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Leukotriene-receptor antagonists. Pharmacologic considerations

Last updated on November 14th, 2021

Pharmacokinetics of montelukast (Singulair)

Montelukast (marketed as Singulair) is rapidly and nearly completely absorbed following oral administration. Peak plasma concentrations are reached in 2 to 3 hours for the 5- and 10-mg formulations. Mean plasma half-life is 2.7 to 5.5 hours. Montelukast is metabolized in the liver by CYP-450 enzymes 3A4 and 2C9 and is excreted mainly in the bile. There have been no reported pharmacokinetic differences between dosing in the morning or in the evening. Dosage adjustments are not required for patients with mild to moderate hepatic insufficiency.

Montelukast does not appear to interact with any drugs, including oral contraceptives. Bioavailability of montelukast is not influenced by food ingestion. Currently there is no information on other potent CYP-450 enzyme inducers, such as rifampin, or inhibitors, such as ketoconazole. The safety of montelukast in human pregnancy has not been established. The overall incidence of side effects reported with montelukast is not significantly different from placebo; the more common adverse events are headache and abdominal pain.

Dosing for montelukast

Montelukast is available in 10-mg tablets and 5-mg chewable tablets. Recommended dosage is 5 mg for children 6 to 14 years old and 10 mg for adults, taken daily in the evening.

Pharmacokinetics of zafirlukast (Accolate)

Zafirlukast (marketed as Accolate) is rapidly absorbed following oral administration. Peak plasma concentrations are achieved 3 hours after dosing. Taking zafirlukast with food reduces its bioavailablity. The elimination half-life of zafirlukast is approximately 10 hours. Zafirlukast is metabolized in the liver by the CYP-450 enzyme 2C9 enzyme pathway. Zafirlukast is not recommended for patients with hepatic impairment, including liver cirrhosis.

Coadministration of zafirlukast with erythromycin, theophylline, and terfenadine will result in decreased plasma levels of zafirlukast, but coadministration with ASA can increase levels of zafirlukast. Coadministration with terfenadine does not result in changes in plasma terfenadine levels or in electrocardiographic parameters. Zafirlukast ingestion increases plasma levels of warfarin, so adjustments in anticoagulant therapy might be needed. Oral contraceptives can be administered with zafirlukast without adverse interaction. The safety of zafirlukast during human pregnancy has not been established. Overall incidence of side effects reported with zafirlukast is not significantly different from that with placebo. The most common adverse events reported after long-term therapy with zafirlukast were headache and pharyngitis.

Dosing for zafirlukast

The recommended dosage of zafirlukast is 20 mg twice daily taken at least 1 hour before or 2 hours after meals. Zafirlukast is approved for adults and children 12 years or older.

In rare cases of patients using zafirlukast and montelukast, a reduction in oral steroid therapy has been associated with systemic eosinophilic vasculitis. No causal relationship with zafirlukast or montelukast has been established, and it seems most likely that withdrawal of oral steroids from asthma patients treated successfully with zafirlukast and montelukast has unmasked an existing vasculitis rather than caused one.

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