Muloz Drug Interactions

Montelukast may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma. In drug-interactions studies, the recommended clinical dose of Montelukast did not have clinically important effects on the pharmacokinetics of the following medicinal products: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.
The area under the plasma concentration-time curve (AUC) for Montelukast was decreased approximately 40% in subjects with co-administration of phenobarbital. However, no dosage adjustment for Montelukast is recommended.
Data from in vitro studies indicate that Montelukast is a potent inhibitor of CYP2C8. However, data from several clinical drug interaction studies evaluating Montelukast and rosiglitazone or repaglinide, substrates for the CYP2C8 isoenzyme, indicate that Montelukast does not inhibit CYP2C8 in vivo. Therefore, clinical drug interactions involving Montelukast and CYP2C8 substrates (e.g., paclitaxel, rosiglitazone, repaglinide) are not anticipated.
In vitro studies have shown that Montelukast is a substrate of CYP2C8, CYP2C9 and CYP3A4. In a clinical drug-drug interaction study involving Montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2C9) demonstrated that gemfibrozil increased the systemic exposure of Montelukast by 4.4-fold. Coadministration of itraconazole, a strong CYP3A4 inhibitor, with gemfibrozil and Montelukast did not further increase the systemic exposure of Montelukast. The effect of gemfibrozil on systemic exposure of Montelukast is not considered to be clinically meaningful based on clinical safety data with doses greater than the 10 mg approved dose in adults (e.g., 200 mg/day to adult patients for 22 weeks, and up to 900 mg/day to patients for approximately one week) where clinically important adverse experiences were not observed. Therefore, no dosage adjustment of Montelukast is required upon co-administration with gemfibrozil. Based on in vitro data, clinically important drug interactions with other known inhibitors of CYP2C8 (e.g., trimethoprim) are not anticipated. In addition, co-administration of Montelukast with itraconazole alone resulted in no significant increase in the systemic exposure of Montelukast.