Drug Interactions between brentuximab and rifampin

MONITOR: Coadministration with rifampin may decrease the plasma concentrations of monomethyl auristatin E (MMAE), the microtubule-disrupting component of brentuximab vedotin. MMAE is primarily metabolized by CYP450 3A4. In study subjects, administration of brentuximab vedotin with rifampin resulted in an approximately 46% decrease in MMAE systemic exposure (AUC). The clinical significance is unknown.

MONITOR: Coadministration of brentuximab vedotin with other agents known to induce hepatotoxicity such as rifampin may potentiate the risk of liver injury. Serious cases of hepatotoxicity, some fatal, have occurred in patients treated with brentuximab vedotin. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and typically occurred after the first dose or after a rechallenge. Preexisting liver disease and elevated baseline liver enzymes may also increase the risk.

MANAGEMENT: The potential for diminished efficacy of brentuximab vedotin and increased risk of hepatic injury should be considered when brentuximab vedotin is used with rifampin. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Liver enzymes and bilirubin should be measured before and during treatment, especially in patients with underlying hepatic disease or marked baseline transaminase elevations. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dosage, or discontinuation of brentuximab vedotin in accordance with the product labeling.