Drug Interactions between asciminib and clarithromycin

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of asciminib. According to the prescribing information, asciminib is metabolized by CYP450 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT) 2B7- and 2B17-mediated glucuronidation. When a single 40 mg dose of asciminib was coadministered with clarithromycin, a potent CYP450 3A4 inhibitor, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 19% and 36%, respectively. Coadministration of asciminib 200 mg twice daily and clarithromycin is predicted to increase asciminib Cmax and AUC by 49% and 77%, respectively, per physiologically-based pharmacokinetic (PBPK) models. However, no clinically significant differences in the pharmacokinetics of asciminib were observed when coadministered with itraconazole, another potent CYP450 3A4 inhibitor.

MANAGEMENT: Caution is advised when asciminib is prescribed with potent CYP450 3A4 inhibitors, particularly at higher dosages. The manufacturer recommends that patients treated with asciminib at 200 mg twice daily be monitored closely for adverse reactions, such as nausea, diarrhea, rash, myelosuppression, pancreatitis, hypertension, and cardiovascular toxicity including ischemic cardiac conditions, arterial thrombotic and embolic conditions, cardiac failure, QT prolongation, and arrhythmia.