Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 that also induce P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of apixaban, which is a substrate of both the isoenzyme and the efflux transporter. When apixaban was coadministered with 600 mg/day of rifampin, a dual P-gp and potent CYP450 3A4 inducer, mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 54%, respectively. Reduced efficacy, increased stroke rates, and paradoxically, an increased risk of bleeding have been reported in a clinical study in patients with atrial fibrillation taking apixaban with concomitant dual P-gp and potent CYP450 3A4 inducers compared with apixaban alone.

MANAGEMENT: Concomitant use of apixaban with dual P-gp and potent CYP450 3A4 inducers should generally be avoided, since efficacy of apixaban may be compromised.

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.