Drug Interaction Report

MONITOR: Coadministration with pretomanid may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP1B3), and/or P-glycoprotein (P-gp). The proposed mechanism, based on in vitro data, is decreased clearance due to pretomanid-mediated inhibition of BCRP, OATP1B3, and/or P-gp. The clinical significance is unknown as data are limited and conflicting.

MANAGEMENT: Until more information is available, the manufacturers of pretomanid recommend that clinicians should be aware of the potential for enhanced pharmacologic effects with drugs that are substrates of BCRP, OATP1B3, and/or Pg-p, particularly those with a narrow therapeutic range, when pretomanid is coadministered. Dosage adjustments as well as clinical and laboratory monitoring of the BCRP, OATP1B3, and/or P-gp substrate drug should be considered whenever pretomanid is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

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.

Administration with food may reduce the bioavailability of maraviroc. According to the product labeling, coadministration of a 300 mg dose of maraviroc with a high-fat breakfast reduced maraviroc peak plasma concentration (Cmax) and systemic exposure (AUC) by 33% in healthy volunteers. However, no food restrictions were used in the clinical studies that demonstrated the safety and efficacy of maraviroc. Therefore, maraviroc can be taken with or without food at the recommended dosage.