Drug Interactions between brigatinib 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 brigatinib with other agents that can also slow the heart rate may potentiate the risk of severe bradycardia. In one clinical trial, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients who received brigatinib 90 mg and 7.6% of patients who had the dosage increased from 90 mgto 180 mg. Grade 2 bradycardia occurred in 0.9% of patients in the 90 mg group.

MANAGEMENT: Caution is advised if brigatinib is used concomitantly with beta-blockers, calcium channel blockers, digitalis, or other drugs that can slow the heart rate or atrioventricular conduction such as alectinib, atazanavir, fingolimod, flecainide, ivabradine, lacosamide, lithium, mefloquine, moricizine, propafenone, succinylcholine, thalidomide, H2-receptor antagonists, tricyclic antidepressants, and anticholinesterase or cholinergic agents. Heart rate and blood pressure should be monitored frequently, and patients should be advised to seek medical attention if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. For symptomatic bradycardia, withhold brigatinib until recovery to asymptomatic bradycardia or to a resting heart rate >=60 bpm, then resume brigatinib (at the same or reduced dose depending on whether concomitant medication is discontinued or dose-adjusted) or permanently discontinue in accordance with the recommendations in the product labeling.