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.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.