Drug Interaction Report

Coadministration with inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 may reduce the plasma concentrations of raltegravir, which is primarily metabolized by UGT1A1-mediated glucuronidation. In 9 study subjects, administration of a single 400 mg dose of raltegravir in combination with the potent UGT1A1 inducer rifampin (600 mg daily) resulted in a 38% decrease in raltegravir peak plasma concentration (Cmax), a 40% decrease in systemic exposure (AUC), and a 61% decrease in trough plasma concentration (Cmin) compared to administration of raltegravir alone. The impact of other potent inducers of drug-metabolizing enzymes such as carbamazepine, phenytoin, and phenobarbital on UGT1A1 is unknown. Other, less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, St. John's Wort, pioglitazone) may be used with the recommended dosage of raltegravir.

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.