Zafirlukast

What it is and how it works

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.

Mechanism class: Leukotriene Receptor Antagonists · Cytochrome P450 2C9 Inhibitors

Indications

INDICATIONS AND USAGE Zafirlukast tablets are indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.

Dosage and administration (summary)

DOSAGE AND ADMINISTRATION Because food can reduce the bioavailability of zafirlukast, zafirlukast tablets 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 tablets 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 tablets 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 C max and AUC are approximately twice those of younger adults.

Contraindications

CONTRAINDICATIONS Zafirlukast tablets are contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients. Zafirlukast tablets are contraindicated in patients with hepatic impairment including hepatic cirrhosis.

Warnings and precautions

WARNINGS Hepatotoxicity: Cases of life-threatening hepatic failure have been reported in patients treated with zafirlukast. 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 zafirlukast (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 zafirlukast.

Pregnancy

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 2 basis), up to 2000 mg/kg/day in rats (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m 2 basis) and up to 2000 mg/kg/day in cynomolg…

Storage and supply

HOW SUPPLIED Zafirlukast tablets 10 mg are white to light pink, round, film coated tablets debossed with ‘R’ on one side and ‘625’ on other side and are supplied in bottles of 30, 60, 100, 500 and unit dose blister packages of 100 (10 x 10).

Source: Zafirlukast (Zafirlukast) — US FDA prescribing information, 2018-11-16, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.