Drug Interaction Report

MONITOR: Coadministration with strong CYP450 3A4 inducers may decrease the plasma concentrations and therapeutic effects of rucaparib, which has been shown in vitro to be a substrate of the isoenzyme. However, the effects on the pharmacokinetics of rucaparib have not been evaluated in vivo.

MANAGEMENT: Caution is advised if rucaparib is used concomitantly with potent CYP450 3A4 inducers. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever a potent CYP450 3A4 inducer is added to or withdrawn from therapy with rucaparib.

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.