Drug Interaction Report

MONITOR: Coadministration with asciminib may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 2C9 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 2C9 by asciminib. When warfarin, a probe substrate for CYP450 2C9, was coadministered with asciminib 40 mg twice daily, peak plasma concentration (Cmax) and systemic exposure (AUC) for the biologically more active S(-) enantiomer of warfarin increased by 8% and 41%, respectively. Likewise, the Cmax and AUC of S(-) warfarin increased by 4% and 52%, respectively, following coadministration with asciminib at 80 mg once daily, but increased by 7% and 314%, respectively, following coadministration with asciminib at 200 mg twice daily. These results suggest weak inhibition of CYP450 2C9 by asciminib at the lower dosages and moderate inhibition at the highest dosage.

MANAGEMENT: Caution is advised when asciminib is used concomitantly with drugs that are substrates of CYP450 2C9, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever asciminib is added to or withdrawn from therapy. The prescribing information recommends avoiding concomitant use of asciminib with sensitive CYP450 2C9 substrates or certain substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If treatment with CYP450 2C9 substrate(s) is required, closely monitor for the development of adverse reactions and reduce dosage(s) as necessary in patients receiving asciminib therapy at 80 mg total daily dose. Consider alternative therapy with non-CYP450 2C9 substrates in patients receiving asciminib at the maximum recommended dosage of 200 mg twice daily. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a moderate CYP450 2C9 inhibitor like asciminib and for any dosage adjustments that may be required.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

MANAGEMENT: To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.