Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of eravacycline, which undergoes oxidation by CYP450 3A4 and flavin monooxygenase (FMO). When eravacycline was given with the potent CYP450 3A4 inducer, rifampin, eravacycline systemic exposure (AUC) decreased by 35% and clearance increased by 54%. Reduced therapeutic efficacy of eravacycline may occur.

MANAGEMENT: Eravacycline dosage should be increased to 1.5 mg/kg every 12 hours when used with potent CYP450 3A4 inducers. When a CYP450 3A4 inducer is started, it is important to remember that they exert their effect in a time-dependent manner and may take at least 2 weeks to reach maximal effect. Likewise, when discontinuing a CYP450 3A4 inducer, the induction may take at least 2 weeks to decline. No dosage adjustment is warranted when eravacycline is used with a weak or moderate inducer.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.