Drug Interactions between brimonidine / dorzolamide / timolol ophthalmic and dronedarone

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 with dronedarone may increase the plasma concentrations of some beta-blockers. The mechanism is dronedarone inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of beta-blockers like metoprolol and propranolol. According to the product labeling, dronedarone increased metoprolol systemic exposure (AUC) by 1.6-fold and propranolol AUC by 1.3-fold. Pharmacodynamically, beta-blockers can potentiate the depressant effects of dronedarone on the sinus and AV nodes. In clinical trials, bradycardia was more frequently observed when dronedarone was given in combination with beta-blockers.

MANAGEMENT: Caution is advised if dronedarone is coadministered with a beta-blocker, including ophthalmic formulations. The dosage of the beta-blocker should start low and increased only after ECG verification of good tolerability. Patients should be advised to promptly report potential symptoms of toxicity such as excessive fatigue, fainting, difficulty breathing, chest pain or tightness, bradycardia, or arrhythmia.