Drug Interactions between brigatinib and brimonidine / dorzolamide / latanoprost / timolol ophthalmic

MONITOR: Topically administered alpha-2 adrenergic receptor agonists such as apraclonidine and brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects such as hypotension and bradycardia. The possibility for an additive or potentiating effect on blood pressure and heart rate should be considered when used with other medications that affect these parameters, such as ophthalmic and systemic beta blockers, vasodilators, cardiac glycosides, and antihypertensive agents.

MANAGEMENT: Blood pressure and pulse rate should be monitored regularly when topical alpha-2 adrenergic receptor agonists are prescribed in combination with cardiovascular drugs. Patients should be advised to notify their physician if they experience slow pulse, irregular heartbeat, dizziness, lightheadedness, or syncope.

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.