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: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.