Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of idelalisib, which is a substrate of both the isoenzyme and efflux transporter. In healthy volunteers, administration of a single 150 mg dose of idelalisib with the potent CYP450 3A4 and P-gp inducer rifampin (600 mg daily for 8 days) decreased mean idelalisib peak plasma concentration (Cmax) by 58% and systemic exposure (AUC) by 75%.

MANAGEMENT: Concomitant use of idelalisib with potent CYP450 3A4 or P-gp inducers such as carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifampin, and St. John's wort 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.