Drug Interaction Report

MONITOR: Coadministration with inducers of hepatic CYP450 isoenzymes may decrease the plasma concentrations of montelukast, which is metabolized by CYP450 2C8, 2C9, and 3A4 . When a single 10 mg dose of montelukast was administered in combination with phenobarbital, montelukast systemic exposure (AUC) decreased by approximately 40%.

MANAGEMENT: No dosage adjustment for montelukast is recommended when used concomitantly with CYP450 inducers. However, clinical monitoring for potentially reduced therapeutic effects may be appropriate, especially for potent inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.