indication

For the prophylaxis and chronic treatment of asthma.

pharmacology

Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment 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.

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.

toxicity

Side effects include rash and upset stomach.

biotransformation

Hepatic

absorption

Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.

half life

10 hours

route of elimination

The most common metabolic products are hydroxylated metabolites which are excreted in the feces.

drug interactions

Acenocoumarol: Zafirlukast may inhibit the metabolism of the vitamin K antagonist Acenocoumarol and increase INR and risk of bleeding.

Aminophylline: Zafirlukast serum concentrations may be decreased by the theophylline derivative Aminophylline.

Capecitabine: Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if capecitabine is initiated, discontinued or dose changed.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Delavirdine: Delavirdine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if delavirdine is initiated, discontinued or dose changed.

Erythromycin: Erythromycin may decrease the serum concentration and effect of zafirlukast.

Floxuridine: Floxuridine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if floxuridine is initiated, discontinued or dose changed.

Fluconazole: Fluconazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if fluconazole is initiated, discontinued or dose changed.

Fluorouracil: Fluorouracil, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if fluorouracil is initiated, discontinued or dose changed.

Gemfibrozil: Gemfibrozil, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if gemfibrozil is initiated, discontinued or dose changed.

Ketoconazole: Ketoconazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if ketoconazole is initiated, discontinued or dose changed.

Nicardipine: Nicardipine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if nicardipine is initiated, discontinued or dose changed.

Sitaxentan: Sitaxentan, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if sitaxentan is initiated, discontinued or dose changed.

Sulfadiazine: Sulfadiazine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if sulfadiazine is initiated, discontinued or dose changed.

Sulfisoxazole: Sulfisoxazole, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if sulfisoxazole is initiated, discontinued or dose changed.

Theophylline: Zafirlukast serum concentrations may be decreased by Theophylline.

Tolbutamide: Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if tolbutamide is initiated, discontinued or dose changed.