Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 2C19 may decrease the plasma concentrations of brivaracetam. According to the prescribing information, brivaracetam undergoes hydroxylation mediated primarily by CYP450 2C19, although it appears to be a relatively minor, secondary biotransformation pathway. When a single 150 mg dose of brivaracetam was administered to 26 healthy volunteers following five days of treatment with 600 mg/day of rifampin, a potent CYP450 2C19 inducer, brivaracetam systemic exposure (AUC) and half-life decreased by 45% compared to administration alone. Data are not available for other potent CYP450 2C19 inducers such as apalutamide, but a similar interaction with brivaracetam may be expected.

MANAGEMENT: Dosage adjustments for brivaracetam should be considered when coadministered with potent CYP450 2C19 inducers and following their discontinuation. The manufacturer recommends increasing the brivaracetam dosage by up to 100% (i.e., doubling the dosage) when prescribed with rifampin. Clinical response and tolerability should be monitored closely.

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.