Drug Interaction Report

GENERALLY AVOID: Coadministration with moderate to potent inhibitors of CYP450 3A4 and/or inhibitors of P-glycoprotein (P-gp) efflux transporter system may increase the plasma concentrations of ensartinib, which is a substrate of both the isoenzyme and efflux transporter in vitro. Concomitant use may increase the risk and/or severity of adverse events. Clinical data characterizing the extent of this interaction and data with less potent inhibitors are not available.

MANAGEMENT: Concomitant use of ensartinib with moderate to potent inhibitors of CYP450 3A4 and/or inhibitors of P-gp should generally be avoided. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

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.