Drug Interaction Report

MONITOR: It is uncertain whether asciminib causes clinically significant prolongation of the QT interval of the electrocardiogram. In clinical studies, prolongation of the Fridericia-corrected QT interval (QTcF) was reported in 3 of 356 (0.8%) of patients, with one report of QTcF greater than 500 msec together with more than 60 msec QTcF increase from baseline. Asciminib is not reported to prolong the corrected QT (QTc) interval by greater than 20 msec at the maximum recommended clinical dosage (200 mg twice daily); however, a prolongation of up to 10 msec cannot be excluded. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Some authorities recommend caution and clinical monitoring when asciminib is used with drugs that are known to cause QT interval prolongation. An ECG should be obtained at baseline and during treatment as clinically indicated, particularly in patients with a history of cardiac arrhythmias, uncontrolled or significant cardiac disease (including bradycardia), or congenital or family history of long QT syndrome. Serum electrolytes, including potassium and magnesium should also be corrected prior to starting asciminib therapy and monitored during treatment as clinically indicated. Patients should be advised to seek prompt medical attention if they experience symptoms that indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.