Drug Interaction Report

MONITOR: Coadministration with 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.

MANAGEMENT: Increased monitoring is advised if tucatinib is coadministered with CYP450 2C8 inhibitors. Dosage adjustments may be required based on clinical response and tolerance.

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.