Brands, Medical Use, Clinical Data
Drug Category
Dosage Forms
Brands / Synonyms
Singulair; Singular
Indications
For the treatment of asthma
Pharmacology
Montelukast, like zafirlukast, is a leukotriene receptor antagonist used as an alternative to anti-inflammatory medications in the management and chronic treatment of asthma and exercise-induced bronchospasm (EIB). Unlike zafirlukast, montelukast does not inhibit CYP2C9 or CYP3A4 and is, therefore, not expected to affect the hepatic clearance of drugs metabolized by these enzymes.
Mechanism of Action
Montelukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Montelukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.
Absorption
Rapidly absorbed following oral administration (bioavailability is 64%)
Toxicity
Side effects include headache, abdominal or stomach pain, cough, dental pain, dizziness, fever, heartburn, skin rash, stuffy nose, weakness or unusual tiredness.
Biotrnasformation / Drug Metabolism
Hepatic
Contraindications
Hypersensitivity to any component of this product.
Drug Interactions
Montelukast at a Dose of 10 mg Once Daily Dosed to Pharmacokinetic Steady State
- did not cause clinically significant changes in the kinetics of a single intravenous dose of theophylline
(predominantly a cytochrome P450 1A2 substrate).
- did not change the pharmacokinetic profile of warfarin (a substrate of cytochromes P450 2A6 and 2C9) or
influence the effect of a single 30-mg oral dose of warfarin on prothrombin time or the INR (International
Normalized Ratio).
- did not change the pharmacokinetic profile or urinary excretion of immunoreactive digoxin.
- did not change the plasma concentration profile of terfenadine (a substrate of cytochrome P450 3A4) or
fexofenadine, its carboxylated metabolite, and did not prolong the QTc interval following co-administration with
terfenadine 60 mg twice daily.
Montelukast at Doses of ³100 mg Daily Dosed to Pharmacokinetic Steady State:
- did not significantly alter the plasma concentrations of either component of an oral contraceptive containing
norethindrone 1 mg/ethinyl estradiol 35 mcg.
- did not cause any clinically significant change in plasma profiles of prednisone or prednisolone following
administration of either oral prednisone or intravenous prednisolone.
Phenobarbital, which induces hepatic metabolism, decreased the AUC of montelukast approximately 40% following a
single 10-mg dose of montelukast. No dosage adjustment for montelukast is recommended. It is reasonable to employ
appropriate clinical monitoring when potent cytochrome P450 enzyme inducers, such as phenobarbital or rifampin, are
co-administered with montelukast.
Montelukast has been administered with other therapies routinely used in the prophylaxis and chronic treatment of
asthma with no apparent increase in adverse reactions. In drug-interaction studies, the recommended clinical dose of
montelukast did not have clinically important effects on the pharmacokinetics of the following drugs: theophylline,
prednisone, prednisolone, oral contraceptives (norethindrone 1 mg/ethinyl estradiol 35 mcg), terfenadine, digoxin,
and warfarin.
Although additional specific interaction studies were not performed, montelukast was used concomitantly with a
wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions. These
medications included thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines,
and decongestants.
Phenobarbital, which induces hepatic metabolism, decreased the AUC of montelukast approximately 40% following a
single 10-mg dose of montelukast. No dosage adjustment for montelukast is recommended. It is reasonable to employ
appropriate clinical monitoring when potent cytochrome P450 enzyme inducers, such as phenobarbital or rifampin, are
co-administered with montelukast.
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