Drug Interactions between brimonidine / dorzolamide / latanoprost / timolol ophthalmic and epinephrine topical

MONITOR: Coadministration of non-cardioselective beta-blockers, such as propranolol, with topical solutions containing epinephrine may enhance the hypertensive effect of epinephrine, which may increase the risk of cardiac arrest and hypertensive stroke. The mechanism of this interaction involves beta-blocker antagonism of epinephrine's beta-agonist effects which results in unopposed alpha-stimulated vasoconstriction and reflexive decreases in heart rate. Epinephrine clearance may also be reduced by concomitant beta-blocker use. Following administration of intravenous, local, or subcutaneous epinephrine, patients receiving propranolol have experienced hypertensive reactions, including life-threatening reactions, and often accompanied by bradycardia and/or arrhythmias. Numerous clinical studies have demonstrated significant increases in blood pressure (i.e., 20 to 40 mmHg) and vascular resistance, and decreases in heart rate, in patients receiving non-cardioselective beta-blockers with epinephrine. There are numerous case reports of patients taking propranolol who developed severe hypertension after local infiltration of lidocaine mixed with epinephrine, including one patient who went into cardiac arrest. Theoretically, when a topical solution containing epinephrine is used with local anesthetics to provide pain relief for wound closure, it is possible for a sufficient amount of epinephrine to be absorbed through the skin, particularly via wounds or lacerations, to cause systemic effects; however data are lacking.

MANAGEMENT: Caution and close monitoring of cardiovascular status (i.e., blood pressure, heart rate) are recommended when topical solutions containing epinephrine are administered to patients treated with non-cardioselective beta-blockers. Some authorities recommend avoiding treatment with topical solutions containing epinephrine (AU; Laceraine Topical Wound Anaesthetic(R)) in patients receiving a non-cardioselective beta-blocker.

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.