Drug Interaction Report

Potent inducers of UGT enzymes (e.g., rifampin, carbamazepine, phenobarbital, phenytoin, ritonavir) may increase the metabolism of febuxostat and decrease its therapeutic efficacy. Febuxostat undergoes extensive metabolism by both conjugation via UGT enzymes including UGT1A1, UGT1A3, UGT1A9, and UGT2B7, and oxidation via cytochrome P450 enzymes. The relative contribution of each isoenzyme and the clinical significance is unknown. Conversely, increased plasma levels of febuxostat may occur after a potent UGT inducer is discontinued.

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.