Drug Interaction Report

ADJUST DOSE: Coadministration with inducers of CYP450 2C8 and/or uridine diphosphate glucuronosyltransferase (UGT) 1A3 and/or 2B7 enzymes may reduce the plasma concentrations and therapeutic effects of selexipag and its active metabolite. Following concomitant use with rifampin, an inducer of CYP450 2C8 and UGT enzymes at a dose of 600 mg once daily, systemic exposure to selexipag was not altered; however, exposure to the active metabolite was reduced by 50%.

MANAGEMENT: Caution and clinical monitoring should be considered whenever a CYP450 2C8, UGT 1A3, and/or UGT 2B7 inducer is added to or withdrawn from therapy, and the selexipag dosage adjusted as necessary. Some authorities recommend increasing the selexipag dose up to 2-fold when coadministered with rifampin (US). Patients receiving selexipag with a CYP450 2C8, UGT 1A3, and/or UGT 2B7 inducer should be monitored for reduced efficacy.

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.

Food prolongs the gastrointestinal absorption of selexipag. When taken with food, the time to peak concentration (Tmax) was delayed and peak plasma concentration (Cmax) was approximately 30% lower. Selexipag systemic exposure (AUC) and that of its active metabolite did not significantly change, however. Selexipag may be taken with or without food. Tolerability may be improved when taken with food.