Drug Interaction Report

ADJUST DOSE: Coadministration with rifampin may significantly decrease the plasma concentrations of raltegravir. The proposed mechanism is rifampin induction of raltegravir metabolism via uridine diphosphate glucuronosyltransferase (UGT) 1A1. In 9 study subjects, administration of a single 400 mg dose of raltegravir in combination with 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. When the dosage of raltegravir was increased to 800 mg twice daily and coadministered with rifampin 600 mg daily in 14 subjects, raltegravir Cmax and AUC increased by 62% and 27%, respectively, while Cmin decreased by 53% compared to administration of raltegravir alone at 400 mg twice daily.

MANAGEMENT: Caution is advised when raltegravir must be used in combination with rifampin. A dosage increase for raltegravir to 800 mg twice daily is recommended for adults during coadministration with rifampin. No dosage adjustment recommendations are available for pediatric patients below 18 years of age due to the lack of clinical data.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.