Drug Interactions between alectinib and Prevduo

GENERALLY AVOID: Anticholinergic agents and other agents with significant anticholinergic activity (e.g., clozapine, class IA antiarrhythmics especially disopyramide) may antagonize the effects of cholinergic skeletal muscle stimulants (e.g., ambenonium, edrophonium, guanidine, neostigmine, pyridostigmine). Although this interaction may be desirable in some situations, such as when atropine is used to treat excessive muscarinic side effects and cholinergic crisis induced by anticholinesterase overdose, unintentional or indiscriminate use of anticholinergic agents in the treatment of myasthenia gravis may exacerbate symptoms. In addition, such use may mask the less serious, gastrointestinal signs of cholinergic overdose and lead to inadvertent induction of cholinergic crisis, which can produce respiratory paralysis and death.

MANAGEMENT: Agents with potent anticholinergic activity should preferably be avoided in patients receiving cholinergic skeletal muscle stimulants. If concurrent use is necessary, patients treated for myasthenia gravis should be monitored for potential exacerbation of symptoms. Caution is advised not only because anticholinergic agents may mask the signs of a cholinergic overdose, but also because increasing muscle weakness associated with disease aggravation may be difficult to distinguish from that due to cholinergic crisis.

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.