Drug Interaction Report

MONITOR: Coadministration of alectinib with other agents that can slow the heart rate may increase the risk of bradycardia. In clinical trials, 7.5% of patients developed bradycardia during treatment with alectinib. Twenty percent of 221 patients for whom serial electrocardiograms were available had heart rates of less than 50 beats per minute (bpm).

MANAGEMENT: Caution is advised when alectinib is prescribed with other drugs that can cause bradycardia (e.g., beta-blockers; calcium channel blockers; digitalis; dolasetron; flecainide; ivabradine; lacosamide; mefloquine; moricizine; propafenone; quinine; succinylcholine; sunitinib; thalidomide; anticholinesterase or cholinergic agents; protease inhibitors such as atazanavir, lopinavir/ritonavir, and saquinavir/ritonavir). Heart rate and blood pressure should be monitored regularly, and patients should be counseled to seek medical attention if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. Dosage modification of alectinib is not required in cases of asymptomatic bradycardia. However, if symptomatic bradycardia occurs, the manufacturer recommends withholding alectinib until recovery to asymptomatic bradycardia or to a heart rate of >=60 bpm. Evaluate concomitant medications known to cause bradycardia and all antihypertensive medications, then consider dosage adjustments or discontinuation of concomitant medication(s) or alectinib in accordance with the product labeling.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of alectinib and its major active metabolite, M4. According to the manufacturer, a high-fat, high-calorie meal increased the combined systemic exposure (AUC) of alectinib and M4 by 3.1-fold following oral administration of a single 600 mg dose of alectinib.

MANAGEMENT: To ensure maximal oral absorption, alectinib should be administered with food.

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.