally associated with Campral treatment in at least 3 patients and is not described elsewhere in the labeling. DRUG INTERACTIONS Acamprosate does not affect the pharmacokinetics of alcohol. The pharmacokinetics of acamprosate are not affected by alcohol, diazepam, or disulfiram, and clinically important interactions between naltrexone and acamprosate were not observed.[see CLINICAL PHARMACOLOGY]."" }, ""229"": { ""property.id"": 229, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Renal Impairment Treatment with Campral in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min) requires a dose reduction. Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min). [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, Use in Specific Populations, and CLINICAL PHARMACOLOGY] Suicidality And Depression In controlled clinical trials of Campral, adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides) were Infrequent overall, but were more common in Campral-treated patients than in patients treated with placebo (1.4% vs. 0.5% in studies of 6 months or less; 2.4% vs. 0.8% in year-long studies). Completed suicides occurred in 3 of 2272 (0.13%) patients in the pooled acamprosate group from all controlled studies and 2 of 1962 patients (0.10%) in the placebo group. Adverse events coded as “depression” were reported at similar rates in Campral-treated and placebotreated patients. Although many of these events occurred in the context of alcohol relapse, and the interrelationship between alcohol dependence, depression and suicidality is well-recognized and complex, no consistent pattern of relationship between the clinical course of recovery from alcoholism and the emergence of suicidality was identified. Alcohol-dependent patients, including those patients being treated with Campral, should be monitored for the development of symptoms of depression or suicidal thinking. Families and caregivers of patients being treated with Campral should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient's health care provider. Alcohol Withdrawal Use of Campral does not eliminate or diminish withdrawal symptoms. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Dietary administration of acamprosate calcium for 2 years to Sprague-Dawley rats at doses of 25, 100 and 400 mg/kg/day (up to 3 times the maximum recommended human daily (MRHD) oral dose on an AUC basis) and CD-1 mice at doses of 400, 1200 and 3600 mg/kg/day (up to 25 times the MRHD on an AUC basis) showed no evidence of increased tumor incidence. Acamprosate calcium was negative in all genetic toxicology studies conducted. Acamprosate calcium demonstrated no evidence of genotoxicity in an bacterial reverse point mutation assay (Ames assay) or an mammalian cell gene mutation test using Chinese Hamster Lung V79 cells. No clastogenicity was observed in an chromosomal aberration assay in human lymphocytes and no chromosomal damage detected in an mouse micronucleus assay. in vitroin vitroin vitroin vivo Acamprosate calcium had no effect on fertility after treatment for 70 days prior to mating in male rats and for 14 days prior to mating, throughout mating, gestation and lactation in female rats at doses up to 1000 mg/kg/day (approximately 4 times the MRHD oral dose on a mg/m² basis). In mice, acamprosate calcium administered orally for 60 days prior to mating and throughout gestation in females at doses up to 2400 mg/kg/day (approximately 5 times the MRHD oral dose on a mg/m² basis) had no effect on fertility. Use In Specific Populations Pregnancy Pregnancy Category C. Teratogenic Effects Acamprosate calcium has been shown to be teratogenic in rats when given in doses that are approximately equal to the human dose (on a mg/m² basis) and in rabbits when given in doses that are approximately 3 times the human dose (on a mg/m² basis). Acamprosate calcium produced a dose-related increase in the number of fetuses with malformations in rats at oral doses of 300 mg/kg/day or greater (approximately equal to the maximum recommended human daily (MRHD) oral dose on a mg/m² basis). The malformations included hydronephrosis, malformed iris, retinal dysplasia, and retroesophageal subclavian artery. No findings were observed at an oral dose of 50 mg/kg/day (approximately one-fifth the MRHD oral dose on a mg/m² basis). An increased incidence of hydronephrosis was also noted in Burgundy Tawny rabbits at oral doses of 400 mg/kg/day or greater (approximately 3 times the MRHD oral dose on a mg/m² basis). No developmental effects were observed in New Zealand white rabbits at oral doses up to 1000 mg/kg/day (approximately 8 times the MRHD oral dose on a mg/m² basis). The findings in animals should be considered in relation to known adverse developmental effects of ethyl alcohol, which include the characteristics of fetal alcohol syndrome (craniofacial dysmorphism, intrauterine and postnatal growth retardation, retarded psychomotor and intellectual development) and milder forms of neurological and behavioral disorders in humans. There are no adequate and well controlled studies in pregnant women. Campral should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects A study conducted in pregnant mice that were administered acamprosate calcium by the oral route starting on Day 15 of gestation through the end of lactation on postnatal day 28 demonstrated an increased incidence of still-born fetuses at doses of 960 mg/kg/day or greater (approximately 2 times the MRHD oral dose on a mg/m² basis). No effects were observed at a dose of 320 mg/kg/day (approximately one-half the MRHD dose on a mg/m² basis). Labor And Delivery The potential for Campral to affect the duration of labor and delivery is unknown. Nursing Mothers In animal studies, acamprosate was excreted in the milk of lactating rats dosed orally with acamprosate calcium. The concentration of acamprosate in milk compared to blood was 1.3:1. It is not known whether acamprosate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Campral is administered to a nursing woman. Pediatric Use The safety and efficacy of Campral have not been established in the pediatric population. Geriatric Use Forty-one of the 4234 patients in double-blind, placebo-controlled, clinical trials of Campral were 65 years of age or older, while none were 75 years of age or over. There were too few patients in the ≥ 65 age group to evaluate any differences in safety or effectiveness for geriatric patients compared to younger patients. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. [see CLINICAL PHARMACOLOGY, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION] Renal Impairment Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min).[See DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and CLINICAL PHARMACOLOGY]"" }, ""230"": { ""property.id"": 230, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE In all reported cases of acute overdosage with Campral (total reported doses of up to 56 grams of acamprosate calcium), the only symptom that could be reasonably associated with Campral was diarrhea. Hypercalcemia has not been reported in cases of acute overdose. A risk of hypercalcemia should be considered in chronic overdosage only. Treatment of overdose should be symptomatic and supportive. CONTRAINDICATIONS Hypersensitivity To Acamprosate Calcium Campral is contraindicated in patients who previously have exhibited hypersensitivity to acamprosate calcium or any of its components. Severe Renal Impairment Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min). [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, Use in Specific Populations, and CLINICAL PHARMACOLOGY]"" }, ""231"": { ""property.id"": 231, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Mechanism Of Action The mechanism of action of acamprosate in maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. and studies in animals have provided evidence to suggest acamprosate may interact with glutamate and GABA neurotransmitter systems centrally, and has led to the hypothesis that acamprosate restores this balance. In vitroin vivo Pharmacodynamics Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcoholdependent animals in a dose-dependent manner and that this effect appears to be specific to alcohol and the mechanisms of alcohol dependence. Acamprosate calcium has negligible observable central nervous system (CNS) activity in animals outside of its effects on alcohol dependence, exhibiting no anticonvulsant, antidepressant, or anxiolytic activity. The administration of acamprosate calcium is not associated with the development of tolerance or dependence in animal studies. Campral did not produce any evidence of withdrawal symptoms in patients in clinical trials at therapeutic doses. Post marketing data, collected retrospectively outside the U.S. have provided no evidence of Campral abuse or dependence. Campral is not known to cause alcohol aversion and does not cause a disulfiram-like reaction as a result of ethanol ingestion. Pharmacokinetics Absorption The absolute bioavailability of Campral after oral administration is about 11%. Steady-state plasma concentrations of acamprosate are reached within 5 days of dosing. Steady-state peak plasma concentrations after Campral doses of 2 x 333 mg tablets three times daily average 350 ng/mL and occur at 3-8 hours post-dose. Coadministration of Campral with food decreases bioavailability as measured by Cmax and AUC, by approximately 42% and 23%, respectively. The food effect on absorption is not clinically significant and no adjustment of dose is necessary. Distribution The volume of distribution for acamprosate following intravenous administration is estimated to be 72- 109 liters (approximately 1 L/kg). Plasma protein binding of acamprosate is negligible. Metabolism Acamprosate does not undergo metabolism. Elimination After oral dosing of 2 x 333 mg of Campral, the terminal half-life ranges from approximately 20-33 hours. Following oral administration of Campral, the major route of excretion is via the kidneys as acamprosate. Special Populations Gender: Campral does not exhibit any significant pharmacokinetic differences between male and female subjects. Age: The pharmacokinetics of Campral have not been evaluated in a geriatric population. However, since renal function diminishes in elderly patients and acamprosate is excreted unchanged in urine, acamprosate plasma concentrations are likely to be higher in the elderly population compared to younger adults. Pediatrics: The pharmacokinetics of Campral have not been evaluated in a pediatric population. Renal Impairment : Peak plasma concentrations after administration of a single dose of 2 x 333 mg Campral tablets to patients with moderate or severe renal impairment were about 2-fold and 4-fold higher, respectively, compared to healthy subjects. Similarly, elimination half-life was about 1.8-fold and 2.6-fold longer, respectively, compared to healthy subjects. There is a linear relationship between creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate. A dose of 1 x 333 mg Campral, three times daily, is recommended in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min, [see Use in Specific Populations] Campral is contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min). [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and Use in Specific Populations] Hepatic Impairment: Acamprosate is not metabolized by the liver and the pharmacokinetics of Campral are not altered in patients with mild to moderate hepatic impairment (groups A and B of the Child-Pugh classification). No adjustment of dosage is recommended in such patients. Alcohol-dependent subjects: A cross-study comparison of Campral at doses of 2 x 333 mg three times daily indicated similar pharmacokinetics between alcohol-dependent subjects and healthy subjects. Drug-Drug Interactions Acamprosate had no inducing potential on the cytochrome CYP1A2 and 3A4 systems, and inhibition studies suggest that acamprosate does not inhibit metabolism mediated by cytochrome CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. The pharmacokinetics of Campral were unaffected when co-administered with alcohol, disulfiram or diazepam. Similarly, the pharmacokinetics of ethanol, diazepam and nordiazepam, imipramine and desipramine, naltrexone and 6-beta naltrexol were unaffected following coadministration with Campral. However, co-administration of Campral with naltrexone led to a 33% increase in the Cmax and a 25% increase in the AUC of acamprosate. No adjustment of dosage is recommended in such patients. Clinical Studies The efficacy of Campral in the maintenance of abstinence was supported by three clinical studies involving a total of 998 patients who were administered at least one dose of Campral or placebo as an adjunct to psychosocial therapy. Each study was a double-blind, placebo-controlled trial in alcoholdependent patients who had undergone inpatient detoxification and were abstinent from alcohol on the day of randomization. Study durations ranged from 90 days to 360 days. Campral proved superior to placebo in maintaining abstinence, as indicated by a greater percentage of subjects being assessed as continuously abstinent throughout treatment. In a fourth study, the efficacy of Campral was evaluated in alcoholics, including patients with a history of polysubstance abuse and patients who had not undergone detoxification and were not required to be abstinent at baseline. This study failed to demonstrate superiority of Campral over placebo."" }, ""232"": { ""property.id"": 232, ""property.ts"": ""2017-12-04 04:40:48"", ""property.key"": ""Medication Guide"", ""property.value"": """" } }" 36,"2017-08-31 23:12:57","Acamprosate Calcium",Campral,Multum,"{ ""36"": { ""alphabet_x_drug.id"": 36, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""233"": { ""property.id"": 233, ""property.ts"": ""2017-12-04 04:40:57"", ""property.key"": ""Campral Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Campral Generic Name: acamprosate (Pronunciation: a KAM proe sate) What is acamprosate (Campral)? What are the possible side effects of acamprosate (Campral)? What is the most important information I should know about acamprosate (Campral)? What should I discuss with my healthcare provider before taking acamprosate (Campral)? How should I take acamprosate (Campral)? What happens if I miss a dose (Campral)? What happens if I overdose (Campral)? What should I avoid while taking acamprosate (Campral)? What other drugs will affect acamprosate (Campral)? Where can I get more information? What is acamprosate (Campral)? Acamprosate affects chemicals in the brain that may become unbalanced in a person who is addicted to alcohol. Acamprosate works by restoring this chemical balance in the brain in an alcohol-dependent person who has recently quit drinking.Acamprosate is used to help a person who has recently quit drinking alcohol continue to choose not to drink (remain abstinent from alcohol). It is used together with behavior modification and counseling support to help you stop drinking.Acamprosate is not likely to be helpful to a person who has not already quit drinking or undergone detoxification. It may not be helpful to a person who is also addicted to other substances besides alcohol.Acamprosate may also be used for other purposes not listed in this medication guide. What are the possible side effects of acamprosate (Campral)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Call your doctor at once if you have a serious side effects such as:mood or behavior changes;thoughts about hurting yourself;severe anxiety or depression;feeling like you might pass out;fast or pounding heartbeats;swelling, weight gain, feeling short of breath;confusion, increased thirst; orurinating less than usual or not at all.Less serious side effects may include:nausea, vomiting, stomach pain, loss of appetite;constipation, diarrhea;headache, dizziness, drowsiness;vision problems;problems with memory or thinking;weakness, cold or flu-like symptoms;back pain, joint or muscle pain;dry mouth, decreased or distorted sense of taste;sleep problems (insomnia);impotence, loss of interest in sex;sweating, mild skin rash; ornumbness or tingly feeling.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about acamprosate (Campral)? You should not use this medication if you are allergic to acamprosate, or if you have severe kidney disease.Acamprosate will not treat or prevent alcohol withdrawal symptoms.Before you take acamprosate, tell your doctor if you have any type of kidney problem. You may need a dose adjustment or special tests to safely use this medication.You may have thoughts about suicide while you are taking acamprosate. Tell your doctor if you feel depressed or have any suicidal thoughts or actions during treatment.Your family or other caregivers should also be alert to changes in your mood or behavior. Make sure your caregivers know how to contact your doctor in case you have mood changes or suicidal thoughts or actions.Acamprosate can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.Take this medication for the full prescribed length of time, even if you relapse and drink alcohol. While you are taking acamprosate, tell your doctor about any alcoholic drinks you consume, no matter how many."" }, ""234"": { ""property.id"": 234, ""property.ts"": ""2017-12-04 04:40:57"", ""property.key"": ""Campral Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my healthcare provider before taking acamprosate (Campral)? You should not use this medication if you are allergic to acamprosate, or if you have severe kidney disease.Acamprosate will not treat or prevent alcohol withdrawal symptoms.Before you take acamprosate, tell your doctor if you have any type of kidney problem. You may need a dose adjustment or special tests to safely use this medication.FDA pregnancy category C. It is not known whether acamprosate is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.It is not known whether acamprosate passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.You may have thoughts about suicide while you are taking acamprosate. Tell your doctor if you feel depressed or have any suicidal thoughts or actions during treatment.Your family or other caregivers should also be alert to changes in your mood or behavior. Make sure your caregivers know how to contact your doctor in case you have mood changes or suicidal thoughts or actions. How should I take acamprosate (Campral)? Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.Acamprosate treatment should be started as soon as possible after you have quit drinking.Take this medicine with water.Acamprosate is usually taken 3 times daily, and may be taken with or without food. If you regularly eat 3 meals per day, it may help you remember to take your acamprosate if you take a dose with each meal. Follow your doctor's instructions.Acamprosate is only part of a complete program of treatment that also includes counseling support and continued abstinence from alcohol.Take this medication for the full prescribed length of time, even if you relapse and drink alcohol. While you are taking acamprosate, tell your doctor about any alcoholic drinks you consume, no matter how many.It is important to use acamprosate regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.Store acamprosate at room temperature away from moisture and heat."" }, ""235"": { ""property.id"": 235, ""property.ts"": ""2017-12-04 04:40:57"", ""property.key"": ""Campral Patient Information including If I Miss a Dose"", ""property.value"": """" } }" 37,"2017-08-31 23:12:57","Acanya Gel","Clindamycin Phosphate 1.2% and Benzoyl Peroxide 2.5%",FDA,"{ ""37"": { ""alphabet_x_drug.id"": 37, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""236"": { ""property.id"": 236, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on ACANYA (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5% DESCRIPTION ACANYA (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5% is a combination product with two active ingredients in a white to off-white, opaque, smooth, aqueous gel formulation intended for topical use. Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. The chemical name for clindamycin phosphate is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galactooctopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below: Clindamycin phosphate: Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97 Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula for benzoyl peroxide is represented below: Benzoyl peroxide: Molecular Formula: C14H10O4 Molecular Weight: 242.23 ACANYA Gel contains the following inactive ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide. Each gram of ACANYA Gel contains 1.2% of clindamycin phosphate which is equivalent to 1% clindamycin."" }, ""237"": { ""property.id"": 237, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS ACANYA® Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older. DOSAGE AND ADMINISTRATION Apply a pea-sized amount of ACANYA Gel to the face once daily. Use of ACANYA Gel beyond 12 weeks has not been evaluated. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. ACANYA Gel is not for oral, ophthalmic, or intravaginal use. HOW SUPPLIED Dosage Forms And Strengths Gel, 1.2%/2.5% Each gram of ACANYA Gel contains 10 mg (1%) clindamycin as phosphate, and 25 mg (2.5%) benzoyl peroxide in a white to off-white, opaque, smooth gel. ACANYA Gel is supplied as a 50 g pump (NDC 13548-132-50). Dispensing Instructions For The Pharmacist Dispense ACANYA Gel with a 10 week expiration date. Specify “Store at room temperature up to 25°C (77°F). Do not freeze.” Storage And Handling PHARMACIST: Prior to Dispensing: Store in a refrigerator, 2°C to 8°C (36°F to 46°F). PATIENT: Store at room temperature at or below 25°C (77°F). Protect from freezing. Keep out of the reach of children. Keep container tightly closed. Distributed by: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807. Manufactured by: Contract Pharmaceuticals Limited Mississauga, Ontario, Canada L5N 6L6. Revised 02/2014"" }, ""238"": { ""property.id"": 238, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS Clinical Trials Experience Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. Because clinical trials are also conducted under widely varying conditions, adverse reactions observed in the clinical trials of a drug cannot always be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following selected adverse reactions occurred in less than 0.2% of patients treated with ACANYA Gel: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). During clinical trials, subjects were assessed for local cutaneous signs and symptoms of erythema, scaling, itching, burning and stinging. Most local skin reactions increased and peaked around week 4 and continually decreased over time reaching near baseline levels by week 12. The percentage of subjects that had symptoms present before treatment, the maximum value recorded during treatment, and the percent with symptoms present at week 12 are shown in Table 1. Table 1: Local Skin Reactions -Percent of Subjects with Symptoms Present. Combined Results from the Two Phase 3 Trials (N = 773) Before Treatment (Baseline) Maximum During Treatment End of Treatment (Week 12) Mild Mod.* Severe Mild Mod.* Severe Mild Mod.* Severe Erythema 22 4 0 25 5 < 1 15 2 0 Scaling 8 < 1 0 18 3 0 8 1 0 Itching 10 2 0 15 2 0 6 < 1 0 Burning 3 < 1 0 8 2 0 2 < 1 0 Stinging 2 < 1 0 6 1 0 1 < 1 0 *Mod. = Moderate Postmarketing Experience Anaphylaxis, as well as allergic reactions leading to hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. DRUG INTERACTIONS Erythromycin ACANYA Gel should not be used in combination with topical or oral erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between erythromycin and clindamycin. The clinical significance of this in vitro antagonism is not known. Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, ACANYA Gel should be used with caution in patients receiving such agents."" }, ""239"": { ""property.id"": 239, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Colitis Systemic absorption of clindamycin has been demonstrated following topical use of clindamycin. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. When significant diarrhea occurs, ACANYA Gel should be discontinued. Severe colitis has occurred following oral and parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death. Studies indicate toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically. Ultraviolet Light And Environmental Exposure Minimize sun exposure including use of tanning beds or sun lamps following drug application [See Nonclinical Toxicology]. Patient Counseling Information See FDA-approved patient labeling (PATIENT INFORMATION). Patients who develop allergic reactions such as severe swelling or shortness of breath should discontinue use and contact their physician immediately. ACANYA Gel may cause irritation such as erythema, scaling, itching, or burning, especially when used in combination with other topical acne therapies. Excessive or prolonged exposure to sunlight should be limited. To minimize exposure to sunlight, a hat or other clothing should be worn. Sunscreen may also be used. ACANYA Gel may bleach hair or colored fabric. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity, mutagenicity and impairment of fertility testing of ACANYA Gel have not been performed. Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered topically twice per week for 20 weeks induced skin tumors in transgenic Tg.AC mice. The clinical significance of this is unknown. Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses of 900, 2700, and 15000 mg/kg/day (1.8, 5.4, and 30 times amount of clindamycin and 3.6, 10.8, and 60 times amount of benzoyl peroxide in the highest recommended adult human dose of 2.5 g ACANYA Gel based on mg/m², respectively) did not cause any increase in tumors. However, topical treatment with a different gel formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900 and 3000 mg/kg/day (1.2, 3.6, and 12 times amount of clindamycin and 2.4, 7.2, and 24 times amount of benzoyl peroxide in the highest recommended adult human dose of 2.5 g ACANYA Gel based on mg/m², respectively) for up to 97 weeks did not cause any increase in tumors. In a 52-week dermal photocarcinogenicity study in hairless mice, (40 weeks of treatment followed by 12 weeks of observation), the median time to onset of skin tumor formation decreased and the number of tumors per mouse increased relative to controls following chronic concurrent topical administration of the higher concentration benzoyl peroxide formulation (5000 and 10000 mg/kg/day, 5 days/week) and exposure to ultraviolet radiation. Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Fertility studies have not been performed with ACANYA Gel or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g ACANYA Gel, based on mg/m²) revealed no effects on fertility or mating ability. Use In Specific Populations Pregnancy Pregnancy Category C There are no adequate and well-controlled trials studies in pregnant women treated with ACANYA Gel. ACANYA Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproductive/developmental toxicity studies have not been conducted with ACANYA Gel or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in rats and mice using oral doses of up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) revealed no evidence of teratogenicity. Nursing Mothers It is not known whether clindamycin is excreted in human milk after topical application of ACANYA Gel. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to use ACANYA Gel while nursing, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness of ACANYA Gel in pediatric patients under the age of 12 have not been evaluated. Geriatric Use Clinical trials of ACANYA Gel did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects."" }, ""240"": { ""property.id"": 240, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE No information provided. CONTRAINDICATIONS Hypersensitivity ACANYA Gel is contraindicated in those individuals who have shown hypersensitivity to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. Anaphylaxis, as well as allergic reactions leading to hospitalization, has been reported in postmarketing use with ACANYA Gel. [See Postmarketing Experience] Colitis/Enteritis ACANYA Gel is contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. [see WARNINGS AND PRECAUTIONS]."" }, ""241"": { ""property.id"": 241, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Mechanisms Of Action Clindamycin: Clindamycin is a lincosamide antibacterial [See Microbiology]. Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects but the precise mechanism of action is unknown. Pharmacokinetics The systemic absorption of clindamycin was investigated in an open-label, multiple-dose trial in 16 adult subjects with moderate to severe acne vulgaris treated with 1 gram of ACANYA Gel applied to the face once daily for 30 days. Twelve subjects (75%) had at least one quantifiable clindamycin plasma concentration above the lower limit of quantification (LOQ = 0.5 ng/mL) on Day 1 or Day 30. On Day 1, the mean (± standard deviation) peak plasma concentration (Cmax) was 0.78 ± 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC0-t was 5.29 ± 0.81 h.ng/mL (n=4). On Day 30, the mean Cmax was 1.22 ± 0.88 ng/mL (n=10), and the mean AUC0-t was 8.42 ± 6.01 h.ng/mL (n=6). Clindamycin plasma concentrations were below LOQ in all subjects at 24 hours post-dose on the three tested days (Day 1, 15, and 30). Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. Microbiology Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin and benzoyl peroxide individually have been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes is not known. P. acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin. Clinical Studies The safety and efficacy of once daily use of ACANYA Gel were assessed in two 12-week multi-center, randomized, blinded trials in subjects 12 years and older with moderate to severe acne vulgaris. The two trials were identical in design and compared ACANYA Gel to clindamycin in the vehicle gel, benzoyl peroxide in the vehicle gel, and the vehicle gel alone. The co-primary efficacy variables were: Mean absolute change from baseline at week 12 in Inflammatory lesion counts Non-inflammatory lesion counts Percent of subjects who had a two grade improvement from baseline on an Evaluator's Global Severity (EGS) score. The EGS scoring scale used in all of the clinical trials for ACANYA Gel is as follows: Grade Description Clear Normal, clear skin with no evidence of acne vulgaris Almost Clear Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red) Mild Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions) Moderate Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: several to many comedones and papules/pustules, and there may or may not be one small nodulo-cystic lesion Severe Inflammatory lesions are more apparent, many comedones and papules/pustules, there may or may not be a few nodulocystic lesions Very Severe Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions The results of Trial 1 at week 12 are presented in Table 2: Table 2: Trial 1 Results Trial 1 ACANYA Gel N = 399 Clindamycin Gel N = 408 Benzoyl Peroxide Gel N = 406 Vehicle Gel N = 201 EGSS Clear or Almost Clear 115 (29%) 84 (21%) 76 (19%) 29 (14%) 2 grade reduction from baseline 131 (33%) 100 (25%) 96 (24%) 38 (19%) Inflammatory Lesions: Mean absolute change 14.8 12.2 13 9 Mean percent (%) reduction 55.00% 47.10% 49.30% 34.50% Non-Inflammatory Lesions: Mean absolute change 22.1 17.9 20.6 13.2 Mean percent (%) reduction 45.30% 38.00% 40.20% 28.60% The results of Trial 2 at week 12 are presented in Table 3: Table 3: Trial 2 Results Trial 2 ACANYA Gel N = 398 Clindamycin Gel N = 404 Benzoyl Peroxide Gel N = 403 Vehicle Gel N = 194 EGSS Clear or Almost Clear 113 (28%) 94 (23%) 94 (23%) 21 (11%) 2 grade reduction from baseline 147 (37%) 114 (28%) 114 (28%) 27 (14%) Inflammatory Lesions: Mean absolute change 13.7 11.3 11.2 5.7 Mean percent (%) reduction 54.20% 45.30% 45.70% 23.30% Non-Inflammatory Lesions: Mean absolute change 19 14.9 15.2 8.3 Mean percent (%) reduction 41.20% 34.30% 34.50% 19.20%"" }, ""242"": { ""property.id"": 242, ""property.ts"": ""2017-12-04 04:41:03"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION ACANYA® (AH-CAN'-YAH) (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5% IMPORTANT: For use on skin only (topical use). Do not get ACANYA Gel in your mouth, eyes, or vagina, or on your lips. Read the Patient Information that comes with ACANYA Gel before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment. What is ACANYA Gel? ACANYA Gel is a prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years and older. ACANYA Gel contains clindamycin phosphate and benzoyl peroxide. It is not known if ACANYA Gel is safe and effective for use longer than 12 weeks. It is not known if ACANYA Gel is safe and effective in children under 12 years of age. Who should not use ACANYA Gel? Do not use ACANYA Gel if you have: Crohn's disease ulcerative colitis had inflammation of the colon (colitis), or severe diarrhea with past antibiotic use Talk with your doctor if you are not sure if you have one of these conditions. What should I tell my doctor before using ACANYA Gel? Before using ACANYA Gel, tell your doctor about all of your medical conditions, including if you: have any allergies. have any other medical conditions are pregnant or planning to become pregnant. It is not known if ACANYA Gel will harm your unborn baby. are breastfeeding or plan to breast-feed. It is not known if ACANYA Gel passes into your breast milk. One of the medicines in ACANYA Gel contains clindamycin. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. You and your doctor should decide whether you will use ACANYA Gel while breast-feeding. Tell your doctor about all the medicines and skin products you use. Especially tell your doctor if you will have surgery with general anesthesia. One of the medicines in ACANYA Gel (clindamycin) can affect how certain medicines work when used in general anesthesia. ACANYA Gel should not be used with products that contain erythromycin. Other skin and topical acne products may increase the irritation of your skin when used with ACANYA Gel. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I use ACANYA Gel? Use ACANYA Gel exactly as prescribed. Your doctor will tell you how long to use ACANYA Gel. Throw away (discard) any unused ACANYA Gel. Instructions for applying ACANYA Gel Apply ACANYA Gel to your face one time each day as prescribed. 1. Before you apply ACANYA Gel, wash your face gently with a mild soap, rinse with warm water, and pat your skin dry. 2. To apply ACANYA Gel to your face, use the pump to dispense one pea-sized amount of Acanya Gel onto your fingertip. See Figure 1. One pea-sized amount of ACANYA Gel should be enough to cover your entire face. Figure 1 3. Dot the one pea-sized amount of ACANYA Gel onto six areas of your face (chin, left cheek, right cheek, nose, left forehead, right forehead). See Figure 2. Figure 2 4. After applying the ACANYA Gel this way, spread the gel over your face and gently rub it in. It is important to spread the gel over your whole face. 5. Wash your hands with soap and water after applying ACANYA Gel. 6. If your doctor tells you to put ACANYA Gel on other areas of your skin with acne, be sure to ask how much you should use. 7. Do not get ACANYA Gel in your mouth, eyes, or nose, or on your lips. If this occurs, rinse the affected area with warm water and call your doctor right away if the area becomes very red, itchy, tender, or swollen. 8. Do not get ACANYA Gel on cuts or open wounds. 9. Do not use more ACANYA Gel than prescribed. What should I avoid while using ACANYA Gel? Limit your time in sunlight. Avoid using tanning beds or sun lamps. If you have to be in sunlight, wear a wide-brimmed hat or other protective clothing, and a sunscreen with SPF 15 rating or higher. Your doctor can give you more information about why this is important. Do not wash your face more than 2 to 3 times a day. Washing your face too often or scrubbing it may make your acne worse. Avoid getting ACANYA Gel in your hair or on colored fabric. ACANYA Gel may bleach hair or colored fabric. What are possible side effects with ACANYA Gel? ACANYA Gel can cause serious side effects including: Inflammation of the colon (colitis). Stop using ACANYA Gel and call your doctor right away if you have severe watery diarrhea, or bloody diarrhea. Allergic reactions. Stop using ACANYA Gel, call your doctor and get help right away if you have any of the following symptoms: severe itching swelling of your face, eyes, lips, tongue or throat trouble breathing Common side effects with ACANYA Gel include: Skin irritation. Stop using ACANYA Gel and call your doctor if you have a skin rash or your skin becomes very red, itchy or swollen. Talk to your doctor about any side effect that bothers you or that does not go away. These are not all the possible side effects with ACANYA Gel. Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Valeant Pharmaceuticals North America LLC at 1-800-321-4576. How should I store ACANYA Gel? Store ACANYA Gel at room temperature at or below 25°C (77°F). The expiration date of Acanya Gel is 10 weeks from the date you fill your prescription. Safely throw away expired ACANYA Gel. Do not freeze. Keep the container tightly closed. Keep ACANYA Gel and all medicines out of the reach of children. General information about ACANYA Gel Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use ACANYA Gel for a condition for which it was not prescribed. Do not give ACANYA Gel to other people, even if they have the same condition you have. It may harm them. This leaflet summarizes the most important information about ACANYA Gel. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about ACANYA Gel that is written for healthcare professionals. For more information about ACANYA Gel, call 1-800-321-4576. What are the ingredients in ACANYA Gel? Active Ingredients: clindamycin phosphate 1.2% and benzoyl peroxide 2.5% Inactive Ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide"" } }" 38,"2017-08-31 23:12:57","Acanya Gel","Clindamycin Phosphate 1.2% and Benzoyl Peroxide 2.5%",Multum,"{ ""38"": { ""alphabet_x_drug.id"": 38, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""243"": { ""property.id"": 243, ""property.ts"": ""2017-12-04 04:41:10"", ""property.key"": ""Acanya Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Acanya, BenzaClin, BenzaClin with pump, Duac, Z-Clinz 10, Z-Clinz 5 Generic Name: benzoyl peroxide and clindamycin topical (Pronunciation: BEN zoyl per OX ide and clin da MYE sin) What is benzoyl peroxide and clindamycin topical (Acanya, BenzaClin, BenzaClin with pump, Duac, Z-Clinz 10, Z-Clinz 5)? What are the possible side effects of benzoyl peroxide and clindamycin topical? What is the most important information I should know about benzoyl peroxide and clindamycin topical? What should I discuss with my healthcare provider before using benzoyl peroxide and clindamycin topical? How should I use benzoyl peroxide and clindamycin topical? What happens if I miss a dose? What happens if I overdose? What should I avoid while taking benzoyl peroxide and clindamycin topical? What other drugs will affect benzoyl peroxide and clindamycin topical? Where can I get more information? What is benzoyl peroxide and clindamycin topical (Acanya, BenzaClin, BenzaClin with pump, Duac, Z-Clinz 10, Z-Clinz 5)? Benzoyl peroxide has an antibacterial effect. It also has a mild drying effect that allows excess oil and dirt to be washed away.Clindamycin is an antibiotic that prevents bacteria from growing on the skin.The combination of benzoyl peroxide and clindamycin topical are used to treat acne.Benzoyl peroxide and clindamycin topical may also be used for purposes not listed in this medication guide. What are the possible side effects of benzoyl peroxide and clindamycin topical? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Stop using this medicine and call your doctor at once if you have any of these serious side effects:severe redness, burning, stinging, or peeling of treated skin areas; ordiarrhea that is watery or bloody.Less serious side effects may include:mild burning or stinging;itching or tingly feeling;dryness or peeling of treated skin; orredness or other irritation.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about benzoyl peroxide and clindamycin topical? Use benzoyl peroxide and clindamycin topical exactly as your doctor has prescribed it for you. Using more medicine or applying it more often than prescribed will not make it work any faster, and may increase side effects. Do not use this medication for longer than your doctor has prescribed.Avoid getting this medication in your eyes, mouth, or nose (or in the creases of your nose), or on your lips. If it does get into any of these areas, wash with water. Do not apply this medicine to sunburned, windburned, dry, chapped, irritated, or broken skin.It may take several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.Although this medicine is applied to the skin, your body may absorb enough clindamycin to cause serious side effects. You may not be able to use this medication if you have inflammation of your intestines (also called enteritis), ulcerative colitis, or if you have ever had severe diarrhea caused by antibiotic medicine.Avoid exposure to sunlight or tanning beds. This medication can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors."" }, ""244"": { ""property.id"": 244, ""property.ts"": ""2017-12-04 04:41:10"", ""property.key"": ""Acanya Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my healthcare provider before using benzoyl peroxide and clindamycin topical? Do not use this medication if you are allergic to benzoyl peroxide or clindamycin (Cleocin, Clina-Derm, Clindets).Although this medicine is applied to the skin, your body may absorb enough clindamycin to cause serious side effects. You may not be able to use this medication if you have:inflammation of your intestines (also called enteritis);ulcerative colitis; orif you have ever had severe diarrhea caused by antibiotic medicine.FDA pregnancy category C. It is not known whether benzoyl peroxide and clindamycin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.It is not known whether benzoyl peroxide and clindamycin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using benzoyl peroxide and clindamycin. How should I use benzoyl peroxide and clindamycin topical? Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Using more medicine or applying it more often than prescribed will not make it work any faster, and may increase side effects. Wash your hands before and after applying this medication.Wash your face with a mild cleanser (not soap) and pat the skin dry with a clean towel.Benzoyl peroxide and clindamycin topical is usually applied twice daily, in the morning and evening.Avoid getting this medication in your eyes, mouth, or nose (or in the creases of your nose), or on your lips. If it does get into any of these areas, wash with water. Do not apply this medicine to sunburned, windburned, dry, chapped, irritated, or broken skin.It may take several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.If you receive more than one supply of Acanya or Duac gel, store the unopened container in a refrigerator until you are ready to start using it. Do not freeze.Once in use, store the gel at room temperature away from moisture and heat. Do not freeze. Throw away any unused medicine after the expiration date on the label has passed. Duac has an expiration date of 60 days. Acanya has an expiration date of 10 weeks. BenzaClin has an expiration date of 3 months."" }, ""245"": { ""property.id"": 245, ""property.ts"": ""2017-12-04 04:41:10"", ""property.key"": ""Acanya Patient Information including If I Miss a Dose"", ""property.value"": """" } }" 39,"2017-08-31 23:12:57",Acarbose,Precose,FDA,"{ ""39"": { ""alphabet_x_drug.id"": 39, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""246"": { ""property.id"": 246, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Drug Description"", ""property.value"": ""Find Lowest Prices on PRECOSE® (acarbose) Tablets DESCRIPTION PRECOSE® (acarbose tablets) is an oral alpha-glucosidase inhibitor for use in the management of type 2 diabetes mellitus. Acarbose is an oligosaccharide which is obtained from fermentation processes of a microorganism, Actinoplanes utahensis, and is chemically known as O-4,6-dideoxy4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino] α-D-glucopyranos yl-(1 → 4)-O-α-D-glucopyranosyl-(1 →4)-D-glucose. It is a white to off-white powder with a molecular weight of 645.6. Acarbose is soluble in water and has a pKa of 5.1. Its empirical formula is C25H43NO18 and its chemical structure is as follows: PRECOSE is available as 25 mg, 50 mg and 100 mg tablets for oral use. The inactive ingredients are starch, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide."" }, ""247"": { ""property.id"": 247, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Indications & Dosage"", ""property.value"": ""INDICATIONS PRECOSE is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. DOSAGE AND ADMINISTRATION There is no fixed dosage regimen for the management of diabetes mellitus with PRECOSE or any other pharmacologic agent. Dosage of PRECOSE must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. PRECOSE should be taken three times daily at the start (with the first bite) of each main meal. PRECOSE should be started at a low dose, with gradual dose escalation as described below, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced. During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to PRECOSE and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of PRECOSE, either as monotherapy or in combination with sulfonylureas, insulin or metformin. Initial Dosage The recommended starting dosage of PRECOSE is 25 mg given orally three times daily at the start (with the first bite) of each main meal. However, some patients may benefit from more gradual dose titration to minimize gastrointestinal side effects. This may be achieved by initiating treatment at 25 mg once per day and subsequently increasing the frequency of administration to achieve 25 mg t.i.d. Maintenance Dosage Once a 25 mg t.i.d. dosage regimen is reached, dosage of PRECOSE should be adjusted at 4–8 week intervals based on one-hour postprandial glucose or glycosylated hemoglobin levels, and on tolerance. The dosage can be increased from 25 mg t.i.d. to 50 mg t.i.d. Some patients may benefit from further increasing the dosage to 100 mg t.i.d. The maintenance dose ranges from 50 mg t.i.d. to 100 mg t.i.d. However, since patients with low body weight may be at increased risk for elevated serum transaminases, only patients with body weight > 60 kg should be considered for dose titration above 50 mg t.i.d. (see PRECAUTIONS). If no further reduction in postprandial glucose or glycosylated hemoglobin levels is observed with titration to 100 mg t.i.d., consideration should be given to lowering the dose. Once an effective and tolerated dosage is established, it should be maintained. Maximum Dosage The maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d. The maximum recommended dose for patients > 60 kg is 100 mg t.i.d. Patients Receiving Sulfonylureas or Insulin Sulfonylurea agents or insulin may cause hypoglycemia. PRECOSE given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the potential for hypoglycemia. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made. HOW SUPPLIED PRECOSE is available as 25 mg, 50 mg or 100 mg round, unscored tablets. Each tablet strength is white to yellow-tinged in color. The 25 mg tablet is coded with the word “PRECOSE” on one side and “25” on the other side. The 50 mg tablet is coded with the word “PRECOSE” and “50” on the same side. The 100 mg tablet is coded with the word “PRECOSE” and “100” on the same side. PRECOSE is available in bottles of 100 and 50 mg strength in unit dose packages of 100. Strength NDC Tablet Identification Bottles of 100: 25 mg 50419-863-51 PRECOSE 25 50 mg 50419-861-51 PRECOSE 50 100 mg 50419-862-51 PRECOSE 100 Unit Dose Packages of 100: 50 mg 50419-861-48 PRECOSE 50 Do not store above 25°C (77°F). Protect from moisture. For bottles, keep container tightly closed. Bayer HealthCare Pharmaceuticals Inc. Wayne, NJ 07470. Made in Germany. 11/11"" }, ""248"": { ""property.id"": 248, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Side Effects & Drug Interactions"", ""property.value"": ""SIDE EFFECTS Digestive Tract Gastrointestinal symptoms are the most common reactions to PRECOSE. In U.S. placebo-controlled trials, the incidences of abdominal pain, diarrhea, and flatulence were 19%, 31%, and 74% respectively in 1255 patients treated with PRECOSE 50–300 mg t.i.d., whereas the corresponding incidences were 9%, 12%, and 29% in 999 placebo-treated patients. In a one-year safety study, during which patients kept diaries of gastrointestinal symptoms, abdominal pain and diarrhea tended to return to pretreatment levels over time, and the frequency and intensity of flatulence tended to abate with time. The increased gastrointestinal tract symptoms in patients treated with PRECOSE are a manifestation of the mechanism of action of PRECOSE and are related to the presence of undigested carbohydrate in the lower GI tract. If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced. Elevated Serum Transaminase Levels See PRECAUTIONS. Other Abnormal Laboratory Findings Small reductions in hematocrit occurred more often in PRECOSE-treated patients than in placebo-treated patients but were not associated with reductions in hemoglobin. Low serum calcium and low plasma vitamin B6 levels were associated with PRECOSE therapy but are thought to be either spurious or of no clinical significance. Postmarketing Adverse Event Reports Additional adverse events reported from worldwide postmarketing experience include fulminant hepatitis with fatal outcome, hypersensitive skin reactions (for example rash, erythema, exanthema and uticaria), edema, ileus/subileus, jaundice and/or hepatitis and associated liver damage, thrombocytopenia, and pneumatosis cystoides intestinalis (see PRECAUTIONS). Pneumatosis Cystoides Intestinalis There have been rare postmarketing reports of pneumatosis cystoides intestinalis associated with the use of alpha-glucosidase inhibitors, including Precose. Pneumatosis cystoides intestinalis may present with symptoms of diarrhea, mucus discharge, rectal bleeding, and constipation. Complications may include pneumoperitoneum, volvulus, intestinal obstruction, intussusception, intestinal hemorrhage, and intestinal perforation. If pneumatosis cystoides intestinalis is suspected, discontinue Precose and perform the appropriate diagnostic imaging. DRUG INTERACTIONS Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel-blocking drugs, and isoniazid. When such drugs are administered to a patient receiving PRECOSE, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from patients receiving PRECOSE in combination with sulfonylureas or insulin, patients should be observed closely for any evidence of hypoglycemia. Patients Receiving Sulfonylureas or Insulin: Sulfonylurea agents or insulin may cause hypoglycemia. PRECOSE given in combination with a sulfonylurea or insulin may cause a further lowering of blood glucose and may increase the potential for hypoglycemia. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made. Very rarely, individual cases of hypoglycemic shock have been reported in patients receiving PRECOSE therapy in combination with sulfonylureas and/or insulin. Intestinal adsorbents (for example, charcoal) and digestive enzyme preparations containing carbohydrate-splitting enzymes (for example, amylase, pancreatin) may reduce the effect of PRECOSE and should not be taken concomitantly. PRECOSE has been shown to change the bioavailability of digoxin when they are coadministered, which may require digoxin dose adjustment. (See CLINICAL PHARMACOLOGY, Drug-Drug Interactions.)"" }, ""249"": { ""property.id"": 249, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Warnings & Precautions"", ""property.value"": ""WARNINGS No information provided PRECAUTIONS General Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with PRECOSE or any other anti-diabetic drug. Hypoglycemia Because of its mechanism of action, PRECOSE when administered alone should not cause hypoglycemia in the fasted or postprandial state. Sulfonylurea agents or insulin may cause hypoglycemia. Because PRECOSE given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose, it may increase the potential for hypoglycemia. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, and no increased incidence of hypoglycemia was observed in patients when PRECOSE was added to metformin therapy. Oral glucose (dextrose), whose absorption is not inhibited by PRECOSE, should be used instead of sucrose (cane sugar) in the treatment of mild to moderate hypoglycemia. Sucrose, whose hydrolysis to glucose and fructose is inhibited by PRECOSE, is unsuitable for the rapid correction of hypoglycemia. Severe hypoglycemia may require the use of either intravenous glucose infusion or glucagon injection. Elevated Serum Transaminase Levels In long-term studies (up to 12 months, and including PRECOSE doses up to 300 mg t.i.d.) conducted in the United States, treatment-emergent elevations of serum transaminases (AST and/or ALT) above the upper limit of normal (ULN), greater than 1.8 times the ULN, and greater than 3 times the ULN occurred in 14%, 6%, and 3%, respectively, of PRECOSE-treated patients as compared to 7%, 2%, and 1%, respectively, of placebo-treated patients. Although these differences between treatments were statistically significant, these elevations were asymptomatic, reversible, more common in females, and, in general, were not associated with other evidence of liver dysfunction. In addition, these serum transaminase elevations appeared to be dose related. In US studies including PRECOSE doses up to the maximum approved dose of 100 mg t.i.d., treatment-emergent elevations of AST and/or ALT at any level of severity were similar between PRECOSE-treated patients and placebo-treated patients (p ≥ 0.496). In approximately 3 million patient-years of international postmarketing experience with PRECOSE, 62 cases of serum transaminase elevations > 500 IU/L (29 of which were associated with jaundice) have been reported. Forty-one of these 62 patients received treatment with 100 mg t.i.d. or greater and 33 of 45 patients for whom weight was reported weighed < 60 kg. In the 59 cases where follow-up was recorded, hepatic abnormalities improved or resolved upon discontinuation of PRECOSE in 55 and were unchanged in two. Cases of fulminant hepatitis with fatal outcome have been reported; the relationship to acarbose is unclear. Loss of Control of Blood Glucose When diabetic patients are exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of control of blood glucose may occur. At such times, temporary insulin therapy may be necessary. Laboratory Tests Therapeutic response to PRECOSE should be monitored by periodic blood glucose tests. Measurement of glycosylated hemoglobin levels is recommended for the monitoring of long-term glycemic control. PRECOSE, particularly at doses in excess of 50 mg t.i.d., may give rise to elevations of serum transaminases and, in rare instances, hyperbilirubinemia. It is recommended that serum transaminase levels be checked every 3 months during the first year of treatment with PRECOSE and periodically thereafter. If elevated transaminases are observed, a reduction in dosage or withdrawal of therapy may be indicated, particularly if the elevations persist. Renal Impairment Plasma concentrations of PRECOSE in renally impaired volunteers were proportionally increased relative to the degree of renal dysfunction. Long-term clinical trials in diabetic patients with significant renal dysfunction (serum creatinine > 2.0 mg/dL) have not been conducted. Therefore, treatment of these patients with PRECOSE is not recommended. Carcinogenesis, Mutagenesis, and Impairment of Fertility Eight carcinogenicity studies were conducted with acarbose. Six studies were performed in rats (two strains, Sprague-Dawley and Wistar) and two studies were performed in hamsters. In the first rat study, Sprague-Dawley rats received acarbose in feed at high doses (up to approximately 500 mg/kg body weight) for 104 weeks. Acarbose treatment resulted in a significant increase in the incidence of renal tumors (adenomas and adenocarcinomas) and benign Leydig cell tumors. This study was repeated with a similar outcome. Further studies were performed to separate direct carcinogenic effects of acarbose from indirect effects resulting from the carbohydrate malnutrition induced by the large doses of acarbose employed in the studies. In one study using Sprague-Dawley rats, acarbose was mixed with feed but carbohydrate deprivation was prevented by the addition of glucose to the diet. In a 26-month study of Sprague-Dawley rats, acarbose was administered by daily postprandial gavage so as to avoid the pharmacologic effects of the drug. In both of these studies, the increased incidence of renal tumors found in the original studies did not occur. Acarbose was also given in food and by postprandial gavage in two separate studies in Wistar rats. No increased incidence of renal tumors was found in either of these Wistar rat studies. In two feeding studies of hamsters, with and without glucose supplementation, there was also no evidence of carcinogenicity. Acarbose did not induce any DNA damage in vitro in the CHO chromosomal aberration assay, bacterial mutagenesis (Ames) assay, or a DNA binding assay. In vivo, no DNA damage was detected in the dominant lethal test in male mice, or the mouse micronucleus test. Fertility studies conducted in rats after oral administration produced no untoward effect on fertility or on the overall capability to reproduce. Pregnancy Teratogenic Effects: Pregnancy Category B. The safety of PRECOSE in pregnant women has not been established. Reproduction studies have been performed in rats at doses up to 480 mg/kg (corresponding to 9 times the exposure in humans, based on drug blood levels) and have revealed no evidence of impaired fertility or harm to the fetus due to acarbose. In rabbits, reduced maternal body weight gain, probably the result of the pharmacodynamic activity of high doses of acarbose in the intestines, may have been responsible for a slight increase in the number of embryonic losses. However, rabbits given 160 mg/kg acarbose (corresponding to 10 times the dose in man, based on body surface area) showed no evidence of embryotoxicity and there was no evidence of teratogenicity at a dose 32 times the dose in man (based on body surface area). There are, however, no adequate and well-controlled studies of PRECOSE in pregnant women. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed. Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies as well as increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Nursing Mothers A small amount of radioactivity has been found in the milk of lactating rats after administration of radiolabeled acarbose. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, PRECOSE should not be administered to a nursing woman. Pediatric Use Safety and effectiveness of PRECOSE in pediatric patients have not been established. Geriatric Use Of the total number of subjects in clinical studies of PRECOSE in the United States, 27% were 65 and over, while 4% were 75 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant."" }, ""250"": { ""property.id"": 250, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Overdosage & Contraindications"", ""property.value"": ""OVERDOSE Unlike sulfonylureas or insulin, an overdose of PRECOSE will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdominal discomfort which shortly subside. In cases of overdosage the patient should not be given drinks or meals containing carbohydrates (polysaccharides, oligosaccharides and disaccharides) for the next 4–6 hours. CONTRAINDICATIONS PRECOSE is contraindicated in patients with known hypersensitivity to the drug. Precose is contraindicated in patients with diabetic ketoacidosis or cirrhosis. PRECOSE is also contraindicated in patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed to intestinal obstruction. In addition, PRECOSE is contraindicated in patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption and in patients who have conditions that may deteriorate as a result of increased gas formation in the intestine."" }, ""251"": { ""property.id"": 251, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Clinical Pharmacology"", ""property.value"": ""CLINICAL PHARMACOLOGY Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, PRECOSE reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time. Mechanism of Action In contrast to sulfonylureas, PRECOSE does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia. Because its mechanism of action is different, the effect of PRECOSE to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance. Pharmacokinetics Absorption In a study of 6 healthy men, less than 2% of an oral dose of acarbose was absorbed as active drug, while approximately 35% of total radioactivity from a 14C-labeled oral dose was absorbed. An average of 51% of an oral dose was excreted in the feces as unabsorbed drug-related radioactivity within 96 hours of ingestion. Because acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound is therapeutically desired. Following oral dosing of healthy volunteers with 14C-labeled acarbose, peak plasma concentrations of radioactivity were attained 14–24 hours after dosing, while peak plasma concentrations of active drug were attained at approximately 1 hour. The delayed absorption of acarbose-related radioactivity reflects the absorption of metabolites that may be formed by either intestinal bacteria or intestinal enzymatic hydrolysis. Metabolism Acarbose is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. A fraction of these metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. At least 13 metabolites have been separated chromatographically from urine specimens. The major metabolites have been identified as 4-methylpyrogallol derivatives (that is, sulfate, methyl, and glucuronide conjugates). One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity. This metabolite, together with the parent compound, recovered from the urine, accounts for less than 2% of the total administered dose. Excretion The fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. When acarbose was given intravenously, 89% of the dose was recovered in the urine as active drug within 48 hours. In contrast, less than 2% of an oral dose was recovered in the urine as active (that is, parent compound and active metabolite) drug. This is consistent with the low bioavailability of the parent drug. The plasma elimination half-life of acarbose activity is approximately 2 hours in healthy volunteers. Consequently, drug accumulation does not occur with three times a day (t.i.d.) oral dosing. Special Populations The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant. Patients with severe renal impairment (Clcr < 25 mL/min/1.73m²) attained about 5 times higher peak plasma concentrations of acarbose and 6 times larger AUCs than volunteers with normal renal function. No studies of acarbose pharmacokinetic parameters according to race have been performed. In U.S. controlled clinical studies of PRECOSE in patients with type 2 diabetes mellitus, reductions in glycosylated hemoglobin levels were similar in Caucasians (n=478) and African-Americans (n=167), with a trend toward a better response in Latinos (n=132). Drug-Drug Interactions Studies in healthy volunteers have shown that PRECOSE has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. PRECOSE did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. PRECOSE may affect digoxin bioavailability and may require dose adjustment of digoxin by 16% (90% confidence interval: 8-23%), decrease mean Cmax of digoxin by 26% (90% confidence interval: 16–34%) and decreases mean trough concentrations of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). (See PRECAUTIONS: DRUG INTERACTIONS.) The amount of metformin absorbed while taking PRECOSE was bioequivalent to the amount absorbed when taking placebo, as indicated by the plasma AUC values. However, the peak plasma level of metformin was reduced by approximately 20% when taking PRECOSE due to a slight delay in the absorption of metformin. There is little if any clinically significant interaction between PRECOSE and metformin. Clinical Trials Clinical Experience from Dose Finding Studies in Type 2 Diabetes Mellitus Patients on Dietary Treatment Only Results from six controlled, fixed-dose, monotherapy studies of PRECOSE in the treatment of type 2 diabetes mellitus, involving 769 PRECOSE-treated patients, were combined and a weighted average of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) was calculated for each dose level as presented below: Table 1 Mean Placebo-Subtracted Change in HbA1c in Fixed-Dose Monotherapy Studies Dose of PRECOSE* N Change in HbA1c % p-Value 25 mg t.i.d. 110 -0.44 0.0307 50 mg t.i.d. 131 -0.77 0.0001 100 mg t.i.d. 244 -0.74 0.0001 200 mg t.i.d.** 231 -0.86 0.0001 300 mg t.i.d.** 53 -1 0.0001 * PRECOSE was statistically significantly different from placebo at all doses. Although there were no statistically significant differences among the mean results for doses ranging from 50 to 300 mg t.i.d., some patients may derive benefit by increasing the dosage from 50 to 100 mg t.i.d. Although studies utilized a maximum dose of 200 or 300 mg t.i.d., the maximum recommended dose for patients < 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d. Results from these six fixed-dose, monotherapy studies were also combined to derive a weighted average of the difference from placebo in mean change from baseline for one-hour postprandial plasma glucose levels as shown in the following figure: Figure 1 * PRECOSE was statistically significantly different from placebo at all doses with respect to effect on one-hour postprandial plasma glucose. **The 300 mg t.i.d. PRECOSE regimen was superior to lower doses, but there were no statistically significant differences from 50 to 200 mg t.i.d. Clinical Experience in Type 2 Diabetes Mellitus Patients on Monotherapy, or in Combination with Sulfonylureas, Metformin or Insulin PRECOSE was studied as monotherapy and as combination therapy to sulfonylurea, metformin, or insulin treatment. The treatment effects on HbA1c levels and one-hour postprandial glucose levels are summarized for four placebo-controlled, double-blind, randomized studies conducted in the United States in Tables 2 and 3, respectively. The placebo-subtracted treatment differences, which are summarized below, were statistically significant for both variables in all of these studies. Study 1 (n=109) involved patients on background treatment with diet only. The mean effect of the addition of PRECOSE to diet therapy was a change in HbA1c of -0.78%, and an improvement of one-hour postprandial glucose of -74.4 mg/dL. In Study 2 (n=137), the mean effect of the addition of PRECOSE to maximum sulfonylurea therapy was a change in HbA1c of -0.54%, and an improvement of one-hour postprandial glucose of -33.5 mg/dL. In Study 3 (n=147), the mean effect of the addition of PRECOSE to maximum metformin therapy was a change in HbA1c of -0.65%, and an improvement of one-hour postprandial glucose of -34.3 mg/dL. Study 4 (n=145) demonstrated that PRECOSE added to patients on background treatment with insulin resulted in a mean change in HbA1c of -0.69%, and an improvement of one-hour postprandial glucose of -36.0 mg/dL. A one year study of PRECOSE as monotherapy or in combination with sulfonylurea, metformin or insulin treatment was conducted in Canada in which 316 patients were included in the primary efficacy analysis (Figure 2). In the diet, sulfonylurea and metformin groups, the mean decrease in HbA1c produced by the addition of PRECOSE was statistically significant at six months, and this effect was persistent at one year. In the PRECOSE-treated patients on insulin, there was a statistically significant reduction in HbA1c at six months, and a trend for a reduction at one year. Table 2: Effect of Precose on HbA1c Study Treatment HbA1c (%)a p-Value Mean Baseline Mean change from baselineb Treatment Difference 1 Placebo Plus Diet 8.67 0.33 — — PRECOSE 100 mg t.i.d. Plus Diet 8.69 -0.45 -0.78 0.0001 2 Placebo Plus SFUc 9.56 0.24 — — PRECOSE 50–300d mg t.i.d. Plus SFUc 9.64 -0.3 -0.54 0.0096 3 Placebo Plus Metformine 8.17 +0.08 g — — PRECOSE 50–100 mg t.i.d. Plus Metformine 8.46 -0.57 g -0.65 0.0001 4 Placebo Plus Insulinf 8.69 0.11 — — PRECOSE 50–100 mg t.i.d. Plus Insulinf 8.77 -0.58 -0.69 0.0001 aHbA1c Normal Range: 4–6% bAfter four months treatment in Study 1, and six months in Studies 2, 3, and 4 cSFU, sulfonylurea, maximum dose dAlthough studies utilized a maximum dose of up to 300 mg t.i.d., the maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d. eMetformin dosed at 2000 mg/day or 2500 mg/day fMean dose of insulin 61 U/day gResults are adjusted to a common baseline of 8.33% Table 3: Effect of Precose on Postprandial Glucose Study Treatment One-Hour Postprandial Glucose (mg/dL) p-Value Mean Baseline Mean change from baselinea Treatment Difference 1 Placebo Plus Diet 297.1 31.8 — — PRECOSE 100 mg t.i.d. Plus Diet 299.1 -42.6 -74.4 0.0001 2 Placebo Plus SFUb 308.6 6.2 — — PRECOSE 50–300c mg t.i.d. Plus SFUb 311.1 -27.3 -33.5 0.0017 3 Placebo Plus Metformind 263.9 +3.3f — — PRECOSE 50–100 mg t.i.d. Plus Metformind 283 -31.0f -34.3 0.0001 4 Placebo Plus Insuline 279.2 8 — — PRECOSE 50–100 mg t.i.d. Plus Insuline 277.8 -28 -36 0.0178 aAfter four months treatment in Study 1, and six months in Studies 2, 3, and 4 bSFU, sulfonylurea, maximum dose cAlthough studies utilized a maximum dose of up to 300 mg t.i.d., the maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d.; the maximum recommended dose for patients > 60 kg is 100 mg t.i.d. dMetformin dosed at 2000 mg/day or 2500 mg/day eMean dose of insulin 61 U/day fResults are adjusted to a common baseline of 273 mg/dL Figure 2 Figure 2: Effects of PRECOSE (III ) and Placebo ( III ) on mean change in HbA1c levels from baseline throughout a one-year study in patients with type 2 diabetes mellitus when used in combination with: (A) diet alone; (B) sulfonylurea; (C) metformin; or (D) insulin. Treatment differences at 6 and 12 months were tested: * p < 0.01; # p = 0.077."" }, ""252"": { ""property.id"": 252, ""property.ts"": ""2017-12-04 04:41:13"", ""property.key"": ""Medication Guide"", ""property.value"": ""PATIENT INFORMATION Patients should be told to take PRECOSE orally three times a day at the start (with the first bite) of each main meal. It is important that patients continue to adhere to dietary instructions, a regular exercise program, and regular testing of urine and/or blood glucose. PRECOSE itself does not cause hypoglycemia even when administered to patients in the fasted state. Sulfonylurea drugs and insulin, however, can lower blood sugar levels enough to cause symptoms or sometimes life-threatening hypoglycemia. Because PRECOSE given in combination with a sulfonylurea or insulin will cause a further lowering of blood sugar, it may increase the hypoglycemic potential of these agents. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, and no increased incidence of hypoglycemia was observed in patients when PRECOSE was added to metformin therapy. The risk of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be well understood by patients and responsible family members. Because PRECOSE prevents the breakdown of table sugar, patients should have a readily available source of glucose (dextrose, D-glucose) to treat symptoms of low blood sugar when taking PRECOSE in combination with a sulfonylurea or insulin. If side effects occur with PRECOSE, they usually develop during the first few weeks of therapy. They are most commonly mild-to-moderate gastrointestinal effects, such as flatulence, diarrhea, or abdominal discomfort, and generally diminish in frequency and intensity with time."" } }" 40,"2017-08-31 23:12:57",Acarbose,Precose,Multum,"{ ""40"": { ""alphabet_x_drug.id"": 40, ""alphabet.id"": 1, ""alphabet.ts"": ""2017-08-31 22:18:43"", ""alphabet.title"": ""A"" } }","{ ""253"": { ""property.id"": 253, ""property.ts"": ""2017-12-04 04:41:15"", ""property.key"": ""Precose Patient Information Including Side Effects"", ""property.value"": ""Find Lowest Prices on Brand Names: Precose Generic Name: acarbose (Pronunciation: ah KAR bose) What is acarbose (Precose)? What are the possible side effects of acarbose (Precose)? What is the most important information I should know about acarbose (Precose)? What should I discuss with my healthcare provider before taking acarbose (Precose)? How should I take acarbose (Precose)? What happens if I miss a dose (Precose)? What happens if I overdose (Precose)? What should I avoid while taking acarbose (Precose)? What other drugs will affect acarbose (Precose)? Where can I get more information? What is acarbose (Precose)? Acarbose slows the digestion of carbohydrates in the body, which helps control blood sugar levels.Acarbose is used to treat type 2 diabetes. Acarbose is sometimes used in combination with insulin or other diabetes medications you take by mouth.Acarbose may also be used for purposes not listed in this medication guide. What are the possible side effects of acarbose (Precose)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Call your doctor at once if you have a serious side effect such as:severe stomach pain, severe constipation;diarrhea that is watery or bloody;easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin; ornausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).Less serious side effects may include:mild stomach pain, gas, bloating;mild diarrhea; ormild skin rash or itching.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about acarbose (Precose)? Do not use this medication if you are allergic to acarbose, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin). You also should not use acarbose if you have inflammatory bowel disease, an ulcer or blockage in your intestines, or cirrhosis of the liver.Before taking acarbose, tell your doctor if you have liver disease, or any type of stomach or intestinal disorder.Take acarbose with the first bite of a main meal, unless your doctor tells you otherwise.Your medication needs may change if you become sick or injured, if you have a serious infection, or if you have any type of surgery. Do not change your dose or stop taking acarbose without first talking to your doctor.If you take acarbose with insulin or other diabetes medications, your blood sugar could get too low. Low blood sugar (hypoglycemia) can occur if you skip a meal, exercise too long, drink alcohol, or are under stress. Symptoms include headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating. Carry hard candy or glucose tablets with you in case you have low blood sugar. Other sugar sources include orange juice and milk. Be sure your family and close friends know how to help you in an emergency.Acarbose is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels."" }, ""254"": { ""property.id"": 254, ""property.ts"": ""2017-12-04 04:41:15"", ""property.key"": ""Precose Patient Information including How Should I Take"", ""property.value"": ""What should I discuss with my healthcare provider before taking acarbose (Precose)? Do not use this medication if you are allergic to acarbose, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin). You also should not use acarbose if you have:inflammatory bowel disease;a blockage in your intestines;a digestive disorder affecting your intestines;intestinal ulcer (of your colon); orcirrhosis of the liver.To make sure you can safely take acarbose, tell your doctor if you have any of these other conditions:liver disease; ora bowel or intestinal disorder; ora stomach disorder.FDA pregnancy category B. Acarbose is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.It is not known whether acarbose passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using acarbose. How should I take acarbose (Precose)? Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.Take acarbose with the first bite of a main meal, unless your doctor tells you otherwise.Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office. Visit your doctor regularly.If you take acarbose with insulin or other diabetes medications, your blood sugar could get too low. Low blood sugar (hypoglycemia) can occur if you skip a meal, exercise too long, drink alcohol, or are under stress. Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating.Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection. Be sure your family and close friends know how to help you in an emergency.Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change. Your doctor may want you to stop taking acarbose for a short time if you become ill, have a fever or infection, or if you have surgery or a medical emergency. Ask your doctor how to adjust your acarbose dose if needed. Do not change your medication dose or schedule without your doctor's advice.Acarbose is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use."" }, ""255"": { ""property.id"": 255, ""property.ts"": ""2017-12-04 04:41:15"", ""property.key"": ""Precose Patient Information including If I Miss a Dose"", ""property.value"": """" } }"