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

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.

GENERALLY AVOID: Crizotinib can cause bradycardia and may have additive effects with other drugs that also slow the heart rate. Bradycardia with a heart rate less than 50 beats per minute occurred in 10% to 14% of patients treated with crizotinib in two clinical studies.

MANAGEMENT: Concomitant use of crizotinib with other agents known to cause bradycardia such as beta-blockers, calcium channel blockers, cholinesterase inhibitors, clonidine, and digoxin should generally be avoided whenever possible. Otherwise, heart rate and blood pressure should be monitored closely. If Grade 2 or 3 symptomatic bradycardia occurs, crizotinib should be withheld, the use of concomitant medications re-evaluated, and the dosage of crizotinib adjusted accordingly. Crizotinib should be permanently discontinued for Grade 4 bradycardia. In patients who develop Grade 4 bradycardia associated with concomitant medications known to cause bradycardia or hypotension, crizotinib should be withheld until Grade 1 or less, and if concomitant medications can be discontinued, crizotinib may be restarted at 250 mg once daily with frequent monitoring.