Drug information of Zafirlukast

Mechanism of effect

 Inhibits bronchoconstriction as competitive receptor antagonist of leukotrienes D4 & E4; receptor occupation and cysteinyl leukotriene production has been associated with the pathophysiology of asthma.

Pharmacodynamic

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.

Pharmacokinetics

Half-Life: 8-16 hr

Onset: 3-14 days

Peak plasma concentration: 326 ng/mL (healthy subjects); 568 ng/mL (asthmatics)

Peak plasm time: 3 hr (healthy subjects); 3.5 hr (asthmatics)

Clearance: 20 L/hr; significantly decreased in cirrhosis and age 65 yr

Protein bound: 99%

Vd: 70 L

Bioavailability: Reduced 40% with food

Metabolism: Hepatic CYP2C9

Excretion: Feces (90%); urine (10%)

Enzymes inhibited: Hepatic CYP2C9, CYP3A4

Dosage

Adults

20 mg PO twice daily  

Pediatrics

Less than 5 years: The safety and effectiveness has not been established.

5 to 11 years:
10 mg orally twice a day, 1 hour before or 2 hours after meals

12 years or older:
20 mg orally twice a day, 1 hour before or 2 hours after meals

Drug contraindications

liver failure , cirrhosis , Hypersensitivity to this drug

Side effects

Headache , nausea , vomiting , Diarrhea , asthenia , myalgia , Increased ALT , Abdominal pain , indigestion , Infection

Interactions

Erythromycin , Pimozide , Everolimus , Dihydroergotamine , Sirolimus , Cisapride , Simvastatin , Lovastatin , silodosin , ergotamine , Ranolazine , Sertindole , Terfenadine , Pazopanib , tolvaptan , Phenindione , Peginterferon alfa-2b , Halofantrine , Methacholine , Gefitinib , Remdesivir , Cannabidiol

Alerts

• Not immediately effective and not for acute bronchospasm
• Increased risk of infection if age >55 yr
• Discontinue if hepatic dysfunction suspected, do not resume if confirmed
• May cause eosinophilia, eosinophilic pneumonia, or vasculitis consistent with emergence of Churg-Strauss syndrome
• Behavioral changes reported with therapy
• Concomitant use with warfarin can result in clinical significant increase in INR
• Not for use in the treatment of acute asthma attacks, including status asthmaticus

Points of recommendation

• Take even during sign-free periods.
• Take on an empty stomach. Take 1 hour before or 2 hours after meals.
• Take this medicine at the same time of day.
• To gain the most benefit, do not miss doses.
• Keep taking zafirlukast as you have been told by your doctor or other health care provider, even if you feel well.

Pregnancy level

B

Related drugs

Montelukast , Zileuton