Drug Interactions between brincidofovir and Rifadin IV

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.

ADJUST DOSING INTERVAL: Administration with food decreases the oral bioavailability of brincidofovir. According to the product labeling, administration of brincidofovir tablets with a low-fat meal (approximately 400 calories, 25% of calories from fat) was associated with a reduction in the systemic exposure (AUC) and peak plasma concentration (Cmax) of brincidofovir by 31% and 49%, respectively, compared to administration under fasting. However, no clinically meaningful changes in intracellular concentrations of cidofovir diphosphate were observed. The effect of food on the oral suspension formulation has not been evaluated.

MANAGEMENT: Brincidofovir oral tablets and suspension should be taken on an empty stomach. If necessary, the oral tablets may be taken with a low-fat meal.