Drug Interactions between Plavix and tucatinib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 2C8 may increase the plasma concentrations of tucatinib, which is primarily metabolized by the isoenzyme. When gemfibrozil (600 mg twice daily), a potent CYP450 2C8 inhibitor, was administered with a single tucatinib dose of 300 mg, tucatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.6-fold and 3-fold, respectively. Increased exposure to tucatinib may increase the risk of toxicity. In clinical trials involving tucatinib, serious adverse reactions such as death, hepatotoxicity, diarrhea, vomiting, nausea, abdominal pain, and seizure were reported.

MANAGEMENT: Concomitant use of tucatinib with potent CYP450 2C8 inhibitors should be avoided. If coadministration is required, a reduction in the dosage of tucatinib to 100 mg orally twice daily is recommended. After discontinuation of the potent CYP450 2C8 inhibitor for 3 elimination half-lives, the tucatinib dosage that was taken prior to initiating the inhibitor may be resumed.