Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A1 inducers (e.g., rifampicin, phenytoin, carbamazepine), may decrease the systemic exposure of ponesimod. Experiments with human liver preparations indicate that metabolism of ponesimod to inactive metabolites occurs through a combination of non-CYP450 oxidative enzymes, multiple CYP450 (2J2, 3A4, 3A5, 4F3A, and 4F12) enzymes, and direct glucuronidation (mainly UGT1A1 and UGT2B7). Limited clinical data are available, and it is unclear whether this decrease in ponesimod systemic exposure would be considered of clinical relevance.

MANAGEMENT: Until more information is available, concomitant use of ponesimod with potent CYP450 3A4 and UGT1A1 inducers should generally be avoided.

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.