Zafirlukast

Zafirlukast is an oral cysteinyl leukotriene receptor antagonist used as add-on controller therapy in asthma. It is taken twice daily and is not a reliever.

Classification. Leukotriene receptor antagonist.

Mechanism. Selective antagonist of the CysLT1 receptor.

Pharmacokinetics. Absorption is reduced by food (about 40%). Highly protein bound. Metabolised by CYP2C9 and inhibits CYP2C9 and CYP3A4. Half-life about 10 hours. Faecal elimination.

Add-on, asthma, adults and adolescents from 12 years. 20 mg twice daily, taken at least 1 hour before or 2 hours after a meal. Some labels allow 40 mg twice daily under specialist direction.

Children 5 to 11 years. 10 mg twice daily on an empty stomach.

Alternative first-line, mild asthma. Another controller, preferably an inhaled corticosteroid, is more effective.

Emergency. Not used.

Titration and loading. None.

Contraindications. Hypersensitivity. Hepatic impairment including cirrhosis.

Serious adverse effects. Hepatotoxicity including rare fulminant hepatic failure, eosinophilic granulomatosis with polyangiitis unmasked as corticosteroid doses fall, neuropsychiatric events, hypersensitivity.

Common adverse effects. Headache, nausea, diarrhoea, abdominal pain.

Interactions. Warfarin: zafirlukast raises INR, so reduce the warfarin dose and monitor closely. Erythromycin lowers zafirlukast levels. Theophylline interactions are variable; monitor levels. Aspirin raises zafirlukast levels.

Common prescribing errors. Giving with food. Prescribing with warfarin without INR monitoring. Missing the liver baseline.

Special groups.

• Pregnancy: limited data; use only if the benefit outweighs risk. Breastfeeding: excreted in milk; avoid.

• Older adults: clearance is lower and peak levels higher; consider lower exposure and monitor.

• Kidney impairment: no adjustment. Liver impairment: contraindicated.

• East Africa: availability is limited; montelukast is more often stocked.

Formulations. Tablets 10 mg and 20 mg.

Administration. On an empty stomach, twice daily.

Baseline. Liver function tests and a record of anticoagulant use.

Monitoring. Control and reliever use. Liver tests if nausea, right upper quadrant pain, pruritus, jaundice or dark urine occur. INR with warfarin.

Stop and reduce rules. Stop for any sign of liver injury or if alanine aminotransferase exceeds 3 times the upper limit of normal with symptoms; do not restart after hepatotoxicity. Therapeutic drug monitoring is not used.

Referral and escalation. Refer for suspected liver injury or vasculitis features.