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drug.id | drug.ts | drug.title | drug.alias | drug.az_source | drug.alphabet_x_drug_id | drug.property_id |
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41 | 2017-08-31 23:12:57 | Accolate | Zafirlukast | FDA | { "41": { "alphabet_x_drug.id": 41, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"256": {
"property.id": 256,
"property.ts": "2017-12-04 04:41:27",
"property.key": "Drug Description",
"property.value": "Find Lowest Prices on ACCOLATE® (zafirlukast) Tablets DESCRIPTION Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA), with the chemical name 4-(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-N-otolylsulfonylbenzamide. The molecular weight of zafirlukast is 575.7 and the structural formula is: The empirical formula is: C31H33N3O6S Zafirlukast, a fine white to pale yellow amorphous powder, is practically insoluble in water. It is slightly soluble in methanol and freely soluble in tetrahydrofuran, dimethylsulfoxide, and acetone. ACCOLATE is supplied as 10 and 20 mg tablets for oral administration. Inactive Ingredients Film-coated tablets containing croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide."
},
"257": {
"property.id": 257,
"property.ts": "2017-12-04 04:41:27",
"property.key": "Indications & Dosage",
"property.value": "INDICATIONS ACCOLATE is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older. DOSAGE AND ADMINISTRATION Because food can reduce the bioavailability of zafirlukast, ACCOLATE should be taken at least 1 hour before or 2 hours after meals. Adults and Children 12 years of age and older The recommended dose of ACCOLATE in adults and children 12 years and older is 20 mg twice daily. Pediatric Patients 5 through 11 years of age The recommended dose of ACCOLATE in children 5 through 11 years of age is 10 mg twice daily. Elderly Patients Based on cross-study comparisons, the clearance of zafirlukast is reduced in elderly patients (65 years of age and older), such that Cmax and AUC are approximately twice those of younger adults. In clinical trials, a dose of 20 mg twice daily was not associated with an increase in the overall incidence of adverse events or withdrawals because of adverse events in elderly patients. Patients with Hepatic Impairment ACCOLATE is contraindicated in patients with hepatic impairment including hepatic cirrhosis (see CONTRAINDICATIONS). The clearance of zafirlukast is reduced in patients with stable alcoholic cirrhosis such that the Cmax and AUC are approximately 50 - 60% greater than those of normal adults. ACCOLATE has not been evaluated in patients with hepatitis or in long-term studies of patients with cirrhosis. Patients with Renal Impairment Dosage adjustment is not required for patients with renal impairment. HOW SUPPLIED ACCOLATE 10 mg Tablets, (NDC 0310-0401) white, unflavored, round, biconvex, film-coated, minitablets identified with “ACCOLATE 10” debossed on one side are supplied in opaque HDPE bottles of 60 tablets. ACCOLATE 20 mg Tablets, (NDC 0310-0402) white, round, biconvex, coated tablets identified with “ACCOLATE 20” debossed on one side are supplied in opaque HDPE bottles of 60 tablets. Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Protect from light and moisture. Dispense in the original air-tight container. Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850. Revised: Nov 2013"
},
"258": {
"property.id": 258,
"property.ts": "2017-12-04 04:41:27",
"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS Adults And Children 12 Years Of Age And Older The safety database for ACCOLATE consists of more than 4000 healthy volunteers and patients who received ACCOLATE, of which 1723 were asthmatics enrolled in trials of 13 weeks duration or longer. A total of 671 patients received ACCOLATE for 1 year or longer. The majority of the patients were 18 years of age or older; however, 222 patients between the age of 12 and 18 years received ACCOLATE. A comparison of adverse events reported by ≥ 1% of zafirlukast-treated patients, and at rates numerically greater than in placebo-treated patients, is shown for all trials in the table below. Adverse Event ACCOLATE N=4058 PLACEBO N=2032 Headache 12.9% 11.7% Infection 3.5% 3.4% Nausea 3.1% 2.0% Diarrhea 2.8% 2.1% Pain (generalized) 1.9% 1.7% Asthenia 1.8% 1.6% Abdominal Pain 1.8% 1.1% Accidental Injury 1.6% 1.5% Dizziness 1.6% 1.5% Myalgia 1.6% 1.5% Fever 1.6% 1.1% Back Pain 1.5% 1.2% Vomiting 1.5% 1.1% SGPT Elevation 1.5% 1.1% Dyspepsia 1.3% 1.2% The frequency of less common adverse events was comparable between ACCOLATE and placebo. Rarely, elevations of one or more liver enzymes have occurred in patients receiving ACCOLATE in controlled clinical trials. In clinical trials, most of these have been observed at doses four times higher than the recommended dose. The following hepatic events (which have occurred predominantly in females) have been reported from postmarketing adverse event surveillance of patients who have received the recommended dose of ACCOLATE (40 mg/day): cases of symptomatic hepatitis (with or without hyperbilirubinemia) without other attributable cause; and rarely, hyperbilirubinemia without other elevated liver function tests. In most, but not all postmarketing reports, the patient's symptoms abated and the liver enzymes returned to normal or near normal after stopping ACCOLATE. In rare cases, patients have presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death (see WARNINGS, Hepatotoxicity and PRECAUTIONS, PATIENT INFORMATION). In clinical trials, an increased proportion of zafirlukast patients over the age of 55 years reported infections as compared to placebo-treated patients. A similar finding was not observed in other age groups studied. These infections were mostly mild or moderate in intensity and predominantly affected the respiratory tract. Infections occurred equally in both sexes, were dose-proportional to total milligrams of zafirlukast exposure, and were associated with coadministration of inhaled corticosteroids. The clinical significance of this finding is unknown. In rare cases, patients with asthma on ACCOLATE may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that ACCOLATE may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (see PRECAUTIONS, Eosinophilic Conditions). Neuropsychiatric adverse events, including insomnia and depression, have been reported in association with ACCOLATE therapy (see PRECAUTIONS, Neuropsychiatric Events). Hypersensitivity reactions, including urticaria, angioedema and rashes, with or without blistering, have also been reported in association with ACCOLATE therapy. Additionally, there have been reports of patients experiencing agranulocytosis, bleeding, bruising, or edema, arthralgia, myalgia, malaise, and pruritus in association with ACCOLATE therapy. Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of ACCOLATE to an existing theophylline regimen have been reported. The mechanism of the interaction between ACCOLATE and theophylline in these patients is unknown and not predicted by available in vitro metabolism data and the results of two clinical drug interaction studies (see CLINICAL PHARMACOLOGY and PRECAUTIONS: DRUG INTERACTIONS). Pediatric Patients 5 Through 11 Years Of Age ACCOLATE has been evaluated for safety in 788 pediatric patients 5 through 11 years of age. Cumulatively, 313 pediatric patients were treated with ACCOLATE 10 mg twice daily or higher for at least 6 months, and 113 of them were treated for one year or longer in clinical trials. The safety profile of ACCOLATE 10 mg twice daily-versus placebo in the 4- and 6-week double-blind trials was generally similar to that observed in the adult clinical trials with ACCOLATE 20 mg twice daily. In pediatric patients receiving ACCOLATE in multi-dose clinical trials, the following events occurred with a frequency of ≥ 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: headache (4.5 vs. 4.2%) and abdominal pain (2.8 vs. 2.3%). The post-marketing experience in this age group is similar to that seen in adults, including hepatic dysfunction, which may lead to liver failure. DRUG INTERACTIONS In a drug interaction study in 16 healthy male volunteers, coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin resulted in a significant increase in the mean AUC (+ 63%) and half-life (+36%) of S-warfarin. The mean prothrombin time (PT) increased by approximately 35%. This interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system. Patients on oral warfarin anticoagulant therapy and ACCOLATE should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see WARNINGS, Concomitant Warfarin Administration). No formal drug-drug interaction studies with ACCOLATE and other drugs known to be metabolized by the cytochrome P450 2C9 isoenzyme (eg, tolbutamide, phenytoin, carbamazepine) have been conducted; however, care should be exercised when ACCOLATE is coadministered with these drugs. In a drug interaction study in 11 asthmatic patients, coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state resulted in decreased mean plasma levels of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability. Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline. Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients, 18 to 44 years of age, resulted in decreased mean plasma levels of zafirlukast by approximately 30%, but no effect on plasma theophylline levels was observed. Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of ACCOLATE to an existing theophylline regimen have been reported. The mechanism of the interaction between ACCOLATE and theophylline in these patients is unknown (see ADVERSE REACTIONS). Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma levels of zafirlukast by approximately 45%. In a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, 40 mg twice daily of zafirlukast had no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy. Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by approximately 58% (90% CI:28, 95). The clinical significance of this interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors. Coadministration of zafirlukast with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast. No other formal drug-drug interaction studies between ACCOLATE and marketed drugs known to be metabolized by the P450 3A4 (CYP3A4) isoenzyme (eg, dihydropyridine calcium-channel blockers, cyclosporin, cisapride) have been conducted. As ACCOLATE is known to be an inhibitor of CYP3A4 in vitro, it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with ACCOLATE."
},
"259": {
"property.id": 259,
"property.ts": "2017-12-04 04:41:27",
"property.key": "Warnings & Precautions",
"property.value": "WARNINGS Hepatotoxicity Cases of life-threatening hepatic failure have been reported in patients treated with ACCOLATE. Cases of liver injury without other attributable cause have been reported from post-marketing adverse event surveillance of patients who have received the recommended dose of ACCOLATE (40 mg/day). In most, but not all post-marketing reports, the patient's symptoms abated and the liver enzymes returned to normal or near normal after stopping ACCOLATE. In rare cases, patients have either presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death. In extremely rare postmarketing cases, no clinical symptoms or signs suggestive of liver dysfunction were reported to precede the latter observations. Physicians may consider the value of liver function testing. Periodic serum transaminase testing has not proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Patients should be advised to be alert for signs and symptoms of liver dysfunction (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia) and to contact their physician immediately if they occur. Ongoing clinical assessment of patients should govern physician interventions, including diagnostic evaluations and treatment. If liver dysfunction is suspected based upon clinical signs or symptoms (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, anorexia, and enlarged liver), ACCOLATE should be discontinued. Liver function tests, in particular serum ALT, should be measured immediately and the patient managed accordingly. If liver function tests are consistent with hepatic dysfunction, ACCOLATE therapy should not be resumed. Patients in whom ACCOLATE was withdrawn because of hepatic dysfunction where no other attributable cause is identified should not be re-exposed to ACCOLATE (see PRECAUTIONS, PATIENT INFORMATION and ADVERSE REACTIONS). Bronchospasm ACCOLATE is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Therapy with ACCOLATE can be continued during acute exacerbations of asthma. Concomitant Warfarin Administration Coadministration of zafirlukast with warfarin results in a clinically significant increase in prothrombin time (PT). Patients on oral warfarin anticoagulant therapy and ACCOLATE should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see PRECAUTIONS: DRUG INTERACTIONS). PRECAUTIONS Information For Patients Patients should be told that a rare side effect of ACCOLATE is hepatic dysfunction, and to contact their physician immediately if they experience symptoms of hepatic dysfunction (eg. right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia). Liver failure resulting in liver transplantation and death has occurred in patients taking zafirlukast (see WARNINGS, Hepatotoxicity and ADVERSE REACTIONS). ACCOLATE is indicated for the chronic treatment of asthma and should be taken regularly as prescribed, even during symptom-free periods. ACCOLATE is not a bronchodilator and should not be used to treat acute episodes of asthma. Patients receiving ACCOLATE should be instructed not to decrease the dose or stop taking any other antiasthma medications unless instructed by a physician. Patients should be instructed to notify their physician if neuropsychiatric events occur while using ACCOLATE (see PRECAUTIONS, Neuropsychiatric Events). Women who are breast-feeding should be instructed not to take ACCOLATE (see PRECAUTIONS, Nursing Mothers). Alternative antiasthma medication should be considered in such patients. The bioavailability of ACCOLATE may be decreased when taken with food. Patients should be instructed to take ACCOLATE at least 1 hour before or 2 hours after meals. Eosinophilic Conditions In rare cases, patients with asthma on ACCOLATE may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that ACCOLATE may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (see ADVERSE REACTIONS). Neuropsychiatric Events Neuropsychiatric events have been reported in adult, adolescent and pediatric patients taking ACCOLATE. Post-marketing reports with ACCOLATE include insomnia and depression. The clinical details of some post-marketing reports involving ACCOLATE appear consistent with a drug-induced effect. Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with ACCOLATE if such events occur (see ADVERSE REACTIONS). Carcinogenesis, Mutagenesis, Impairment Of Fertility In two-year carcinogenicity studies, zafirlukast was administered at dietary doses of 10, 100, and 300 mg/kg to mice and 40, 400, and 2000 mg/kg to rats. Male mice at an oral dose of 300 mg/kg/day (approximately 30 times the maximum recommended daily oral dose in adults and in children on a mg/m² basis) showed an increased incidence of hepatocellular adenomas; female mice at this dose showed a greater incidence of whole body histocytic sarcomas. Male and female rats at an oral dose of 2000 mg/kg/day (resulting in approximately 160 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma area-under the curve [AUC] values) of zafirlukast showed an increased incidence of urinary bladder transitional cell papillomas. Zafirlukast was not tumorigenic at oral doses up to 100 mg/kg (approximately 10 times the maximum recommended daily oral dose in adults and in children on a mg/m² basis) in mice and at oral doses up to 400 mg/kg (resulting in approximately 140 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma AUC values) in rats. The clinical significance of these findings for the longterm use of ACCOLATE is unknown. Zafirlukast showed no evidence of mutagenic potential in the reverse microbial assay, in 2 forward point mutation (CHO-HGPRT and mouse lymphoma) assays or in two assays for chromosomal aberrations (the in vitro human peripheral blood lymphocyte clastogenic assay and the in vivo rat bone marrow micronucleus assay). No evidence of impairment of fertility and reproduction was seen in male and female rats treated with zafirlukast at oral doses up to 2000 mg/kg (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m² basis). Pregnancy Category B No teratogenicity was observed at oral doses up to 1600 mg/kg/day in mice (approximately 160 times the maximum recommended daily oral dose in adults on a mg/m² basis), up to 2000 mg/kg/day in rats (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m² basis) and up to 2000 mg/kg/day in cynomolgus monkeys (which resulted in approximately 20 times the exposure to drug plus metabolites compared to that from the maximum recommended daily oral dose in adults based on comparison of the AUC values). At an oral dose of 2000 mg/kg/day in rats, maternal toxicity and deaths were seen with increased incidence of early fetal resorption. Spontaneous abortions occurred in cynomolgus monkeys at the maternally toxic oral dose of 2000 mg/kg/day. There are no adequate and well-controlled trials in pregnant women. Because animal reproductive studies are not always predictive of human response, ACCOLATE should be used during pregnancy only if clearly needed. Nursing Mothers Zafirlukast is excreted in breast milk. Following repeated 40 mg twice-a-day dosing in healthy women, average steady-state concentrations of zafirlukast in breast milk were 50 ng/mL compared to 255 ng/mL in plasma. Because of the potential for tumorigenicity shown for zafirlukast in mouse and rat studies and the enhanced sensitivity of neonatal rats and dogs to the adverse effects of zafirlukast, ACCOLATE should not be administered to mothers who are breast-feeding. Pediatric Use The safety of ACCOLATE at doses of 10 mg twice daily has been demonstrated in 205 pediatric patients 5 through 11 years of age in placebo-controlled trials lasting up to six weeks and with 179 patients in this age range participating in 52 weeks of treatment in an open-label extension. The effectiveness of ACCOLATE for the prophylaxis and chronic treatment of asthma in pediatric patients 5 through 11 years of age is based on an extrapolation of the demonstrated efficacy of ACCOLATE in adults with asthma and the likelihood that the disease course, and pathophysiology and the drug's effect are substantially similar between the two populations. The recommended dose for the patients 5 through 11 years of age is based upon a cross-study comparison of the pharmacokinetics of zafirlukast in adults and pediatric subjects, and on the safety profile of zafirlukast in both adult and pediatric patients at doses equal to or higher than the recommended dose. The safety and effectiveness of zafirlukast for pediatric patients less than 5 years of age has not been established. The effect of ACCOLATE on growth in children has not been determined. Geriatric Use Based on cross-study comparison, the clearance of zafirlukast is reduced in patients 65 years of age and older such that Cmax and AUC are approximately 2- to 3-fold greater than those of younger patients (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY). A total of 8094 patients were exposed to zafirlukast in North American and European short-term placebocontrolled clinical trials. Of these, 243 patients were elderly (age 65 years and older). No overall difference in adverse events was seen in the elderly patients, except for an increase in the frequency of infections among zafirlukast-treated elderly patients compared to placebo-treated elderly patients (7.0% vs. 2.9%). The infections were not severe, occurred mostly in the lower respiratory tract, and did not necessitate withdrawal of therapy. An open-label, uncontrolled, 4-week trial of 3759 asthma patients compared the safety and efficacy of ACCOLATE 20 mg given twice daily in three patient age groups, adolescents (12-17 years), adults (18- 65 years), and elderly (greater than 65 years). A higher percentage of elderly patients (n=384) reported adverse events when compared to adults and adolescents. These elderly patients showed less improvement in efficacy measures. In the elderly patients, adverse events occurring in greater than 1% of the population included headache (4.7%), diarrhea and nausea (1.8%), and pharyngitis (1.3%). The elderly reported the lowest percentage of infections of all three age groups in this study."
},
"260": {
"property.id": 260,
"property.ts": "2017-12-04 04:41:27",
"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE No deaths occurred at oral zafirlukast doses of 2000 mg/kg in mice (approximately 210 times the maximum recommended daily oral dose in adults and children on a mg/m² basis), 2000 mg/kg in rats (approximately 420 times the maximum recommended daily oral dose in adults and children on a mg/m² basis), and 500 mg/kg in dogs (approximately 350 times the maximum recommended daily oral dose in adults and children on a mg/m² basis). Overdosage with ACCOLATE has been reported in four patients surviving reported doses as high as 200 mg. The predominant symptoms reported following ACCOLATE overdose were rash and upset stomach. There were no acute toxic effects in humans that could be consistently ascribed to the administration of ACCOLATE. It is reasonable to employ the usual supportive measures in the event of an overdose; eg, remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required. CONTRAINDICATIONS ACCOLATE is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients. ACCOLATE is contraindicated in patients with hepatic impairment including hepatic cirrhosis."
},
"261": {
"property.id": 261,
"property.ts": "2017-12-04 04:41:27",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Mechanism Of Action Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Patients with asthma were found in one study to be 25- 100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. Inhalational challenge studies in sensitized sheep showed that zafirlukast suppressed the airway responses to antigen; this included both the early- and late-phase response and the nonspecific hyperresponsiveness. In humans, zafirlukast inhibited bronchoconstriction caused by several kinds of inhalational challenges. Pretreatment with single oral doses of zafirlukast inhibited the bronchoconstriction caused by sulfur dioxide and cold air in patients with asthma. Pretreatment with single doses of zafirlukast attenuated the early- and late-phase reaction caused by inhalation of various antigens such as grass, cat dander, ragweed, and mixed antigens in patients with asthma. Zafirlukast also attenuated the increase in bronchial hyperresponsiveness to inhaled histamine that followed inhaled allergen challenge. Clinical Pharmacokinetics And Bioavailability Absorption Zafirlukast is rapidly absorbed following oral administration. Peak plasma concentrations are generally achieved 3 hours after oral administration. The absolute bioavailability of zafirlukast is unknown. In two separate studies, one using a high fat and the other a high protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%. Distribution Zafirlukast is more than 99% bound to plasma proteins, predominantly albumin. The degree of binding was independent of concentration in the clinically relevant range. The apparent steady-state volume of distribution (Vss/F) is approximately 70 L, suggesting moderate distribution into tissues. Studies in rats using radiolabeled zafirlukast indicate minimal distribution across the blood-brain barrier. Metabolism Zafirlukast is extensively metabolized. The most common metabolic products are hydroxylated metabolites which are excreted in the feces. The metabolites of zafirlukast identified in plasma are at least 90 times less potent as LTD4 receptor antagonists than zafirlukast in a standard in vitro test of activity. In vitro studies using human liver microsomes showed that the hydroxylated metabolites of zafirlukast excreted in the feces are formed through the cytochrome P450 2C9 (CYP2C9) pathway. Additional in vitro studies utilizing human liver microsomes show that zafirlukast inhibits the cytochrome P450 CYP3A4 and CYP2C9 isoenzymes at concentrations close to the clinically achieved total plasma concentrations (see DRUG INTERACTIONS). Excretion The apparent oral clearance (CL/f) of zafirlukast is approximately 20 L/h. Studies in the rat and dog suggest that biliary excretion is the primary route of excretion. Following oral administration of radiolabeled zafirlukast to volunteers, urinary excretion accounts for approximately 10% of the dose and the remainder is excreted in feces. Zafirlukast is not detected in urine. In the pivotal bioequivalence study, the mean terminal half-life of zafirlukast is approximately 10 hours in both normal adult subjects and patients with asthma. In other studies, the mean plasma half-life of zafirlukast ranged from approximately 8 to 16 hours in both normal subjects and patients with asthma. The pharmacokinetics of zafirlukast are approximately linear over the range from 5 mg to 80 mg. Steadystate plasma concentrations of zafirlukast are proportional to the dose and predictable from single-dose pharmacokinetic data. Accumulation of zafirlukast in the plasma following twice-daily dosing is approximately 45%. The pharmacokinetic parameters of zafirlukast 20 mg administered as a single dose to 36 male volunteers are shown with the table below. Mean (% Coefficient of Variation) pharmacokinetic parameters of zafirlukast following single 20 mg oral dose administration to male volunteers (n=36) Cmax ng/ml tmax1 h AUC ng•h/mL t½ h CL/f L/h 326 (31.0) 2 (0.5 - 5.0) 1137(34) 13.3 (75.6) 19.4 (32) 1. Median and range Special Populations Gender: The pharmacokinetics of zafirlukast are similar in males and females. Weight-adjusted apparent oral clearance does not differ due to gender. Race: No differences in the pharmacokinetics of zafirlukast due to race have been observed. Elderly: The apparent oral clearance of zafirlukast decreases with age. In patients above 65 years of age, there is an approximately 2-3 fold greater Cmax and AUC compared to young adult patients. Children: Following administration of a single 20 mg dose of zafirlukast to 20 boys and girls between 7 and 11 years of age, and in a second study, to 29 boys and girls between 5 and 6 years of age, the following pharmacokinetic parameters were obtained: Parameter Children age 5-6 years Mean (% Coefficient of Variation) Children age 7-11 years Mean (% Coefficient of Variation) Cmax (ng/mL) 756 (39%) 601 (45%) AUC (ng•h/mL) 2458 (34%) 2027 (38%) tmax (h) 2.1 (61%) 2.5 (55%) CL/f (L/h) 9.2 (37%) 11.4 (42%) Weight unadjusted apparent clearance was 11.4 L/h (42%) in the 7-11 year old children and 9.2 L/h (37%) in the 5-6 year old children, which resulted in greater systemic drug exposures than that obtained in adults for an identical dose. To maintain similar exposure levels in children compared to adults, a dose of 10 mg twice daily is recommended in children 5-11 years of age (see DOSAGE AND ADMINISTRATION). Zafirlukast disposition was unchanged after multiple dosing (20 mg twice daily) in children and the degree of accumulation in plasma was similar to that observed in adults. Hepatic Insufficiency: In a study of patients with hepatic impairment (biopsy-proven cirrhosis), there was a reduced clearance of zafirlukast resulting in a 50-60% greater Cmax and AUC compared to normal subjects. Renal Insufficiency: Based on a cross-study comparison, there are no apparent differences in the pharmacokinetics of zafirlukast between renally-impaired patients and normal subjects. Drug-Drug Interactions The following drug interaction studies have been conducted with zafirlukast (see PRECAUTIONS: DRUG INTERACTIONS). Coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin (a substrate of CYP2C9) resulted in a significant increase in the mean AUC (+63%) and half-life (+36%) of S-warfarin. The mean prothrombin time increased by approximately 35%. The pharmacokinetics of zafirlukast were unaffected by coadministration with warfarin. Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients, 18 to 44 years of age, resulted in decreased mean plasma concentrations of zafirlukast by approximately 30%, but no effect on plasma theophylline concentrations was observed. Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline. Coadministration of zafirlukast dosed at 40 mg twice daily in a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, resulted in no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy. Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma concentrations of zafirlukast by approximately 45%. Coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state in 11 asthmatic patients resulted in decreased mean plasma concentrations of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability. Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by approximately 58% (90% CI:28, 95). The clinical significance of this interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors. Coadministration of zafirlukast with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast. Clinical Studies Three U.S. double-blind, randomized, placebo-controlled, 13-week clinical trials in 1380 adults and children 12 years of age and older with mild-to-moderate asthma demonstrated that ACCOLATE improved daytime asthma symptoms, nighttime awakenings, mornings with asthma symptoms, rescue beta2-agonist use, FEV1, and morning peak expiratory flow rate. In these studies, the patients had a mean baseline FEV1 of approximately 75% of predicted normal and a mean baseline beta2-agonist requirement of approximately 4-5 puffs of albuterol per day. The results of the largest of the trials are shown in the table below. Mean Change from Baseline at Study End Point ACCOLATE 20 mg twice daily N=514 Placebo N=248 Daytime Asthma symptom score (0-3 scale) -0.441 -0.25 Nightime Awakenings (number per week) -1.271 -0.43 Mornings with Asthma Symptoms (days per week) -1.321 -0.75 Rescue β2-agonist use (puffs per day) -1.151 -0.24 FEV1 (L) +0.151 +0.05 Morning PEFR (L/min) +22.061 +7.63 Evening PEFR (L/min) +13.12 +10.14 1. p < 0.05, compared to placebo In a second and smaller study, the effect of ACCOLATE on most efficacy parameters was comparable to the active control (inhaled cromolyn sodium 1600 mcg four times per day) and superior to placebo at end point for decreasing rescue beta2-agonist use (figure below). In these trials, improvement in asthma symptoms occurred within one week of initiating treatment with ACCOLATE. The role of ACCOLATE in the management of patients with more severe asthma, patients receiving antiasthma therapy other than as-needed, inhaled beta2-agonists, or as an oral or inhaled corticosteroid-sparing agent remains to be fully characterized."
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42 | 2017-08-31 23:12:57 | Accolate | Zafirlukast | Multum | { "42": { "alphabet_x_drug.id": 42, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.value": "Find Lowest Prices on Brand Names: Accolate Generic Name: zafirlukast (Pronunciation: za FIR loo kast) What is zafirlukast (Accolate)? What are the possible side effects of zafirlukast (Accolate)? What is the most important information I should know about zafirlukast (Accolate)? What should I discuss with my healthcare provider before taking zafirlukast (Accolate)? How should I take zafirlukast (Accolate)? What happens if I miss a dose (Accolate)? What happens if I overdose (Accolate)? What should I avoid while taking zafirlukast (Accolate)? What other drugs will affect zafirlukast (Accolate)? Where can I get more information? What is zafirlukast (Accolate)? Zafirlukast is a leukotriene (loo-koe-TRY-een) inhibitor. Leukotrienes are chemicals your body releases when you breathe in an allergen (such as pollen). These chemicals cause swelling in your lungs and tightening of the muscles around your airways, which can result in asthma symptoms.Zafirlukast is used to for chronic treatment of asthma, and to prevent asthma attacks in adults and children as young as 5 years old.Do not give this medication to a child without a doctor's advice.Zafirlukast may also be used for purposes not listed in this medication guide. What are the possible side effects of zafirlukast (Accolate)? 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:worsening asthma symptoms;new or worsening cough, fever, trouble breathing;mood or behavior changes, anxiety, depression, sleep problems (insomnia);skin rash, bruising, severe tingling, numbness, pain, muscle weakness; ornausea, pain in your upper stomach, loss of appetite, flu symptoms, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).Less serious side effects may include:headache;diarrhea, stomach pain;weakness;dizziness;muscle pain; orsore throat, cold symptoms.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 zafirlukast (Accolate)? Zafirlukast will not work fast enough to treat an asthma attack that has already begun. Use only a fast-acting inhalation medicine to treat an asthma attack. Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks.It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after several weeks of treatment.Call your doctor right away if you feel that this medicine is not working as well as usual, or if it makes your condition worse. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor."
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"property.value": "What should I discuss with my healthcare provider before taking zafirlukast (Accolate)? You should not use this medication if you are allergic to zafirlukast, or if you have liver disease (including cirrhosis).To make sure you can safely take zafirlukast, tell your doctor if you have liver disease.The chewable tablet form of this medication may contain up to 0.842 milligrams of phenylalanine. Talk to your doctor before using this form of zafirlukast if you have phenylketonuria (PKU).FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.Zafirlukast can pass into breast milk and may harm a nursing baby. Do not breast-feed while you are taking zafirlukast. How should I take zafirlukast (Accolate)? 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.Zafirlukast is usually taken twice daily. Follow your doctor's instructions.Take zafirlukast on an empty stomach, at least 1 hour before or 2 hours after a meal.Zafirlukast will not work fast enough to treat an asthma attack that has already begun. Use only a fast-acting inhalation medicine to treat an asthma attack. Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks.It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after several weeks of treatment.Asthma is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice, even if you have no asthma symptoms.Call your doctor right away if you feel that this medicine is not working as well as usual, or if it makes your condition worse. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor.Store at room temperature away from moisture and heat."
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43 | 2017-08-31 23:12:57 | Accretropin | Somatropin Injection | FDA | { "43": { "alphabet_x_drug.id": 43, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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44 | 2017-08-31 23:12:57 | AccuNeb | Albuterol Sulfate Inhalation Solution | FDA | { "44": { "alphabet_x_drug.id": 44, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"273": {
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"property.key": "Drug Description",
"property.value": "AccuNeb® (albuterol sulfate) 1.25 mg*/3 mL and 0.63 mg*/3 mL Inhalation Solution *(Potency expressed as albuterol, equivalent to 1.5 mg and 0.75 mg albuterol sulfate) DESCRIPTION AccuNeb® (albuterol sulfate) inhalation solution is a sterile, clear, colorless solution of the sulfate salt of racemic albuterol, albuterol sulfate. Albuterol sulfate is a relatively selective beta2-adrenergic bronchodilator (see CLINICAL PHARMACOLOGY). The chemical name for albuterol sulfate is α1 [(tert-butylamino) methyl]-4-hydroxy-mxylene-α, α'-diol sulfate (2:1) (salt), and its established chemical structure is as follows: The molecular weight of albuterol sulfate is 576.7 and the empirical formula is (C13H21NO3)2•H2SO4. Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization recommended name for albuterol is salbutamol. AccuNeb (albuterol sulfate) Inhalation Solution is supplied in two strengths in unit dose vials. Each unit dose vial contains either 0.75 mg of albuterol sulfate (equivalent to 0.63 mg of albuterol) or 1.50 mg of albuterol sulfate (equivalent to 1.25 mg of albuterol) with sodium chloride and sulfuric acid in a 3-mL isotonic, sterile, aqueous solution. Sodium chloride is added to adjust isotonicity of the solution and sulfuric acid is added to adjust pH of the solution to 3.5 (see HOW SUPPLIED). AccuNeb (albuterol sulfate) Inhalation Solution does not require dilution prior to administration by nebulization. For AccuNeb (albuterol sulfate inhalation solution) , like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the jet nebulizer utilized, and compressor performance. Using the Pari LC Plus™ nebulizer (with face mask or mouthpiece) connected to a Pari PRONEB™ compressor, under in vitro conditions, the mean delivered dose from the mouth piece (% nominal dose) was approximately 43% of albuterol (1.25 mg strength) and 39% of albuterol (0.63 mg strength) at a mean flow rate of 3.6 L/min. The mean nebulization time was 15 minutes or less. AccuNeb (albuterol sulfate inhalation solution) should be administered from a jet nebulizer at an adequate flow rate, via a mouthpiece or face mask (see DOSAGE AND ADMINISTRATION)."
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"property.key": "Indications & Dosage",
"property.value": "INDICATIONS AccuNeb (albuterol sulfate inhalation solution) is indicated for the relief of bronchospasm in patients 2 to 12 years of age with asthma (reversible obstructive airway disease). DOSAGE AND ADMINISTRATION The usual starting dosage for patients 2 to 12 years of age is 1.25 mg or 0.63 mg of AccuNeb (albuterol sulfate inhalation solution) administered 3 or 4 times daily, as needed, by nebulization. More frequent administration is not recommended. To administer 1.25 mg or 0.63 mg of albuterol, use the entire contents of one unit-dose vial (3 mL of 1.25 mg or 0.63 mg inhalation solution) by nebulization. Adjust nebulizer flow rate to deliver AccuNeb (albuterol sulfate inhalation solution) over 5 to 15 minutes. The use of AccuNeb (albuterol sulfate inhalation solution) can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimum benefit from regular use of the inhalation solution. Patients 6 to 12 years of age with more severe asthma (baseline FEV1 less than 60% predicted), weight > 40 kg, or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose. AccuNeb (albuterol sulfate inhalation solution) has not been studied in the setting of acute attacks of bronchospasm. A 2.5 mg dose of albuterol provided by a higher concentration product (2.5 mg albuterol per 3 mL) may be more appropriate for treating acute exacerbations, particularly in children 6 years old and above. If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately, as this is often a sign of seriously worsening asthma which would require reassessment of therapy. The drug compatibility (physical and chemical), clinical efficacy and safety of AccuNeb (albuterol sulfate inhalation solution) solution, when mixed with other drugs in a nebulizer have not been established. The safety and efficacy of AccuNeb (albuterol sulfate inhalation solution) have been established in clinical trials when administered using the Pari LC Plus™ nebulizer and Pari PRONEB™ compressor. The safety and efficacy of AccuNeb (albuterol sulfate inhalation solution) when administered with other nebulizer systems have not been established. AccuNeb (albuterol sulfate inhalation solution) should be administered via jet nebulizer connected to an air compressor with adequate air flow, equipped with a mouthpiece or suitable face mask. HOW SUPPLIED AccuNeb (albuterol sulfate) Inhalation Solution is supplied as a 3 mL, clear, colorless, sterile, preservative-free, aqueous solution in two different strengths, 0.63 mg and 1.25 mg, of albuterol (equivalent to 0.75 mg of albuterol sulfate or 1.5 mg of albuterol sulfate per 3 mL) in unit-dose low-density polyethylene (LDPE) vials. Each unit-dose LDPE vial is protected in a foil pouch, and each foil pouch contains 5 unit-dose LDPE vials. Each strength of AccuNeb (albuterol sulfate inhalation solution) (albuterol sulfate) Inhalation Solution is available in a shelf carton containing multiple foil pouches. AccuNeb® (albuterol sulfate) Inhalation Solution, 0.63 mg (potency expressed as albuterol) contains 0.75 mg albuterol sulfate per 3 mL in unit-dose vials and is available in the following packaging configuration. NDC 49502-692-03 5 foil pouches, each containing 5 vials, total 25 vials per carton AccuNeb® (albuterol sulfate) Inhalation Solution, 1.25 mg (potency expressed as albuterol) contains 1.50 mg albuterol sulfate per 3 mL in unit-dose vials and is available in the following packaging configuration. NDC 49502-693-03 5 foil pouches, each containing 5 vials, total 25 vials per carton Storage Store between 2°C and 25°C (36°F - 77°F). Protect from light and excessive heat. Store unit-dose vials in protective foil pouch at all times. Once removed from the foil pouch, use vial(s) within one week. Discard the vial if the solution is not colorless. Keep out of the reach of children. DEY®, Napa, CA 94558. JAN 07"
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"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS Clinical Trial Experience: Adverse events reported in > 1% of patients receiving AccuNeb (albuterol sulfate inhalation solution) and more frequently than in patients receiving placebo in a four-week double-blind study are listed in the following table. Table 1: Adverse Events with an Incidence of > 1% of Patients Receiving AccuNeb (albuterol sulfate inhalation solution) and Greater than Placebo (expressed as % of treatment group) 1.25 mg AccuNeb (N=115) 0.63 mg AccuNeb (N=117) Placebo (N=117) Asthma Exacerbation 13 11.1 8.5 Otitis Media 4.3 0.9 0 Allergic Reaction 0.9 3.4 1.7 Gastroenteritis 0.9 3.4 0.9 Cold Symptoms 0 3.4 1.7 Flu Syndrome 2.6 2.6 1.7 Lymphadenopathy 2.6 0.9 1.7 Skin/Appendage Infection 1.7 0 0 Urticaria 1.7 0.9 0 Migraine 0.9 1.7 0 Chest Pain 0.9 1.7 0 Bronchitis 0.9 1.7 0.9 Nausea 1.7 0.9 0.9 There was one case of ST segment depression in the 1.25 mg AccuNeb (albuterol sulfate inhalation solution) treatment group. No clinically relevant laboratory abnormalities related to AccuNeb (albuterol sulfate inhalation solution) administration were seen in this study. Postmarketing Experience Metabolic acidosis has been reported after the use of albuterol sulfate inhalation solution. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure.. DRUG INTERACTIONS Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with AccuNeb (albuterol sulfate inhalation solution) . AccuNeb (albuterol sulfate inhalation solution) should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or within 2 weeks of discontinuation of such agents, since the action of albuterol on the vascular system may be potentiated. Beta-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as AccuNeb (albuterol sulfate inhalation solution) , but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances (e.g., prophylaxis after myocardial infarction), there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers should be considered, although they should be administered with caution. The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, caution is advised in the coadministration of beta-agonists with non-potassium sparing diuretics. Mean decreases of 16% to 22% in serum digoxin levels were demonstrated after single dose intravenous and oral administration of albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear. Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and albuterol."
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"property.value": "WARNINGS Paradoxical Bronchospasm As with other inhaled beta-adrenergic agonists, AccuNeb (albuterol sulfate inhalation solution) can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, AccuNeb (albuterol sulfate inhalation solution) should be discontinued immediately and alternative therapy instituted. It should be noted that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister or vial. Use of Anti-Inflammatory Agents The use of beta-adrenergic bronchodilators alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents (e.g., corticosteroids). Deterioration of Asthma Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of AccuNeb (albuterol sulfate inhalation solution) than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration of the possible need for anti-inflammatory treatment (e.g., corticosteroids). Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs and with the home use of nebulizers. It is, therefore, essential that the physician instruct the patient in the need for further evaluation, if his/her asthma becomes worse. Cardiovascular Effects AccuNeb (albuterol sulfate inhalation solution) , like other beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon for AccuNeb (albuterol sulfate inhalation solution) at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T-wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, AccuNeb (albuterol sulfate inhalation solution) like all other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions may occur after administration of albuterol as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema. PRECAUTIONS General Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, inhaled and intravenous albuterol may produce a significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring potassium supplementation. Information for Patients The action of AccuNeb (albuterol sulfate inhalation solution) may last up to six hours, and therefore it should not be used more frequently than recommended. Do not increase the dose or frequency of medication without consulting your physician. If you find that treatment with AccuNeb (albuterol sulfate inhalation solution) becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, you should seek medical attention immediately. All asthma medication should only be used under the supervision and direction of a physician. Common effects with medications such as AccuNeb (albuterol sulfate inhalation solution) include palpitations, chest pain, rapid heart rate, tremor, or nervousness. If you are pregnant or nursing, contact your physician about the use of AccuNeb (albuterol sulfate inhalation solution) . Effective and safe use of AccuNeb (albuterol sulfate inhalation solution) includes an understanding of the way it should be administered. If the solution in the vial changes color or becomes cloudy, you should not use it. The drug compatibility (physical and chemical), clinical efficacy, and safety of AccuNeb (albuterol sulfate inhalation solution) solution, when mixed with other drugs in a nebulizer, has not been established. See illustrated Patient's Instructions for Use. Carcinogenesis, Mutagenesis, and Impairment of Fertility In a 2-year study in Sprague-Dawley rats, albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium and above dietary doses of 2 mg/kg (approximately equivalent to the maximum recommended daily inhalation dose for AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). In another study, this effect was blocked by the coadministration of propranolol, a non-selective beta-adrenergic antagonist. In an 18-month study in CD-1 mice, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 500 mg/kg (approximately 140 times the maximum recommended daily inhalation dose of AccuNeb on a mg/m² basis). In a 22-month study in Golden hamsters, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 50 mg/kg (approximately 20 times the maximum recommended daily inhalation dose of AccuNeb on a mg/m² basis). Albuterol sulfate was not mutagenic in the Ames test or a mutation test in yeast. Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay. Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of albuterol sulfate up to 50 mg/kg (approximately 30 times the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). Pregnancy Teratogenic Effects: Pregnancy Category C: Albuterol has been shown to be teratogenic in mice. A study in CD-1 mice given albuterol subcutaneously showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg (less than the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis) and cleft palate formation in 10 of 108 (9.3%) fetuses at 2.5 mg/kg (approximately equal to the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). The drug did not induce cleft palate formation when administered subcutaneously at a dose of 0.025 mg/kg (less than the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). Cleft palate formation also occurred in 23 of 72 (30.5%) fetuses from females treated subcutaneously with 2.5 mg/kg isoproterenol (positive control). A reproduction study in Stride rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol sulfate was administered orally at 50 mg/kg (approximately 60 times the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). A study in which pregnant rats were dosed with radiolabelled albuterol sulfate demonstrated that drug-related material was transferred from the maternal circulation to the fetus. There are no adequate and well-controlled studies of the use of albuterol sulfate in pregnant women. Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, a relationship between albuterol use and congenital anomalies has not been established. Labor and Delivery Oral albuterol has been shown to delay pre-term labor in some reports. There are presently no well-controlled studies that demonstrate that it will stop pre-term labor or prevent labor at term. Because of the potential for beta agonist interference with uterine contractility, use of AccuNeb (albuterol sulfate inhalation solution) for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk. Albuterol has not been approved for the management of pre-term labor. The benefit:risk ratio when albuterol is administered for tocolysis has not been established. Serious adverse reactions, including pulmonary edema, have been reported following administration of albuterol to women in labor. Nursing Mothers It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in some animal studies, 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 Safety and effectiveness of AccuNeb (albuterol sulfate inhalation solution) 1.25 mg and 0.63 mg have been established in pediatric patients between the ages of 2 and 12 years. The use of AccuNeb (albuterol sulfate inhalation solution) in these age groups is supported by evidence from adequate and well-controlled studies of AccuNeb (albuterol sulfate inhalation solution) in children age 6 to 12 years and published reports of albuterol sulfate trials in pediatric patients 3 years of age and older. The safety and effectiveness of AccuNeb (albuterol sulfate inhalation solution) in children below 2 years of age have not been established."
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"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of symptoms such as seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, and exaggeration of the pharmacological effects listed in ADVERSE REACTIONS. Hypokalemia may also occur. As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of AccuNeb (albuterol sulfate inhalation solution) . Treatment consists of discontinuation of AccuNeb (albuterol sulfate inhalation solution) together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of AccuNeb (albuterol sulfate inhalation solution) . The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 580 times the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). The subcutaneous median lethal dose of albuterol sulfate in mature rats and small young rats is approximately 450 mg/kg and 2000 mg/kg, respectively (approximately 260 and 1200 times the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). The inhalation median lethal dose has not been determined in animals. CONTRAINDICATIONS AccuNeb (albuterol sulfate inhalation solution) is contraindicated in patients with a history of hypersensitivity to any of its components."
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"property.ts": "2017-12-04 04:41:49",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY The prime action of beta-adrenergic drugs is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic-3',5'-adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP). The cyclic AMP thus formed mediates the cellular responses. In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta2-adrenergic receptors compared with isoproterenol. While it is recognized that beta2-adrenergic receptors are the predominant receptors in bronchial smooth muscle, recent data indicate that 10% to 50% of the beta-receptors in the human heart may be beta2-receptors. The precise function of these receptors, however, is not yet established. Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes. Albuterol is longer acting than isoproterenol in most patients by any route of administration because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol-O-methyl transferase. Pharmacokinetics Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following either intermittent positive-pressure breathing (IPPB) or nebulizer administration; the remaining amount was recovered from the nebulizer and apparatus, and expired air. Most of the absorbed dose was recovered in urine collected during the 24 hours after drug administration. Following oral administration of 4 mg albuterol, the elimination half-life was five to six hours. Following a 3 mg dose of nebulized albuterol in adults, the mean maximum albuterol plasma level at 0.5 hours was 2.1 ng/mL (range, 1.4 to 3.2 ng/mL). The pharmacokinetics of albuterol following administration of 0.63 mg or 1.25 mg albuterol sulfate inhalation solution by nebulization have not been determined in children 2 to 12 years old. Animal Pharmacology/Toxicology Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those found in whole brain. Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown. Clinical Trials The safety and efficacy of AccuNeb (albuterol sulfate inhalation solution) was evaluated in a 4-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study in 349 children 6 to 12 years of age with mild-to-moderate asthma (mean baseline FEV1 60% to 70% of predicted). Approximately half of the patients were also receiving inhaled corticosteroids. Patients were randomized to receive AccuNeb (albuterol sulfate inhalation solution) 0.63 mg, AccuNeb (albuterol sulfate inhalation solution) 1.25 mg, or placebo three times a day administered via a Pari LC Plus™ nebulizer and a Pari PRONEB™ compressor. Racemic albuterol, delivered by a chlorofluorocarbon (CFC) metered dose inhaler (MDI) or nebulized, was used on an as-needed basis as the rescue medication. Efficacy, as measured by the mean percent change from baseline in the area under the 6hour curve for FEV1, was demonstrated for both active treatment regimens (n=112 [1.25 mg group] and n=110 [0.63 mg group]) compared with placebo (n=110) on day 1 and day 28. Figures 1 and 2 illustrate the mean percentage change from pre-dose FEV1 on day 1 and day 28, respectively. The mean baseline FEV1 for all patients was 1.49 L. Figure 1 : % Change from Pre-Dose FEV1 Intent-to-Treat Population Day 1 Figure 2 : % Change from Pre-Dose FEV1 Intent-to-Treat Population Day 28 The onset of a 15% increase in FEV1 over baseline for both doses of AccuNeb (albuterol sulfate inhalation solution) was seen at 30 minutes (the first post-dose assessment). The mean time to peak effect was approximately 30 to 60 minutes for both doses on day 1 and after 4 weeks of treatment. The mean duration of effect, as measured by a > 15% increase from baseline in FEV1, was approximately 2.5 hours for both doses on day 1 and approximately 2 hours for both doses after 4 weeks of treatment. In some patients, the duration of effect was as long as 6 hours."
},
"279": {
"property.id": 279,
"property.ts": "2017-12-04 04:41:49",
"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION AccuNeb® (Ack-u-neb) (albuterol sulfate) Inhalation Solution 1.25 mg*/3 mL and 0.63 mg*/3 mL (*Potency expressed as albuterol, equivalent to 1.5 mg and 0.75 mg albuterol sulfate) Read the patient information that comes with AccuNeb® (albuterol sulfate inhalation solution) before using it and each time you get a refill for your child. There may be new information. This leaflet does not take the place of talking to your child's doctor about your child's medical condition or treatment. What is AccuNeb® (albuterol sulfate inhalation solution) ? AccuNeb® (albuterol sulfate inhalation solution) is a medicine that is used for the relief of bronchospasms caused by asthma in children ages 2 to 12 years. Bronchospasm is the tightening and swelling of the muscles around the airways. AccuNeb® (albuterol sulfate inhalation solution) can help relax these airway muscles for up to 6 hours so that your child may breathe more easily. Who should not use AccuNeb® (albuterol sulfate inhalation solution) ? Do not give your child AccuNeb® (albuterol sulfate inhalation solution) if he or she is allergic to any of its ingredients. The active ingredient is albuterol sulfate. See the end of this leaflet for a complete list of ingredients. What should I tell my child's doctor before giving AccuNeb® (albuterol sulfate inhalation solution) ? Tell your child's doctor about all of your child's medical conditions including if your child has: Heart problems High blood pressure Seizures A thyroid problem called hyperthyroidism Diabetes Tell your child's doctor about all the medicines your child takes, including prescription and non-prescription medicines, vitamins and herbal supplements. AccuNeb® (albuterol sulfate inhalation solution) and some other medicines can affect each other and may cause serious side effects. Especially tell your child's doctor if your child is taking or using: Any short-acting bronchodilator medicines (sometimes called rescue inhalers) Epinephrine Medicines called monoamine oxidase inhibitors (MAOIs) or tricyclic anti-depressants or has stopped taking them in the past 2 weeks. These medicines are usually used for mental problems. Medicines called beta-blockers (used for heart problems and high blood pressure) Certain diuretic medicines (water pills) Digoxin Know the medicines your child takes. Keep a list of them and show it to your child's doctor and pharmacist each time your child gets a new medicine. How should AccuNeb® (albuterol sulfate inhalation solution) be given? Read the Patient's Instructions for Use that comes with AccuNeb® (albuterol sulfate inhalation solution) . Ask your pharmacist for these instructions if they are not with your medicine. Keep the instructions with AccuNeb® (albuterol sulfate inhalation solution) because you may want to read them again. Give AccuNeb® (albuterol sulfate inhalation solution) exactly as prescribed for your child. Do not change your child's dose or how often it is used without talking to your child's doctor first. AccuNeb® (albuterol sulfate inhalation solution) is breathed into the lungs. AccuNeb® (albuterol sulfate inhalation solution) is used with a special breathing machine called a nebulizer. Do not mix other medicines with AccuNeb® (albuterol sulfate inhalation solution) in the nebulizer. Do not use AccuNeb® (albuterol sulfate inhalation solution) that is not clear and colorless. Call your child's doctor or get emergency help right away if your child's breathing is not helped or gets worse during treatment with AccuNeb® (albuterol sulfate inhalation solution) . Call your child's doctor right away if your child needs to use AccuNeb® (albuterol sulfate inhalation solution) more often than prescribed. AccuNeb® (albuterol sulfate inhalation solution) has not been studied for treating acute attacks of bronchospasm (rescue use). Your child may need a different medicine for rescue use. If you give your child too much AccuNeb® (albuterol sulfate inhalation solution) , call your child's doctor right away. What are the side effects with AccuNeb® (albuterol sulfate inhalation solution) ? AccuNeb® (albuterol sulfate inhalation solution) may cause the following serious side effects: Worsening of the tightening and swelling of the muscles around your child's airways (bronchospasm). This side effect can be life threatening. Call your child's doctor or get emergency help right away if your child's breathing is not helped or gets worse during treatment with AccuNeb® (albuterol sulfate inhalation solution) . Serious and life threatening allergic reactions. Symptoms of a serious allergic reaction include: Hives, rash Swelling of your child's face, eyelids, lips, tongue, or throat, and trouble swallowing Worsening of your child's breathing problems such as wheezing, chest tightness or shortness of breath Shock (loss of blood pressure and consciousness). The most common side effects with AccuNeb® (albuterol sulfate inhalation solution) include a fast or irregular heartbeat, chest pain, shakiness, or nervousness. How should AccuNeb® (albuterol sulfate inhalation solution) be stored? Store AccuNeb® (albuterol sulfate inhalation solution) at room temperature, 36° to 77°F (2° to 25°C) in its tightly closed container. Protect vials from light before use. Therefore, keep unused vials in the foil pouch or carton. Once removed from the foil pouch, use vial(s) within one week. Do not use AccuNeb® (albuterol sulfate inhalation solution) after the expiration (EXP) date printed on the vial. Do not use AccuNeb® (albuterol sulfate inhalation solution) that is not clear and colorless. Safely, discard AccuNeb® (albuterol sulfate inhalation solution) that is out-of-date or no longer needed. Keep AccuNeb® (albuterol sulfate inhalation solution) and all medicines out of the reach of children. General Information about AccuNeb® (albuterol sulfate inhalation solution) Medicines are sometimes prescribed for conditions that are not mentioned in the patient information leaflets. Do not use AccuNeb® (albuterol sulfate inhalation solution) for a condition for which it was not prescribed. Do not give AccuNeb® (albuterol sulfate inhalation solution) to other people, even if they have the same symptoms your child has. It may harm them. This leaflet summarizes the most important information about AccuNeb® (albuterol sulfate inhalation solution) . If you would like more information, talk with your child's doctor. You can ask your child's doctor or pharmacist for information about AccuNeb® (albuterol sulfate inhalation solution) that is written for health professionals. You can also call the company that makes AccuNeb® (albuterol sulfate inhalation solution) toll free at 1-800-755-5560, or visit their website at www.dey.com. What are the ingredients in AccuNeb®? Active Ingredient: albuterol sulfate Inactive Ingredients:sodium chloride and sulfuric acid PATIENT'S INSTRUCTIONS FOR USE Read this patient information completely every time your prescription is filled as information may have changed.Keep these instructions with your medication,as you may want to read them again. AccuNeb (albuterol sulfate inhalation solution) should only be used under the direction of a physician. Your physician and pharmacist have more information about AccuNeb (albuterol sulfate inhalation solution) and the condition for which it has been prescribed. Contact them if you have additional questions. Storing your Medicine Store AccuNeb (albuterol sulfate inhalation solution) between 2° and 25°C (36°and 77°F).Vials should be protected from light before use, therefore, keep unused vials in the foil pouch.Do not use after the expiration (EXP) date printed on the vial. Dose AccuNeb (albuterol sulfate inhalation solution) is supplied as a single-dose, ready-to-use vial containing 3 mL of solution.No mixing or dilution is needed.Use one new vial with each nebulizer treatment. Instructions for Use 1. Remove one vial from the foil pouch.Place remaining vials back into foil pouch for storage. 2. Twist the cap completely off the vial and squeeze the contents into the nebulizer reservoir (Figure 1). Figure 1 3. Connect the nebulizer to the mouthpiece or face mask (Figure 2). Figure 2 4. Connect the nebulizer to the compressor. 5. Sit in a comfortable, upright position;place the mouthpiece in your mouth (Figure 3) or put on the face mask (Figure 4);and turn on the compressor. Figure 3 Figure 4 6. Breathe as calmly, deeply and evenly as possible through your mouth until no more mist is formed in the nebulizer chamber (about 5-15 minutes).At this point, the treatment is finished. 7. Clean the nebulizer (see manufacturer's instructions)."
}
} |
45 | 2017-08-31 23:12:57 | AccuNeb | Albuterol Sulfate Inhalation Solution | Multum | { "45": { "alphabet_x_drug.id": 45, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"280": {
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"property.key": "AccuNeb Patient Information Including Side Effects",
"property.value": "Brand Names: Accuneb, ProAir HFA, Proventil, Proventil HFA, ReliOn Ventolin HFA, Ventolin HFA Generic Name: albuterol inhalation (Pronunciation: al BYOO ter all) What is albuterol inhalation (Accuneb, ProAir HFA, Proventil, Proventil HFA, ReliOn Ventolin HFA, Ventolin HFA)? What are the possible side effects of albuterol inhalation? What is the most important information I should know about albuterol inhalation? What should I discuss with my healthcare provider before using albuterol inhalation? How should I use albuterol inhalation? What happens if I miss a dose? What happens if I overdose? What should I avoid while using albuterol inhalation? What other drugs will affect albuterol inhalation? Where can I get more information? What is albuterol inhalation (Accuneb, ProAir HFA, Proventil, Proventil HFA, ReliOn Ventolin HFA, Ventolin HFA)? Albuterol is a bronchodilator that relaxes muscles in the airways and increases air flow to the lungs.Albuterol inhalation is used to treat or prevent bronchospasm in people with reversible obstructive airway disease. Albuterol is also used to prevent exercise-induced bronchospasm.Albuterol inhalation may also be used for purposes not listed in this medication guide. What are the possible side effects of albuterol inhalation? 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:bronchospasm (wheezing, chest tightness, trouble breathing), especially after starting a new canister of this medicine;chest pain and fast, pounding, or uneven heart beats;tremor, nervousness;low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling); ordangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).Less serious side effects may include:headache, dizziness;sleep problems (insomnia);cough, hoarseness, sore throat, runny or stuffy nose;mild nausea, vomiting;dry mouth and throat;muscle pain; ordiarrhea.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 albuterol inhalation? It is important to keep this medication on hand at all times. Get your prescription refilled before you run out of medicine completely. Keep using all of your other medications as prescribed by your doctor.Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor. An increased need for medication could be an early sign of a serious asthma attack.Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of albuterol can be fatal.Extreme heat can cause the medicine canister to burst. Do not store your inhaler in your car on hot days. Do not throw an empty canister into open flame."
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"281": {
"property.id": 281,
"property.ts": "2017-12-04 04:41:57",
"property.key": "AccuNeb Patient Information including How Should I Take",
"property.value": "What should I discuss with my healthcare provider before using albuterol inhalation? You should not use this medication if you are allergic to albuterol.To make sure you can safely use albuterol, tell your doctor if you have any of these other conditions:heart disease, high blood pressure, or congestive heart failure;a heart rhythm disorder;a seizure disorder such as epilepsy;diabetes; oroveractive thyroid.FDA pregnancy category C. It is not known whether albuterol 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 albuterol passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using albuterol.An albuterol inhaler should not be given to a child younger than 4 years old. Albuterol solution in a nebulizer should not be given to a child younger than 2 years of age. How should I use albuterol inhalation? 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.Use only the prescribed dose of this medicine and follow all patient instructions for safe use. Talk with your doctor about your individual risks and benefits of using albuterol.When using the inhaler device for the first time, prime it by spraying 4 test sprays into the air, away from your face. Shake well before priming. Also prime the inhaler if you have not used it for 2 weeks or longer, or if you have dropped the inhaler.The instructions below are for standard use of the inhaler and nebulizer devices. Your doctor may want you to use your device differently. Use only the inhaler device provided with your medicine or you may not get the correct dose.To use the inhaler:Shake the canister well just before each spray.Uncap the mouthpiece of the inhaler. Breathe out fully. Put the mouthpiece into your mouth and close your lips. Breathe in slowly while pushing down on the canister. Hold your breath for 10 seconds, then breathe out slowly.If you use more than one inhalation at a time, wait at least 1 minute before using the second inhalation and shake the inhaler again.Keep your inhaler clean and dry, and store it with the cap on the mouthpiece. Clean your inhaler once a week by removing the canister and placing the mouthpiece under warm running water for at least 30 seconds. Shake out the excess water and allow the parts to air dry completely before putting the inhaler back together.To use the solution with a nebulizer:Measure the correct amount of medicine using the dropper provided, or use the proper number of ampules. Place the liquid into the medication chamber of the nebulizer.Attach the mouthpiece or face mask to the drug chamber. Then, attach the drug chamber to the compressor.Sit upright in a comfortable position. Place the mouthpiece into your mouth or put the face mask on, covering your nose and mouth. Turn on the compressor.Breathe in slowly and evenly until you have inhaled all of the medicine (usually 5 to 15 minutes). The treatment is complete when no more mist is formed by the nebulizer and the drug chamber is empty.Clean the nebulizer after each use. Follow the cleaning directions that came with your nebulizer.Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor.An increased need for medication could be an early sign of a serious asthma attack.It is important to keep this medication on hand at all times. Get your prescription refilled before you run out of medicine completely. Keep using all of your other medications as prescribed by your doctor.Store this medication at room temperature away from moisture and heat. Extreme heat can cause the medicine canister to burst. Do not store it in your car on hot days. Do not throw an empty canister into open flame."
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"282": {
"property.id": 282,
"property.ts": "2017-12-04 04:41:57",
"property.key": "AccuNeb Patient Information including If I Miss a Dose",
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46 | 2017-08-31 23:12:57 | Accupril | Quinapril Hydrochloride | FDA | { "46": { "alphabet_x_drug.id": 46, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"283": {
"property.id": 283,
"property.ts": "2017-12-04 04:42:02",
"property.key": "Drug Description",
"property.value": "Find Lowest Prices on Accupril® (quinapril hydrochloride) Tablets WARNING FETAL TOXICITY When pregnancy is detected, discontinue ACCUPRIL as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity DESCRIPTION ACCUPRIL® (quinapril hydrochloride) is the hydrochloride salt of quinapril, the ethyl ester of a non-sulfhydryl, angiotensin-converting enzyme (ACE) inhibitor, quinaprilat. Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]]-2-[2-[[1(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3isoquinolinecarboxylic acid, monohydrochloride. Its empirical formula is C25H30N2O5•HCl and its structural formula is: Quinapril hydrochloride is a white to off-white amorphous powder that is freely soluble in aqueous solvents. ACCUPRIL tablets contain 5 mg, 10 mg, 20 mg, or 40 mg of quinapril for oral administration. Each tablet also contains candelilla wax, crospovidone, gelatin, lactose, magnesium carbonate, magnesium stearate, synthetic red iron oxide, and titanium dioxide."
},
"284": {
"property.id": 284,
"property.ts": "2017-12-04 04:42:02",
"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Hypertension ACCUPRIL is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with ACCUPRIL. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. ACCUPRIL may be used alone or in combination with thiazide diuretics. Heart Failure ACCUPRIL is indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis. In using ACCUPRIL, consideration should be given to the fact that another ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease. Available data are insufficient to show that ACCUPRIL does not have a similar risk (see WARNINGS). Angioedema in black patients: Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to non-blacks. It should also be noted that in controlled clinical trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. DOSAGE AND ADMINISTRATION Hypertension Monotherapy The recommended initial dosage of ACCUPRIL in patients not on diuretics is 10 or 20 mg once daily. Dosage should be adjusted according to blood pressure response measured at peak (2–6 hours after dosing) and trough (predosing). Generally, dosage adjustments should be made at intervals of at least 2 weeks. Most patients have required dosages of 20, 40, or 80 mg/day, given as a single dose or in two equally divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients an increase in dosage or twice daily administration may be warranted. In general, doses of 40–80 mg and divided doses give a somewhat greater effect at the end of the dosing interval. Concomitant Diuretics If blood pressure is not adequately controlled with ACCUPRIL monotherapy, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of ACCUPRIL. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with ACCUPRIL (see WARNINGS). Then, if blood pressure is not controlled with ACCUPRIL alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 5 mg ACCUPRIL should be used with careful medical supervision for several hours and until blood pressure has stabilized. The dosage should subsequently be titrated (as described above) to the optimal response (see WARNINGS, PRECAUTIONS, and DRUG INTERACTIONS). Renal Impairment Kinetic data indicate that the apparent elimination half-life of quinaprilat increases as creatinine clearance decreases. Recommended starting doses, based on clinical and pharmacokinetic data from patients with renal impairment, are as follows: Creatinine Clearance Maximum Recommended Initial Dose >60 mL/min 10 mg 30–60 mL/min 5 mg 10–30 mL/min 2.5 mg 10–30 mL/min Insufficient data for dosage recommendation Patients should subsequently have their dosage titrated (as described above) to the optimal response. Elderly (≥65 Years) The recommended initial dosage of ACCUPRIL in elderly patients is 10 mg given once daily followed by titration (as described above) to the optimal response. Heart Failure ACCUPRIL is indicated as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis. The recommended starting dose is 5 mg twice daily. This dose may improve symptoms of heart failure, but increases in exercise duration have generally required higher doses. Therefore, if the initial dosage of ACCUPRIL is well tolerated, patients should then be titrated at weekly intervals until an effective dose, usually 20 to 40 mg daily given in two equally divided doses, is reached or undesirable hypotension, orthostatis, or azotemia (see WARNINGS) prohibit reaching this dose. Following the initial dose of ACCUPRIL, the patient should be observed under medical supervision for at least two hours for the presence of hypotension or orthostatis and, if present, until blood pressure stabilizes. The appearance of hypotension, orthostatis, or azotemia early in dose titration should not preclude further careful dose titration. Consideration should be given to reducing the dose of concomitant diuretics. Dose Adjustments In Patients With Heart Failure And Renal Impairment Or Hyponatremia Pharmacokinetic data indicate that quinapril elimination is dependent on level of renal function. In patients with heart failure and renal impairment, the recommended initial dose of ACCUPRIL is 5 mg in patients with a creatinine clearance above 30 mL/min and 2.5 mg in patients with a creatinine clearance of 10 to 30 mL/min. There is insufficient data for dosage recommendation in patients with a creatinine clearance less than 10 mL/min (see DOSAGE AND ADMINISTRATION, Heart Failure,WARNINGS, and PRECAUTIONS, DRUG INTERACTIONS). If the initial dose is well tolerated, ACCUPRIL may be administered the following day as a twice daily regimen. In the absence of excessive hypotension or significant deterioration of renal function, the dose may be increased at weekly intervals based on clinical and hemodynamic response. HOW SUPPLIED ACCUPRIL tablets are supplied as follows: 5-mg tablets: brown, film-coated, elliptical scored tablets, coded “PD 527’’ on one side and “5’’ on the other. NDC 0071-0527-23 bottles of 90 tablets NDC 0071-0527-40 10 x 10 unit dose blisters 10-mg tablets: brown, film-coated, triangular tablets, coded “PD 530’’ on one side and “10’’ on the other. NDC 0071-0530-23 bottles of 90 tablets NDC 0071-0530-40 10 x 10 unit dose blisters 20-mg tablets: brown, film-coated, round tablets, coded “PD 532’’ on one side and “20’’ on the other. NDC 0071-0532-23 bottles of 90 tablets NDC 0071-0532-40 10 x 10 unit dose blisters 40-mg tablets: brown, film-coated, elliptical tablets, coded “PD 535’’ on one side and “40’’ on the other. NDC 0071-0535-23 bottles of 90 tablets Dispense in well-closed containers as defined in the USP. Storage Store at controlled room temperature 15°–30°C (59°–86°F). Protect from light. Distributed by : pfizer Parke-Davis,Division of pfizer Inc,NY 10017. Revised : Feb 2017."
},
"285": {
"property.id": 285,
"property.ts": "2017-12-04 04:42:02",
"property.key": "Side Effects & Drug Interactions",
"property.value": ""
},
"286": {
"property.id": 286,
"property.ts": "2017-12-04 04:42:02",
"property.key": "Warnings & Precautions",
"property.value": "WARNINGS Anaphylactoid And Possibly Related Reactions Presumably because ACE inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including ACCUPRIL) may be subject to a variety of adverse reactions, some of them serious. Head And Neck Angioedema Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors and has been seen in 0.1% of patients receiving ACCUPRIL. In two similarly sized U.S. postmarketing trials that, combined, enrolled over 3,000 black patients and over 19,000 non-blacks, angioedema was reported in 0.30% and 0.55% of blacks (in study 1 and 2 respectively) and 0.39% and 0.17% of non-blacks. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with ACCUPRIL should be discontinued immediately, the patient treated in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy including, but not limited to, subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) should be promptly administered (see ADVERSE REACTIONS). Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema. Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Patients With A History Of Angioedema Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see CONTRAINDICATIONS). Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge. Anaphylactoid Reactions During Membrane Exposure Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. Hepatic Failure Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. Hypotension Excessive hypotension is rare in patients with uncomplicated hypertension treated with ACCUPRIL alone. Patients with heart failure given ACCUPRIL commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. Caution should be observed when initiating therapy in patients with heart failure (see DOSAGE AND ADMINISTRATION). In controlled studies, syncope was observed in 0.4% of patients (N=3203); this incidence was similar to that observed for captopril (1%) and enalapril (0.8%). Patients at risk of excessive hypotension, sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death, include patients with the following conditions or characteristics: heart failure, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis, or severe volume and/or salt depletion of any etiology. It may be advisable to eliminate the diuretic (except in patients with heart failure), reduce the diuretic dose or cautiously increase salt intake (except in patients with heart failure) before initiating therapy with ACCUPRIL in patients at risk for excessive hypotension who are able to tolerate such adjustments. In patients at risk of excessive hypotension, therapy with ACCUPRIL should be started under close medical supervision. Such patients should be followed closely for the first two weeks of treatment and whenever the dose of ACCUPRIL and/or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident. If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses of ACCUPRIL, which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of ACCUPRIL or concomitant diuretic may be necessary. Neutropenia/Agranulocytosis Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease, such as systemic lupus erythematosus or scleroderma. Agranulocytosis did occur during ACCUPRIL treatment in one patient with a history of neutropenia during previous captopril therapy. Available data from clinical trials of ACCUPRIL are insufficient to show that, in patients without prior reactions to other ACE inhibitors, ACCUPRIL does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered. Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ACCUPRIL as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue ACCUPRIL, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to ACCUPRIL for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use). No teratogenic effects of ACCUPRIL were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose. PRECAUTIONS General Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensinaldosterone system, treatment with ACE inhibitors, including ACCUPRIL, may be associated with oliguria and/or progressive azotemia and rarely acute renal failure and/or death. In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine have been observed in some patients following ACE inhibitor therapy. These increases were almost always reversible upon discontinuation of the ACE inhibitor and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy. Some patients with hypertension or heart failure with no apparent preexisting renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when ACCUPRIL has been given concomitantly with a diuretic. This is more likely to occur in patients with preexisting renal impairment. Dosage reduction and/or discontinuation of any diuretic and/or ACCUPRIL may be required. Evaluation of patients with hypertension or heart failure should always include assessment of renal function (see DOSAGE AND ADMINISTRATION). Hyperkalemia In clinical trials, hyperkalemia (serum potassium ≥5.8 mmol/L) occurred in approximately 2% of patients receiving ACCUPRIL. In most cases, elevated serum potassium levels were isolated values which resolved despite continued therapy. Less than 0.1% of patients discontinued therapy due to hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of other drugs that raise serum potassium levels. Monitor serum potassium in such patients (see PRECAUTIONS, DRUG INTERACTIONS). Cough Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent non-productive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, ACCUPRIL will block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion. Dual Blockade Of The Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on ACCUPRIL and other agents that affect the RAS. Do not co-administer aliskiren with ACCUPRIL in patients with diabetes. Avoid concomitant use of aliskiren with ACCUPRIL in patients with renal impairment (GFR<60 mL/min/1.73 m2). Carcinogenesis, Mutagenesis, Impairment Of Fertility Quinapril hydrochloride was not carcinogenic in mice or rats when given in doses up to 75 or 100 mg/kg/day (50 to 60 times the maximum human daily dose, respectively, on an mg/kg basis and 3.8 to 10 times the maximum human daily dose when based on an mg/m2 basis) for 104 weeks. Female rats given the highest dose level had an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas. Neither quinapril nor quinaprilat were mutagenic in the Ames bacterial assay with or without metabolic activation. Quinapril was also negative in the following genetic toxicology studies: in vitro mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test with mice, in vitro chromosome aberration with V79 cultured lung cells, and in anin vivo cytogenetic study with rat bone marrow. There were no adverse effects on fertility or reproduction in rats at doses up to 100 mg/kg/day (60 and 10 times the maximum daily human dose when based on mg/kg and mg/m2 , respectively). Nursing Mothers Because ACCUPRIL is secreted in human milk, caution should be exercised when this drug is administered to a nursing woman. Pediatric Use Neonates With A History Of In Utero Exposure To ACCUPRIL: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of ACCUPRIL, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means. The safety and effectiveness of ACCUPRIL in pediatric patients have not been established. Geriatric Use Clinical studies of ACCUPRIL did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. 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. Elderly patients exhibited increased area under the plasma concentration time curve and peak levels for quinaprilat compared to values observed in younger patients; this appeared to relate to decreased renal function rather than to age itself."
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"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE Doses of 1440 to 4280 mg/kg of quinapril cause significant lethality in mice and rats. No specific information is available on the treatment of overdosage with quinapril. The most likely clinical manifestation would be symptoms attributable to severe hypotension. Laboratory determinations of serum levels of quinapril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of quinapril overdose. No data are available to suggest physiological maneuvers (eg, maneuvers to change pH of the urine) that might accelerate elimination of quinapril and its metabolites. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat. Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of quinapril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of quinapril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat quinapril overdose by infusion of normal saline solution. CONTRAINDICATIONS ACCUPRIL is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an ACE inhibitor. Do not co-administer ACCUPRIL with aliskiren in patients with diabetes."
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"288": {
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"property.ts": "2017-12-04 04:42:02",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Mechanism Of Action Quinapril is deesterified to the principal metabolite, quinaprilat, which is an inhibitor of ACE activity in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. The effect of quinapril in hypertension and in congestive heart failure (CHF) appears to result primarily from the inhibition of circulating and tissue ACE activity, thereby reducing angiotensin II formation. Quinapril inhibits the elevation in blood pressure caused by intravenously administered angiotensin I, but has no effect on the pressor response to angiotensin II, norepinephrine or epinephrine. Angiotensin II also stimulates the secretion of aldosterone from the adrenal cortex, thereby facilitating renal sodium and fluid reabsorption. Reduced aldosterone secretion by quinapril may result in a small increase in serum potassium. In controlled hypertension trials, treatment with ACCUPRIL alone resulted in mean increases in potassium of 0.07 mmol/L (see PRECAUTIONS). Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA). While the principal mechanism of antihypertensive effect is thought to be through the reninangiotensin-aldosterone system, quinapril exerts antihypertensive actions even in patients with low renin hypertension. ACCUPRIL was an effective antihypertensive in all races studied, although it was somewhat less effective in blacks (usually a predominantly low renin group) than in nonblacks. ACE is identical to kininase II, an enzyme that degrades bradykinin, a potent peptide vasodilator; whether increased levels of bradykinin play a role in the therapeutic effect of quinapril remains to be elucidated. Pharmacokinetics And Metabolism Following oral administration, peak plasma quinapril concentrations are observed within one hour. Based on recovery of quinapril and its metabolites in urine, the extent of absorption is at least 60%. The rate and extent of quinapril absorption are diminished moderately (approximately 25–30%) when ACCUPRIL tablets are administered during a high-fat meal. Following absorption, quinapril is deesterified to its major active metabolite, quinaprilat (about 38% of oral dose), and to other minor inactive metabolites. Following multiple oral dosing of ACCUPRIL, there is an effective accumulation half-life of quinaprilat of approximately 3 hours, and peak plasma quinaprilat concentrations are observed approximately 2 hours post-dose. Quinaprilat is eliminated primarily by renal excretion, up to 96% of an IV dose, and has an elimination half-life in plasma of approximately 2 hours and a prolonged terminal phase with a half-life of 25 hours. The pharmacokinetics of quinapril and quinaprilat are linear over a single-dose range of 5–80 mg doses and 40–160 mg in multiple daily doses. Approximately 97% of either quinapril or quinaprilat circulating in plasma is bound to proteins. In patients with renal insufficiency, the elimination half-life of quinaprilat increases as creatinine clearance decreases. There is a linear correlation between plasma quinaprilat clearance and creatinine clearance. In patients with end-stage renal disease, chronic hemodialysis or continuous ambulatory peritoneal dialysis has little effect on the elimination of quinapril and quinaprilat. Elimination of quinaprilat may be reduced in elderly patients (≥65 years) and in those with heart failure; this reduction is attributable to decrease in renal function (see DOSAGE AND ADMINISTRATION). Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired deesterification of quinapril. Studies in rats indicate that quinapril and its metabolites do not cross the blood-brain barrier. Pharmacodynamics And Clinical Effects Hypertension Single doses of 20 mg of ACCUPRIL provide over 80% inhibition of plasma ACE for 24 hours. Inhibition of the pressor response to angiotensin I is shorter-lived, with a 20 mg dose giving 75% inhibition for about 4 hours, 50% inhibition for about 8 hours, and 20% inhibition at 24 hours. With chronic dosing, however, there is substantial inhibition of angiotensin II levels at 24 hours by doses of 20–80 mg. Administration of 10 to 80 mg of ACCUPRIL to patients with mild to severe hypertension results in a reduction of sitting and standing blood pressure to about the same extent with minimal effect on heart rate. Symptomatic postural hypotension is infrequent although it can occur in patients who are salt-and/or volume-depleted (see WARNINGS). Antihypertensive activity commences within 1 hour with peak effects usually achieved by 2 to 4 hours after dosing. During chronic therapy, most of the blood pressure lowering effect of a given dose is obtained in 1–2 weeks. In multiple-dose studies, 10–80 mg per day in single or divided doses lowered systolic and diastolic blood pressure throughout the dosing interval, with a trough effect of about 5–11/3–7 mm Hg. The trough effect represents about 50% of the peak effect. While the dose-response relationship is relatively flat, doses of 40–80 mg were somewhat more effective at trough than 10–20 mg, and twice daily dosing tended to give a somewhat lower trough blood pressure than once daily dosing with the same total dose. The antihypertensive effect of ACCUPRIL continues during long-term therapy, with no evidence of loss of effectiveness. Hemodynamic assessments in patients with hypertension indicate that blood pressure reduction produced by quinapril is accompanied by a reduction in total peripheral resistance and renal vascular resistance with little or no change in heart rate, cardiac index, renal blood flow, glomerular filtration rate, or filtration fraction. Use of ACCUPRIL with a thiazide diuretic gives a blood-pressure lowering effect greater than that seen with either agent alone. In patients with hypertension, ACCUPRIL 10–40 mg was similar in effectiveness to captopril, enalapril, propranolol, and thiazide diuretics. Therapeutic effects appear to be the same for elderly (≥65 years of age) and younger adult patients given the same daily dosages, with no increase in adverse events in elderly patients. Heart Failure In a placebo-controlled trial involving patients with congestive heart failure treated with digitalis and diuretics, parenteral quinaprilat, the active metabolite of quinapril, reduced pulmonary capillary wedge pressure and systemic vascular resistance and increased cardiac output/index. Similar favorable hemodynamic effects were seen with oral quinapril in baseline-controlled trials, and such effects appeared to be maintained during chronic oral quinapril therapy. Quinapril reduced renal hepatic vascular resistance and increased renal and hepatic blood flow with glomerular filtration rate remaining unchanged. A significant dose response relationship for improvement in maximal exercise tolerance has been observed with ACCUPRIL therapy. Beneficial effects on the severity of heart failure as measured by New York Heart Association (NYHA) classification and Quality of Life and on symptoms of dyspnea, fatigue, and edema were evident after 6 months in a double-blind, placebo-controlled study. Favorable effects were maintained for up to two years of open label therapy. The effects of quinapril on long-term mortality in heart failure have not been evaluated."
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"289": {
"property.id": 289,
"property.ts": "2017-12-04 04:42:02",
"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Pregnancy Tell female patients of childbearing age about the consequences of exposure to ACCUPRIL during pregnancy. Discuss treatment options with women planning to become pregnant. Ask patients to report pregnancies to their physicians as soon as possible. Angioedema Angioedema, including laryngeal edema can occur with treatment with ACE inhibitors, especially following the first dose. Advise patients and tell them to immediately report any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their physician (see WARNINGS). Symptomatic Hypotension Caution patients that lightheadedness can occur, especially during the first few days of ACCUPRIL therapy, and that it should be reported to a physician. If actual syncope occurs, tell patients to temporarily discontinue the drug until they have consulted with their physician (see WARNINGS). Caution all patients that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure because of reduction in fluid volume, with the same consequences of lightheadedness and possible syncope. Tell patients planning to undergo any surgery and/or anesthesia to inform their physician that they are taking an ACE inhibitor. Hyperkalemia Tell patients not to use potassium supplements or salt substitutes containing potassium without consulting their physician (see PRECAUTIONS). Neutropenia Tell patients to promptly report any indication of infection (eg, sore throat, fever) which could be a sign of neutropenia. NOTE: As with many other drugs, certain advice to patients being treated with ACCUPRIL is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects."
}
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47 | 2017-08-31 23:12:57 | Accupril | Quinapril Hydrochloride | Multum | { "47": { "alphabet_x_drug.id": 47, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"290": {
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"property.key": "Accupril Patient Information Including Side Effects",
"property.value": "Find Lowest Prices on Brand Names: Accupril Generic Name: quinapril (Pronunciation: KWIN a pril) What is quinapril (Accupril)? What are the possible side effects of quinapril (Accupril)? What is the most important information I should know about quinapril (Accupril)? What should I discuss with my healthcare provider before taking quinapril (Accupril)? How should I take quinapril (Accupril)? What happens if I miss a dose (Accupril)? What happens if I overdose (Accupril)? What should I avoid while taking quinapril (Accupril)? What other drugs will affect quinapril (Accupril)? Where can I get more information? What is quinapril (Accupril)? Quinapril is an ACE inhibitor. ACE stands for angiotensin converting enzyme.Quinapril is used to treat high blood pressure (hypertension) and heart failure.Quinapril may also be used for purposes not listed in this medication guide. What are the possible side effects of quinapril (Accupril)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.Call your doctor at once if you have a serious side effect such as:feeling like you might pass out;fever, chills, body aches, flu symptoms;pale or yellowed skin, dark colored urine, fever, confusion or weakness;high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);chest pain;urinating more or less than usual, or not at all;swelling, rapid weight gain; orjaundice (yellowing of the skin or eyes).Less serious side effects may include:headache;cough;muscle pain, back pain;dizziness, tired feeling;nausea, vomiting, diarrhea, stomach discomfort; ormild skin itching or rash.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 quinapril (Accupril)? FDA pregnancy category D. Do not use quinapril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Avoid drinking alcohol. It can further lower your blood pressure and may increase some of the side effects of quinapril.Do not use salt substitutes or potassium supplements while taking quinapril, unless your doctor has told you to.Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking this medication, which can lead to severely low blood pressure or a serious electrolyte imbalance. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life."
},
"291": {
"property.id": 291,
"property.ts": "2017-12-04 04:42:05",
"property.key": "Accupril Patient Information including How Should I Take",
"property.value": "What should I discuss with my healthcare provider before taking quinapril (Accupril)? You should not use this medication if you are allergic to quinapril or to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), ramipril (Altace), or trandolapril (Mavik).To make sure you can safely take quinapril, tell your doctor if you have any of these other conditions:kidney disease (or if you are on dialysis);liver disease;heart disease or congestive heart failure;diabetes; ora connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.FDA pregnancy category D. Do not use quinapril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Quinapril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking quinapril.Quinapril can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I take quinapril (Accupril)? 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.Your doctor may occasionally change your dose to make sure you get the best results.Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking this medication, which can lead to severely low blood pressure or a serious electrolyte imbalance. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.Drink plenty of water while you are taking quinapril.Your blood pressure will need to be checked often. To be sure this medication is not causing harmful effects, your kidney or liver function will need to be checked with blood tests. Visit your doctor regularly.If you need surgery, tell the surgeon ahead of time that you are using quinapril. You may need to stop using the medicine for a short time.If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.Store at room temperature away from moisture, heat, and light."
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"property.id": 292,
"property.ts": "2017-12-04 04:42:05",
"property.key": "Accupril Patient Information including If I Miss a Dose",
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48 | 2017-08-31 23:12:57 | Accuretic | Quinapril HCl/Hydrochlorothiazide | FDA | { "48": { "alphabet_x_drug.id": 48, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"293": {
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"property.ts": "2017-12-04 04:42:12",
"property.key": "Drug Description",
"property.value": "Find Lowest Prices on ACCURETIC™ (quinapril HCl/hydrochlorothiazide) Tablets WARNING FETAL TOXICITY When pregnancy is detected, discontinue ACCURETIC as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity DESCRIPTION ACCURETIC is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride, and a thiazide diuretic, hydrochlorothiazide. Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]]-2-[2-[[1(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3isoquinolinecarboxylic acid, monohydrochloride. Its empirical formula is C25H30N2O5• HCl and its structural formula is: Quinapril hydrochloride is a white to off-white amorphous powder that is freely soluble in aqueous solvents. Hydrochlorothiazide is chemically described as: 6-Chloro-3,4-dihydro-2H-1,2,4benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8CIN3O4S2 and its structural formula is: Hydrochlorothiazide is a white to off-white, crystalline powder which is slightly soluble in water but freely soluble in sodium hydroxide solution. ACCURETIC is available for oral use as fixed combination tablets in three strengths of quinapril with hydrochlorothiazide: 10 mg with 12.5 mg (ACCURETIC 10/12.5), 20 mg with 12.5 mg (ACCURETIC 20/12.5), and 20 mg with 25 mg (ACCURETIC 20/25). Inactive ingredients: candelilla wax, crospovidone, hydroxypropyl cellulose, hypromellose, iron oxide red, iron oxide yellow, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide."
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"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Hypertension ACCURETIC is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with ACCURETIC. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. This fixed combination is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION). In using ACCURETIC, consideration should be given to the fact that another angiotensinconverting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that quinapril does not have a similar risk (see WARNINGS: Neutropenia/Agranulocytosis). Angioedema In Black Patients Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to non-blacks. It should also be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. DOSAGE AND ADMINISTRATION As individual monotherapy, quinapril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg and hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of quinapril/hydrochlorothiazide combination therapy using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing dose of either component. The side effects (see WARNINGS) of quinapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of quinapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but regimens that combine low doses of hydrochlorothiazide with quinapril produce minimal effects on serum potassium. In clinical trials of ACCURETIC, the average change in serum potassium was near zero in subjects who received HCTZ 6.25 mg in the combination, and the average subject who received 10 to 40/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy. To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy. Therapy Guided By Clinical Effect Patients whose blood pressures are not adequately controlled with quinapril monotherapy may instead be given ACCURETIC 10/12.5 or 20/12.5. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to ACCURETIC 10/12.5 or 20/12.5. Replacement Therapy For convenience, patients who are adequately treated with 20 mg of quinapril and 25 mg of hydrochlorothiazide and experience no significant electrolyte disturbances may instead wish to receive ACCURETIC 20/25. Use In Renal Impairment Regimens of therapy with ACCURETIC need not take account of renal function as long as the patient's creatinine clearance is > 30 mL/min/1.73 m² (serum creatinine roughly ≤ 3 mg/dL or 265 μmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides. Therefore, ACCURETIC is not recommended for use in these patients. HOW SUPPLIED ACCURETIC is available in tablets of three different strengths: 10/12.5 tablets: pink, scored elliptical, biconvex, film-coated tablets coded “PD 222” on one side. Each tablet contains 10 mg of quinapril and 12.5 mg of hydrochlorothiazide. NDC 0071-0222-23: 90 tablet bottles 20/12.5 tablets: pink, scored triangular, film-coated tablets coded “PD 220” on one side. Each tablet contains 20 mg of quinapril and 12.5 mg of hydrochlorothiazide. NDC 0071-0220-23: 90 tablet bottles 20/25 tablets: pink, round, biconvex, film-coated tablets coded “PD 223” on one side. Each tablet contains 20 mg of quinapril and 25 mg of hydrochlorothiazide. NDC 0071-0223-23: 90 tablet bottles Dispense in tight containers as defined in the USP. Store at Controlled Room Temperature 20–25°C (68–77°F) [see USP]. Distributed by: Parke-Davis, Division of Pfizer Inc., NY, NY 10017. Revised September 2015"
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"property.value": "WARNINGS Anaphylactoid And Possibly Related Reactions Presumably because angiotensin converting inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including quinapril) may be subject to a variety of adverse reactions, some of them serious. Head And Neck Angioedema Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors and has been seen in 0.1% of patients receiving quinapril. In two similarly sized US postmarketing quinapril trials that, combined, enrolled over 3,000 black patients and over 19,000 non-blacks, angioedema was reported in 0.30% and 0.55% of blacks (in Study 1 and 2, respectively) and 0.39% and 0.17% of non-blacks. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with ACCURETIC should be discontinued immediately, the patient treated in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy including, but not limited to, subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) should be promptly administered (see PRECAUTIONS and ADVERSE REACTIONS). Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema. Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Patients With A History Of Angioedema Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also CONTRAINDICATIONS). Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with Hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent challenge. Anaphylactoid Reactions During Membrane Exposure Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. Hepatic Failure Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. Hypotension ACCURETIC can cause symptomatic hypotension, probably not more frequently than either monotherapy. It was reported in 1.2% of 1,571 patients receiving ACCURETIC during clinical trials. Like other ACE inhibitors, quinapril has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension sometimes associated with oliguria and/or progressive azotemia, and rarely acute renal failure and/or death, include patients with the following conditions or characteristics: heart failure, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis or severe volume and/or salt depletion of any etiology. Volume and/or salt depletion should be corrected before initiating therapy with ACCURETIC. ACCURETIC should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of ACCURETIC may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergicblocking drugs. The antihypertensive effects of the thiazide component may also be enhanced in the postsympathectomy patients. In patients at risk of excessive hypotension, therapy with ACCURETIC should be started under close medical supervision. Such patients should be followed closely for the first 2 weeks of treatment and whenever the dosage of quinapril or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident. If excessive hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with intravenous infusion of normal saline. ACCURETIC treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of ACCURETIC may be necessary. Impaired Renal Function ACCURETIC should be used with caution in patients with severe renal disease. Thiazides may precipitate azotemia in such patients, and the effects of repeated dosing may be cumulative. When the renin-angiotensin-aldosterone system is inhibited by quinapril, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensinaldosterone system, treatment with angiotensin-converting enzyme inhibitors (including quinapril) may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. In clinical studies in hypertensive patients with unilateral renal artery stenosis, treatment with ACE inhibitors was associated with increases in blood urea nitrogen and serum creatinine; these increases were reversible upon discontinuation of ACE inhibitor, concomitant diuretic, or both. When such patients are treated with ACCURETIC, renal function should be monitored during the first few weeks of therapy. Some quinapril-treated hypertensive patients with no apparent preexisting renal vascular diseases have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when quinapril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of ACCURETIC may be required. Evaluation of the hypertensive patients should also include assessment of the renal function (see DOSAGE AND ADMINISTRATION). Neutropenia/Agranulocytosis Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease, such as systemic lupus erythematosus or scleroderma. Agranulocytosis did occur during quinapril treatment in one patient with a history of neutropenia during previous captopril therapy. Available data from clinical trials of quinapril are insufficient to show that, in patients without prior reactions to other ACE inhibitors, quinapril does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered. Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ACCURETIC as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue ACCURETIC, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to ACCURETIC for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use). Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that occurred in adults. No teratogenic effects of quinapril were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose. No teratogenic effects of ACCURETIC were seen in studies of pregnant rats and rabbits. On a mg/kg (quinapril/hydrochlorothiazide) basis, the doses used were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose. Impaired Hepatic Function ACCURETIC should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Also, since the metabolism of quinapril to quinaprilat is normally dependent upon hepatic esterases, patients with impaired liver function could develop markedly elevated plasma levels of quinapril. No normal pharmacokinetic studies have been carried out in hypertensive patients with impaired liver function. Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus. Acute Myopia And Secondary Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy. PRECAUTIONS General Serum Electrolyte Abnormalities In clinical trials, hyperkalemia (serum potassium ≥ 5.8 mmol/L) occurred in approximately 2% of patients receiving quinapril. In most cases, elevated serum potassium levels were isolated values which resolved despite continued therapy. Less than 0.1% of patients discontinued therapy due to hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of other drugs that raise serum potassium levels. Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. The risk of hyperkalemia may be increased in patients with renal insufficiency, diabetes mellitus or with concomitant use of drugs that raise serum potassium (see DRUG INTERACTIONS). The risk of hypokalemia may be increased in patients with cirrhosis, brisk diuresis, or with concomitant use of drugs that lower serum potassium. Monitor serum electrolytes periodically. Other Metabolic Disturbances Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels in patients with hypercalcemia receiving ACCURETIC. Cough Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. Surgery/Anesthesia In patients undergoing surgery or during anesthesia with agents that produce hypotension, quinapril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion. Laboratory Tests The hydrochlorothiazide component of ACCURETIC may decrease serum PBI levels without signs of thyroid disturbance. Therapy with ACCURETIC should be interrupted for a few days before carrying out tests of parathyroid function. Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with ACCURETIC. Quinapril hydrochloride was not carcinogenic in mice or rats when given in doses up to 75 or 100 mg/kg/day (50 or 60 times the maximum human daily dose, respectively, on a mg/kg basis and 3.8 or 10 times the maximum human daily dose on a mg/m² basis) for 104 weeks. Female rats given the highest dose level had an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas. Neither quinapril nor quinaprilat were mutagenic in the Ames bacterial assay with or without metabolic activation. Quinapril was also negative in the following genetic toxicology studies: in vitro mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test with mice, in vitro chromosome aberration with V79 cultured lung cells, and in an in vivo cytogenetic study with rat bone marrow. There were no adverse effects on fertility or reproduction in rats at doses up to 100 mg/kg/day (60 and 10 times the maximum daily human dose when based on mg/kg and mg/m², respectively). Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide in their feed for 2 years, at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in rats or female mice, but there was “equivocal” evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (the Ames test); in the Chinese hamster ovary (CHO) test for chromosomal aberrations; or in vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO sister chromatid exchange (clastogenicity) test and in the mouse lymphoma cell (mutagenicity) assays, using concentrations of hydrochlorothiazide of 43 to 1300 μg/mL. Positive test results were also obtained in the Aspergillus nidulans nondisjunction assay, using an unspecified concentration of hydrochlorothiazide. Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diets, to doses of up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation. Nursing Mothers Because quinapril and hydrochlorothiazide are secreted in human milk, caution should be exercised when ACCURETIC is administered to a nursing woman. Because of the potential for serious adverse reactions in nursing infants from hydrochlorothiazide and the unknown effects of quinapril in infants, a decision should be made whether to discontinue nursing or to discontinue ACCURETIC, taking into account the importance of the drug to the mother. Geriatric Use Clinical studies of quinapril HCl/hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Pediatric Use Neonates With A History Of In Utero Exposure To ACCURETIC: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of quinapril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means. Safety and effectiveness of ACCURETIC in children have not been established."
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"property.value": "CLINICAL PHARMACOLOGY Mechanism Of Action The principal metabolite of quinapril, quinaprilat, is an inhibitor of ACE activity in human subjects and animals. ACE is peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. The effect of quinapril in hypertension appears to result primarily from the inhibition of circulating and tissue ACE activity, thereby reducing angiotensin II formation. Quinapril inhibits the elevation in blood pressure caused by intravenously administered angiotensin I, but has no effect on the pressor response to angiotensin II, norepinephrine, or epinephrine. Angiotensin II also stimulates the secretion of aldosterone from the adrenal cortex, thereby facilitating renal sodium and fluid reabsorption. Reduced aldosterone secretion by quinapril may result in a small increase in serum potassium. In controlled hypertension trials, treatment with quinapril alone resulted in mean increases in potassium of 0.07 mmol/L (see PRECAUTIONS). Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA). While the principal mechanism of antihypertensive effect is thought to be through the renin-angiotensin-aldosterone system, quinapril exerts antihypertensive actions even in patients with low renin hypertension. Quinapril was an effective antihypertensive in all races studied, although it was somewhat less effective in blacks (usually a predominantly low renin group) than in non-blacks. ACE is identical to kininase II, an enzyme that degrades bradykinin, a potent peptide vasodilator; whether increased levels of bradykinin play a role in the therapeutic effect of quinapril remains to be elucidated. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldolsterone link is mediated by angiotensin, so coadministration of an ACE inhibitor tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown. Pharmacokinetics And Metabolism The rate and extent of absorption of quinapril and hydrochlorothiazide from ACCURETIC tablets are not different, respectively, from the rate and extent of absorption of quinapril and hydrochlorothiazide from immediate-release monotherapy formulations, either administered concurrently or separately. Following oral administration of Accupril (quinapril monotherapy) tablets, peak plasma quinapril concentrations are observed within 1 hour. Based on recovery of quinapril and its metabolites in urine, the extent of absorption is at least 60%. The absorption of hydrochlorothiazide is somewhat slower (1 to 2.5 hours) and more complete (50% to 80%). The rate of quinapril absorption was reduced by 14% when ACCURETIC tablets were administered with a high-fat meal as compared to fasting, while the extent of absorption was not affected. The rate of hydrochlorothiazide absorption was reduced by 12% when ACCURETIC tablets were administered with a high-fat meal, while the extent of absorption was not significantly affected. Therefore, ACCURETIC may be administered without regard to food. Following absorption, quinapril is deesterified to its major active metabolite, quinaprilat (about 38% of oral dose), and to other minor inactive metabolites. Following multiple oral dosing of quinapril, there is an effective accumulation half-life of quinaprilat of approximately 3 hours, and peak plasma quinaprilat concentrations are observed approximately 2 hours postdose. Approximately 97% of either quinapril or quinaprilat circulating in plasma is bound to proteins. Hydrochlorothiazide is not metabolized. Its apparent volume of distribution is 3.6 to 7.8 L/kg, consistent with measured plasma protein binding of 67.9%. The drug also accumulates in red blood cells, so that whole blood levels are 1.6 to 1.8 times those measured in plasma. Some placental passage occurred when quinapril was administered to pregnant rats. Studies in rats indicate that quinapril and its metabolites do not cross the blood-brain barrier. Hydrochlorothiazide crosses the placenta freely but not the blood-brain barrier. Quinaprilat is eliminated primarily by renal excretion, up to 96% of an IV dose, and has an elimination half-life in plasma of approximately 2 hours and a prolonged terminal phase with a half-life of 25 hours. Hydrochlorothiazide is excreted unchanged by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 4 to 15 hours. At least 61% of the oral dose is eliminated unchanged within 24 hours. In patients with renal insufficiency, the elimination half-life of quinaprilat increases as creatinine clearance decreases. There is a linear correlation between plasma quinaprilat clearance and creatinine clearance. In patients with end-stage renal disease, chronic hemodialysis or continuous ambulatory peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat. Elimination of quinaprilat is reduced in elderly patients ( ≥ 65 years) and in those with heart failure; this reduction is attributable to decrease in renal function (see DOSAGE AND ADMINISTRATION). Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired deesterification of quinapril. In a study of patients with impaired renal function (mean creatinine clearance of 19 mL/min), the half-life of hydrochlorothiazide elimination was lengthened to 21 hours. The pharmacokinetics of quinapril and quinaprilat are linear over a single-dose range of 5- to 80-mg doses and 40- to 160-mg in multiple daily doses. Pharmacodynamics And Clinical Effects Single doses of 20 mg of quinapril provide over 80% inhibition of plasma ACE for 24 hours. Inhibition of the pressor response to angiotensin I is shorter-lived, with a 20-mg dose giving 75% inhibition for about 4 hours, 50% inhibition for about 8 hours, and 20% inhibition at 24 hours. With chronic dosing, however, there is substantial inhibition of angiotensin II levels at 24 hours by doses of 20 to 80 mg. Administration of 10 to 80 mg of quinapril to patients with mild to severe hypertension results in a reduction of sitting and standing blood pressure to about the same extent with minimal effect on heart rate. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted (see WARNINGS ). Antihypertensive activity commences within 1 hour with peak effects usually achieved by 2 to 4 hours after dosing. During chronic therapy, most of the blood pressure lowering effect of a given dose is obtained in 1 to 2 weeks. In multiple-dose studies, 10 to 80 mg per day in single or divided doses lowered systolic and diastolic blood pressure throughout the dosing interval, with a trough effect of about 5 to 11/3 to 7 mm Hg. The trough effect represents about 50% of the peak effect. While the dose-response relationship is relatively flat, doses of 40 to 80 mg were somewhat more effective at trough than 10 to 20 mg, and twice-daily dosing tended to give a somewhat lower trough blood pressure than once-daily dosing with the same total dose. The antihypertensive effect of quinapril continues during long-term therapy, with no evidence of loss of effectiveness. Hemodynamic assessments in patients with hypertension indicate that blood pressure reduction produced by quinapril is accompanied by a reduction in total peripheral resistance and renal vascular resistance with little or no change in heart rate, cardiac index, renal blood flow, glomerular filtration rate, or filtration fraction. Therapeutic effects of quinapril appear to be the same for elderly ( ≥ 65 years of age) and younger adult patients given the same daily dosages, with no increase in adverse events in elderly patients. In patients with hypertension, quinapril 10 to 40 mg was similar in effectiveness to captopril, enalapril, propranolol, and thiazide diuretics. After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours. Use of quinapril with a thiazide diuretic gives blood pressure lowering effect greater than that seen with either agent alone. In clinical trials of quinapril/hydrochlorothiazide using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects were sustained for at least 24 hours, and increased with increasing dose of either component. Although quinapril monotherapy is somewhat less effective in blacks than in non-blacks, the efficacy of combination therapy appears to be independent of race. By blocking the reninangiotensin-aldosterone axis, administration of quinapril tends to reduce the potassium loss associated with the diuretic. In clinical trials of ACCURETIC, the average change in serum potassium was near zero when 2.5 to 40 mg of quinapril was combined with hydrochlorothiazide 6.25 mg, and the average subject who received 10 to 20/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy."
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"property.value": "PATIENT INFORMATION Angioedema Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. Tell patients receiving ACCURETIC to immediately report any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) and to temporarily discontinue Accuretic until after consulting with the prescribing physician. Pregnancy Tell female patients of childbearing age about the consequences of exposure to ACCURETIC during pregnancy. Discuss treatment options with women planning to become pregnant. Ask patients to report pregnancies to their physicians as soon as possible. Symptomatic Hypotension Tell patients receiving ACCURETIC that lightheadedness can occur, especially during the first days of therapy, and to report it to the prescribing physician. Tell the patient if syncope occurs, discontinue ACCURETIC until the physician has been consulted. Tell patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure because of reduction in fluid volume, with the same consequences of lightheadedness and possible syncope. Tell patients planning to undergo major surgery and/ or general or spinal anesthesia to inform their physicians that they are taking an ACE inhibitor. Hyperkalemia Tell patients receiving ACCURETIC not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician. Neutropenia Tell patients to promptly report any indication of infection (e.g., sore throat, fever) which could be a sign of neutropenia. NOTE: As with many other drugs, certain advice to patients being treated with quinapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects."
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"property.key": "Accuretic Patient Information Including Side Effects",
"property.value": "Find Lowest Prices on Brand Names: Accuretic Generic Name: hydrochlorothiazide and quinapril (Pronunciation: HYE droe klor oh THY a zide and KWIN a pril) What is hydrochlorothiazide and quinapril (Accuretic)? What are the possible side effects of hydrochlorothiazide and quinapril (Accuretic)? What is the most important information I should know about hydrochlorothiazide and quinapril (Accuretic)? What should I discuss with my healthcare provider before taking hydrochlorothiazide and quinapril (Accuretic)? How should I take hydrochlorothiazide and quinapril (Accuretic)? What happens if I miss a dose (Accuretic)? What happens if I overdose (Accuretic)? What should I avoid while taking hydrochlorothiazide and quinapril (Accuretic)? What other drugs will affect hydrochlorothiazide and quinapril (Accuretic)? Where can I get more information? What is hydrochlorothiazide and quinapril (Accuretic)? Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.Quinapril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme. Quinapril lowers blood pressure and also relieves symptoms of fluid retention.The combination of hydrochlorothiazide and quinapril is used to treat hypertension (high blood pressure).Hydrochlorothiazide and quinapril may also be used for purposes not listed in this medication guide. What are the possible side effects of hydrochlorothiazide and quinapril (Accuretic)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.Call your doctor at once if you have a serious side effect such as:eye pain, vision problems;high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling);dry mouth, thirst, nausea, vomiting;feeling weak, drowsy, restless, or light-headed;a red, blistering, peeling skin rash;jaundice (yellowing of the skin or eyes);urinating less than usual or not at all;swelling, weight gain, feeling short of breath; orfever, chills, body aches, flu symptoms.Less serious side effects may include:cough;dizziness, headache, tired feeling;muscle or back pain;runny nose;sleep problems (insomnia);diarrhea, constipation, upset stomach; ormild skin rash, increased sweating.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 hydrochlorothiazide and quinapril (Accuretic)? Do not use this medication if you are unable to urinate.You should not use this medication if you are allergic to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).Before taking hydrochlorothiazide and quinapril, tell your doctor if you have kidney disease (or are on dialysis), liver disease, glaucoma, congestive heart failure, gout, lupus, diabetes, or an allergy to sulfa drugs or penicillin.Do not use this medication if you are pregnant. It could harm the unborn baby.Do not use potassium supplements or salt substitutes while you are taking hydrochlorothiazide and quinapril, unless your doctor has told you to.Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking hydrochlorothiazide and quinapril. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting."
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"property.value": "What should I discuss with my healthcare provider before taking hydrochlorothiazide and quinapril (Accuretic)? Do not use this medication if you are allergic to hydrochlorothiazide or quinapril, or if you are unable to urinate.You should not use this medication if you are allergic to other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).To make sure you can safely take hydrochlorothiazide and quinapril, tell your doctor if you have any of these other conditions:kidney disease (or if you are on dialysis);liver disease;glaucoma;congestive heart failure;gout;lupus;diabetes; oran allergy to sulfa drugs or penicillin.FDA pregnancy category D. Do not use hydrochlorothiazide and quinapril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Use effective birth control while taking hydrochlorothiazide and quinapril.Hydrochlorothiazide can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I take hydrochlorothiazide and quinapril (Accuretic)? 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.Your doctor may occasionally change your dose to make sure you get the best results.Take this medicine with a full glass of water.Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking hydrochlorothiazide and quinapril. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.Your blood pressure will need to be checked often. Your blood and urine may also be tested if you have been vomiting or are dehydrated. Visit your doctor regularly.If you need surgery or medical tests, tell the doctor ahead of time that you are taking medication that contains hydrochlorothiazide. You may need to stop using the medicine for a short time.Keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.Store at room temperature away from moisture, heat, and light."
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50 | 2017-08-31 23:12:57 | Accutane | Isotretinoin | FDA | { "50": { "alphabet_x_drug.id": 50, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.value": "ACCUTANE® (isotretinoin) Capsules CAUSES BIRTH DEFECTS DO NOT GET PREGNANT CONTRAINDICATIONS AND WARNINGS Accutane (isotretinoin) 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 Accutane (isotretinoin) in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected. Birth defects which have been documented following Accutane (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. 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 of the abnormalities previously noted. If pregnancy does occur during treatment of a female patient who is taking Accutane (isotretinoin) , Accutane (isotretinoin) must be discontinued immediately and she should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling. Special Prescribing Requirements Because of Accutane (isotretinoin) 's teratogenicity and to minimize fetal exposure, Accutane (isotretinoin) is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called iPLEDGE™. Accutane (isotretinoin) must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Accutane (isotretinoin) must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE (see PRECAUTIONS). Table 1 : Monthly Required iPLEDGE Interactions Female Patients of Childbearing Potential Male Patients, And Female Patients Not of Childbearing Potential PRESCRIBER Confirms patient counseling X X Enters the 2 contraception methods chosen by the patient X Enters pregnancy test results X PATIENT Answers educational questions before every prescription X Enters 2 forms of contraception X PHARMACIST Contacts system to get an authorization X X DESCRIPTION Isotretinoin, a retinoid, is available as Accutane (isotretinoin) in 10-mg, 20-mg and 40-mg soft gelatin capsules for oral administration. Each capsule contains beeswax, butylated hydroxyanisole, edetate disodium, hydrogenated soybean oil flakes, hydrogenated vegetable oil, and soybean oil. Gelatin capsules contain glycerin and parabens (methyl and propyl), with the following dye systems: 10 mg — iron oxide (red) and titanium dioxide; 20 mg — FD&C Red No. 3, FD&C Blue No. 1, and titanium dioxide; 40 mg — FD&C Yellow No. 6, D&C Yellow No. 10, 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. The structural formula is:"
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"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Severe Recalcitrant Nodular Acne Accutane (isotretinoin) is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition,2 means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Accutane (isotretinoin) should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Accutane (isotretinoin) is indicated only for those female patients who are not pregnant, because Accutane (isotretinoin) can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS). 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.1,3,4 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 has shown that patients may continue to improve while off Accutane (isotretinoin) . The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). DOSAGE AND ADMINISTRATION Accutane (isotretinoin) should be administered with a meal (see PATIENT INFORMATION). The recommended dosage range for Accutane (isotretinoin) is 0.5 to 1.0 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1.0 mg/kg/day,8 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 2.0 mg/kg/day, as tolerated. Failure to take Accutane (isotretinoin) with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions. The safety of once daily dosing with Accutane (isotretinoin) has not been established. Once daily dosing is not recommended. 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 Accutane (isotretinoin) , even in low doses, has not been studied, and is not recommended. It is important that Accutane (isotretinoin) be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Accutane on bone loss is unknown (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure). Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS). Table 4 : Accutane (isotretinoin) Dosing by Body Weight (Based on Administration With Food) Body Weight Total mg/day 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 *See DOSAGE AND ADMINISTRATION: the recommended dosage range is 0.5 to 1.0 mg/kg/day. INFORMATION FOR PHARMACISTS Access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866495-0654) to obtain an authorization and the “do not dispense to patient after” date. Accutane (isotretinoin) must only be dispensed in no more than a 30-day supply. REFILLS REQUIRE A NEW PRESCRIPTION AND A NEW AUTHORIZATION FROM THE iPLEDGE SYSTEM. An Accutane (isotretinoin) Medication Guide must be given to the patient each time Accutane (isotretinoin) is dispensed, as required by law. This Accutane (isotretinoin) Medication Guide is an important part of the risk management program for the patient. HOW SUPPLIED Soft gelatin capsules, 10 mg (light pink), imprinted ACCUTANE (isotretinoin) 10 ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0155-49). Soft gelatin capsules, 20 mg (maroon), imprinted ACCUTANE (isotretinoin) 20 ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0169-49). Soft gelatin capsules, 40 mg (yellow), imprinted ACCUTANE (isotretinoin) 40 ROCHE. Boxes of 100 containing 10 Prescription Paks of 10 capsules (NDC 0004-0156-49). Storage Store at controlled room temperature (59° to 86°F, 15° to 30°C). Protect from light. REFERENCES 1. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med 300:329-333, 1979. 2. Pochi PE, Shalita AR, Strauss JS, Webster SB. Report of the consensus conference on acne classification. J Am Acad Dermatol 24:495-500, 1991. 3. Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acne with 13-cis-retinoic acid: evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol 3:602-611, 1980. 4. Jones H, Blanc D, Cunliffe WJ. 13-cisretinoic acid and acne. Lancet 2:1048-1049, 1980. 8. Strauss JS, Rapini RP, Shalita AR, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 10:490-496, 1984. Distributed by: Roche Laboratories Inc., 340 Kingsland Street, Nutley, New Jersey 07110-1199. PI Revised: January 2010."
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"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS Clinical Trials and Postmarketing Surveillance The adverse reactions listed below reflect the experience from investigational studies of Accutane (isotretinoin) , and the postmarketing experience. The relationship of some of these events to Accutane (isotretinoin) therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving Accutane (isotretinoin) are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, eg, of the lips, nasal passage, and eyes). Dose Relationship Cheilitis and hypertriglyceridemia are usually dose related. Most adverse reactions reported in clinical trials were reversible when therapy was discontinued; however, some persisted after cessation of therapy (see WARNINGS and ADVERSE REACTIONS). Body as a Whole allergic reactions, including vasculitis, systemic hypersensitivity (see PRECAUTIONS: Hypersensitivity), edema, fatigue, lymphadenopathy, weight loss Cardiovascular palpitation, tachycardia, vascular thrombotic disease, stroke Endocrine/Metabolic hypertriglyceridemia (see WARNINGS: Lipids), alterations in blood sugar levels (see PRECAUTIONS: Laboratory Tests) Gastrointestinal inflammatory bowel disease (see WARNINGS: Inflammatory Bowel Disease), hepatitis (see WARNINGS: Hepatotoxicity), pancreatitis (see WARNINGS: Lipids), bleeding and inflammation of the gums, colitis, esophagitis/esophageal ulceration, ileitis, nausea, other nonspecific gastrointestinal symptoms Hematologic allergic reactions (see PRECAUTIONS: Hypersensitivity), anemia, thrombocytopenia, neutropenia, rare reports of agranulocytosis (see PATIENT INFORMATION). See PRECAUTIONS: Laboratory Tests for other hematological parameters. Musculoskeletal skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density (see WARNINGS: Skeletal), musculoskeletal symptoms (sometimes severe) including back pain, myalgia, and arthralgia (see PATIENT INFORMATION), transient pain in the chest (see PATIENT INFORMATION ), arthritis, tendonitis, other types of bone abnormalities, elevations of CPK/rare reports of rhabdomyolysis (see PRECAUTIONS: Laboratory Tests). Neurological pseudotumor cerebri (see WARNINGS: Pseudotumor Cerebri), dizziness, drowsiness, headache, insomnia, lethargy, malaise, nervousness, paresthesias, seizures, stroke, syncope, weakness Psychiatric suicidal ideation, suicide attempts, suicide, depression, psychosis, aggression, violent behaviors (see WARNINGS: Psychiatric Disorders), emotional instability Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy. Reproductive System abnormal menses Respiratory bronchospasms (with or without a history of asthma), respiratory infection, voice alteration Skin and Appendages acne fulminans, alopecia (which in some cases persists), bruising, cheilitis (dry lips), dry mouth, dry nose, dry skin, epistaxis, eruptive xanthomas,7 erythema multiforme, flushing, fragility of skin, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, infections (including disseminated herpes simplex), 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; see PRECAUTIONS: Hypersensitivity), abnormal wound healing (delayed healing or exuberant granulation tissue with crusting; see PATIENT INFORMATION) Special Senses Hearing - hearing impairment (see WARNINGS: Hearing Impairment), tinnitus. Vision- corneal opacities (see WARNINGS: Corneal Opacities), decreased night vision which may persist (see WARNINGS: Decreased Night Vision), cataracts, color vision disorder, conjunctivitis, dry eyes, eyelid inflammation, keratitis, optic neuritis, photophobia, visual disturbances Urinary System glomerulonephritis (see PRECAUTIONS: Hypersensitivity), nonspecific urogenital findings (see PRECAUTIONS: Laboratory Tests for other urological parameters) Laboratory Elevation of plasma triglycerides (see WARNINGS: Lipids), decrease in serum high-density lipoprotein (HDL) levels, elevations of serum cholesterol during treatment Increased alkaline phosphatase, SGOT (AST), SGPT (ALT), GGTP or LDH (see WARNINGS: Hepatotoxicity) Elevation of fasting blood sugar, elevations of CPK (see PRECAUTIONS: Laboratory Tests), hyperuricemia Decreases in red blood cell parameters, decreases in white blood cell counts (including severe neutropenia and rare reports of agranulocytosis; see PATIENT INFORMATION), elevated sedimentation rates, elevated platelet counts, thrombocytopenia White cells in the urine, proteinuria, microscopic or gross hematuria DRUG INTERACTIONS Vitamin A: Because of the relationship of Accutane (isotretinoin) to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects. Tetracyclines: Concomitant treatment with Accutane (isotretinoin) and tetracyclines should be avoided because Accutane (isotretinoin) use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Micro-dosed Progesterone Preparations: Micro-dosed progesterone preparations (“minipills” that do not contain an estrogen) may be an inadequate method of contraception during Accutane (isotretinoin) therapy. Although other hormonal contraceptives are highly effective, there have been reports of pregnancy from female patients who have used combined oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products. These reports are more frequent for female patients who use only a single method of contraception. It is not known if hormonal contraceptives differ in their effectiveness when used with Accutane (isotretinoin) . Therefore, it is critically important for female patients of childbearing potential to select and commit to use 2 forms of effective contraception simultaneously, at least 1 of which must be a primary form (see PRECAUTIONS). Norethindrone/ethinyl estradiol: In a study of 31 premenopausal female patients with severe recalcitrant nodular acne receiving OrthoNovum® 7/7/7 Tablets as an oral contraceptive agent, Accutane (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. St. John's Wort: Accutane (isotretinoin) use is associated with depression in some patients (see WARNINGS: Psychiatric Disorders and ADVERSE REACTIONS: Psychiatric). 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. Phenytoin: Accutane (isotretinoin) has not been shown to alter the pharmacokinetics of phenytoin in a study 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 CYP 2C9 human hepatic P450 enzyme. Phenytoin is known to cause osteomalacia. No formal clinical studies have been conducted to assess if there is an interactive effect on bone loss between phenytoin and Accutane (isotretinoin) . Therefore, caution should be exercised when using these drugs together. Systemic Corticosteroids: Systemic corticosteroids are known to cause osteoporosis. No formal clinical studies have been conducted to assess if there is an interactive effect on bone loss between systemic corticosteroids and Accutane (isotretinoin) . Therefore, caution should be exercised when using these drugs together. Laboratory Tests Pregnancy Test Female patients of childbearing potential must have had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial Accutane (isotretinoin) prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for Accutane (isotretinoin) . 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, the second pregnancy test must be done during the first 5 days of the menstrual period immediately preceding the beginning of Accutane (isotretinoin) 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, the second pregnancy test must be done immediately preceding the beginning of Accutane (isotretinoin) therapy and after the patient has used 2 forms of contraception for 1 month. Each month of 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. Lipids: 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 Accutane (isotretinoin) is established. The incidence of hypertriglyceridemia is 1 patient in 4 on Accutane therapy (see WARNINGS: Lipids). Liver Function Tests: Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to Accutane has been established (see WARNINGS: Hepatotoxicity). Glucose: Some patients receiving Accutane (isotretinoin) have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during Accutane (isotretinoin) therapy, although no causal relationship has been established. CPK: Some patients undergoing vigorous physical activity while on Accutane (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 a clinical trial of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, transient 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 trial. REFERENCES 7. Dicken CH, Connolly SM. Eruptive xanthomas associated with isotretinoin (13-cis-retinoic acid). Arch Dermatol 116:951-952, 1980."
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"property.value": "WARNINGS Psychiatric Disorders Accutane (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 events (see ADVERSE REACTIONS: Psychiatric). 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Accutane (isotretinoin) therapy. Pseudotumor Cerebri Accutane (isotretinoin) use has been associated with a number of 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 Accutane (isotretinoin) immediately and be referred to a neurologist for further diagnosis and care (see ADVERSE REACTIONS: Neurological). Serious Skin Reactions There have been post-marketing reports of erythema multiforme and severe skin reactions [eg, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)] associated with isotretinoin use. These events 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 Accutane (isotretinoin) should be considered if warranted. Pancreatitis Acute pancreatitis has been reported in patients with either elevated or normal serum triglyceride levels. In rare instances, fatal hemorrhagic pancreatitis has been reported. Accutane (isotretinoin) should be stopped if hypertriglyceridemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur. Lipids Elevations of serum triglycerides in excess of 800 mg/dL have been reported in patients treated with Accutane (isotretinoin) . Marked elevations of serum triglycerides were reported in approximately 25% of patients receiving Accutane (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 on triglycerides, HDL, and cholesterol were reversible upon cessation of Accutane (isotretinoin) therapy. Some patients have been able to reverse triglyceride elevation by reduction in weight, restriction of dietary fat and alcohol, and reduction in dose while continuing Accutane (isotretinoin) .5 Blood lipid determinations should be performed before Accutane (isotretinoin) is given and then at intervals until the lipid response to Accutane (isotretinoin) 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 during Accutane (isotretinoin) therapy (patients with diabetes, obesity, increased alcohol intake, lipid metabolism disorder or familial history of lipid metabolism disorder). If Accutane (isotretinoin) therapy is instituted, more frequent checks of serum values for lipids and/or blood sugar are recommended (see PRECAUTIONS: Laboratory Tests). The cardiovascular consequences of hypertriglyceridemia associated with Accutane (isotretinoin) are unknown. Animal Studies: In rats given 8 or 32 mg/kg/day of isotretinoin (1.3 to 5.3 times the recommended clinical dose of 1.0 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 1.0 mg/kg/day, respectively, after normalization for total body surface area). Hearing Impairment Impaired hearing has been reported in patients taking Accutane (isotretinoin) ; in some cases, the hearing impairment has been reported to persist after therapy has been discontinued. Mechanism(s) and causality for this event have not been established. Patients who experience tinnitus or hearing impairment should discontinue Accutane (isotretinoin) treatment and be referred for specialized care for further evaluation (see ADVERSE REACTIONS: Special Senses). Hepatotoxicity Clinical hepatitis considered to be possibly or probably related to Accutane (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, 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 Accutane (isotretinoin) , the drug should be discontinued and the etiology further investigated. Inflammatory Bowel Disease Accutane (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 Accutane (isotretinoin) treatment has been stopped. Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue Accutane immediately (see ADVERSE REACTIONS: Gastrointestinal). Skeletal Bone Mineral Density Effects of multiple courses of Accutane (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. In an open-label clinical trial (N=217) of a single course of therapy with Accutane (isotretinoin) for 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 studies 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 study of 10 patients, ages 13-18 years, who started a second course of Accutane (isotretinoin) 4 months after the first course, two patients showed a decrease in mean lumbar spine bone mineral density up to 3.25% (see PRECAUTIONS: Pediatric Use). Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the Accutane (isotretinoin) population. While causality to Accutane (isotretinoin) has not been established, an effect cannot be ruled out. Longer term effects have not been studied. It is important that Accutane (isotretinoin) 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. Additionally, skeletal hyperostosis was noted in 6 of 8 patients in a prospective study of disorders of keratinization.6 Minimal skeletal hyperostosis and calcification of ligaments and tendons have also been observed by x-ray in prospective studies of nodular acne patients treated with a single course of therapy at recommended doses. The skeletal effects of multiple Accutane (isotretinoin) treatment courses for acne are unknown. In a clinical study 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 Accutane (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 reports of premature epiphyseal closure in acne patients receiving recommended doses of Accutane (isotretinoin) . The effect of multiple courses of Accutane (isotretinoin) on epiphyseal closure is unknown. Vision Impairment Visual problems should be carefully monitored. All Accutane (isotretinoin) patients experiencing visual difficulties should discontinue Accutane (isotretinoin) treatment and have an ophthalmological examination (see ADVERSE REACTIONS: Special Senses). Corneal Opacities Corneal opacities have occurred in patients receiving Accutane (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 Accutane (isotretinoin) have either completely resolved or were resolving at follow-up 6 to 7 weeks after discontinuation of the drug (see ADVERSE REACTIONS: Special Senses). Decreased Night Vision Decreased night vision has been reported during Accutane (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. PRECAUTIONS Accutane (isotretinoin) must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Accutane (isotretinoin) must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE. Registered and activated pharmacies must receive Accutane (isotretinoin) only from wholesalers registered with iPLEDGE. iPLEDGE program requirements for wholesalers, prescribers, and pharmacists are described below: Wholesalers For the purpose of the iPLEDGE program, the term wholesaler refers to wholesaler, distributor, and/or chain pharmacy distributor. To distribute Accutane (isotretinoin) , wholesalers must be registered with iPLEDGE, and agree to meet all iPLEDGE requirements for wholesale distribution of isotretinoin products. Wholesalers must register with iPLEDGE by signing and returning the iPLEDGE wholesaler agreement that affirms they will comply with all iPLEDGE requirements for distribution of isotretinoin. These include: Registering prior to distributing isotretinoin and re-registering annually thereafter Distributing only FDA approved isotretinoin product Only shipping isotretinoin to wholesalers registered in the iPLEDGE program with prior written consent from the manufacturer or pharmacies licensed in the US and registered and activated in the iPLEDGE program Notifying the isotretinoin manufacturer (or delegate) of any non-registered and/or nonactivated pharmacy or unregistered wholesaler that attempts to order isotretinoin Complying with inspection of wholesaler records for verification of compliance with the iPLEDGE program by the isotretinoin manufacturer (or delegate) Returning to the manufacturer (or delegate) any undistributed product if registration is revoked by the manufacturer or if the wholesaler chooses to not re-register annually Prescribers To prescribe isotretinoin, the prescriber must be registered and activated with the pregnancy risk management program iPLEDGE. Prescribers can register by signing and returning the completed registration form. Prescribers can only activate their registration by affirming that they meet requirements and will comply with all iPLEDGE requirements by attesting to the following points: I know the risk and severity of fetal injury/birth defects from isotretinoin. I know the risk factors for unplanned pregnancy and the effective measures for avoidance of unplanned pregnancy. I have the expertise to provide the patient with detailed pregnancy prevention counseling or I will refer her to an expert for such counseling, reimbursed by the manufacturer. I will comply with the iPLEDGE program requirements described in the booklets entitled The Guide to Best Practices for the iPLEDGE Program and The iPLEDGE Program Prescriber Contraception Counseling Guide. Before beginning treatment of female patients of childbearing potential with isotretinoin and on a monthly basis, the patient will be counseled to avoid pregnancy by using two forms of contraception simultaneously and continuously one month before, during, and one month after isotretinoin therapy, unless the patient commits to continuous abstinence. I will not prescribe isotretinoin to any female patient of childbearing potential until verifying she has a negative screening pregnancy test and monthly negative CLIA-certified (Clinical Laboratory Improvement Amendment) pregnancy tests. Patients should have a pregnancy test at the completion of the entire course of isotretinoin and another pregnancy test 1 month later. I will report any pregnancy case that I become aware of while the female patient is on isotretinoin or 1 month after the last dose to the pregnancy registry. To prescribe isotretinoin, the prescriber must access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) to: Register each patient in the iPLEDGE program. Confirm monthly that each patient has received counseling and education. For female patients of childbearing potential: Enter patient's two chosen forms of contraception each month. Enter monthly result from CLIA-certified laboratory conducted pregnancy test. Isotretinoin 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. Isotretinoin must only be dispensed by a pharmacy registered and activated with the pregnancy risk management program iPLEDGE and only when the registered patient meets all the requirements of the iPLEDGE program. Meeting the requirements for a female patient of childbearing potential signifies that she: Has been counseled and has signed a Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form that contains warnings about the risk of potential birth defects if the fetus is exposed to isotretinoin. The patient must sign the informed consent form before starting treatment and patient counseling must also be done at that time and on a monthly basis thereafter. Has had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial isotretinoin prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for isotretinoin. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the 2 tests should be at least 19 days. For patients with regular menstrual cycles, the second pregnancy test should be done during the first 5 days of the menstrual period immediately preceding the beginning of isotretinoin 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, the second pregnancy test must be done immediately preceding the beginning of isotretinoin therapy and after the patient has used 2 forms of contraception for 1 month. Has had a negative result from a urine or serum pregnancy test in a CLIA-certified laboratory before receiving each subsequent course of isotretinoin. A pregnancy test must be repeated every month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription. Has selected and has committed to 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 isotretinoin therapy, during isotretinoin therapy, and for 1 month after discontinuing isotretinoin therapy. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis. If the patient has unprotected heterosexual intercourse at any time 1 month before, during, or 1 month after therapy, she must: Stop taking Accutane (isotretinoin) 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 Accutane (isotretinoin) 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. 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 oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products; these pregnancies occurred while these patients were taking Accutane (isotretinoin) . These reports are more frequent for female patients who use only a single method of contraception. Therefore, it is critically important that female patients of childbearing potential use 2 effective forms of contraception simultaneously. Patients must receive written warnings about the rates of possible contraception failure (included in patient education kits). 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 Accutane (see PRECAUTIONS: DRUG INTERACTIONS). 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. If a pregnancy does occur during isotretinoin treatment, isotretinoin 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 isotretinoin therapy must be reported immediately to the FDA via the MedWatch number 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com). All Patients Isotretinoin is contraindicated in female patients who are pregnant. To receive isotretinoin all patients must meet all of the following conditions: Must be registered with the iPLEDGE program by the prescriber Must understand that severe birth defects can occur with the use of isotretinoin by female patients Must be reliable in understanding and carrying out instructions Must sign a Patient Information/Informed Consent (for all patients) form that contains warnings about the potential risks associated with isotretinoin Must fill and pick up the prescription within 7 days of the date of specimen collection for the pregnancy test for female patients of childbearing potential Must fill and pick up the prescription within 30 days of the office visit for male patients and female patients not of childbearing potential Must not donate blood while on isotretinoin and for 1 month after treatment has ended Must not share isotretinoin with anyone, even someone who has similar symptoms Female Patients of Childbearing Potential Isotretinoin is contraindicated in female patients who are pregnant. In addition to the requirements for all patients described above, female patients of childbearing potential must meet the following conditions: Must NOT be pregnant or breast-feeding Must comply with the required pregnancy testing at a CLIA-certified laboratory Must fill and pick up the prescription within 7 days of the date of specimen collection for the pregnancy test Must be capable of complying with the mandatory contraceptive measures required for isotretinoin therapy, or commit to continuous abstinence from heterosexual intercourse, and understand behaviors associated with an increased risk of pregnancy Must understand that it is her responsibility to avoid pregnancy one month before, during and one month after isotretinoin therapy Must have signed an additional Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form, before starting isotretinoin, that contains warnings about the risk of potential birth defects if the fetus is exposed to isotretinoin Must access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654), before starting isotretinoin, on a monthly basis during therapy, and 1 month after the last dose to answer questions on the program requirements and to enter the patient's two chosen forms of contraception Must have been informed of the purpose and importance of providing information to the iPLEDGE program should she become pregnant while taking isotretinoin or within 1 month of the last dose Pharmacists To dispense isotretinoin, pharmacies must be registered and activated with the pregnancy risk management program iPLEDGE. The Responsible Site Pharmacist must register the pharmacy by signing and returning the completed registration form. After registration, the Responsible Site Pharmacist can only activate the pharmacy registration by affirming that they meet requirements and will comply with all iPLEDGE requirements by attesting to the following points: I know the risk and severity of fetal injury/birth defects from isotretinoin. I will train all pharmacists, who participate in the filling and dispensing of isotretinoin prescriptions, on the iPLEDGE program requirements. I will comply and seek to ensure all pharmacists who participate in the filling and dispensing of isotretinoin prescriptions comply with the iPLEDGE program requirements described in the booklet entitled Pharmacist Guide for the iPLEDGE Program. I will obtain Accutane (isotretinoin) product only from iPLEDGE registered wholesalers. I will not sell, buy, borrow, loan or otherwise transfer isotretinoin in any manner to or from another pharmacy. I will return to the manufacturer (or delegate) any unused product if registration is revoked by the manufacturer or if the pharmacy chooses to not reactivate annually. I will not fill isotretinoin for any party other than a qualified patient. To dispense isotretinoin, the pharmacist must: be trained by the Responsible Site Pharmacist concerning the iPLEDGE program requirements. obtain authorization from the iPLEDGE program via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) for every isotretinoin prescription. Authorization signifies that the patient has met all program requirements and is qualified to receive isotretinoin. write the Risk Management Authorization (RMA) number on the prescription. Accutane (isotretinoin) must only be dispensed: in no more than a 30-day supply with an Accutane Medication Guide after authorization from the iPLEDGE program prior to the “do not dispense to patient after” date provided by the iPLEDGE system (within 30 days of the office visit for male patients and female patients not of childbearing potential and within 7 days of the date of specimen collection for female patients of childbearing potential) with a new prescription for refills and another authorization from the iPLEDGE program (No automatic refills are allowed) An Accutane Medication Guide must be given to the patient each time Accutane (isotretinoin) is dispensed, as required by law. This Accutane Medication Guide is an important part of the risk management program for the patients. Accutane (isotretinoin) must not be prescribed, dispensed or otherwise obtained through the internet or any other means outside of the iPLEDGE program. Only FDA-approved Accutane (isotretinoin) products must be distributed, prescribed, dispensed, and used. Patients must fill Accutane (isotretinoin) prescriptions only at US licensed pharmacies. A description of the iPLEDGE program educational materials available with iPLEDGE is provided below. The main goal of these educational materials is to explain the iPLEDGE program requirements and to reinforce the educational messages. The Guide to Best Practices for the iPLEDGE Program includes: isotretinoin teratogenic potential, information on pregnancy testing, and the method to complete a qualified isotretinoin prescription. The iPLEDGE Program Prescriber Contraception Counseling Guide includes: specific information about effective contraception, the limitations of contraceptive methods, behaviors associated with an increased risk of contraceptive failure and pregnancy and the methods to evaluate pregnancy risk. The Pharmacist Guide for the iPLEDGE Program includes: isotretinoin teratogenic potential and the method to obtain authorization to dispense an isotretinoin prescription. The iPLEDGE program is a systematic approach to comprehensive patient education about their responsibilities and includes education for contraception compliance and reinforcement of educational messages. The iPLEDGE program includes information on the risks and benefits of isotretinoin which is linked to the Medication Guide dispensed by pharmacists with each isotretinoin prescription. Female patients not of childbearing potential and male patients, and female patients of childbearing potential are provided with separate booklets. Each booklet contains information on isotretinoin therapy including precautions and warnings, a Patient Information/Informed Consent (for all patients) form, and a toll-free line which provides isotretinoin information in 2 languages. The booklet for female patients not of childbearing potential and male patients, The iPLEDGE Program Guide to Isotretinoin for Male Patients and Female Patients Who Cannot Get Pregnant, also includes information about male reproduction and a warning not to share isotretinoin with others or to donate blood during isotretinoin therapy and for 1 month following discontinuation of isotretinoin. The booklet for female patients of childbearing potential, The iPLEDGE Program Guide to Isotretinoin for Female Patients Who Can Get Pregnant, includes a referral program that offers female patients free contraception counseling, reimbursed by the manufacturer, by a reproductive specialist; and a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form concerning birth defects. The booklet, The iPLEDGE Program Birth Control Workbook includes information on the types of contraceptive methods, the selection and use of appropriate, effective contraception, the rates of possible contraceptive failure and a toll-free contraception counseling line. In addition, there is a patient educational DVD with the following videos — “Be Prepared, Be Protected” and “Be Aware: The Risk of Pregnancy While on Isotretinoin” (see PATIENT INFORMATION ). General Although an effect of Accutane (isotretinoin) on bone loss is not established, physicians should use caution when prescribing Accutane (isotretinoin) to patients with a genetic predisposition for age-related osteoporosis, 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. Patients may be at increased risk when participating in sports with repetitive impact where the risks of spondylolisthesis with and without pars fractures and hip growth plate injuries in early and late adolescence are known. There are spontaneous reports of fractures and/or delayed healing in patients while on therapy with Accutane (isotretinoin) or following cessation of therapy with Accutane (isotretinoin) while involved in these activities. While causality to Accutane (isotretinoin) has not been established, an effect must not be ruled out. Information for Patients See PRECAUTIONS and Boxed CONTRAINDICATIONS AND WARNINGS. Patients must be instructed to read the Medication Guide supplied as required by law when Accutane (isotretinoin) is dispensed. The complete text of the Medication Guide is reprinted at the end of this document. For additional information, patients must also be instructed to read the iPLEDGE program patient educational materials. All patients must sign the Patient Information/Informed Consent (for all patients) form. Female patients of childbearing potential must be instructed that they must not be pregnant when Accutane (isotretinoin) therapy is initiated, and that they should use 2 forms of effective contraception simultaneously for 1 month before starting Accutane (isotretinoin) , while taking Accutane (isotretinoin) , and for 1 month after Accutane (isotretinoin) has been stopped, unless they commit to continuous abstinence from heterosexual intercourse. They should also sign a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form prior to beginning Accutane (isotretinoin) therapy. They should be given an opportunity to view the patient DVD provided by the manufacturer to the prescriber. The DVD 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 Accutane (isotretinoin) at any time during pregnancy. 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 Accutane prescription is written (see Boxed CONTRAINDICATIONS AND WARNINGS and PRECAUTIONS). Accutane (isotretinoin) is found in the semen of male patients taking Accutane (isotretinoin) , but the amount delivered to a female partner would be about 1 million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin induced embryopathy is unknown, 20 years of postmarketing reports include 4 with isolated defects compatible with features of retinoid exposed fetuses; however 2 of these reports were incomplete, and 2 had other possible explanations for the defects observed. 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 Accutane (isotretinoin) 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. Signs and 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Accutane (isotretinoin) therapy. Patients must be informed that some patients, while taking Accutane (isotretinoin) or soon after stopping Accutane (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 Accutane (isotretinoin) 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. There were reports that some of these people did not appear depressed. There have been reports of patients on Accutane (isotretinoin) becoming aggressive or violent. No one knows if Accutane (isotretinoin) caused these behaviors or if they would have happened even if the person did not take Accutane (isotretinoin) . Some people have had other signs of depression while taking Accutane (isotretinoin) . Patients must be informed that they must not share Accutane (isotretinoin) with anyone else because of the risk of birth defects and other serious adverse events. 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 Accutane (isotretinoin) . Patients should be reminded to take Accutane with a meal (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 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 Accutane (isotretinoin) therapy and for at least 6 months thereafter due to the possibility of scarring (see ADVERSE REACTIONS: Skin and Appendages). Patients should be advised to avoid prolonged exposure to UV rays or sunlight. Patients should be informed that they may experience decreased tolerance to contact lenses during and after therapy. Patients should be informed that approximately 16% of patients treated with Accutane (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 Accutane (isotretinoin) , but in some cases persisted (see ADVERSE REACTIONS: Musculoskeletal). There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity (see Laboratory Tests: CPK). Pediatric patients and their caregivers should be informed that approximately 29% (104/358) of pediatric patients treated with Accutane (isotretinoin) 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 Accutane (isotretinoin) . Consideration should be given to discontinuation of Accutane (isotretinoin) if any significant abnormality is found. Neutropenia and rare cases of agranulocytosis have been reported. Accutane (isotretinoin) 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. Accutane (isotretinoin) should be discontinued if clinically significant skin reactions occur. Hypersensitivity Anaphylactic reactions and other allergic reactions have been reported. 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. 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 1.0 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 1.0 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 1.0 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 studies 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 Accutane (isotretinoin) therapy for nodular acne, no significant effects were seen on ejaculate volume, sperm count, total sperm motility, morphology or seminal plasma fructose. Pregnancy Category X. See Boxed CONTRAINDICATIONS AND WARNINGS. Nursing Mothers It is not known whether this drug is excreted in human milk. Because of the potential for adverse effects, nursing mothers should not receive Accutane (isotretinoin) . Pediatric Use The use of Accutane (isotretinoin) in pediatric patients less than 12 years of age has not been studied. The use of Accutane (isotretinoin) 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 PRECAUTIONS: General). Use of Accutane (isotretinoin) in this age group for severe recalcitrant nodular acne is supported by evidence from a clinical study comparing 103 pediatric patients (13 to 17 years) to 197 adult patients ( ≥ 18 years). Results from this study demonstrated that Accutane (isotretinoin) , at a dose of 1 mg/kg/day given in two divided doses, was equally effective in treating severe recalcitrant nodular acne in both pediatric and adult patients. In studies with Accutane (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 (see ADVERSE REACTIONS). In an open-label clinical trial (N=217) of a single course of therapy with Accutane (isotretinoin) for 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 studies 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 study of 10 patients, ages 13 to 18 years, who started a second course of Accutane (isotretinoin) 4 months after the first course, two patients showed a decrease in mean lumbar spine bone mineral density up to 3.25% (see WARNINGS: Skeletal: Bone Mineral Density). Geriatric Use Clinical studies of isotretinoin 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 isotretinoin therapy (see WARNINGS and PRECAUTIONS). REFERENCES 5. Katz RA, Jorgensen H, Nigra TP. Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization. Arch Dermatol 116:1369-1372, 1980. 6. Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ. Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol 10:1024-1029, 1984."
},
"307": {
"property.id": 307,
"property.ts": "2017-12-04 04:42:19",
"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE The oral LD50 of isotretinoin is greater than 4000 mg/kg in rats and mice ( > 600 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the rat dose for total body surface area and > 300 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1.0 mg/kg/day after normalization for total body surface area). 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. Accutane (isotretinoin) causes serious birth defects at any dosage (see Boxed CONTRAINDICATIONS AND WARNINGS). Female patients of childbearing potential who present with isotretinoin 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 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 isotretinoin overdose should not donate blood for at least 1 month. CONTRAINDICATIONS Pregnancy Category X. See Boxed CONTRAINDICATIONS AND WARNINGS. Allergic Reactions Accutane (isotretinoin) is contraindicated in patients who are hypersensitive to this medication or to any of its components. Accutane (isotretinoin) should not be given to patients who are sensitive to parabens, which are used as preservatives in the gelatin capsule (see PRECAUTIONS: Hypersensitivity)."
},
"308": {
"property.id": 308,
"property.ts": "2017-12-04 04:42:19",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Isotretinoin is a retinoid, which when administered in pharmacologic dosages of 0.5 to 1.0 mg/kg/day (see DOSAGE AND ADMINISTRATION), inhibits sebaceous gland function and keratinization. The exact mechanism of action of isotretinoin is unknown. Nodular Acne 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 Accutane (isotretinoin) , and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.1 Pharmacokinetics Absorption Due to its high lipophilicity, oral absorption of isotretinoin is enhanced when given with a high-fat meal. In a crossover study, 74 healthy adult subjects received a single 80 mg oral dose (2 x 40 mg capsules) of Accutane (isotretinoin) under fasted and fed conditions. Both peak plasma concentration (Cmax) and the total exposure (AUC) of isotretinoin were more than doubled following a standardized high-fat meal when compared with Accutane (isotretinoin) given under fasted conditions (see Table 2). The observed elimination half-life was unchanged. This lack of change in half-life suggests that food increases the bioavailability of isotretinoin without altering its disposition. The time to peak concentration (Tmax) was also increased with food and may be related to a longer absorption phase. Therefore, Accutane (isotretinoin) capsules should always be taken with food (see DOSAGE AND ADMINISTRATION). Clinical studies have shown that there is no difference in the pharmacokinetics of isotretinoin between patients with nodular acne and healthy subjects with normal skin. Table 2 : Pharmacokinetic Parameters of Isotretinoin Mean (%CV), N=74 Accutane 2 x 40 mg Capsules AUC0-∞ (ng×hr/mL) Cmax (ng/mL) Tmax (hr) t½ (hr) Fed* 10,004 (22%) 862 (22%) 5.3 (77%) 21 (39%) Fasted 3,703 (46%) 301 (63%) 3.2 (56%) 21 (30%) *Eating a standardized high-fat meal 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-oxotretinoin). 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 80 mg oral dose of Accutane (isotretinoin) to 74 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. After multiple oral dose administration of isotretinoin to adult cystic acne patients ( ≥ 18 years), the exposure of patients to 4-oxo-isotretinoin at steady-state under fasted and fed conditions was approximately 3.4 times higher than that of isotretinoin. 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, 14Cactivity 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 80 mg oral dose of Accutane (isotretinoin) to 74 healthy adult subjects under fed conditions, the mean ± SD elimination half-lives (t½) of isotretinoin and 4-oxo-isotretinoin were 21.0 ± 8.2 hours and 24.0 ± 5.3 hours, respectively. After both single and multiple doses, the observed accumulation ratios of isotretinoin ranged from 0.90 to 5.43 in patients with cystic acne. Special Patient Populations Pediatric Patients 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 Accutane (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. The dose-normalized pharmacokinetic parameters for isotretinoin following single and multiple doses are summarized in Table 3 for pediatric patients. There were no statistically significant differences in the pharmacokinetics of isotretinoin between pediatric and adult patients. Table 3 : Pharmacokinetic Parameters of Isotretinoin Following Single and Multiple Dose Administration in Pediatric Patients, 12 to 15 Years of Age Mean (± SD), N=38* Parameter Isotretinoin (Single Dose) Isotretinoin (Steady-State) Cmax (ng/mL) 573.25 (278.79) 731.98 (361.86) AUC(0-12) (nghr/mL) × 3033.37 (1394.17) 5082.00 (2184.23) AUC(0-24) (ng x hr/mL) 6003.81 (2885.67) – Tmax (hr)† 6.00 (1.00-24.60) 4.00 (0-12.00) Cssmin (ng/mL) – 352.32 (184.44) T½ (hr) – 15.69 (5.12) CL/F (L/hr) – 17.96 (6.27) *The single and multiple dose data in this table were obtained following a non-standardized meal that is not comparable to the high-fat meal that was used in the study in Table 2. †Median (range) In pediatric patients (12 to 15 years), the mean ± SD elimination half-lives (t½) of isotretinoin and 4-oxo-isotretinoin were 15.7 ± 5.1 hours and 23.1 ± 5.7 hours, respectively. The accumulation ratios of isotretinoin ranged from 0.46 to 3.65 for pediatric patients. REFERENCES 1. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med 300:329-333, 1979."
},
"309": {
"property.id": 309,
"property.ts": "2017-12-04 04:42:19",
"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) To be completed by the patient (and her parent or guardian* if patient is under age 18) and signed by her doctor. Read each item below and initial in the space provided to show that you understand each item and agree to follow your doctor's instructions. Do not sign this consent and do not take isotretinoin if there is anything that you do not understand. *A parent or guardian of a minor patient (under age 18) must also read and initial each item before signing the consent. ______________________________________________________________ (Patient's Name) 1. I understand that there is a very high chance that my unborn baby could have severe birth defects if I am pregnant or become pregnant while taking isotretinoin. This can happen with any amount and even if taken for short periods of time. This is why I must not be pregnant while taking isotretinoin. Initial: ______ 2. I understand that I must not get pregnant 1 month before, during the entire time of my treatment, and for 1 month after the end of my treatment with isotretinoin. Initial: ______ 3. I understand that I must avoid sexual intercourse completely, o r I must use 2 separate, effective forms of birth control (contraception) at the same time. The only exceptions are if I have had surgery to remove the uterus (a hysterectomy) or both of my ovaries (bilateral oophorectomy), or my doctor has medically confirmed that I am post-menopausal. Initial: ______ 4. I understand that hormonal birth control products are among the most effective forms of birth control. Combination birth control pills and other hormonal products include skin patches, shots, under-the-skin implants, vaginal rings, and intrauterine devices (IUDs). Any form of birth control can fail. That is why I must use 2 different birth control methods at the same time, starting 1 month before, during, and for 1 month after stopping therapy every time I have sexual intercourse, even if 1 of the methods I choose is hormonal birth control. Initial: ______ 5. I understand that the following are effective forms of birth control: Primary forms tying my tubes (tubal sterilization) partner's vasectomy intrauterine device hormonal (combination birth control pills, skin patches, shots, under-the-skin implants, or vaginal ring) Secondary forms Barrier: male latex condom with or without spermicide diaphragm with spermicide cervical cap with spermicide Other: vaginal sponge (contains spermicide) A diaphragm and cervical cap must each be used with spermicide, a special cream that kills sperm I understand that at least 1 of my 2 forms of birth control must be a primary method. Initial: ______ 6. I will talk with my doctor about any medicines including herbal products I plan to take during my isotretinoin treatment because hormonal birth control methods may not work if I am taking certain medicines or herbal products. Initial: ______ 7. I may receive a free birth control counseling session from a doctor or other family planning expert. My isotretinoin doctor can give me an isotretinoin Patient Referral Form for this free consultation. Initial: ______ 8. I must begin using the birth control methods I have chosen as described above at least 1 month before I start taking isotretinoin. Initial: ______ 9. I cannot get my first prescription for isotretinoin unless my doctor has told me that I have 2 negative pregnancy test results. The first pregnancy test should be done when my doctor decides to prescribe isotretinoin. The second pregnancy test must be done in a lab during the first 5 days of my menstrual period right before starting isotretinoin therapy treatment, or as instructed by my doctor. I will then have 1 pregnancy test; in a lab. every month during treatment at the end of treatment and 1 month after stopping treatment I must not start taking isotretinoin until I am sure that I am not pregnant, have negative results from 2 pregnancy tests, and the second test has been done in a lab. Initial: ______ 10. I have read and understand the materials my doctor has given to me, including The iPLEDGE Program Guide for Isotretinoin for Female Patients Who Can Get Pregnant, The iPLEDGE Birth Control Workbook and The Ipledge Program Patient Introductory Brochure. My doctor gave me and asked me to watch the DVD containing a video about birth control and a video about birth defects and isotretinoin. I was told about a private counseling line that I may call for more information about birth control. I have received information on emergency birth control. Initial: ______ 11. I must stop taking isotretinoin right away and call my doctor if I get pregnant, miss my expected menstrual period, stop using birth control, or have sexual intercourse without using my 2 birth control methods at any time. Initial: ______ 12. My doctor gave me information about the purpose and importance of providing information to the iPLEDGE program should I become pregnant while taking isotretinoin or within 1 month of the last dose. If I become pregnant, I agree to be contacted by the iPLEDGE program and be asked questions about my pregnancy. I also understand that if I become pregnant, information about my pregnancy, my health, and my baby's health may be given to the maker of isotretinoin and government health regulatory authorities. Initial: ______ 13. I understand that being qualified to receive isotretinoin in the iPLEDGE program means that I: have had 2 negative urine or blood pregnancy tests before receiving the first isotretinoin prescription. The second test must be done in a lab. I must have a negative result from a urine or blood pregnancy test done in a lab repeated each month before I receive another isotretinoin prescription. have chosen and agreed to use 2 forms of effective birth control at the same time. At least 1 method must be a primary form of birth control, unless I have chosen never to have sexual contact with a male (abstinence), or I have undergone a hysterectomy. I must use 2 forms of birth control for at least 1 month before I start isotretinoin therapy, during therapy, and for 1 month after stopping therapy. I must receive counseling, repeated on a monthly basis, about birth control and behaviors associated with an increased risk of pregnancy. have signed a Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) that contains warnings about the chance of possible birth defects if I am pregnant or become pregnant and my unborn baby is exposed to isotretinoin. have been informed of and understand the purpose and importance of providing information to the iPLEDGE program should I become pregnant while taking isotretinoin or within 1 month of the last dose. I agree to be contacted by the iPLEDGE program and be asked questions about my pregnancy. have interacted with the iPLEDGE program before starting isotretinoin and on a monthly basis to answer questions on the program requirements and to enter my two chosen forms of birth control. Initial: ______ My doctor has answered all my questions about isotretinoin and I understand that it is my responsibility not to get pregnant 1 month before, during isotretinoin treatment, or for 1 month after I stop taking isotretinoin. Initial: ______ I now authorize my doctor ________________ to begin my treatment with isotretinoin. Patient Signature:_____________________________________ Date: ______ Parent/Guardian Signature (if under age 18):________________ Date:______ Please print: Patient Name and Address_______________________________ ______________________________ Telephone _______________________ have fully explained to the patient, __________________, the nature and purpose of the treatment described above and the risks to female patients of childbearing potential. I have asked the patient if she has any questions regarding her treatment with isotretinoin and have answered those questions to the best of my ability. Doctor Signature: __________________________________ Date: ______ PLACE THE ORIGINAL SIGNED DOCUMENTS IN THE PATIENT'S MEDICAL RECORD. PLEASE PROVIDE A COPY TO THE PATIENT. Patient Information/Informed Consent (for all patients): To be completed by patient (and parent or guardian if patient is under age 18) and signed by the doctor. Read each item below and initial in the space provided if you understand each item and agree to follow your doctor's instructions. A parent or guardian of a patient under age 18 must also read and understand each item before signing the agreement. Do not sign this agreement and do not take isotretinoin if there is anything that you do not understand about all the information you have received about using isotretinoin. 1. I, ______________________________________________________, (Patient's Name) understand that isotretinoin is a medicine used to treat severe nodular acne that cannot be cleared up by any other acne treatments, including antibiotics. In severe nodular acne, many red, swollen, tender lumps form in the skin. If untreated, severe nodular acne can lead to permanent scars. Initials: ______ 2. My doctor has told me about my choices for treating my acne. Initials: ______ 3. I understand that there are serious side effects that may happen while I am taking isotretinoin. These have been explained to me. These side effects include serious birth defects in babies of pregnant patients. [Note: There is a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant)]. Initials: ______ 4. I understand 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 people tried to end their own lives. And some people 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. No one knows if isotretinoin caused these behaviors or if they would have happened even if the person did not take isotretinoin. Some people have had other signs of depression while taking isotretinoin (see #7 below). Initials: ______ 5. Before I start taking isotretinoin, I agree to tell my doctor if I have ever had symptoms of depression (see #7 below), been psychotic, attempted suicide, had any other mental problems, or take medicine for any of these problems. Being psychotic means having a loss of contact with reality, such as hearing voices or seeing things that are not there. Initials: ______ 6. Before I start taking isotretinoin, I agree to tell my doctor if, to the best of my knowledge, anyone in my family has ever had symptoms of depression, been psychotic, attempted suicide, or had any other serious mental problems. Initials: ______ 7. Once I start taking isotretinoin, I agree to stop using isotretinoin and tell my doctor right away if any of the following signs and symptoms of depression or psychosis happen. I: Start to feel sad or have crying spells Lose interest in activities I 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 my appetite or body weight Have trouble concentrating Withdraw from my friends or family Feel like I have no energy Have feelings of worthlessness or guilt Start having thoughts about hurting myself or taking my own life (suicidal thoughts) Start acting on dangerous impulses Start seeing or hearing things that are not real Initials: ______ 8. I agree to return to see my doctor every month I take isotretinoin to get a new prescription for isotretinoin, to check my progress, and to check for signs of side effects. Initials: ______ 9. Isotretinoin will be prescribed just for me — I will not share isotretinoin with other people because it may cause serious side effects, including birth defects. Initials: ______ 10. I will not give blood while taking isotretinoin or for 1 month after I stop taking isotretinoin. I understand that if someone who is pregnant gets my donated blood, her baby may be exposed to isotretinoin and may be born with serious birth defects. Initials: ______ 11. I have read The iPLEDGE Program Patient Introductory Brochure, and other materials my provider gave me containing important safety information about isotretinoin. I understand all the information I received. Initials: ______ 12. My doctor and I have decided I should take isotretinoin. I understand that I must be qualified in the iPLEDGE program to have my prescription filled each month. I understand that I can stop taking isotretinoin at any time. I agree to tell my doctor if I stop taking isotretinoin. Initials: ______ I now allow my doctor ___________________________ to begin my treatment with isotretinoin. Patient Signature: ____________________________________ Date: ______ Parent/Guardian Signature (if under age 18): _______________ Date: ______ Patient Name (print) ___________________________________ Patient Address ___________________________ Telephone (___.___.___) ____________________________________ I have: fully explained to the patient, __________________, the nature and purpose of isotretinoin treatment, including its benefits and risks given the patient the appropriate educational materials, The iPLEDGE Program Patient Introductory Brochure and asked the patient if he/she has any questions regarding his/her treatment with isotretinoin answered those questions to the best of my ability Doctor Signature: _________________________________ Date: ______ PLACE THE ORIGINAL SIGNED DOCUMENTS IN THE PATIENT'S MEDICAL RECORD. PLEASE PROVIDE A COPY TO THE PATIENT. MEDICATION GUIDE ACCUTANE (ACK-U-TANE) (isotretinoin capsules) Read the Medication Guide that comes with Accutane (isotretinoin) 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 Accutane (isotretinoin) ? Accutane (isotretinoin) is used to treat a type of severe acne (nodular acne) that has not been helped by other treatments, including antibiotics. Because Accutane (isotretinoin) can cause birth defects, Accutane (isotretinoin) is only for patients who can understand and agree to carry out all of the instructions in the iPLEDGE program. Accutane (isotretinoin) 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. Female patients who are pregnant or who plan to become pregnant must not take Accutane (isotretinoin) . Female patients must not get pregnant: for 1 month before starting Accutane (isotretinoin) while taking Accutane (isotretinoin) for 1 month after stopping Accutane (isotretinoin) . If you get pregnant while taking Accutane (isotretinoin) , 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. Accutane (isotretinoin) may cause: depression psychosis (seeing or hearing things that are not real) suicide. Some patients taking Accutane (isotretinoin) 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) , you may also need follow-up mental health care if you had any of these symptoms. What is Accutane (isotretinoin) ? Accutane (isotretinoin) 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. Accutane (isotretinoin) can cause serious side effects (see “What is the most important information I should know about Accutane (isotretinoin) ?”). Accutane (isotretinoin) 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 Accutane (isotretinoin) ? Do not take Accutane (isotretinoin) if you are pregnant, plan to become pregnant, or become pregnant during Accutane (isotretinoin) treatment. Accutane (isotretinoin) causes severe birth defects. See “What is the most important information I should know about Accutane (isotretinoin) ?” Do not take Accutane (isotretinoin) if you are allergic to anything in it. Accutane (isotretinoin) contains parabens as the preservative. See the end of this Medication Guide for a complete list of ingredients in Accutane (isotretinoin) . What should I tell my doctor before taking Accutane (isotretinoin) ? 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. Accutane (isotretinoin) must not be used by women who are pregnant or breastfeeding. Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Accutane (isotretinoin) 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 Accutane (isotretinoin) . Taking both together may increase your chance of getting side effects. Tetracycline antibiotics. Tetracycline antibiotics taken with Accutane (isotretinoin) 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 Accutane (isotretinoin) . Ask your doctor or pharmacist if you are not sure what type you are using. Dilantin (phenytoin). This medicine taken with Accutane (isotretinoin) may weaken your bones. Corticosteroid medicines. These medicines taken with Accutane (isotretinoin) 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 Accutane (isotretinoin) 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 Accutane (isotretinoin) ? You must take Accutane (isotretinoin) exactly as prescribed. You must also follow all the instructions of the iPLEDGE program. Before prescribing Accutane (isotretinoin) , your doctor will: explain the iPLEDGE program to you have you sign the Patient Information/Informed Consent (for all patients). Female patients who can get pregnant must also sign another consent form. You will not be prescribed Accutane (isotretinoin) 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 Accutane (isotretinoin) at a time. This is to make sure you are following the Accutane (isotretinoin) iPLEDGE program. You should talk with your doctor each month about side effects. The amount of Accutane (isotretinoin) you take has been specially chosen for you. It is based on your body weight, and may change during treatment. Take Accutane (isotretinoin) 2 times a day with a meal, unless your doctor tells you otherwise. Swallow your Accutane (isotretinoin) capsules whole with a full glass of liquid. Do not chew or suck on the capsule. Accutane (isotretinoin) 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 2 doses at the same time. If you take too much Accutane (isotretinoin) or overdose, call your doctor or poison control center right away. Your acne may get worse when you first start taking Accutane (isotretinoin) . 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 Accutane (isotretinoin) . Female patients who can get pregnant will get a pregnancy test each month. Female patients who can get pregnant must agree to use 2 separate forms of effective birth control at the same time 1 month before, while taking, and for 1 month after taking Accutane (isotretinoin) . You must access the iPLEDGE system to answer questions about the program requirements and to enter your 2 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 Accutane (isotretinoin) . If you have sex at any time without using 2 forms of effective birth control, get pregnant, or miss your expected period, stop using Accutane (isotretinoin) and call your doctor right away. What should I avoid while taking Accutane (isotretinoin) ? Do not get pregnant while taking Accutane (isotretinoin) and for 1 month after stopping Accutane (isotretinoin) . See “What is the most important information I should know about Accutane (isotretinoin) ?” Do not breast feed while taking Accutane (isotretinoin) and for 1 month after stopping Accutane (isotretinoin) . We do not know if Accutane (isotretinoin) can pass through your milk and harm the baby. Do not give blood while you take Accutane (isotretinoin) and for 1 month after stopping Accutane (isotretinoin) . If someone who is pregnant gets your donated blood, her baby may be exposed to Accutane (isotretinoin) and may be born with birth defects. Do not take other medicines or herbal products with Accutane (isotretinoin) unless you talk to your doctor. See “What should I tell my doctor before taking Accutane (isotretinoin) ?” Do not drive at night until you know if Accutane (isotretinoin) has affected your vision. Accutane (isotretinoin) 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 Accutane (isotretinoin) and for at least 6 months after you stop. Accutane (isotretinoin) 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. Accutane (isotretinoin) may make your skin more sensitive to light. Do not share Accutane (isotretinoin) with other people. It can cause birth defects and other serious health problems. What are the possible side effects of Accutane (isotretinoin) ? Accutane (isotretinoin) 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 Accutane (isotretinoin) ?” Accutane (isotretinoin) may cause serious mental health problems. See “What is the most important information I should know about Accutane (isotretinoin) ?” serious brain problems. Accutane (isotretinoin) can increase t he pressure in your brain. This can lead to permanent loss of eyesight and, in rare cases, death. Stop taking Accutane (isotretinoin) 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 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 Accutane (isotretinoin) . Stop taking Accutane (isotretinoin) and call your doctor if you get: severe stomach, chest or bowel pain trouble swallowing or painful swallowing new or worsening heartburn diarrhea rectal bleeding yellowing of your skin or eyes dark urine bone and muscle problems. Accutane (isotretinoin) 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 Accutane (isotretinoin) . Tell your doctor if you get: back pain joint pain broken bone. Tell all healthcare providers that you take Accutane (isotretinoin) if you break a bone. Stop Accutane (isotretinoin) 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. Accutane (isotretinoin) may stop long bone growth in teenagers who are still growing. hearing problems. Stop using Accutane (isotretinoin) 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. Accutane (isotretinoin) may affect your ability to see in the dark. This condition usually clears up after you stop taking Accutane (isotretinoin) , but it may be permanent. Other serious eye effects can occur. Stop taking Accutane (isotretinoin) 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 Accutane (isotretinoin) and after treatment. lipid (fats and cholesterol in blood) problems. Accutane (isotretinoin) 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 Accutane (isotretinoin) treatment is finished. serious allergic reactions. Stop taking Accutane (isotretinoin) and get emergency care right away if you develop hives, a swollen face or mouth, or have trouble breathing. Stop taking Accutane (isotretinoin) and call your doctor if you get a fever, rash, or red patches or bruises on your legs. blood sugar problems. Accutane (isotretinoin) 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 Accutane (isotretinoin) are dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds. Call your doctor if you get any side effect that bothers you or that does not go away. These are not all of the possible side effects with Accutane (isotretinoin) . Your doctor or pharmacist can give you more detailed information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or Roche at 1-800-526-6367. How should I store Accutane (isotretinoin) ? Store Accutane (isotretinoin) at room temperature, between 59° and 86°F. Protect from light. Keep Accutane (isotretinoin) and all medicines out of the reach of children. General Information about Accutane (isotretinoin) Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use Accutane (isotretinoin) for a condition for which it was not prescribed. Do not give Accutane (isotretinoin) 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 Accutane (isotretinoin) . If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Accutane (isotretinoin) 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 Accutane? Active Ingredient: Isotretinoin Inactive Ingredients: beeswax, butylated hydroxyanisole, edetate disodium, hydrogenated soybean oil flakes, hydrogenated vegetable oil, and soybean oil. Gelatin capsules contain glycerin and parabens (methyl and propyl), with the following dye systems: 10 mg — iron oxide (red) and titanium dioxide; 20 mg — FD&C Red No. 3, FD&C Blue No. 1, and titanium dioxide; 40 mg — FD&C Yellow No. 6, D&C Yellow No. 10, and titanium dioxide. This Medication Guide has been approved by the U.S. Food and Drug Administration."
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51 | 2017-08-31 23:12:57 | Accutane | Isotretinoin | Multum | { "51": { "alphabet_x_drug.id": 51, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.value": "Brand Names: Amnesteem, Claravis, Sotret Generic Name: isotretinoin (oral) (Pronunciation: EYE so TRET i noyn) What is isotretinoin (Amnesteem, Claravis, Sotret)? What are the possible side effects of isotretinoin (Amnesteem, Claravis, Sotret)? What is the most important information I should know about isotretinoin (Amnesteem, Claravis, Sotret)? What should I discuss with my healthcare provider before taking isotretinoin (Amnesteem, Claravis, Sotret)? How should I take isotretinoin (Amnesteem, Claravis, Sotret)? What happens if I miss a dose (Amnesteem, Claravis, Sotret)? What happens if I overdose (Amnesteem, Claravis, Sotret)? What should I avoid while taking isotretinoin (Amnesteem, Claravis, Sotret)? What other drugs will affect isotretinoin (Amnesteem, Claravis, Sotret)? Where can I get more information? What is isotretinoin (Amnesteem, Claravis, Sotret)? Isotretinoin is a form of vitamin A. It reduces the amount of oil released by oil glands in your skin, and helps your skin renew itself more quickly.Isotretinoin is used to treat severe nodular acne that has not responded to other treatments, including antibiotics.Isotretinoin may also be used for purposes not listed in this medication guide. What are the possible side effects of isotretinoin (Amnesteem, Claravis, Sotret)? 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 isotretinoin and call your doctor at once if you have any of these serious side effects:depressed mood, trouble concentrating, sleep problems, crying spells, aggression or agitation, changes in behavior, hallucinations, thoughts of suicide or hurting yourself;sudden numbness or weakness, especially on one side of the body;blurred vision, sudden and severe headache or pain behind your eyes, sometimes with vomiting;hearing problems, hearing loss, or ringing in your ears;seizure (convulsions);severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);severe diarrhea, rectal bleeding, black, bloody, or tarry stools;fever, chills, body aches, flu symptoms, purple spots under your skin, easy bruising or bleeding;severe blistering, peeling, and red skin rash; orjoint stiffness, bone pain or fracture.Less serious side effects may include:joint pain, back pain;feeling dizzy, drowsy, or nervous;dryness of the lips, mouth, nose, or skin; orcracking or peeling skin, itching, rash, changes in your fingernails or toenails.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 isotretinoin (Amnesteem, Claravis, Sotret)? Isotretinoin can cause severe, life-threatening birth defects. Never use isotretinoin if you are pregnant.Women of child-bearing potential must agree in writing to use two specific forms of birth control and have regular pregnancy tests before, during, and after taking isotretinoin.Isotretinoin is available only under a special program called iPLEDGE. It is dangerous to try and purchase isotretinoin on the Internet or from vendors outside of the United States.Do not take vitamin supplements containing vitamin A while you are taking isotretinoin.Do not donate blood while taking isotretinoin and for at least 30 days after you stop taking it."
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"property.value": "What should I discuss with my healthcare provider before taking isotretinoin (Amnesteem, Claravis, Sotret)? Isotretinoin is available only under a special program called iPLEDGE. You must be registered in the program and sign documents stating that you understand the dangers of this medication and that you agree to use birth control as required by the program. Ask your doctor or call the drug maker if you have questions about the program or the written requirements.It is dangerous to try and purchase isotretinoin on the Internet or from vendors outside of the United States. The sale and distribution of isotretinoin outside of the iPLEDGE program violates the regulations of the U.S. Food and Drug Administration for the safe use of this medication.Do not use this medication if you are allergic to isotretinoin or to parabens, or if you are pregnant or may become pregnant.To make sure you can safely take isotretinoin, tell your doctor if you have any of these other conditions:a personal or family history of depression or mental illness;heart disease, high cholesterol or triglycerides;osteoporosis or other bone disorders;an intestinal disorder such as inflammatory bowel disease, ulcerative colitis, or Crohn's disease;diabetes;asthma;an eating disorder (anorexia nervosa); orliver disease.Isotretinoin can cause severe, life-threatening birth defects if the mother takes the medication during pregnancy. Even one dose of isotretinoin can cause major birth defects of the baby's ears, eyes, face, skull, heart, and brain. Never use isotretinoin if you are pregnant.For Women: Unless you have had your uterus and ovaries removed (total hysterectomy) or have been in menopause for at least 12 months in a row, you are considered to be of child-bearing potential.Even women who have had their tubes tied are required to use birth control while taking isotretinoin.You must have a negative pregnancy test 30 days before you start taking isotretinoin. A pregnancy test is also required before each prescription is refilled, right after you take your last dose of isotretinoin, and again 30 days later. All pregnancy testing is required by the iPLEDGE program.You must agree in writing to use two specific forms of birth control beginning 30 days before you start taking isotretinoin and ending 30 days after you stop taking it. Both a primary and a secondary form of birth control must be used together. Primary forms of birth control include:tubal ligation (tubes tied);vasectomy of the male sexual partner;an IUD (intrauterine device);estrogen-containing birth control pills (not mini-pills); andhormonal birth control patches, implants, injections, or vaginal ring.Secondary forms of birth control include:a male latex condom plus spermicidal foam or gel;a diaphragm plus spermicidal foam or gel;a cervical cap plus spermicidal foam or gel; anda vaginal sponge containing spermicide.Stop using isotretinoin and call your doctor at once if you have unprotected sex, if you quit using birth control, if your period is late, or if you think you might be pregnant. If you get pregnant while taking isotretinoin, call the iPLEDGE pregnancy registry at 1-866-495-0654.It is not known whether isotretinoin passes into breast milk. Do not take isotretinoin without first talking to your doctor if you are breast-feeding a baby. How should I take isotretinoin (Amnesteem, Claravis, Sotret)? 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.Each prescription of isotretinoin must be filled within 7 days of the date it was prescribed by your doctor. You will receive no more than a 30-day supply of isotretinoin at one time.Always take isotretinoin with a full glass of water to prevent the capsule from melting in your esophagus (food pipe), causing irritation. Do not chew or suck on the capsule. Swallow it as quickly as possible.Take isotretinoin with food or milk.Take this medication for the entire length of time prescribed by your doctor. Your acne may seem to get worse at first, but should then begin to improve.To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your liver function may also need to be tested. Visit your doctor regularly.Never share this medicine with another person, even if they have the same symptoms you have. Store at room temperature away from moisture, heat, and light."
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52 | 2017-08-31 23:12:57 | Accuzyme | Papain and Urea | FDA | { "52": { "alphabet_x_drug.id": 52, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.ts": "2017-12-04 04:42:23",
"property.key": "Drug Description",
"property.value": "DESCRIPTION ACCUZYME (papain and urea) enzymatic debriding ointment contains papain, USP (8.3 x 105 USP units of activity per gram) and urea, USP 10% in a hydrophilic ointment base composed of emulsifying wax, fragrance, glycerin, isopropyl palmitate, lactose, methylparaben, potassium phosphate monobasic, propylparaben, and purified water."
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"property.ts": "2017-12-04 04:42:23",
"property.key": "Indications & Dosage",
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"property.ts": "2017-12-04 04:42:23",
"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS ACCUZYME (papain and urea) Ointment is generally well-tolerated and non-irritating. A transient \"burning\" sensation may be experienced by a small percentage of patients upon applying ACCUZYME (papain and urea) Ointment. Occasionally, the profuse exudate from enzymatic digestion may irritate the skin. In such cases, more frequent dressing changes will alleviate discomfort until exudate decreases. DRUG INTERACTIONS No Information Provided."
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"property.ts": "2017-12-04 04:42:23",
"property.key": "Warnings & Precautions",
"property.value": "WARNINGS No Information Provided. PRECAUTIONS See Dosage and Administration . Not to be used in eyes."
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"property.ts": "2017-12-04 04:42:23",
"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE No Information Provided. CONTRAINDICATIONS Do not use if you are allergic to or have known or suspected hypersensitivity to any ingredient in this product."
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"318": {
"property.id": 318,
"property.ts": "2017-12-04 04:42:23",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Papain, the proteolytic enzyme from the fruit of carica papaya, is a potent digestant of nonviable protein matter but is harmless to viable tissue. It is active over a pH range of 3 to 12. Papain is relatively ineffective when used alone as a debriding agent and requires the presence of activators to stimulate its digestive potency. In ACCUZYME (papain and urea) , papain is combined with urea, a denaturant of proteins, to bring about two supplemental chemical actions: (1) to expose by solvent action the activators of papain, and (2) to denature the nonviable protein matter in lesions and thereby render it more susceptible to enzymatic digestion. Pharmacologic studies have shown that the combination of papain and urea result in twice as much digestive activity as papain alone."
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"property.id": 319,
"property.ts": "2017-12-04 04:42:23",
"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION No Information Provided."
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53 | 2017-08-31 23:12:57 | Acebutolol | Sectral | FDA | { "53": { "alphabet_x_drug.id": 53, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.ts": "2017-12-04 04:42:28",
"property.key": "Drug Description",
"property.value": "Find Lowest Prices on SECTRAL (acebutolol hydrochloride) Capsules DESCRIPTION Sectral (acebutolol HCl) is a selective, hydrophilic beta-adrenoreceptor blocking agent with mild intrinsic sympathomimetic activity for use in treating patients with hypertension and ventricular arrhythmias. It is marketed in capsule form for oral administration. Sectral capsules are provided in two dosage strengths which contain 200 or 400 mg of acebutolol as the hydrochloride salt. The inactive ingredients present are D&C Red 22, FD&C Blue 1, FD&C Yellow 6, gelatin, povidone, starch, stearic acid, and titanium dioxide. The 200 mg dosage strength also contains D&C Red 28 and the 400 mg dosage strength also contains FD&C Red 40. Acebutolol HCl has the following structural formula: Acebutolol HCl is a white or slightly off-white powder freely soluble in water, and less soluble in alcohol. Chemically it is defined as the hydrochloride salt of (±)N-[3-Acetyl-4-[2- hydroxy-3-[(1- methylethyl)amino]propoxy]phenyl] butanamide."
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"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Hypertension Sectral is indicated for the management of hypertension in adults. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Ventricular Arrhythmias Sectral is indicated in the management of ventricular premature beats; it reduces the total number of premature beats, as well as the number of paired and multiform ventricular ectopic beats, and R-on-T beats. DOSAGE AND ADMINISTRATION Hypertension The initial dosage of Sectral in uncomplicated mild-to-moderate hypertension is 400 mg. This can be given as a single daily dose, but in occasional patients twice daily dosing may be required for adequate 24-hour blood-pressure control. An optimal response is usually achieved with dosages of 400 to 800 mg per day, although some patients have been maintained on as little as 200 mg per day. Patients with more severe hypertension or who have demonstrated inadequate control may respond to a total of 1200 mg daily (administered b.i.d.), or to the addition of a second antihypertensive agent. Beta-1 selectivity diminishes as dosage is increased. Ventricular Arrhythmia The usual initial dose of Sectral is 400 mg daily given as 200 mg b.i.d. Dosage should be increased gradually until an optimal clinical response is obtained, generally at 600 to 1200 mg per day. If treatment is to be discontinued, the dosage should be reduced gradually over a period of about two weeks. Use In Older Patients Older patients have an approximately 2-fold increase in bioavailability and may require lower maintenance doses. Doses above 800 mg/day should be avoided in the elderly. HOW SUPPLIED Sectral® (acebutolol HCl) is available in the following dosage strengths: 200 mg, opaque purple and orange capsule marked “RP 700” and “Sectral 200” NDC 67857-700-01, in bottles of 100 capsules. 400 mg, opaque brown and orange capsule marked “RP 701” and “Sectral 400” NDC 67857-701-01, in bottles of 100 capsules. Keep tightly closed Store at controlled room temperature 20° to 25°C (68° to 77°F) Protect from light Dispense in a light-resistant, tight container Us e carton to protect contents from light Distributed by: Promius Pharma, LLC, Bridgewater, NJ 08807. Manufactured by: PATHEON, Puerto Rico, Inc., Manatí, Puerto Rico 00674, USA. Revised: April 2008"
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"property.ts": "2017-12-04 04:42:28",
"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS Sectral is well tolerated in properly selected patients. Most adverse reactions have been mild, not required discontinuation of therapy, and tended to decrease as duration of treatment increases. The following table shows the frequency of treatment-related side effects derived from controlled clinical trials in patients with hypertension, angina pectoris, and arrhythmia. These patients received Sectral, propranolol, or hydrochlorothiazide as monotherapy, or placebo. TOTAL VOLUNTEERED AND ELICITED (U.S. STUDIES) Body System/ Adverse Reaction SECTRAL (N=1002) % Propranolol (N=424) % Hydrochloro- thiazide (N=178) % Placebo (N=314) % Cardiovascular Chest Pain 2 4 4 1 Edema 2 2 4 1 Central Nervous System Depression 2 1 3 1 Dizziness 6 7 12 2 Fatigue 11 17 10 4 Headache 6 9 13 4 Insomnia 3 6 5 1 Abnormal dreams 2 3 0 1 Dermatologic Rash 2 2 4 1 Gastrointestinal Constipation 4 2 7 0 Diarrhea 4 5 5 1 Dyspepsia 4 6 3 1 Flatulence 3 4 7 1 Nausea 4 6 3 0 Genitourinary Micturition (frequency) 3 1 9 < 1 Musculoskeletal Arthralgia 2 1 3 2 Myalgia 2 1 4 0 Respiratory Cough 1 1 2 0 Dyspnea 4 6 4 2 Rhinitis 2 1 4 < 1 Special Senses Abnormal Vision 2 2 3 0 The following selected (potentially important) side effects were seen in up to 2% of Sectral patients: Cardiovascular: hypotension, bradycardia, heart failure. Central Nervous System: anxiety, hyper/hypoesthesia, impotence. Dermatological: pruritus. Gastrointestinal: vomiting, abdominal pain. Genitourinary: dysuria, nocturia. Liver and Biliary System: A small number of cases of liver abnormalities (increased SGOT, SGPT, LDH) have been reported in association with acebutolol therapy. In some cases increased bilirubin or alkaline phosphatase, fever, malaise, dark urine, anorexia, nausea, headache, and/or other symptoms have been reported. In some of the reported cases, the symptoms and signs were confirmed by rechallenge with acebutolol. The abnormalities were reversible upon cessation of acebutolol therapy. Musculoskeletal: back pain, joint pain. Respiratory: pharyngitis, wheezing. Special Senses: conjunctivitis, dry eye, eye pain. Autoimmune: In extremely rare instances, systemic lupus erythematosus has been reported. The incidence of drug-related adverse effects (volunteered and solicited) according to Sectral dose is shown below. (Data from 266 hypertensive patients treated for 3 months on a constant dose.) Body System 400 mg/day (N=132) 800 mg/day (N=63) 1200 mg/day (N=71) Cardiovascular 5% 2% 1% Gastrointestinal 3% 3% 7% Musculoskeletal 2% 3% 4% Central Nervous System 9% 13% 17% Respiratory 1% 5% 6% Skin 1% 2% 1% Special Senses 2% 2% 6% Genitourinary 2% 3% 1% Potential Adverse Events In addition, certain adverse effects not listed above have been reported with other β-blocking agents and should also be considered as potential adverse effects of Sectral. Central Nervous System: Reversible mental depression progressing to catatonia (an acute syndrome characterized by disorientation for time and place), short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance (neuropsychometrics). Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS). Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress. Hematologic: Agranulocytosis, nonthrombocytopenic, and thrombocytopenic purpura. Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis. Miscellaneous: Reversible alopecia and Peyronie's disease. The oculomucocutaneous syndrome associated with the β-blocker practolol has not been reported with Sectral during investigational use and extensive foreign clinical experience. DRUG INTERACTIONS Catecholamine-depleting drugs, such as reserpine, may have an additive effect when given with β- blocking agents. Patients treated with Sectral plus catecholamine depletors should, therefore, be observed closely for evidence of marked bradycardia or hypotension which may present as vertigo, syncope/presyncope, or orthostatic changes in blood pressure without compensatory tachycardia. Exaggerated hypertensive responses have been reported from the combined use of β-adrenergic antagonists and α-adrenergic stimulants, including those contained in proprietary cold remedies and vasoconstrictive nasal drops. Patients receiving β-blockers should be warned of this potential hazard. Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported. No significant interactions with digoxin, hydrochlorothiazide, hydralazine, sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been observed. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia."
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"property.key": "Warnings & Precautions",
"property.value": "WARNINGS Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by β-adrenergic receptor blockade may precipitate more severe failure. Although β-blockers should be avoided in overt cardiac failure, Sectral can be used with caution in patients with a history of heart failure who are controlled with digitalis and/or diuretics. Both digitalis and Sectral impair AV conduction. If cardiac failure persists, therapy with Sectral should be withdrawn. In Patients Without A History Of Cardiac Failure In patients with aortic or mitral valve disease or compromised left ventricular function, continued depression of the myocardium with β-blocking agents over a period of time may lead to cardiac failure. At the first signs of failure, patients should be digitalized and/or be given a diuretic and the response observed closely. If cardiac failure continues despite adequate digitalization and/or diuretic, Sectral therapy should be withdrawn. Exacerbation Of Is Chemic Heart Disease Following Abrupt Withdrawal Following abrupt cessation of therapy with certain β-blocking agents in patients with coronary artery disease, exacerbation of angina pectoris and, in some cases, myocardial infarction and death have been reported. Therefore, such patients should be cautioned against interruption of therapy without a physician's advice. Even in the absence of overt ischemic heart disease, when discontinuation of Sectral is planned, the patient should be carefully observed, and should be advised to limit physical activity to a minimum while Sectral is gradually withdrawn over a period of about two weeks. (If therapy with an alternative β-blocker is desired, the patient may be transferred directly to comparable doses of another agent without interruption of β-blocking therapy.) If an exacerbation of angina pectoris occurs, antianginal therapy should be restarted immediately in full doses and the patient hospitalized until his condition stabilizes. Peripheral Vascular Disease Treatment with β-antagonists reduces cardiac output and can precipitate or aggravate the symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease. Caution should be exercised with such patients, and they should be observed closely for evidence of progression of arterial obstruction. Bronchospastic Disease PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE A β-BLOCKER. Because of its relative β1 -selectivity, however, low doses of Sectral may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate, alternative treatment. Since β1-selectivity is not absolute and is dose-dependent, the lowest possible dose of Sectral should be used initially, preferably in divided doses to avoid the higher plasma levels associated with the longer dose-interval. A bronchodilator, such as theophylline or a β2- stimulant, should be made available in advance with instructions concerning its use. Anesthesia And Major Surgery The necessity, or desirability, of withdrawal of a - blocking therapy prior to major surgery is controversial. -adrenergic receptor blockade impairs the ability of the heart to respond to - adrenergically mediated reflex stimuli. While this might be of benefit in preventing arrhythmic response, the risk of excessive myocardial depression during general anesthesia may be enhanced and difficulty in restarting and maintaining the heart beat has been reported with beta-blockers. If treatment is continued, particular care should be taken when using anesthetic agents which depress the myocardium, such as ether, cyclopropane, and trichlorethylene, and it is prudent to use the lowest possible dose of Sectral. Sectral, like other -blockers, is a competitive inhibitor of -receptor agonists, and its effect on the heart can be reversed by cautious administration of such agents (e.g., dobutamine or isoproterenol—see OVERDOSAGE). Manifestations of excessive vagal tone (e.g., profound bradycardia, hypotension) may be corrected Diabetes And Hypoglycemia β-blockers may potentiate insulin-induced hypoglycemia and mask some of its manifestations such as tachycardia; however, dizziness and sweating are usually not significantly affected. Diabetic patients should be warned of the possibility of masked hypoglycemia. Thyrotoxicosis β-adrenergic blockade may mask certain clinical signs (tachycardia) of hyperthyroidism. Abrupt withdrawal of β-blockade may precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom Sectral therapy is to be withdrawn should be monitored closely. PRECAUTIONS Risk Of Anaphylactic Reaction While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. Impaired Renal Or Hepatic Function Studies on the effect of acebutolol in patients with renal insufficiency have not been performed in the U.S. Foreign published experience shows that acebutolol has been used successfully in chronic renal insufficiency. Acebutolol is excreted through the GI tract, but the active metabolite, diacetolol, is eliminated predominantly by the kidney. There is a linear relationship between renal clearance of diacetolol and creatinine clearance. Therefore, the daily dose of acebutolol should be reduced by 50% when the creatinine clearance is less than 50 mL/min and by 75% when it is less than 25 mL/min. Sectral should be used cautiously in patients with impaired hepatic function. Sectral has been used successfully and without problems in elderly patients in the U.S. clinical trials without specific adjustment of dosage. However, elderly patients may require lower maintenance doses because the bioavailability of both Sectral and its metabolite are approximately doubled in this age group. Clinical Laboratory Findings Sectral®, like other β-blockers, has been associated with the development of antinuclear antibodies (ANA). In prospective clinical trials, patients receiving Sectral had a dose-dependent increase in the development of positive ANA titers, and the overall incidence was higher than that observed with propranolol. Symptoms (generally persistent arthralgias and myalgias) related to this laboratory abnormality were infrequent (less than 1% with both drugs). Symptoms and ANA titers were reversible upon discontinuation of treatment. Carcinogenesis, Mutagenesis, Impairment Of Fertility Chronic oral toxicity studies in rats and mice, employing dose levels as high as 300 mg/kg/day, which is equivalent to 15 times the maximum recommended (60 kg) human dose, did not indicate a carcinogenic potential for Sectral. Diacetolol, the major metabolite of Sectral in man, was without carcinogenic potential in rats when tested at doses as high as 1800 mg/kg/day. Sectral and diacetolol were also shown to be devoid of mutagenic potential in the Ames Test. Sectral, administered orally to two generations of male and female rats at doses of up to 240 mg/kg/day (equivalent to 12 times the maximum recommended therapeutic dose in a 60-kg human) and diacetolol, administered to two generations of male and female rats at doses of up to 1000 mg/kg/day, had no significant impact on reproductive performance or fertility. Pregnancy Teratogenic Effects Pregnancy Category B: Reproduction studies have been performed with Sectral in rats (up to 630 mg/kg/day) and rabbits (up to 135 mg/kg/day). These doses are equivalent to approximately 31.5 and 6.8 times the maximum recommended therapeutic dose in a 60-kg human, respectively. The compound was not teratogenic in either species. In the rabbit, however, doses of 135 mg/kg/day caused slight fetal growth retardation; this effect was considered to be a result of maternal toxicity, as evidenced by reduced food intake, a lowered rate of body weight gain, and mortality. Studies have also been performed in these species with diacetolol (at doses of up to 450 mg/kg/day in rabbits and up to 1800 mg/kg/day in rats). Other than a significant elevation in postimplantation loss with 450 mg/kg/day diacetolol, a level at which food consumption and body weight gain were reduced in rabbit dams and a nonstatistically significant increase in incidence of bilateral cataract in rat fetuses from dams treated with 1800 mg/kg/day diacetolol, there was no evidence of harm to the fetus. There are no adequate and well-controlled trials in pregnant women. Because animal teratology studies are not always predictive of the human response, Sectral should be used during pregnancy only if the potential benefit justifies the risk to the fetus. Nonteratogenic Effects Studies in humans have shown that both acebutolol and diacetolol cross the placenta. Neonates of mothers who have received acebutolol during pregnancy have reduced birth weight, decreased blood pressure, and decreased heart rate. In the newborn the elimination half-life of acebutolol was 6 to 14 hours, while the half-life of diacetolol was 24 to 30 hours for the first 24 hours after birth, followed by a half-life of 12 to 16 hours. Adequate facilities for monitoring these infants at birth should be available. Labor And Delivery The effect of Sectral on labor and delivery in pregnant women is unknown. Studies in animals have not shown any effect of Sectral on the usual course of labor and delivery. Nursing Mothers Acebutolol and diacetolol also appear in breast milk with a milk:plasma ratio of 7.1 and 12.2, respectively. Use in nursing mothers is not recommended. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Clinical studies of Sectral and other reported clinical experience is inadequate to determine whether there are differences in safety or effectiveness between patients above or below age 65. Elderly subjects evidence greater bioavailability of acebutolol (see CLINICAL PHARMACOLOGY —Pharmacokinetics and Metabolism), presumably because of age-related reduction in first-pass metabolism and renal function. Therefore, it may be appropriate to start elderly patients at the low end of the dosing range (see DOSAGE AND ADMINISTRATION—Use in Older Patients )."
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"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE No specific information on emergency treatment of overdosage is available for Sectral. However, overdosage with other β-blocking agents has been accompanied by extreme bradycardia, advanced atrioventricular block, intraventricular conduction defects, hypotension, severe congestive heart failure, seizures, and in susceptible patients, bronchospasm and hypoglycemia. Although specific information on the emergency treatment of Sectral overdose is not available, on the basis of the pharmacological actions and the observations in treating overdoses with other β-blockers, the following general measures should be considered: Empty stomach by emesis or lavage. Bradycardia: IV atropine (1 to 3 mg in divided doses). If antivagal response is inadequate, administer isoproterenol cautiously since larger than usual doses of isoproterenol may be required. Persistent hypotension in spite of correction of bradycardia: Administer vasopressor (e.g., epinephrine, levarterenol, dopamine, or dobutamine) with frequent monitoring of blood pressure and pulse rate. Bronchospasm: A theophylline derivative, such as aminophylline and/or parenteral β2-stimulant, such as terbutaline. Cardiac failure: Digitalize the patient and/or administer a diuretic. It has been reported that glucagon is useful in this situation. Sectral is dialyzable. CONTRAINDICATIONS Sectral is contraindicated in: 1) persistently severe bradycardia; 2) second- and third-degree heart block; 3) overt cardiac failure; and 4) cardiogenic shock. (See WARNINGS.)"
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"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Sectral is a cardioselective, β-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. Pharmacodynamics β1 -cardioselectivity has been demonstrated in experimental animal studies. In anesthetized dogs and cats, Sectral is more potent in antagonizing isoproterenol-induced tachycardia (β1) than in antagonizing isoproterenol-induced vasodilatation (β2).In guinea pigs and cats, it is more potent in antagonizing this tachycardia than in antagonizing isoproterenol- induced bronchodilatation (β2). ISA of Sectral has been demonstrated in catecholamine-depleted rats by tachycardia induced by intravenous administration of this agent. A membrane-stabilizing effect has been detected in animals, but only with high concentrations of Sectral. Clinical studies have demonstrated β -blocking activity at the recommended doses by: a) reduction in the resting heart rate and decrease in exercise-induced tachycardia; b) reduction in cardiac output at rest and after exercise; c) reduction of systolic and diastolic blood pressures at rest and postexercise; d) inhibition of isoproterenol-induced tachycardia. The β1-selectivity of Sectral has also been demonstrated on the basis of the following vascular and bronchial effects: Vascular Effects Sectral has less antagonistic effects on peripheral vascular β2-receptors at rest and after epinephrine stimulation than nonselective β-antagonists. Bronchial Effects In single-dose studies in asthmatics examining effects of various beta-blockers on pulmonary function, low doses of acebutolol produce less evidence of bronchoconstriction and less reduction of beta2 agonist, bronchodilating effects, than nonselective agents like propranolol but more than atenolol. ISA has been observed with Sectral in man, as shown by a slightly smaller (about 3 beats per minute) decrease in resting heart rate when compared to equivalent β-blocking doses of propranolol, metoprolol or atenolol. Chronic therapy with Sectral induced no significant alteration in the blood lipid profile. Sectral has been shown to delay AV conduction time and to increase the refractoriness of the AV node without significantly affecting sinus node recovery time, atrial refractory period, or the HV conduction time. The membrane-stabilizing effect of Sectral is not manifest at the doses used clinically. Significant reductions in resting and exercise heart rates and systolic blood pressures have been observed 1.5 hours after Sectral administration with maximal effects occurring between 3 and 8 hours postdosing in normal volunteers. Sectral has demonstrated a significant effect on exercise-induced tachycardia 24 to 30 hours after drug administration. There are significant correlations between plasma levels of acebutolol and both the reduction in resting heart rate and the percent of β-blockade of exercise-induced tachycardia. The antihypertensive effect of Sectral has been shown in double-blind controlled studies to be superior to placebo and similar to propranolol and hydrochlorothiazide. In addition, patients responding to Sectral administered twice daily had a similar response whether the dosage regimen was changed to once daily administration or continued on a b.i.d. regimen. Most patients responded to 400 to 800 mg per day in divided doses. The antiarrhythmic effect of Sectral was compared with placebo, propranolol, and quinidine. Compared with placebo, Sectral significantly reduced mean total ventricular ectopic beats (VEB), paired VEB, multiform VEB, R-on-T beats, and ventricular tachycardia (VT). Both Sectral and propranolol significantly reduced mean total and paired VEB and VT. Sectral and quinidine significantly reduced resting total and complex VEB; the antiarrhythmic efficacy of Sectral was also observed during exercise. Pharmacokinetics And Metabolism Sectral is well absorbed from the GI tract. It is subject to extensive first-pass hepatic biotransformation, with an absolute bioavailability of approximately 40% for the parent compound. The major metabolite, an N-acetyl derivative (diacetolol), is pharmacologically active. This metabolite is equipotent to Sectral and in cats is more cardioselective than Sectral; therefore, this first-pass phenomenon does not attenuate the therapeutic effect of Sectral. Food intake does not have a significant effect on the area under the plasma concentration-time curve (AUC) of Sectral although the rate of absorption and peak concentration decreased slightly. The plasma elimination half-life of Sectral is approximately 3 to 4 hours, while that of its metabolite, diacetolol, is 8 to 13 hours. The time to reach peak concentration for Sectral is 2.5 hours and for diacetolol, after oral administration of Sectral, 3.5 hours. Within the single oral dose range of 200 to 400 mg, the kinetics are dose proportional. However, this linearity is not seen at higher doses, probably due to saturation of hepatic biotransformation sites. In addition, after multiple dosing the lack of linearity is also seen by AUC increases of approximately 100% as compared to single oral dosing. Elimination via renal excretion is approximately 30% to 40% and by nonrenal mechanisms 50% to 60%, which includes excretion into the bile and direct passage through the intestinal wall. Sectral has a low binding affinity for plasma proteins (about 26%). Sectral and its metabolite, diacetolol, are relatively hydrophilic and, therefore, only minimal quantities have been detected in the cerebrospinal fluid (CSF). Drug interaction studies with tolbutamide and warfarin indicated no influence on the therapeutic effects of these compounds. Digoxin and hydrochlorothiazide plasma levels were not affected by concomitant Sectral administration. The kinetics of Sectral were not significantly altered by concomitant administration of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives. In patients with renal impairment, there is no effect on the elimination half-life of Sectral, but there is decreased elimination of the metabolite, diacetolol, resulting in a two- to three-fold increase in its halflife. For this reason, the drug should be administered with caution in patients with renal insufficiency (see PRECAUTIONS). Sectral and its major metabolite are dialyzable. Sectral crosses the placental barrier and is secreted in breast milk. In geriatric patients, the bioavailability of Sectral and its metabolite is increased, approximately twofold, probably due to decreases in the first-pass metabolism and renal function in the elderly."
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"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Patients, especially those with evidence of coronary artery disease, should be warned against interruption or discontinuation of Sectral therapy without a physician's supervision. Although cardiac failure rarely occurs in properly selected patients, those being treated with β-adrenergic blocking agents should be advised to consult a physician if they develop signs or symptoms suggestive of impending CHF, or unexplained respiratory symptoms. Patients should also be warned of possible severe hypertensive reactions from concomitant use of α- adrenergic stimulants, such as the nasal decongestants commonly used in OTC cold preparations and nasal drops."
}
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54 | 2017-08-31 23:12:57 | Acebutolol | Sectral | Multum | { "54": { "alphabet_x_drug.id": 54, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.key": "Sectral Patient Information Including Side Effects",
"property.value": "Find Lowest Prices on Brand Names: Sectral Generic Name: acebutolol (Pronunciation: A se BUE toe lol) What is acebutolol (Sectral)? What are the possible side effects of acebutolol (Sectral)? What is the most important information I should know about acebutolol (Sectral)? What should I discuss with my healthcare provider before taking acebutolol (Sectral)? How should I take acebutolol (Sectral)? What happens if I miss a dose (Sectral)? What happens if I overdose (Sectral)? What should I avoid while taking acebutolol (Sectral)? What other drugs will affect acebutolol (Sectral)? Where can I get more information? What is acebutolol (Sectral)? Acebutolol is in a group of drugs called beta-blockers. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).Acebutolol is used to treat hypertension (high blood pressure) and heart rhythm disorders.Acebutolol may also be used for other purposes not listed in this medication guide. What are the possible side effects of acebutolol (Sectral)? 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 any of these serious side effects:slow or uneven heartbeats;feeling light-headed, fainting;feeling short of breath, even with mild exertion;swelling of your ankles or feet;nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);depression; orcold feeling in your hands and feet.Less serious side effects may include:decreased sex drive, impotence, or difficulty having an orgasm;sleep problems (insomnia);tired feeling; oranxiety, nervousness.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 acebutolol (Sectral)? Do not stop taking acebutolol without first talking to your doctor. Stopping suddenly may make your condition worse.If you need to have any type of surgery, you may need to temporarily stop using acebutolol. Be sure the surgeon knows ahead of time that you are using acebutolol.Acebutolol 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.Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking acebutolol.Acebutolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life."
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"property.key": "Sectral Patient Information including How Should I Take",
"property.value": "What should I discuss with my healthcare provider before taking acebutolol (Sectral)? If you have any of these conditions, you may not be able to use acebutolol, or you may need a dosage adjustment or special tests during treatment:asthma, bronchitis, emphysema;diabetes;low blood pressure;a heart problem such as heart block, sick sinus syndrome, slow heart rate, or congestive heart failure;depression;liver or kidney disease;a thyroid disorder;myasthenia gravis;pheochromocytoma; orproblems with circulation (such as Raynaud's syndrome).FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.Acebutolol can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I take acebutolol (Sectral)? Take acebutolol exactly as it was prescribed for you. Do not take the medication in larger amounts or for longer than recommended by your doctor. Follow the directions on your prescription label.Take this medication with a full glass of water.Take acebutolol at the same time every day.Do not skip doses or stop taking acebutolol without first talking to your doctor. Stopping suddenly may make your condition worse.To be sure this medication is helping your condition, your blood pressure will need to be checked on a regular basis. It is important that you not miss any scheduled visits to your doctor.If you need to have any type of surgery, tell the surgeon that you are using acebutolol. You may need to briefly stop using acebutolol before having surgery.Acebutolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.Store acebutolol at room temperature away from moisture and heat."
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55 | 2017-08-31 23:12:57 | Aceon | Perindopril Erbumine | FDA | { "55": { "alphabet_x_drug.id": 55, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.ts": "2017-12-04 04:42:34",
"property.key": "Drug Description",
"property.value": "Find Lowest Prices on ACEON (perindopril erbumine) 2, 4, and 8 mg Tablets WARNING FETAL TOXICITY When pregnancy is detected, discontinue ACEON as soon as possible. WARNINGS AND PRECAUTIONS Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. WARNINGS AND PRECAUTIONS DESCRIPTION ACEON® (perindopril erbumine) Tablets contain the tert-butylamine salt of perindopril, the ethyl ester of a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Perindopril erbumine is chemically described as (2S,3DS,7DS)-1-[(S)-N-[(S)-1-Carboxy-butyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester, compound with tert-butylamine (1:1). Its molecular formula is C19H32N2O5C4H11N. Its structural formula is: Perindopril erbumine is a white, crystalline powder with a molecular weight of 368.47 (free acid) or 441.61 (salt form). It is freely soluble in water (60% w/w), alcohol and chloroform. Perindopril is the free acid form of perindopril erbumine, is a pro-drug and metabolized in vivo by hydrolysis of the ester group to form perindoprilat, the biologically active metabolite. ACEON is available in 2 mg, 4 mg and 8 mg strengths for oral administration. In addition to perindopril erbumine, each tablet contains the following inactive ingredients: colloidal silica (hydrophobic), lactose, magnesium stearate and microcrystalline cellulose. The 4 mg and 8 mg tablets also contain iron oxide."
},
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"property.ts": "2017-12-04 04:42:34",
"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Hypertension ACEON is indicated for the treatment of patients with essential hypertension. ACEON may be used alone or given with other classes of antihypertensives, especially thiazide diuretics. Stable Coronary Artery Disease ACEON is indicated for treatment of patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction. ACEON can be used with conventional treatment for management of coronary artery disease, such as antiplatelet, antihypertensive or lipid-lowering therapy. DOSAGE AND ADMINISTRATION Hypertension Use In Uncomplicated Hypertensive Patients In patients with essential hypertension, the recommended initial dose is 4 mg once a day. The dose may be titrated, as needed to a maximum of 16 mg per day. The usual maintenance dose range is 4 mg to 8 mg administered as a single daily dose or in two divided doses. Use In Elderly Patients The recommended initial daily dosage of ACEON for the elderly is 4 mg daily, given in one or two divided doses. Experience with ACEON is limited in the elderly at doses exceeding 8 mg. Dosages above 8 mg should be administered with careful blood pressure monitoring and dose titration [see Use In Specific Populations]. Use With Diuretics In patients who are currently being treated with a diuretic, symptomatic hypotension can occur following the initial dose of ACEON. Consider reducing the dose of diuretic prior to starting ACEON [see DRUG INTERACTIONS]. Stable Coronary Artery Disease In patients with stable coronary artery disease, ACEON should be given at an initial dose of 4 mg once daily for 2 weeks, and then increased as tolerated, to a maintenance dose of 8 mg once daily. In elderly patients (greater than 70 years), ACEON should be given as a 2 mg dose once daily in the first week, followed by 4 mg once daily in the second week and 8 mg once daily for maintenance dose if tolerated. Dose Adjustment In Renal Impairment And Dialysis Perindoprilat elimination is decreased in renally impaired patients. ACEON is not recommended in patients with creatinine clearance <30 mL/min. For patients with lesser degrees of impairment, the initial dosage should be 2 mg/day and dosage should not exceed 8 mg/day. During dialysis, perindopril is removed with the same clearance as in patients with normal renal function. HOW SUPPLIED Dosage Forms And Strengths Tablets are oblong with a score on one side. 2 mg tablet is white and debossed on the unscored side with \"ACN 2\". 4 mg tablet is pink and debossed on the unscored side with \"ACN 4\". 8 mg tablet is salmon and debossed on the unscored side with \"ACN 8\". Storage And Handling Tablets are oblong with a score on one side. Tablets Appearance NDC (Bottles of 100) 2 mg White, debossed \"ACN 2\" on unscored side NDC 61894-001-02 4 mg Pink, debossed \"ACN 4\" on unscored side NDC 61894-001-02 8 mg Salmon-colored, debossed \"ACN 8\" on unscored side NDC 61894-002-02 Keep out of the reach of children. Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP]. Protect from moisture. For further information, please call our medical communications department toll-free at 888-985-7657. Manufactured by: Patheon Pharmaceuticals, Inc. Cincinnati, OH 45237 USA. Revised: Sep 2017"
},
"332": {
"property.id": 332,
"property.ts": "2017-12-04 04:42:34",
"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS 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. Clinical Trials Experience The following adverse reactions are discussed elsewhere in labeling: Anaphylactoid reactions, including angioedema [see WARNINGS AND PRECAUTIONS] Hypotension [see WARNINGS AND PRECAUTIONS] Neutropenia and agranulocytosis [see WARNINGS AND PRECAUTIONS] Impaired renal function [see WARNINGS AND PRECAUTIONS] Hyperkalemia [see WARNINGS AND PRECAUTIONS] Cough [see WARNINGS AND PRECAUTIONS] Hypertension ACEON has been evaluated for safety in approximately 3,400 patients with hypertension in U.S. and foreign clinical trials. The data presented here are based on results from the 1,417 ACEON-treated patients who participated in the U.S. clinical trials. Over 220 of these patients were treated with ACEON® (perindopril erbumine) for at least one year. In placebo-controlled U.S. clinical trials, the incidence of premature discontinuation of therapy due to adverse events was 6.5% in patients treated with ACEON and 6.7% in patients treated with placebo. The most common causes were cough, headache, asthenia and dizziness. Among 1,012 patients in placebo-controlled U.S. trials, the overall frequency of reported adverse events was similar in patients treated with ACEON and in those treated with placebo (approximately 75% in each group). The only adverse events whose incidence on ACEON was at least 2% greater than on placebo were cough (12% vs. 4.5%) and back pain (5.8% vs. 3.1%). Dizziness was not reported more frequently in the perindopril group (8.2%) than in the placebo group (8.5%), but its likelihood increased with dose, suggesting a causal relationship with perindopril. Stable Coronary Artery Disease Perindopril has been evaluated for safety in EUROPA, a double-blind, placebo-controlled study in 12,218 patients with stable coronary artery disease. The overall rate of discontinuation was about 22% on drug and placebo. The most common medical reasons for discontinuation that were more frequent on perindopril than placebo were cough, drug intolerance and hypotension. Postmarketing Experience Voluntary reports of adverse events in patients taking ACEON that have been received since market introduction and are of unknown causal relationship to ACEON include: cardiac arrest, eosinophilic pneumonitis, neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), thrombocytopenia, acute renal failure, nephritis, hepatic failure, jaundice (hepatocellular or cholestatic), symptomatic hyponatremia, bullous pemphigoid, pemphigus, acute pancreatitis, falls, psoriasis, exfoliative dermatitis and a syndrome which may include: arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermatologic manifestations, a positive antinuclear antibody (ANA), leukocytosis, eosinophilia or an elevated erythrocyte sedimentation rate (ESR). Clinical Laboratory Test Findings Hematology Small decreases in hemoglobin and hematocrit occur frequently in hypertensive patients treated with ACEON, but are rarely of clinical importance. In controlled clinical trials, no patient was discontinued from therapy due to the development of anemia. Leukopenia (including neutropenia) was observed in 0.1% of patients in U.S. clinical trials [see WARNINGS AND PRECAUTIONS]. Liver Function Tests Elevations in ALT (1.6% ACEON versus 0.9% placebo) and AST (0.5% ACEON versus 0.4% placebo) have been observed in placebo-controlled clinical trials. The elevations were generally mild and transient and resolved after discontinuation of therapy. DRUG INTERACTIONS Diuretics Patients on diuretics, and especially those started recently, may occasionally experience an excessive reduction of blood pressure after initiation of ACEON therapy. The possibility of hypotensive effects can be minimized by either decreasing the dose of or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with perindopril. If diuretic therapy cannot be altered, provide close medical supervision with the first dose of ACEON, for at least two hours and until blood pressure has stabilized for another hour [see WARNINGS AND PRECAUTIONS]. The rate and extent of perindopril absorption and elimination are not affected by concomitant diuretics. The bioavailability of perindoprilat was reduced by diuretics, however, and this was associated with a decrease in plasma ACE inhibition. Potassium Supplements And Potassium-Sparing Diuretics ACEON may increase serum potassium because of its potential to decrease aldosterone production. Use of potassium-sparing diuretics (spironolactone, amiloride, triamterene and others), potassium supplements or other drugs capable of increasing serum potassium (indomethacin, heparin, cyclosporine and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently. Lithium Increased serum lithium and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. Frequent monitoring of serum lithium concentration is recommended. Use of a diuretic may further increase the risk of lithium toxicity. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE Inhibitor therapy including ACEON. Digoxin A controlled pharmacokinetic study has shown no effect on plasma digoxin concentrations when coadministered with ACEON, but an effect of digoxin on the plasma concentration of perindopril/perindoprilat has not been excluded. Gentamicin Animal data have suggested the possibility of interaction between perindopril and gentamicin. However, this has not been investigated in human studies. Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including perindopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving perindopril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including perindopril, may be attenuated by NSAIDs including selective COX-2 inhibitors. Dual Blockade Of The Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on ACEON and other agents that affect the RAS. Do not co-administer aliskiren with ACEON in patients with diabetes. Avoid use of aliskiren with ACEON in patients with renal impairment (GFR <60 ml/min). mTOR Inhibitors Patients taking concomitant mTOR (mammalian target of rapamycin) inhibitor therapy may be at increased risk for angioedema [see WARNINGS AND PRECAUTIONS]. Neprilysin Inhibitor Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema. [see WARNINGS AND PRECAUTIONS]"
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"property.key": "Warnings & Precautions",
"property.value": "WARNINGS Included as part of the \"PRECAUTIONS\" Section PRECAUTIONS Anaphylactoid And Possibly Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including ACEON) may be subject to a variety of adverse events, some of them serious. Black patients receiving ACE inhibitors have a higher incidence of angioedema compared to nonblacks. Head And Neck Angioedema Angioedema of the face, extremities, lips, tongue, glottis, or larynx has been reported in patients treated with ACE inhibitors, including ACEON (0.1% of patients treated with ACEON in U.S. clinical trials). Angioedema associated with involvement of the tongue, glottis or larynx may be fatal. In such cases, discontinue ACEON treatment immediately and observe until the swelling disappears. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, administer appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), promptly. Patients taking concomitant mTOR inhibitor (e.g., temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema [see DRUG INTERACTIONS]. Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Hypotension ACEON can cause symptomatic hypotension. ACEON has been associated with hypotension in 0.3% of uncomplicated hypertensive patients in U.S. placebo-controlled trials. Symptoms related to orthostatic hypotension were reported in another 0.8% of patients. Symptomatic hypotension is most likely to occur in patients who have been volume or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting [see DOSAGE AND ADMINISTRATION]. ACE inhibitors may cause excessive hypotension, and may be associated with oliguria or azotemia, and rarely with acute renal failure and death. In patients with ischemic heart disease or cerebrovascular disease, an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident. In patients at risk of excessive hypotension, ACEON therapy should be started under very close medical supervision. Patients should be followed closely for the first two weeks of treatment and whenever the dose of ACEON and/or diuretic is increased. If excessive hypotension occurs, the patient should be placed immediately in a supine position and, if necessary, treated with an intravenous infusion of physiological saline. ACEON treatment can usually be continued following restoration of volume and blood pressure. Neutropenia/Agranulocytosis ACE inhibitors have been associated with agranulocytosis and bone marrow depression, most frequently in patients with renal impairment, especially patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma. Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected discontinue ACEON as soon as possible [see Use In Specific Populations]. Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. Renal function should be monitored periodically in patients receiving ACEON [see DOSAGE AND ADMINISTRATION], [see DRUG INTERACTIONS]. In patients with severe congestive heart failure, where renal function may depend on the activity of the renin-angiotensinaldosterone system, treatment with ACE inhibitors, including ACEON, may be associated with oliguria, progressive azotemia, and, rarely, acute renal failure and death. In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur; usually reversible upon discontinuation of the ACE inhibitor. In such patients, renal function should be monitored during the first few weeks of therapy. Some ACEON-treated patients have developed minor and transient increases in blood urea nitrogen and serum creatinine especially in those concomitantly treated with a diuretic. Hyperkalemia Elevations of serum potassium have been observed in some patients treated with ACE inhibitors, including ACEON. Most cases were isolated single values that did not appear clinically relevant and were rarely a cause for withdrawal. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus and the concomitant use of agents such as potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes [see DRUG INTERACTIONS]. Serum potassium should be monitored periodically in patients receiving ACEON. Cough Presumably because of the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, generally resolving after discontinuation of therapy. Consider ACE inhibitor-induced cough in the differential diagnosis of cough. Hepatic Failure Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. Surgery/Anesthesia In patients undergoing surgery or during anesthesia with agents that produce hypotension, ACEON may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension attributable to this mechanism can be corrected by volume expansion. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity No evidence of carcinogenic effect was observed in studies in rats and mice when perindopril was administered at dosages up to 20 times (mg/kg) or 2 to 4 times (mg/m2) the maximum proposed clinical doses (16 mg/day) for 104 weeks. Mutagenesis No genotoxic potential was detected for ACEON, perindoprilat and other metabolites in various in vitro and in vivo investigations, including the Ames test, the Saccharomyces cerevisiae D4 test, cultured human lymphocytes, TK ± mouse lymphoma assay, mouse and rat micronucleus tests and Chinese hamster bone marrow assay. Impairment Of Fertility There was no meaningful effect on reproductive performance or fertility in the rat given up to 30 times (mg/kg) or 6 times (mg/m2) the proposed maximum clinical dosage of ACEON during the period of spermatogenesis in males or oogenesis and gestation in females. Use In Specific Populations Pregnancy Pregnancy Category D [see BOX WARNING and WARNINGS AND PRECAUTIONS]. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ACEON as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue ACEON, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to ACEON for hypotension, oliguria, and hyperkalemia [see Pediatric Use]. Radioactivity was detectable in fetuses after administration of 14C-perindopril to pregnant rats. Nursing Mothers Milk of lactating rats contained radioactivity following administration of 14C-perindopril. It is not known whether perindopril is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when ACEON is given to nursing mothers. Pediatric Use Neonates With A History Of In Utero Exposure To ACEON If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Perindopril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means, but limited experience has not shown that such removal is central to the treatment of these infants. Safety and effectiveness of ACEON in pediatric patients have not been established. Geriatric Use The mean blood pressure effect of perindopril was somewhat smaller in patients over 60 than in younger patients, although the difference was not significant. Plasma concentrations of both perindopril and perindoprilat were increased in elderly patients compared to concentrations in younger patients. No adverse effects were clearly increased in older patients with the exception of dizziness and possibly rash. Start at a low dose and titrate slowly as needed. Monitor for dizziness because of potential for falls. Experience with ACEON in elderly patients at daily doses exceeding 8 mg is limited. Renal Impairment Dosage adjustment may be necessary in renally impaired patients [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. Hepatic Impairment The bioavailability of perindoprilat is increased in patients with impaired hepatic function [see CLINICAL PHARMACOLOGY]."
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"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE In animals, doses of perindopril up to 2,500 mg/kg in mice, 3,000 mg/kg in rats and 1,600 mg/kg in dogs were non-lethal. Past experiences were scant but suggested that overdosage with other ACE inhibitors was also fairly well tolerated by humans. The most likely manifestation is hypotension, and treatment should be symptomatic and supportive. Therapy with the ACE inhibitor should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance and hypotension should be treated by established procedures. Among the reported cases of perindopril overdosage, patients who were known to have ingested a dose of 80 mg to 120 mg required assisted ventilation and circulatory support. One additional patient developed hypothermia, circulatory arrest and died following ingestion of up to 180 mg of perindopril. The intervention for perindopril overdose may require vigorous support. Laboratory determinations of serum levels of perindopril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of perindopril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of perindopril and its metabolites. Perindopril can be removed by hemodialysis, with clearance of 52 mL/min for perindopril and 67 mL/min for perindoprilat. Angiotensin II could presumably serve as a specific antagonist-antidote in the settling of perindopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of perindopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat perindopril overdose by infusion of normal saline solution. CONTRAINDICATIONS ACEON® (perindopril erbumine) is contraindicated in patients known to be hypersensitive (including angioedema) to this product or to any other ACE inhibitor. ACEON is also contraindicated in patients with hereditary or idiopathic angioedema. Do not co-administer aliskiren with ACEON in patients with diabetes. [see DRUG INTERACTIONS] ACEON is contraindicated in combination with neprilysin inhibitor (e.g., sacubitril). Do not administer ACEON within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see WARNINGS AND PRECAUTIONS]."
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"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Mechanism Of Action ACEON® (perindopril erbumine) is a pro-drug for perindoprilat, which inhibits ACE in human subjects and animals. The mechanism through which perindoprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes conversion of the inactive decapeptide, angiotensin I, to the vasoconstrictor, angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor, which stimulates aldosterone secretion by the adrenal cortex, and provides negative feedback on renin secretion. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity and decreased aldosterone secretion. The latter results in diuresis and natriuresis and may be associated with a small increase of serum potassium. ACE is identical to kininase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of ACEON remains to be elucidated. While the principal mechanism of perindopril in blood pressure reduction is believed to be through the renin-angiotensinaldosterone system, ACE inhibitors have some effect even in apparent low-renin hypertension. Perindopril has been studied in relatively few black patients, usually a low-renin population, and the average response of diastolic blood pressure to perindopril was about half the response seen in nonblack patients, a finding consistent with previous experience of other ACE inhibitors. Pharmacodynamics After administration of perindopril, ACE is inhibited in a dose and blood concentration-related fashion, with the maximal inhibition of 80 to 90% attained by 8 mg persisting for 10 to 12 hours. Twenty-four hour ACE inhibition is about 60% after these doses. The degree of ACE inhibition achieved by a given dose appears to diminish over time (the ID50 increases). The pressor response to an angiotensin I infusion is reduced by perindopril, but this effect is not as persistent as the effect on ACE; there is about 35% inhibition at 24 hours after a 12 mg dose. Pharmacokinetics Absorption Oral administration of ACEON results in peak plasma concentrations that occur at approximately 1 hour. The absolute oral bioavailability of perindopril is about 75%. Following absorption, approximately 30 to 50% of systemically available perindopril is hydrolyzed to its active metabolite, perindoprilat, which has a mean bioavailability of about 25%. Peak plasma concentrations of perindoprilat are attained 3 to 7 hours after perindopril administration. Oral administration of ACEON with food does not significantly lower the rate or extent of perindopril absorption relative to the fasted state. However, the extent of biotransformation of perindopril to the active metabolite, perindoprilat, is reduced approximately 43%, resulting in a reduction in the plasma ACE inhibition curve of approximately 20%, probably clinically insignificant. In clinical trials, perindopril was generally administered in a non-fasting state. With 4 mg, 8 mg and 16 mg doses of ACEON, Cmax and AUC of perindopril and perindoprilat increase in a dose-proportional manner following both single oral dosing and at steady state during a once-a-day multiple dosing regimen. Distribution Approximately 60% of circulating perindopril is bound to plasma proteins, and only 10 to 20% of perindoprilat is bound. Therefore, drug interactions mediated through effects on protein binding are not anticipated. Metabolism And Elimination Following oral administration perindopril exhibits multicompartment pharmacokinetics including a deep tissue compartment (ACE binding sites). The mean half-life of perindopril associated with most of its elimination is approximately 0.8 to 1 hours. Perindopril is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine. Six metabolites resulting from hydrolysis, glucuronidation and cyclization via dehydration have been identified. These include the active ACE inhibitor, perindoprilat (hydrolyzed perindopril), perindopril and perindoprilat glucuronides, dehydrated perindopril and the diastereoisomers of dehydrated perindoprilat. In humans, hepatic esterase appears to be responsible for the hydrolysis of perindopril. The active metabolite, perindoprilat, also exhibits multicompartment pharmacokinetics following the oral administration of ACEON. Formation of perindoprilat is gradual with peak plasma concentrations occurring between 3 and 7 hours. The subsequent decline in plasma concentration shows an apparent mean half-life of 3 to 10 hours for the majority of the elimination, with a prolonged terminal elimination half-life of 30 to 120 hours resulting from slow dissociation of perindoprilat from plasma/tissue ACE binding sites. During repeated oral once daily dosing with perindopril, perindoprilat accumulates about 1.5 to 2 fold and attains steady state plasma levels in 3 to 6 days. The clearance of perindoprilat and its metabolites is almost exclusively renal. Elderly Plasma concentrations of both perindopril and perindoprilat in elderly patients (greater than 70 years) are approximately twice those observed in younger patients, reflecting both increased conversion of perindopril to perindoprilat and decreased renal excretion of perindoprilat [see DOSAGE AND ADMINISTRATION and Use In Specific Populations]. Heart Failure Perindoprilat clearance is reduced in congestive heart failure patients, resulting in a 40% higher dose interval AUC. Renal Impairment With perindopril doses of 2 mg to 4 mg, perindoprilat AUC increases with decreasing renal function. At creatinine clearances of 30 to 80 mL/min, AUC is about double that at 100 mL/min. When creatinine clearance drops below 30 mL/min, AUC increases more markedly. In a limited number of patients studied, perindopril clearance by dialysis ranged from about 40 to 80 mL/min. Perindoprilat clearance by dialysis ranged from about 40 to 90 mL/min [see DOSAGE AND ADMINISTRATION]. Hepatic Impairment The bioavailability of perindoprilat is increased in patients with impaired hepatic function. Plasma concentrations of perindoprilat in patients with impaired liver function were about 50% higher than those observed in healthy subjects or hypertensive patients with normal liver function. Clinical Studies Hypertension In placebo-controlled studies of perindopril monotherapy (2 mg to 16 mg once daily) in patients with a mean blood pressure of about 150/100 mm Hg, 2 mg had little effect, but doses of 4 mg to 16 mg lowered blood pressure. The 8 mg and 16 mg doses were indistinguishable, and both had a greater effect than the 4 mg dose. In these studies, doses of 8 mg and 16 mg per day gave supine, trough blood pressure reductions of 9 to 15/5 to 6 mm Hg. When once daily and twice daily dosing were compared, the twice daily dosing regimen was generally slightly superior, but by not more than about 0.5 mm Hg to 1 mm Hg. After 2 mg to 16 mg doses of perindopril, the trough mean systolic and diastolic blood pressure effects were about 75 to 100% of peak effects. Perindopril’s effects on blood pressure were similar when given alone or on a background of 25 mg hydrochlorothiazide In general, the effect of perindopril occurred promptly, with effects increasing slightly over several weeks. Formal interaction studies of ACEON® (perindopril erbumine) have not been carried out with antihypertensive agents other than thiazides. Limited experience in controlled and uncontrolled trials coadministering ACEON with a calcium channel blocker, a loop diuretic or triple therapy (beta-blocker, vasodilator and a diuretic), does not suggest any unexpected interactions. In general, ACE inhibitors have less than additive effects when given with beta-adrenergic blockers, presumably because both work in part through the renin angiotensin system. In uncontrolled studies in patients with insulin-dependent diabetes, perindopril did not appear to affect glycemic control. In long-term use, no effect on urinary protein excretion was seen in these patients. The effectiveness of ACEON was not influenced by sex and it was less effective in black patients than in nonblack patients. In elderly patients (greater than or equal to 60 years), the mean blood pressure effect was somewhat smaller than in younger patients, although the difference was not significant. Stable Coronary Artery Disease The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) was a multicenter, randomized, double-blind and placebo-controlled study conducted in 12,218 patients who had evidence of stable coronary artery disease without clinical heart failure. Patients had evidence of coronary artery disease documented by previous myocardial infarction more than 3 months before screening, coronary revascularization more than 6 months before screening, angiographic evidence of stenosis (at least 70% narrowing of one or more major coronary arteries), or positive stress test in men with a history of chest pain. After a run-in period of 4 weeks during which all patients received perindopril 2 mg to 8 mg, the patients were randomly assigned to perindopril 8 mg once daily (n=6,110) or matching placebo (n=6,108). The mean follow-up was 4.2 years. The study examined the long-term effects of perindopril on time to first event of cardiovascular mortality, nonfatal myocardial infarction, or cardiac arrest in patients with stable coronary artery disease. The mean age of patients was 60 years; 85% were male, 92% were taking platelet inhibitors, 63% were taking β blockers, and 56% were taking lipid-lowering therapy. The EUROPA study showed that perindopril significantly reduced the relative risk for the primary endpoint events (Table 1). This beneficial effect is largely attributable to a reduction in the risk of nonfatal myocardial infarction. This beneficial effect of perindopril on the primary outcome was evident after about one year of treatment (Figure 1). The outcome was similar across all predefined subgroups by age, underlying disease or concomitant medication (Figure 2). Table 1. Primary Endpoint and Relative Risk Reduction Perindopril (N = 6,110) Placebo (N = 6,108) RRR (95% CI) P Combined Endpoint Cardiovascular mortality, nonfatal MI or cardiac arrest 488 (8%) 603 (9.9%) 20% (9 to 29) 0.0003 Component Endpoint Cardiovascular mortality 215 (3.5%) 249 (4.1%) 14% (-3 to 28) 0.107 Nonfatal MI 295 (4.8%) 378 (6.2%) 22% (10 to 33) 0.001 Cardiac arrest 6 (0.1%) 11 (0.2%) 46% (-47 to 80) 0.22 CI=confidence interval; RRR: relative risk reduction; MI: myocardial infarction Figure 1. Time to First Occurrence of Primary Endpoint Figure 2. Beneficial Effect of Perindopril Treatment on Primary Endpoint in Predefined Subgroups"
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"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Female patients of childbearing age should be told about the consequences of exposure to ACEON during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible. Tell patients to report promptly any indication of infection (e.g., sore throat, fever) which could be a sign of neutropenia."
}
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56 | 2017-08-31 23:12:57 | Aceon | Perindopril Erbumine | Multum | { "56": { "alphabet_x_drug.id": 56, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.key": "Aceon Patient Information Including Side Effects",
"property.value": "Find Lowest Prices on Brand Names: Aceon Generic Name: perindopril (Pronunciation: per IN doe pril) What is perindopril (Aceon)? What are the possible side effects of perindopril (Aceon)? What is the most important information I should know about perindopril (Aceon)? What should I discuss with my healthcare provider before taking perindopril (Aceon)? How should I take perindopril (Aceon)? What happens if I miss a dose (Aceon)? What happens if I overdose (Aceon)? What should I avoid while taking perindopril (Aceon)? What other drugs will affect perindopril (Aceon)? Where can I get more information? What is perindopril (Aceon)? Perindopril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme.Perindopril is used to treat high blood pressure (hypertension) and to prevent heart attack in people with coronary artery disease.Perindopril may also be used for purposes not listed in this medication guide. What are the possible side effects of perindopril (Aceon)? 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:feeling like you might pass out;fever, chills, body aches, flu symptoms, sores in your mouth and throat;urinating less than usual or not at all;swelling, rapid weight gain;high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);pale skin, easy bruising or bleeding; orjaundice (yellowing of the skin or eyes).Less serious side effects may include:dizziness;back pain; orcough.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 perindopril (Aceon)? Do not use perindopril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Drinking alcohol can further lower your blood pressure and may increase certain side effects of perindopril.Do not use salt substitutes or potassium supplements while taking perindopril, unless your doctor has told you to.Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting."
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"property.key": "Aceon Patient Information including How Should I Take",
"property.value": "What should I discuss with my healthcare provider before taking perindopril (Aceon)? Do not use this medication if you are allergic to perindopril or to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).You should not use perindopril if you have hereditary angioedema.To make sure you can safely take perindopril, tell your doctor if you have any of these other conditions:kidney disease (or if you are on dialysis);liver disease;heart disease or congestive heart failure;diabetes; ora connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.FDA pregnancy category D. Do not use perindopril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Perindopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking perindopril.It is not known whether perindopril 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. How should I take perindopril (Aceon)? 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.Your doctor may occasionally change your dose to make sure you get the best results.Take each dose with a full glass of water. Drink plenty of liquids while you are taking perindopril.Perindopril can be taken with or without food.Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.Your blood pressure will need to be checked often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.If you need surgery, tell the surgeon ahead of time that you are using perindopril. You may need to stop using the medicine for a short time.If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.Store at room temperature away from moisture and heat."
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57 | 2017-08-31 23:12:57 | Acetadote | Acetylcysteine Injection | FDA | { "57": { "alphabet_x_drug.id": 57, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.value": "Find Lowest Prices on ACETADOTE (acetylcysteine) Intravenous Injection DESCRIPTION Acetylcysteine injection is an intravenous antidote for the treatment of acetaminophen overdose. Acetylcysteine is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine (N-acetyl-L-cysteine). The compound is a white crystalline powder, which melts in the range of 104° to 110°C and has a very slight odor. The molecular formula of the compound is C5H9NO3S, and its molecular weight is 163.2. Acetylcysteine has the following structural formula: Acetadote is supplied as a sterile solution in vials containing 20% w/v (200 mg/mL) acetylcysteine. The pH of the solution ranges from 6.0 to 7.5. Acetadote contains the following inactive ingredients: sodium hydroxide (used for pH adjustment), and Sterile Water for Injection, USP."
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"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Acetadote is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen. Overdose incidences are divided into two types; Acute Ingestion or Repeated Supratherapeutic Ingestion (RSI). [see DOSAGE AND ADMINISTRATION and Acetaminophen Assays – Interpretation and Methodology-(Acute or Repeated Supratherapeutic Ingestion)]. On admission for suspected acute acetaminophen overdose, a serum blood sample should be drawn at least 4 hours after ingestion to determine the acetaminophen level and will serve as a basis for determining the need for treatment with acetylcysteine. If the patient presents after 4 hours post-ingestion, the serum acetaminophen sample should be determined immediately. Acetadote should be administered within 8 hours from acetaminophen ingestion for maximal protection against hepatic injury for patients whose serum acetaminophen levels fall above the “possible” toxicity line on the Rumack-Matthew nomogram (line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours); [see Acetaminophen Assays – Interpretation and Methodology]. If the time of ingestion is unknown, or the serum acetaminophen level is not available, cannot be interpreted, or is not available within the 8 hour time interval from acetaminophen ingestion, Acetadote should be administered immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen, regardless of the quantity reported to have been ingested. The aspartate aminotransferase (AST, SGOT), alanine aminotranferase (ALT, SGPT), bilirubin, prothrombin time, creatinine, blood urea nitrogen (BUN), blood glucose, and electrolytes also should be determined in order to monitor hepatic and renal function and electrolyte and fluid balance. NOTE: The critical ingestion-treatment interval for maximal protection against severe hepatic injury is between 0 – 8 hours. Efficacy diminishes progressively after 8 hours and treatment initiation between 15 and 24 hours post-ingestion of acetaminophen yields limited efficacy. However, it does not appear to worsen the condition of patients and it should not be withheld, since the reported time of ingestion may not be correct. Acetaminophen Assays Interpretation And Methodology – Acute Ingestion The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. However, the reported history of the quantity of a drug ingested as an overdose is often inaccurate and is not a reliable guide to therapy of the overdose. Therefore, plasma or serum acetaminophen concentrations, determined as early as possible, but no sooner than four hours following an acute overdose, are essential in assessing the potential risk of hepatotoxicity. If an assay for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic. Interpretation Of Acetaminophen Assays When results of the plasma acetaminophen assay are available, refer to the nomogram in Figure 1 to determine if plasma concentration is in the potentially toxic range. Values above the line connecting 200 mcg/mL at 4 hours with 50 mcg/mL at 12 hours (probable line) are associated with a probability of hepatic toxicity if an antidote is not administered. If the predetoxification plasma level is above the line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours (possible line), continue with maintenance doses of acetylcysteine. It is better to err on the safe side and thus this line, defining possible toxicity, is plotted 25% below the line defining probable toxicity. If the predetoxification plasma level is below the line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours (possible line), there is minimal risk of hepatic toxicity, and acetylcysteine treatment may be discontinued. Estimating Potential for Hepatotoxicity: The following depiction of the Rumack-Matthew nomogram has been developed to estimate the probability that plasma levels in relation to intervals post-ingestion will result in hepatotoxicity. The Rumack-Matthew nomogram may underestimate the risk for hepatotoxicity in some patients with risk factors such as chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid). Figure 1: Rumack-Matthew Nomogram Figure 1. Michael J Hodgman, Alexander R Garrard, A Review of Acetaminophen Poisoning. Crit Care Clin. 28 (2012) 499-516. Stephen J. Wolf, Kennon Heard, et.al, Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose. Ann Emerg Med. 2007:50:292-313. Acetaminophen Assays Interpretation And Methodology – Repeated Supratherapeutic Ingestion Repeated Supratherapeutic Ingestion (RSI) is defined as ingestion of acetaminophen at doses higher than those recommended for extended periods of time. The nomogram does not apply to patients with RSI. Treatment is based on the acetaminophen and elevated AST/ALT levels indicative of potential toxicity due to acetaminophen. For specific treatment information regarding the clinical management of repeated supratherapeutic acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115. Figure 2: Acetadote Treatment Flow Chart 1Acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. 2With an extended-release preparation, an acetaminophen level drawn less than 8 hours post-ingestion may be misleading. Draw a second level at 4 to 6 hours after the initial level. If either falls above the toxicity line, acetylcysteine treatment should be initiated. 3Acetylcysteine may be withheld until acetaminophen assay results are available as long as initiation of treatment is not delayed beyond 8 hours post-ingestion. If more than 8 hours post-ingestion, start acetylcysteine treatment immediately. DOSAGE AND ADMINISTRATION The total dose of Acetadote is 300 mg/kg given as 3 separate doses and administered over a total of 21 hours. Please refer to the guidelines below for dose preparation based upon patient weight. The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (see Tables 1 and 2). Administration Instructions (Three–Bag Method: Loading, Second and Third Dose) Dosing for Patients Who Weigh 5 kg to 20 kg (Table 1) Loading Dose: 150 mg/kg diluted in 3 mL/kg of diluent* administered over 1 hr Second Dose: 50 mg/kg diluted in 7 mL/kg of diluent* administered over 4 hrs Third Dose: 100 mg/kg diluted in 14 mL/kg of diluent* administered over 16 hrs Table 1: Three Bag Method Dosage Guide by Weight in Patients 5 kg to 20 kg Body Weight (kg) Bag 1 (loading dose): 150 mg/kg in 3 mL/kg of diluent* infused over 1 hour Bag 2 (second dose) 50 mg/kg in 7mL/kg of diluent* infused over 4 hours Bag 3 (third dose) 100 mg/kg diluted in 14 mL/kg of diluent* infused over 16 hours Acetadote Total Dose Diluent volume Acetadote Total Dose Diluent volume Acetadote Total Dose Diluent volume 5 kg 750 mg 15 mL 250 mg 35 mL 500 mg 70 mL 10 kg 1,500 mg 30 mL 500 mg 70 mL 1,000 mg 140mL 15 kg 2,250 mg 45 mL 750 mg 105mL 1,500 mg 210mL 20 kg 3,000 mg 60 mL 1,000mg 140mL 2,000 mg 280mL *Acetadote is compatible with the following diluents; 5% Dextrose in Water, 0.45% Sodium Chloride Injection, and Sterile Water for Injection. See also Section titled Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction Dosing for Patients Who Weigh 21 kg to 40 kg (Table 2) Loading Dose: 150 mg/kg diluted in 100 mL of diluent* administered over 1 hr Second Dose: 50 mg/kg diluted in 250 mL of diluent* administered over 4 hrs Third Dose: 100 mg/kg diluted in 500 mL of diluent* administered over 16 hrs Table 2: Three Bag Method Dosage Guide by Weight in Patients 21 kg to 40 kg Body Weight (kg) Bag 1 (loading dose): 150 mg/kg in 100 mL of diluent* infused over 1 hr Bag 2 (second dose) 50 mg/kg in 250 mL of diluent* infused over 4 hrs Bag 3 (third dose) 100 mg/kg in 500 mL of diluent* infused over 16 hrs Acetadote Total Dose (mg) Acetadote Total Dose (mg) Acetadote Total Dose (mg) 21 kg 3,150 mg 1,050 mg 2,100 mg 30 kg 4,500 mg 1,500 mg 3,000 mg 40 kg 6,000 mg 2,000 mg 4,000 mg *Acetadote is compatible with the following diluents; 5% Dextrose in Water 0.45% Sodium Chloride Injection, and Sterile Water for Injection. See also Section on Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction. Dosing for Patients Who Weigh 41 kg to 100 kg (Table 3) Loading Dose: 150 mg/kg diluted in 200 mL of diluent* administered over 1 hr Second Dose: 50 mg/kg diluted in 500 mL of diluent* administered over 4 hrs Third Dose: 100 mg/kg diluted in 1000 mL of diluent* administered over 16 hrs Table 3: Three Bag Method Dosage Guide by Weight in Patients 41 kg to 100 kg Body Weight (kg) Bag 1 (loading dose): 150 mg/kg diluted in 200 mL of diluent* infused over 1 hr Bag 2 (second dose): 50 mg/kg diluted in 500 mL of diluent* infused over 4 hrs Bag 3 (third dose): 100 mg/kg diluted in 1000 mL of diluent* infused over 16 hrs Acetadote Total Dose (mg) Acetadote Total Dose (mg) Acetadote Total Dose (mg) 41 kg 6,150 mg 2,050 mg 4,100 mg 50 kg 7,500 mg 2,500 mg 5,000 mg 60 kg 9,000 mg 3,000 mg 6,000 mg 70 kg 10,500 mg 3,500 mg 7,000 mg 80 kg 12,000 mg 4,000 mg 8,000 mg 90 kg 13,500 mg 4,500 mg 9,000 mg 100 kg 15,000 mg 5,000 mg 10,000 mg *Acetadote is compatible with the following diluents; 5% Dextrose 0.45% Sodium Chloride Injection, and Sterile Water for Injection. Patients Weighing More Than 100 kg No specific studies have been conducted to evaluate the use of or necessity of dosing adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg. The dose of Acetadote recommended in these patients should be a loading dose of 15,000 mg infused over a period of one hour followed by a first maintenance dose of 5,000 mg over 4 hours and a second maintenance dose of 10,000 mg over 16 hours (See Table 3). Continued Therapy beyond 21 Hours While there is no clinical trial data to support infusions beyond 21 hours there is literature that supports continued infusion of acetylcysteine in some rare instances. In cases of suspected massive overdose, or with concomitant ingestion of other substances, or in patients with preexisting liver disease, the absorption and/or the half-life of acetaminophen may be prolonged, in such cases consideration should be given to the need for continued infusion of N-acetylcysteine beyond 21 hours. Acetaminophen levels and ALT/AST & INR should be checked before the end of the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which the ALT/AST are still increasing or the INR remains elevated, the infusion should be continued, and the treating physician should contact a US regional poison center at 1-800-222-1222, or alternatively, a “special health professional assistance line for acetaminophen overdose” at 1-800-525-6115 for assistance with dosing recommendations. Volume Adjustment: Patients Less Than 40 kg And Requiring Fluid Restriction The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as clinically needed. If the volume of the infusion is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure and death. [see DOSAGE AND ADMINISTRATION]. As Acetadote is hyperosmolar (2600 mOsmol/L), caution is advised when the diluent volume is decreased as the hyperosmolarity of the solution is increased. See Table 4 below for examples. Table 4: Acetadote Concentration and Osmolarity Acetadote Concentration (mg/mL) Osmolarity in ½Normal Saline Osmolarity in D5W Osmolarity in Sterile Water for Injection 7 mg/mL 245 mOsmol/L 343 mOsmol/L 91 mOsmol/L* 24 mg/m/L 466 mOsmol/L 564 mOsmol/L 312 mOsmol/L *Osmolarity should be adjusted to a physiologically safe level, (generally not less than 150mOsmol/L in children). Single dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for intravenous administration. Stability studies indicate that the diluted solution is stable for 24 hours at controlled room temperature. Note: The color of Acetadote may turn from essentially colorless to a slight pink or purple once the stopper is punctured. The color change does not affect the quality of the product. Renal Impairment No data are available to determine if a dose adjustment in patients with moderate or severe renal impairment is required. Hepatic Impairment Although there was a threefold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, no data are available to determine if a dose adjustment in these patients is required. The published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced. HOW SUPPLIED Dosage Forms And Strengths Each single dose vial contains 6g/30mL (200 mg/mL) of Acetadote (acetylcysteine) Injection. Acetadote is sterile and can be used for intravenous administration. Storage And Handling Acetadote (acetylcysteine) Injection is available as a 20% solution (200mg/mL) in 30 mL single dose glass vials. Each single dose vial contains 6g/30mL (200 mg/mL) of Acetadote Injection. Acetadote is sterile and can be used for intravenous administration. It is available as follows: 30 mL vials, carton of 4 (NDC 66220-207-30) Do not use previously opened vials for intravenous administration. Note: The color of Acetadote may turn from essentially colorless to a slight pink or purple once the stopper is punctured. The color change does not affect the quality of the product. The stopper in the Acetadote vial is formulated with a synthetic base-polymer and does not contain Natural Rubber Latex, Dry Natural Rubber, or blends of Natural Rubber. Storage Store unopened vials at controlled room temperature, 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. *Sections or subsections omitted from the Full Prescribing Information are not listed. Manufactured for: Cumberland Pharmaceuticals Inc., Nashville, TN 37203. Revised: June 2013"
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"property.value": "SIDE EFFECTS Clinical Studies 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. In the literature the most frequently reported adverse reactions attributed to intravenous acetylcysteine administration were rash, urticaria and pruritus. The frequency of adverse reactions has been reported to be between 0.2% and 20.8%, and they most commonly occur during the initial loading dose of acetylcysteine. Loading Dose/Infusion Rate Study The incidence of drug-related adverse reactions occurring within the first 2 hours following acetylcysteine administration reported in a randomized study in patients with acetaminophen poisoning is presented in Table 5 by preferred term. In this study patients were randomized to a 15-minute or a 60-minute loading dose regimen. Within the first 2 hours following intravenous acetylcysteine administration, 17% developed an anaphylactoid reaction (18% in the 15-minute treatment group; 14% in the 60-minute treatment group) in this randomized, open-label, multi-center clinical study conducted in Australia to compare the rates of anaphylactoid reactions between two rates of infusion for the intravenous acetylcysteine loading dose [see WARNINGS and Clinical Studies - Loading Dose/Infusion Rate Study (Section 14)]. Table 5: Incidence of Drug-Related Adverse Reactions Occurring Within the First 2 Hours Following Study Drug Administration by Preferred Term: Loading Dose/Infusion Rate Study Treatment Group 15-min 60-min Number of Patients n=109 n=71 Cardiac disorders 5 (5%) 2 (3%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Tachycardia NOS 4 (4%) 1 (1%) 2 (3%) Gastrointestinal disorders 16 (15%) 7 (10%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Nausea Vomiting 1 (1%) 6 (6%) 1 (1%) 1 (1%) NOS 2 (2%) 11 (10%) 2 (3%) 4 (6%) Immune System Disorders 20 (18%) 10 (14%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Anaphylactoid reaction 2 (2%) 6 (6%) 11 (10%) 1 (1%) 4 (6%) 5 (7%) 1 (1%) Respiratory, thoracic and mediastinal disorders 2 (2%) 2 (3%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Pharyngitis 1 (1%) Rhinorrhoea 1(1%) Rhonchi 1 (1%) Throat tightness 1 (1%) Skin & subcutaneous tissue disorders 6 (6%) 5 (7%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Pruritus 1 (1%) 2 (3%) Rash NOS 3 (3%) 2 (2%) 3 (4%) Vascular disorders 2 (2%) 3 (4%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Flushing 1 (1%) 1 (1%) 2 (3%) 1 (1%) Unkn=Unknown Postmarketing Safety Study A large multi-center study was performed in Canada where data were collected from patients who were treated with intravenous acetylcysteine for acetaminophen overdose between 1980 and 2005. This study evaluated 4709 adult cases and 1905 pediatric cases. The incidence of anaphylactoid reactions in adult (overall incidence 7.9%) and pediatric (overall incidence 9.5%) patients is presented in Tables 6 and 7. Table 6: Distribution of reported reactions in adult patients receiving intravenous acetylcysteine Incidence (%) Reaction % of Patients (n=4709) Urticaria/Facial Flushing 6.1% Pruritus 4.3% Respiratory Symptoms* 1.9% Edema 1.6% Hypotension 0.1% Anaphylaxis 0.1% Table 7: Distribution of reported reactions in pediatric patients receiving intravenous acetylcysteine Incidence (%) Reaction % of Patients (n=1905) Urticaria/Facial Flushing 7.6% Pruritus 4.1% Respiratory Symptoms* 2.2% Edema 1.2% Anaphylaxis 0.2% Hypotension 0.1% *Respiratory symptoms are defined as presence of any of the following: cough, wheezing, stridor, shortness of breath, chest tightness, respiratory distress, or bronchospasm. DRUG INTERACTIONS No drug-drug interaction studies have been conducted."
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"property.key": "Warnings & Precautions",
"property.value": "WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Anaphylactoid Reactions Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously. Acute flushing and erythema of the skin may occur in patients receiving acetylcysteine intravenously. These reactions usually occur 30 to 60 minutes after initiating the infusion and often resolve spontaneously despite continued infusion of acetylcysteine. Anaphylactoid reactions (defined as the occurrence of an acute hypersensitivity reaction during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath), have been observed in patients receiving intravenous acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion [see ADVERSE REACTIONS]. If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as an anaphylactoid reaction. This usually entails administering antihistaminic drugs and in severe cases may require administration of epinephrine. In addition, the acetylcysteine infusion may be interrupted until treatment of the anaphylactoid symptoms has been initiated and then carefully restarted. If the anaphylactoid reaction returns upon reinitiation of treatment or increases in severity, intravenous acetylcysteine should be discontinued and alternative patient management should be considered. Monitoring Patients With Asthma Acetadote should be used with caution in patients with asthma, or where there is a history of bronchospasm. Volume Adjustment: Patients Less Than 40 kg And Requiring Fluid Restriction The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as needed [see DOSAGE AND ADMINISTRATION]. If volume is not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure and death. For specific treatment information regarding the clinical management of acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential of acetylcysteine. Acetylcysteine was not genotoxic in the Ames test or the in vivo mouse micronucleus test. It was, however, positive in the in vitro mouse lymphoma cell (L5178Y/TK+/-) forward mutation test. Treatment of male rats with acetylcysteine at an oral dose of 250 mg/kg/day for 15 weeks (0.1 times the recommended total human intravenous dose of 300 mg/kg based on body surface comparison) did not affect the fertility or general reproductive performance. Use In Specific Populations Pregnancy Pregnancy Category B There are no adequate and well-controlled studies of Acetadote in pregnant women. However, limited case reports of pregnant women exposed to acetylcysteine during various trimesters did not report any adverse maternal, fetal or neonatal outcomes. There are published reports on four pregnant women with acetaminophen toxicity, who were treated with oral or intravenous acetylcysteine at the time of delivery. Acetylcysteine crossed the placenta and was measurable following delivery in serum and cord blood of three viable infants and in cardiac blood of a fourth infant at autopsy (22 weeks gestational age who died 3 hours after birth). No adverse sequelae developed in the three viable infants. All mothers recovered and none of the infants had evidence of acetaminophen poisoning. Reproduction studies were performed in rats at oral doses up to 2000 mg/kg/day (1.1 times the recommended total human intravenous dose of 300 mg/kg based on body surface area comparison) and in rabbits at oral doses up to 1000 mg/kg/day (1.1 times the recommended total human intravenous dose of 300 mg/kg based on body surface area comparison). No effects on fertility or harm to the fetus due to acetylcysteine were observed. Nursing Mothers It is not known whether Acetadote is present in human milk. Because many drugs are excreted in human milk, caution should be exercised when acetylcysteine is administered to a nursing woman. Based on the pharmacokinetics of acetylcysteine, it should be nearly completely cleared 30 hours after administration. Nursing women may consider resuming nursing 30 hours after administration. Pediatric Use No adverse effects were noted during intravenous infusion with acetylcysteine at a mean rate of 4.2 mg/kg/h for 24 hours to 10 preterm newborns ranging in gestational age from 25 to 31 weeks and in weight from 500 to 1380 grams in one study or in 6 newborns ranging in gestational age from 26 to 30 weeks and in weight from 520 to 1335 grams infused with acetylcysteine at 0.1 to 1.3 mg/kg/h for 6 days. Elimination of acetylcysteine was slower in these infants than in adults; mean elimination half-life was 11 hours. There are no adequate and well-controlled studies in pediatric patients. Geriatric Use The clinical studies do not provide a sufficient number of geriatric subjects to determine whether the elderly respond differently."
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"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE Single intravenous doses of acetylcysteine at 1000 mg/kg in mice, 2445 mg/kg in rats, 1500 mg/kg in guinea pigs, 1200 mg/kg in rabbits and 500 mg/kg in dogs were lethal. Symptoms of acute toxicity were ataxia, hypoactivity, labored respiration, cyanosis, loss of righting reflex and convulsions. CONTRAINDICATIONS Acetadote is contraindicated in patients with previous anaphylactoid reactions to acetylcysteine."
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"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY Mechanism Of action Acetaminophen Overdose Acetaminophen is absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. It is extensively metabolized in the liver to form principally the sulfate and glucuronide conjugates which are excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by isozyme CYP2E1 of the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite. The toxic metabolite preferentially conjugates with hepatic glutathione to form nontoxic cysteine and mercapturic acid derivatives, which are then excreted by the kidney. Recommended therapeutic doses of acetaminophen are not believed to saturate the glucuronide and sulfate conjugation pathways and therefore are not expected to result in the formation of sufficient reactive metabolite to deplete glutathione stores. However, following ingestion of a large overdose, the glucuronide and sulfate conjugation pathways are saturated resulting in a larger fraction of the drug being metabolized via the cytochrome P-450 pathway and therefore, the amount of acetaminophen metabolized to the reactive intermediate increases. The increased formation of the reactive metabolite may deplete the hepatic stores of glutathione with subsequent binding of the metabolite to protein molecules within the hepatocyte resulting in cellular necrosis. Acetylcysteine Intravenous Treatment Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. It is most effective when given early, with benefit seen principally in patients treated within 8-10 hours of the overdose. Acetylcysteine likely protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite. Pharmacokinetics Distribution The steady-state volume of distribution (Vdss) and the protein binding for acetylcysteine were reported to be 0.47 liter/kg and 83%, respectively. Metabolism Acetylcysteine may form cysteine, disulfides and conjugates in vivo (N, N'-diacetylcysteine, N-acetylcysteine-cysteine, N-acetylcysteine-glutathione, N-acetylcysteine-protein, etc). Based on published data, it was reported that after an oral dose of 35S-acetylcysteine, about 22% of total radioactivity was excreted in urine after 24 hours. No metabolites were identified. Elimination After a single intravenous dose of acetylcysteine, the plasma concentration of total acetylcysteine declined in a poly-exponential decay manner with a mean terminal half-life (T½) of 5.6 hours. The mean clearance (CL) for acetylcysteine was reported to be 0.11 liter/hr/kg and renal CL constituted about 30% of total CL. Special Populations Gender: Adequate information is not available to assess if there are differences in pharmacokinetics (PK) between males and females. Pediatric: The mean elimination T½ of acetylcysteine is longer in newborns (11 hours) than in adults (5.6 hours). Pharmacokinetic information is not available in other age groups. Pregnant Women: In four pregnant women with acetaminophen toxicity, oral or intravenous acetylcysteine was administered at the time of delivery. Acetylcysteine was detected in the cord blood of 3 viable infants and in cardiac blood of a fourth infant sampled at autopsy [see Pregnancy]. Hepatic Impairment: In subjects with severe liver damage, i.e., cirrhosis due to alcohol (with Child-Pugh score of 7-13), or primary and/or secondary biliary cirrhosis (with Child-Pugh score of 5-7), mean T½ increased by 80% while mean CL decreased by 30% compared to the control group. Renal Impairment: Pharmacokinetic information is not available in patients with renal impairment. Geriatric Patients: Adequate information on acetylcysteine PK in geriatric patients is not available. Clinical Studies Loading Dose/Infusion Rate Study A randomized, open-label, multi-center clinical study was conducted in Australia to compare the rates of anaphylactoid reactions between two rates of infusion for the intravenous acetylcysteine loading dose. One hundred nine subjects were randomized to a 15 minute infusion rate and seventy-one subjects were randomized to a 60 minute infusion rate. The loading dose was 150 mg/kg followed by a maintenance dose of 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours. Of the 180 patients, 27% were male and 73% were female. Ages ranged from 15 to 83 years, with the mean age being 29.9 years (+13.0). A subgroup of 58 subjects (33 in the 15-minute treatment group; 25 in the 60-minute treatment group) was treated within 8 hours of acetaminophen ingestion. No hepatotoxicity occurred within this subgroup; however with 95% confidence, the true hepatotoxicity rates could range from 0% to 9% for the 15-minute treatment group and from 0% to 12% for the 60-minute treatment group. Observational Study An open-label, observational database contained information on 1749 patients who sought treatment for acetaminophen overdose over a 16-year period. Of the 1749 patients, 65% were female, 34% were male and less than 1% was transgender. Ages ranged from 2 months to 96 years, with 71.4% of the patients falling in the 16-40 year old age bracket. A total of 399 patients received acetylcysteine treatment. A post-hoc analysis identified 56 patients who (1) were at high or probable risk for hepatotoxicity (APAP greater than 150 mg/L at the four hours line according to the Australian nomogram) and (2) had a liver function test. Of the 53 patients who were treated with intravenous acetylcysteine (300 mg/kg intravenous acetylcysteine administered over 20-21 hours) within 8 hours, two (4%) developed hepatotoxicity (AST or ALT greater than 1000 U/L). Twenty-one of 48 (44%) patients treated with acetylcysteine after 15 hours developed hepatotoxicity. The actual number of hepatotoxicity outcomes may be higher than what is reported here. For patients with multiple admissions for acetaminophen overdose, only the first overdose treated with intravenous acetylcysteine was examined. Hepatotoxicity may have occurred in subsequent admissions. Evaluable data were available from a total of 148 pediatric patients (less than 16 years of age) who were admitted for poisoning following ingestion of acetaminophen, of whom 23 were treated with intravenous acetylcysteine. Of the 23 patients who received intravenous acetylcysteine treatment, 3 patients (13%) had an adverse reaction (anaphylactoid reaction, rash and flushing, transient erythema). There were no deaths of pediatric patients. None of the pediatric patients receiving intravenous acetylcysteine developed hepatotoxicity while two patients not receiving intravenous acetylcysteine developed hepatotoxicity. The number of pediatric patients is too small to provide a statistically significant finding of efficacy; however the results appear to be consistent to those observed for adults. Postmarketing Safety Study [see Clinical Studies Experience]"
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"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Sensitivity to acetylcysteine: Patients should be advised to report to their physician any history of sensitivity to acetylcysteine [see CONTRAINDICATIONS]. Asthma Patients should be advised to report to their physician any history of asthma [see WARNINGS AND PRECAUTIONS]. For all questions concerning adverse reactions associated with the use of this product or for inquiries concerning our products, please contact us at 1-877-484-2700. For specific treatment information regarding the clinical management of acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115."
}
} |
58 | 2017-08-31 23:12:57 | Acetaminophen | Tylenol | FDA | { "58": { "alphabet_x_drug.id": 58, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
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"property.key": "Drug Description",
"property.value": "Find Lowest Prices on Tylenol® 325 mg (acetaminophen) Regular Strength DESCRIPTION Active Ingredient Acetaminophen Regular Strength Drug Facts Active Ingredient (in each caplet) Acetaminophen 325 mg"
},
"348": {
"property.id": 348,
"property.ts": "2017-12-04 04:42:47",
"property.key": "Indications & Dosage",
"property.value": "INDICATIONS Purpose Pain reliever/fever reducer Keep Out of Reach of Children This package is intended for institutional use only. Keep this and all drugs out of the reach of children. Uses For Hospital and Government Use Only Temporarily relieves minor aches and pains due to: the common cold, headache, backache, minor pain of arthritis, toothache, premenstrual and menstrual cramps, and temporarily reduces fever. DOSAGE AND ADMINISTRATION Directions Directions do not take more than directed (see OVERDOSE WARNING) adults and children 12 years and over take 2 caplets every 4 to 6 hours while symptoms last do not take more than 12 caplets in 24 hours do not use for more than 10 days unless directed by a doctor children 6-11 years take 1 caplet every 4 to 6 hours while symptoms last do not take more than 5 caplets in 24 hours do not use for more than 5 days unless directed by a doctor 1children under 6 years do not use this adult product in children under 6 years of age: this will provide more than the recommended dose (overdose) and may cause liver damage. HOW SUPPLIED Inactive ingredients Carnauba wax, castor oil, corn starch, FD&C red #40 aluminum lake, hypromellose, magnesium stearate, powdered cellulose, pregelatinized starch, propylene glycol, shellac, sodium starch glycolate, titanium dioxide. Storage Store between 20-25°C (68-77°F) Other See New WARNINGS Information Distributed By: Mcneil Consumer Healthcare, Division Of Mcneil - ppc, Inc., Fort Washington, PA 19034 USA"
},
"349": {
"property.id": 349,
"property.ts": "2017-12-04 04:42:47",
"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS No information provided. DRUG INTERACTIONS No information provided."
},
"350": {
"property.id": 350,
"property.ts": "2017-12-04 04:42:47",
"property.key": "Warnings & Precautions",
"property.value": "WARNINGS Do not use if pouch is opened Liver warning: This product contains acetaminophen. Severe liver damage may occur if: adult takes more than 12 caplets in 24 hours, which is the maximum daily amount child takes more than 5 doses in 24 hours, which is the maximum daily amount taken with other drugs containing acetaminophen adult has 3 or more alcoholic drinks every day while using this product. Do not use with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. if you are allergic to acetaminophen or any of the inactive ingredients in this product Stop use and ask a doctor if pain gets worse or lasts more than 10 days in adults pain gets worse or lasts more than 5 days in children under 12 years fever gets worse or lasts more than 3 days new symptoms occur redness or swelling is present These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. Ask a doctor before use if the user has liver disease Ask a doctor or pharmacist before use if the user is taking blood thinning drug warfarin. PRECAUTIONS No information provided."
},
"351": {
"property.id": 351,
"property.ts": "2017-12-04 04:42:47",
"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE Taking more than the recommended dose (overdose) may cause liver damage. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222) Quick medical attention is critical for adults as well as for children even if you do not notice an signs or symptoms. CONTRAINDICATIONS No information provided."
},
"352": {
"property.id": 352,
"property.ts": "2017-12-04 04:42:47",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY No information provided."
},
"353": {
"property.id": 353,
"property.ts": "2017-12-04 04:42:47",
"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Liver warning: This product contains acetaminophen. Severe liver damage may occur if: adult takes more than 12 caplets in 24 hours, which is the maximum daily amount child takes more than 5 doses in 24 hours, which is the maximum daily amount taken with other drugs containing acetaminophen adult has 3 or more alcoholic drinks every day while using this product. Do not use with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. if you are allergic to acetaminophen or any of the inactive ingredients in this product Stop use and ask a doctor if pain gets worse or lasts more than 10 days in adults pain gets worse or lasts more than 5 days in children under 12 years fever gets worse or lasts more than 3 days new symptoms occur redness or swelling is present These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. Ask a doctor before use if the user has liver disease Ask a doctor or pharmacist before use if the user is taking blood thinning drug warfarin."
}
} |
59 | 2017-08-31 23:12:57 | Acetaminophen | Tylenol | Multum | { "59": { "alphabet_x_drug.id": 59, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"354": {
"property.id": 354,
"property.ts": "2017-12-04 04:42:57",
"property.key": "Tylenol Patient Information Including Side Effects",
"property.value": "Find Lowest Prices on Brand Names: Acetaminophen Quickmelt, Actamin, Adprin B, Anacin AF, Apra, Bromo Seltzer, Children's Tylenol, Children's Tylenol Meltaway, Ed-APAP, Elixsure Fever/Pain, Genebs, Infants Tylenol Concentrated Drops, Leader 8 Hour Pain Reliever, Little Fevers, Little Fevers Children's Fever/Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Extra Strength Rapid Burst, Mapap Infant Drops, Mapap Infants', Mapap Meltaway, Mapap Rapid Release Gelcaps, Mapap Rapid Tabs, Medi-Tabs, Q-Pap, Q-Pap Extra Strength, Silapap Childrens, Silapap Infants, St. Joseph Aspirin-Free, Tactinal, Tempra, Tempra Quicklets, Triaminic Fever & Pain, Triaminic Infant Drops, Tycolene, Tylenol, Tylenol Arthritis Caplet, Tylenol Arthritis Gelcap, Tylenol Caplet, Tylenol Caplet Extra Strength, Tylenol Childrens, Tylenol Cool Caplet Extra Strength, Tylenol Extra Strength, Tylenol Extra Strength Cool Caplet, Tylenol Extra Strength EZ, Tylenol Gelcap Extra Strength, Tylenol Geltab Extra Strength, Tylenol Infant's Drops, Tylenol Junior Meltaway, Tylenol Rapid Release Gelcap, Tylenol Sore Throat Daytime, Vitapap Generic Name: acetaminophen (oral) (Pronunciation: a SEET a MIN oh fen) What is acetaminophen (Acetaminophen Quickmelt, Actamin, Adprin B, Anacin AF, Apra, Bromo Seltzer, Children's Tylenol, Children's Tylenol Meltaway, Ed-APAP, Elixsure Fever/Pain, Genebs, Infants Tylenol Concentrated Drops, Leader 8 Hour Pain Reliever, Little Fevers, Little Fevers Children's Fever/Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Extra Strength Rapid Burst, Mapap Infant Drops, Mapap Infants', Mapap Meltaway, Mapap Rapid Release Gelcaps, Mapap Rapid Tabs, Medi-Tabs, Q-Pap, Q-Pap Extra Strength, Silapap Childrens, Silapap Infants, St. Joseph Aspirin-Free, Tactinal, Tempra, Tempra Quicklets, Triaminic Fever & Pain, Triaminic Infant Drops, Tycolene, Tylenol, Tylenol Arthritis Caplet, Tylenol Arthritis Gelcap, Tylenol Caplet, Tylenol Caplet Extra Strength, Tylenol Childrens, Tylenol Cool Caplet Extra Strength, Tylenol Extra Strength, Tylenol Extra Strength Cool Caplet, Tylenol Extra Strength EZ, Tylenol Gelcap Extra Strength, Tylenol Geltab Extra Strength, Tylenol Infant's Drops, Tylenol Junior Meltaway, Tylenol Rapid Release Gelcap, Tylenol Sore Throat Daytime, Vitapap)? What are the possible side effects of acetaminophen? What is the most important information I should know about acetaminophen? What should I discuss with my healthcare provider before taking acetaminophen? How should I take acetaminophen? What happens if I miss a dose? What happens if I overdose? What should I avoid while taking acetaminophen? What other drugs will affect acetaminophen? Where can I get more information? What is acetaminophen (Acetaminophen Quickmelt, Actamin, Adprin B, Anacin AF, Apra, Bromo Seltzer, Children's Tylenol, Children's Tylenol Meltaway, Ed-APAP, Elixsure Fever/Pain, Genebs, Infants Tylenol Concentrated Drops, Leader 8 Hour Pain Reliever, Little Fevers, Little Fevers Children's Fever/Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Extra Strength Rapid Burst, Mapap Infant Drops, Mapap Infants', Mapap Meltaway, Mapap Rapid Release Gelcaps, Mapap Rapid Tabs, Medi-Tabs, Q-Pap, Q-Pap Extra Strength, Silapap Childrens, Silapap Infants, St. Joseph Aspirin-Free, Tactinal, Tempra, Tempra Quicklets, Triaminic Fever & Pain, Triaminic Infant Drops, Tycolene, Tylenol, Tylenol Arthritis Caplet, Tylenol Arthritis Gelcap, Tylenol Caplet, Tylenol Caplet Extra Strength, Tylenol Childrens, Tylenol Cool Caplet Extra Strength, Tylenol Extra Strength, Tylenol Extra Strength Cool Caplet, Tylenol Extra Strength EZ, Tylenol Gelcap Extra Strength, Tylenol Geltab Extra Strength, Tylenol Infant's Drops, Tylenol Junior Meltaway, Tylenol Rapid Release Gelcap, Tylenol Sore Throat Daytime, Vitapap)? There are many brands and forms of acetaminophen available and not all brands are listed on this leaflet.Acetaminophen is a pain reliever and a fever reducer.Acetaminophen is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers.Acetaminophen may also be used for purposes not listed in this medication guide. What are the possible side effects of acetaminophen? 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 taking this medication and call your doctor at once if you have a serious side effect such as:nausea, upper stomach pain, itching, loss of appetite;dark urine, clay-colored stools; orjaundice (yellowing of the skin or eyes).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 acetaminophen? There are many brands and forms of acetaminophen available and not all brands are listed on this leaflet.Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.Know the amount of acetaminophen in the specific product you are taking.Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take acetaminophen.Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Ask a doctor or pharmacist if it is safe for you to take this medicine if you have liver disease or a history of alcoholism.Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP."
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"355": {
"property.id": 355,
"property.ts": "2017-12-04 04:42:57",
"property.key": "Tylenol Patient Information including How Should I Take",
"property.value": "What should I discuss with my healthcare provider before taking acetaminophen? You should not take acetaminophen if you are allergic to it.Ask a doctor or pharmacist if it is safe for you to take acetaminophen if you have:liver disease; ora history of alcoholism.Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take acetaminophen.FDA pregnancy category C. Your doctor will determine whether acetaminophen is safe for you to use during pregnancy. Do not use this medicine without the advice of your doctor if you are pregnant.Acetaminophen can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.Do not give the medication to a child younger than 2 years old without the advice of a doctor. How should I take acetaminophen? Take exactly as directed on the label, or as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended.Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.If you are treating a child, use a pediatric form of acetaminophen. Use only the special dose-measuring dropper or oral syringe that comes with the specific pediatric form you are using. Carefully follow the dosing directions on the medicine label. Acetaminophen made for infants is available in two different dose concentrations, and each concentration comes with its own medicine dropper or oral syringe. These dosing devices are not equal between the different concentrations. Using the wrong device may cause you to give your child an overdose of acetaminophen. Never mix and match dosing devices between infant formulations of acetaminophen.You may need to shake the liquid before each use. Follow the directions on the medicine label.The chewable tablet must be chewed thoroughly before you swallow it.Make sure your hands are dry when handling the acetaminophen disintegrating tablet. Place the tablet on your tongue. It will begin to dissolve right away. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.To use the acetaminophen effervescent granules, dissolve one packet of the granules in at least 4 ounces of water. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.Stop taking acetaminophen and call your doctor if:you still have a fever after 3 days of use;you still have pain after 7 days of use (or 5 days if treating a child);you have a skin rash, ongoing headache, or any redness or swelling; orif your symptoms get worse, or if you have any new symptoms.This medication can cause unusual results with certain lab tests for glucose (sugar) in the urine. Tell any doctor who treats you that you are using acetaminophen.Store at room temperature away from heat and moisture."
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"property.key": "Tylenol Patient Information including If I Miss a Dose",
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60 | 2017-08-31 23:12:57 | Acetaminophen and Codeine | Tylenol-Codeine | FDA | { "60": { "alphabet_x_drug.id": 60, "alphabet.id": 1, "alphabet.ts": "2017-08-31 22:18:43", "alphabet.title": "A" } } | {
"357": {
"property.id": 357,
"property.ts": "2017-12-04 04:42:59",
"property.key": "Drug Description",
"property.value": "TYLENOL® with Codeine (acetaminophen with codeine phosphate) Tablets, USP DESCRIPTION TYLENOL® with Codeine is supplied in tablet form for oral administration. Acetaminophen, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula: C8H9NO2 M.W. 151.16 Codeine phosphate, 7,8-didehydro-4, 5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate, a white crystalline powder, is a narcotic analgesic and antitussive. It has the following structural formula: C18H21NO3•H3PO4•1/2 H2O M.W. 406.37 Each tablet contains: Acetaminophen. . . . . . . . . . . . . . . . . . . 300 mg No. 3 Codeine Phosphate . . . . . . . . . . . 30 mg (Warning: May be habit forming) Acetaminophen. . . . . . . . . . . . . . . . . . . 300 mg No. 4 Codeine Phosphate . . . . . . . . . . . 60 mg (Warning: May be habit forming) In addition, each tablet contains the following inactive ingredients: TYLENOL® with Codeine (acetaminophen and codeine) No. 3 contains powdered cellulose, magnesium stearate, sodium metabisulfite†, pregelatinized starch (corn), and modified starch (corn). TYLENOL® with Codeine (acetaminophen and codeine) No. 4 contains powdered cellulose, magnesium stearate, sodium metabisulfite†, pregelatinized starch (corn), and corn starch. †See WARNINGS"
},
"358": {
"property.id": 358,
"property.ts": "2017-12-04 04:42:59",
"property.key": "Indications & Dosage",
"property.value": "INDICATIONS TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets are indicated for the relief of mild to moderately severe pain. DOSAGE AND ADMINISTRATION Dosage should be adjusted according to severity of pain and response of the patient. The usual adult dosage is: Single Doses (Range) Maximum 24-Hour Dose Codeine Phosphate 15 mg to 60 mg 360 mg Acetaminophen 300 mg to 1000 mg 4000 mg Doses may be repeated up to every 4 hours. The prescriber must determine the number of tablets per dose, and the maximum number of tablets per 24 hours, based upon the above dosage guidance. This information should be conveyed in the prescription. It should be kept in mind, however, that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of undesirable side effects. Equivalently high doses in children would have similar effects. HOW SUPPLIED TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets are white, round, flat-faced, beveled edged tablet imprinted “McNEIL” on one side and “TYLENOL CODEINE” and either “3” or “4” on the other side and are supplied as follows: No. 3 - NDC 0045-0513-60 bottles of 100, NDC 0045-0513-80 bottles of 1000, No. 4 - NDC 0045-0515-60 bottles of 100, NDC 0045-0515-70 bottles of 500. Store TYLENOL® with Codeine (acetaminophen and codeine) tablets at 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.) Dispense in tight, light-resistant container as defined in the official compendium. Manufactured by: JOLLC, Gurabo, Puerto Rico 00778. Distributed by: Omp Division, Ortho-Mcneil Pharmaceutical, Inc. Raritan, New Jersey 08869. Revised January 2008."
},
"359": {
"property.id": 359,
"property.ts": "2017-12-04 04:42:59",
"property.key": "Side Effects & Drug Interactions",
"property.value": "SIDE EFFECTS The most frequently observed adverse reactions include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea and vomiting. These effects seem to be more prominent in ambulatory than in non-ambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include allergic reactions, euphoria, dysphoria, constipation, abdominal pain, pruritus, rash, thrombocytopenia, and agranulocytosis. At higher doses, codeine has most of the disadvantages of morphine including respiratory depression. Drug Abuse And Dependence Controlled Substance TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets are classified as a Schedule III controlled substance. Abuse and Dependence Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic medications. DRUG INTERACTIONS This drug may enhance the effects of other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. Drug/Laboratory Test Interactions Codeine may increase serum amylase levels. Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid."
},
"360": {
"property.id": 360,
"property.ts": "2017-12-04 04:42:59",
"property.key": "Warnings & Precautions",
"property.value": "WARNINGS In the presence of head injury or other intracranial lesions, the respiratory depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure. Narcotics also produce other CNS depressant effects, such as drowsiness, that may further obscure the clinical course of the patients with head injuries. Codeine or other narcotics may obscure signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions. Codeine is habit forming and potentially abusable. Consequently, the extended use of this product is not recommended. TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. PRECAUTIONS General TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets should be prescribed with caution in certain special-risk patients, such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, head injuries, elevated intracranial pressure, acute abdominal conditions, hypothyroidism, urethral stricture, Addison's disease, or prostatic hypertrophy. Ultra-Rapid Metabolizers of Codeine Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. Data is not available for other ethnic groups. When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and inform their patients about these risks and the signs of morphine overdose (see PRECAUTIONS – Nursing Mothers). Laboratory Tests In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests. Carcinogenesis, Mutagenesis, Impairment of Fertility No adequate studies have been conducted in animals to determine whether acetaminophen and codeine have a potential for carcinogenesis or mutagenesis. No adequate studies have been conducted in animals to determine whether acetaminophen has a potential for impairment of fertility. Acetaminophen and codeine have been found to have no mutagenic potential using the Ames Salmonella-Microsomal Activation test, the Basc test on Drosophila germ cells, and the Micronucleus test on mouse bone marrow. Pregnancy Teratogenic Effects: Pregnancy Category C. Codeine A study in rats and rabbits reported no teratogenic effect of codeine administered during the period of organogenesis in doses ranging from 5 to 120 mg/kg. In the rat, doses at the 120 mg/kg level, in the toxic range for the adult animal, were associated with an increase in embryo resorption at the time of implantation. In another study a single 100 mg/kg dose of codeine administered to pregnant mice reportedly resulted in delayed ossification in the offspring. There are no adequate and well-controlled studies in pregnant women. TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Dependence has been reported in newborns whose mothers took opiates regularly during pregnancy. Withdrawal signs include irritability, excessive crying, tremors, hyperreflexia, fever, vomiting, and diarrhea. These signs usually appear during the first few days of life. Labor and Delivery Narcotic analgesics cross the placental barrier. The closer to delivery and the larger the dose used, the greater the possibility of respiratory depression in the newborn. Narcotic analgesics should be avoided during labor if delivery of a premature infant is anticipated. If the mother has received narcotic analgesics during labor, newborn infants should be observed closely for signs of respiratory depression. Resuscitation may be required (see OVERDOSAGE). The effect of codeine, if any, on the later growth, development, and functional maturation of the child is unknown. Nursing Mothers Acetaminophen is excreted in breast milk in small amounts, but the significance of its effect on nursing infants is not known. Because of the potential for serious adverse reactions in nursing infants from acetaminophen, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother. Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants. The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. Data is not available for other ethnic groups. The risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding (see PRECAUTIONS – General, Ultra-Rapid Metabolizers of Codeine)."
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"361": {
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"property.ts": "2017-12-04 04:42:59",
"property.key": "Overdosage & Contraindications",
"property.value": "OVERDOSE Following an acute overdosage, toxicity may result from codeine or acetaminophen. Signs and Symptoms Codeine Toxicity from codeine poisoning includes the opioid triad of: pinpoint pupils, depression of respiration, and loss of consciousness. Convulsions may occur. Acetaminophen In acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma and thrombocytopenia may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. In adults, hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams or fatalities with less than 15 grams. Treatment A single or multiple overdose with acetaminophen and codeine is a potentially lethal polydrug overdose and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endo-tracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration. Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis, may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously. Naloxone, a narcotic antagonist, can reverse respiratory depression and coma associated with opioid overdose. Naloxone hydrochloride 0.4 mg to 2 mg is given parenterally. Since the duration of action of codeine may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression. If the dose of acetaminophen may have exceeded 140 mg/kg, acetylcysteine should be administered as early as possible. Serum acetaminophen levels should be obtained, since levels four or more hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeated at 24-hour intervals. Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration. Toxic Doses (for adults) Acetaminophen: toxic dose 10 g Codeine: toxic dose 240 mg CONTRAINDICATIONS This product should not be administered to patients who have previously exhibited hypersensitivity to codeine or acetaminophen."
},
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"property.id": 362,
"property.ts": "2017-12-04 04:42:59",
"property.key": "Clinical Pharmacology",
"property.value": "CLINICAL PHARMACOLOGY This product combines the analgesic effects of a centrally acting analgesic, codeine, with a peripherally acting analgesic, acetaminophen. Pharmacokinetics The behavior of the individual components is described below. Codeine Codeine is rapidly absorbed from the gastrointestinal tract. It is rapidly distributed from the intravascular spaces to the various body tissues, with preferential uptake by parenchymatous organs such as the liver, spleen and kidney. Codeine crosses the blood-brain barrier and is found in fetal tissue and breast milk. The plasma concentration does not correlate with brain concentration or relief of pain; however, codeine is not bound to plasma proteins and does not accumulate in body tissues. The plasma half-life is about 2.9 hours. The elimination of codeine is primarily via the kidneys, and about 90% of an oral dose is excreted by the kidneys within 24 hours of dosing. The urinary secretion products consist of free and glucuronide conjugated codeine (about 70%), free and conjugated norcodeine (about 10%), free and conjugated morphine (about 10%) normorphine (4%), and hydrocodone (1%). The remainder of the dose is excreted in the feces. At therapeutic doses, the analgesic effect reaches a peak within 2 hours and persists between 4 and 6 hours. See OVERDOSAGE for toxicity information. Acetaminophen Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. See OVERDOSAGE for toxicity information."
},
"363": {
"property.id": 363,
"property.ts": "2017-12-04 04:42:59",
"property.key": "Medication Guide",
"property.value": "PATIENT INFORMATION Codeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking this product. Alcohol and other CNS depressants may produce an additive CNS depression, when taken with this combination product, and should be avoided. Codeine may be habit forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed. Caution patients that some people have a variation in a liver enzyme and change codeine into morphine more rapidly and completely than other people. These people are ultra-rapid metabolizers and are more likely to have higher-than-normal levels of morphine in their blood after taking codeine, which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer. Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby's doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services)."
}
} |
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