Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of apremilast, which is primarily metabolized by the isoenzyme in vitro. According to the product labeling, administration of a single 30 mg oral dose of apremilast with the potent CYP450 inducer rifampin (600 mg once daily for 15 days) resulted in decreases of apremilast peak plasma concentration (Cmax) and systemic exposure (AUC) by 43% and 72%, respectively.

MANAGEMENT: Concomitant use of apremilast with potent CYP450 3A4 inducers should generally be avoided due to the potential for reduced efficacy.

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.