Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 2C9 may decrease the plasma concentrations of lesinurad. According to the manufacturer, administration of lesinurad with the potent CYP450 inducer rifampin (600 mg daily) decreased lesinurad peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 25% and 40%, respectively, compared to administration of lesinurad alone.

MANAGEMENT: The potential for diminished pharmacologic effects of lesinurad should be considered during coadministration with CYP450 2C9 inducers. Alternative treatments may be required if an interaction is suspected.

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.