Drug Interaction Report

GENERALLY AVOID: Coadministration of pretomanid with strong or moderate CYP450 3A4 inducers may decrease the plasma concentrations and antimicrobial effects of pretomanid, which has been shown to be a substrate of the isoenzyme. Following 7 days of concomitant administration, rifampin (600 mg daily) decreased systemic exposure (AUC) and peak plasma concentration (Cmax) of pretomanid by 66% and 53%, respectively. In another 7-day study, efavirenz (600 mg daily) decreased mean AUC and Cmax of pretomanid (200 mg daily) by 35% and 28%, respectively.

MANAGEMENT: The use of pretomanid with strong or moderate CYP450 3A4 inducers should be avoided. Dosage adjustments as well as clinical and laboratory monitoring of pretomanid should be considered whenever a strong or moderate CYP450 3A4 inducer is added to or withdrawn from therapy.

GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of combination drug regimens that include pretomanid.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of pretomanid. The mechanism has not been reported. Compared with the fasted state, oral administration of pretomanid with a high-fat, high-calorie meal (approximately 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively) increased mean systemic exposure (AUC) and peak plasma concentration (Cmax) of pretomanid by 88% and 76%, respectively.

MANAGEMENT: Patients should avoid alcohol use during treatment with pretomanid. In addition, to ensure maximal oral absorption, pretomanid should be administered with food. Tablets should be swallowed whole.