Drug Interaction Report

MONITOR: Coadministration with pretomanid may significantly increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of organic anion transporter 3 (OAT3). The proposed mechanism, based on in vitro data, is decreased clearance due to pretomanid-mediated inhibition of OAT3. No clinical interaction studies have been conducted in humans with OAT3 substrates.

MANAGEMENT: Caution is advised if pretomanid is used concomitantly with drugs that are substrates of OAT3, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring of the OAT3 substrate drug should be considered whenever pretomanid is added to or withdrawn from therapy with these drugs.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.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.