Accolate
Buy AccolateAccolate Information
Brand Name: Accolate
Generic Name: Zafirlukast
Other Common Names: Acculate
Accolate is meant for the prevention and chronic treatment of asthma; it is not meant to stop acute asthma attacks.
Accolate Indications
Accolate (zafirlukast) is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.
Accolate Ingredients and Composition
How Does Accolate Work?
Zafirlukast, the Active ingredient in Accolate, is a selective and competitive receptor antagonist of leukotriene D4 and E4, 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 Accolate 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, the active ingredient in Accolate, 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.
How To Take Accolate and Accolate Dosage and Administration
The recommended Accolate dose is 20 mg twice daily in adults and children 12 years and older. Since food reduces the bioavailability of zafirlukast, zafirlukast should be taken at least 1 hour before or 2 hours after meals.
Elderly Patients Accolate dosage
Based on cross-study comparisons, the clearance of zafirlukast, the active ingredient in Accolate, is reduced in elderly patients (65 years of age and older), such that Cmax and AUC are approximately twice those of younger adults. In Accolate 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.
Accolate Dosage in Patients with Hepatic Impairment
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. Zafirlukast has not been evaluated in patients with hepatitis or in long-term studies of patients with cirrhosis.
Accolate Dosage Patients with Renal Impairment
Dosage adjustment is not required for patients with renal impairment.
Accolate Dosage Pediatric Patients
The safety and effectiveness of Accolate in pediatric patients below the age of 12 years have not been established.
If you suspect a Accolate Overdose
No deaths occurred at oral Accolate doses of 2000 mg/kg in mice (approximately 200 times the maximum recommended human daily oral dose on a mg/m2 basis), 2000 mg/kg in rats (approximately 400 times the maximum recommended human daily oral dose on a mg/m2 basis), and 500 mg/kg in dogs (approximately 330 times the maximum recommended human daily oral dose on a mg/m2 basis).
There is no experience to date with Accolate in overdose in humans. It is reasonable to employ the usual supportive measures in the event of an overdose; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.
Accolate Side Effects
Accolate Warnings
Contraindications to Accolate
Accolate is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.
Taking Accolate during Pregnancy or Breast-feeding
Accolate should not be administered to pregnant women.
Zafirlukast, the active ingredient of Accolate, 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, zafirlukast should not be administered to mothers who are breast-feeding.
Accolate Drug Interactions
In a drug interaction study in 16 healthy male volunteers, co-administration of multiple doses of Accolate (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 zafirlukast should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly. No formal drug-drug interaction studies with zafirlukast and other drugs known to be metabolized by the cytochrome P450 2C9 isoenzyme (e.g., tolbutamide, phenytoin, carbamazepine) have been conducted; however, care should be exercised when Accolate is co-administered with these drugs.
In a drug interaction study in 16 healthy male volunteers, co-administration of Accolate (320 mg/day), with terfenadine (60 mg twice daily) to steady state resulted in a decrease in the mean Cmax (-66%) and AUC (-54%) of zafirlukast. No effect of zafirlukast on terfenadine plasma concentrations or ECG parameters (i.e., QTc interval) was seen. No formal drug-drug interaction studies between zafirlukast and other drugs known to be metabolized by the P450 3A4 (CYP 3A4) isoenzyme (e.g., dihydropyridine calcium-channel blockers, cyclosporin, cisapride, astemizole) have been conducted. As zafirlukast is known to be an inhibitor of CYP 3A4 in vitro, it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with zafirlukast.
In a drug interaction study in 11 asthmatic patients, co-administration of a single dose of the active ingredient of Accolate, 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.
Co-administration of zafirlukast (80 mg/day) at steady state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients 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 zafirlukast to an existing theophylline regimen have been reported. The mechanism of the interaction between zafirlukast and theophylline in these patients is unknown
Co-administration of zafirlukast, the active ingredient in Accolate, (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 Accolate 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.
Accolate Clinical Trials and Studies
Accolate Pill Identification / ID and Appearance
Accolate comes as 20 mg Tablets, white, round, biconvex, coated tablets identified with "ZENECA" debossed on one side and "ACCOLATE 20" debossed on the other side.
Storing Accolate
Store Accola teat controlled room temperature, (20°-25°) (68°-77° F). Protect from light and moisture.
