Overview
DESCRIPTION Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA), with the chemical name N-[3-[[2-Methoxy-4-[[[(2-methylphenyl) sulfonyl]amino]carbonyl] phenyl]methyl]-1-methyl-1H-1H-indol-5-yl]carbamic acid cyclopentyl ester; The molecular weight of zafirlukast is 575.
Mechanism of Action
CLINICAL PHARMACOLOGY Mechanism of Action Zafirlukast is a selective and competitive receptor antagonist of leukotriene D 4 and E 4 (LTD 4 and LTE 4 ), 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 to 100 times more sensitive to the bronchoconstricting activity of inhaled LTD 4 than nonasthmatic subjects.
Indications
- INDICATIONS AND USAGE Zafirlukast is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.
Common Doses
- 20 mg
- 10 mg
Dosage
DOSAGE AND ADMINISTRATION Because food can reduce the bioavailability of zafirlukast, zafirlukast 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 zafirlukast 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 zafirlukast in children 5 through 11 years of age is 10 mg twice daily.
Contraindications
- CONTRAINDICATIONS Zafirlukast is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients. Zafirlukast is contraindicated in patients with hepatic impairment including hepatic cirrhosis.
Side Effects
- ADVERSE REACTIONS Adults and Children 12 years of age and older The safety database for zafirlukast consists of more than 4,000 healthy volunteers and patients who received zafirlukast, of which 1,723 were asthmatics enrolled in trials of 13 weeks duration or longer. A total of 671 patients received zafirlukast 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 zafirlukast.
Interactions
- 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.