Drug Interactions between brentuximab and repotrectinib

MONITOR: Brentuximab vedotin can cause peripheral neuropathy, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk. The peripheral neuropathy associated with brentuximab vedotin treatment is cumulative and primarily sensory, but cases of peripheral motor neuropathy have also been reported. In premarketing clinical trials, 54% of patients experienced neuropathy of any grade. Of these patients, 49% had complete resolution, 31% had partial improvement, and 20% had no improvement. A total of 51% of patients who reported neuropathy had residual neuropathy at the time of their last evaluation.

MONITOR: Coadministration of brentuximab vedotin with other agents known to induce hepatotoxicity 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 increased risk and/or severity of peripheral neuropathy and hepatotoxicity should be considered when brentuximab vedotin is used with other drugs that are also associated with these adverse effects. Patients should be closely monitored for symptoms of neuropathy such as burning, tingling, pain, numbness, or weakness. 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 neuropathy or hepatotoxicity may require a delay, change in dosage, or discontinuation of brentuximab vedotin in accordance with the product labeling. 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.