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ACCOLATE
Overview
What is ACCOLATE?
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-o-tolylsulfonylbenzamide. The molecular weight of zafirlukast is 575.7 and the structural formula is:
The empirical formula is: CHNOS
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:
What does ACCOLATE look like?
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What are the available doses of ACCOLATE?
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What should I talk to my health care provider before I take ACCOLATE?
Sorry No records found
How should I use ACCOLATE?
ACCOLATE is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.
Because food can reduce the bioavailability of zafirlukast, ACCOLATE should be taken at least 1 hour before or 2 hours after meals.
What interacts with ACCOLATE?
ACCOLATE is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.
What are the warnings of ACCOLATE?
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 post-marketing 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 and ).
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 ).
What are the precautions of ACCOLATE?
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 and ).
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 ). Women who are breast-feeding should be instructed not to take ACCOLATE (see ). 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 on ACCOLATE therapy 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. These events usually, but not always, have been associated with the reduction of oral steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between ACCOLATE and these underlying conditions has not been established (see ).
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).
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 ). 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 ).
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.
No 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 , it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with ACCOLATE.
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/m 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/m 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 long-term 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 human peripheral blood lymphocyte clastogenic assay and the 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/m 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/m basis), up to 2000 mg/kg/day in rats (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m 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 C and AUC are approximately 2- to 3-fold greater than those of younger patients (see and ).
A total of 8094 patients were exposed to zafirlukast in North American and European short-term placebo-controlled 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.
What are the side effects of ACCOLATE?
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.
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 and ).
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 on ACCOLATE therapy 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. These events usually, but not always, have been associated with the reduction of oral steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between ACCOLATE and these underlying conditions has not been established (see ).
Neuropsychiatric adverse events, including insomnia and depression, have been reported in association with ACCOLATE therapy (see ). 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 metabolism data and the results of two clinical drug interaction studies (see and ).
| ACCOLATE | PLACEBO | ||||
| Adverse Event | N=4058 | 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% |
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.
What should I look out for while using ACCOLATE?
ACCOLATE is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.
What might happen if I take too much ACCOLATE?
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/m basis), 2000 mg/kg in rats (approximately 420 times the maximum recommended daily oral dose in adults and children on a mg/m basis), and 500 mg/kg in dogs (approximately 350 times the maximum recommended daily oral dose in adults and children on a mg/m 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.
How should I store and handle ACCOLATE?
Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from excessive light and humidity.Dispense in a tight, light-resistant container according to USP/NF.*AN69 is a registered trademark of Hospal Ltd.WockhardtThis Product was Repackaged By:State of Florida DOH Central PharmacyStore at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from excessive light and humidity.Dispense in a tight, light-resistant container according to USP/NF.*AN69 is a registered trademark of Hospal Ltd.WockhardtThis Product was Repackaged By:State of Florida DOH Central PharmacyStore at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from excessive light and humidity.Dispense in a tight, light-resistant container according to USP/NF.*AN69 is a registered trademark of Hospal Ltd.WockhardtThis Product was Repackaged By:State of Florida DOH Central PharmacyStore at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from excessive light and humidity.Dispense in a tight, light-resistant container according to USP/NF.*AN69 is a registered trademark of Hospal Ltd.WockhardtThis Product was Repackaged By:State of Florida DOH Central PharmacyStore at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from excessive light and humidity.Dispense in a tight, light-resistant container according to USP/NF.*AN69 is a registered trademark of Hospal Ltd.WockhardtThis Product was Repackaged By:State of Florida DOH Central PharmacyStore at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from excessive light and humidity.Dispense in a tight, light-resistant container according to USP/NF.*AN69 is a registered trademark of Hospal Ltd.WockhardtThis Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central PharmacyACCOLATE 10 mg Tablets,ACCOLATE 20 mg Tablets,They are supplied by as follows: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.ACCOLATE is a trademark of the AstraZeneca group of companies.©Manufactured for: AstraZeneca Pharmaceuticals LPWilmington, DE 19850By: IPR Pharmaceuticals, Inc.Canovanas, PR 00729 This Product was Repackaged By:State of Florida DOH Central Pharmacy
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Zafirlukast is a selective and competitive receptor antagonist of leukotriene D and E (LTD and LTE), 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 LTD than nonasthmatic subjects.
In vitro
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.
Non-Clinical Toxicology
ACCOLATE is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.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 ). 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 ).
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.
No 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 , it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with ACCOLATE.
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 and ).
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 ). Women who are breast-feeding should be instructed not to take ACCOLATE (see ). 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.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).