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

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.

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MONITOR: Sympathetic ganglion-blocking or catecholamine-depleting agents such as guanethidine, reserpine, and monoamine oxidase (MAO) inhibitors may potentiate the pharmacologic effects of beta-blockers, which are thought to competitively antagonize catecholamines at cardiac and other peripheral adrenergic neurons. Combining these medications may increase the risk of hypotension, orthostasis, bradycardia, and heart failure due to excessive reduction of sympathetic activity. A case report describes two elderly patients who developed bradycardia less than 2 weeks after the initiation of phenelzine during treatment with a beta-blocker (nadolol 40 mg/day or metoprolol 150 mg/day). The pulse rates returned to normal following a 50% reduction of the nadolol dosage and discontinuation of metoprolol. In another report, a young woman developed marked orthostatic hypotension following the addition of pindolol 2.5 mg three times a day to an existing regimen of tranylcypromine. The pindolol dosage was reduced to 2.5 mg twice a day until her blood pressure stabilized, then slowly increased to 5 mg three times a day.

MANAGEMENT: Caution is advised if beta-blockers, including ophthalmic formulations, are prescribed in combination with sympathetic ganglion-blocking or catecholamine-depleting agents. Patients should contact their doctor if they experience dizziness, lightheadedness, syncope, bradycardia, shortness of breath, difficulty breathing, edema, and/or chest pain.

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MONITOR: Topically administered alpha-2 adrenergic receptor agonists such as brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects. Despite relative alpha-2 selectivity, theoretical concerns exist that coadministration with monoamine oxidase inhibitors (MAOIs) may increase the risk of hypertension due to potentiation of alpha-1 stimulation, which produces vasoconstriction. MAOIs may also theoretically interfere with the metabolism of brimonidine, which may result in increased systemic adverse effects such as drowsiness, dizziness, lightheadedness, hypotension, and bradycardia. However, an interaction with MAOIs has not been reported in the medical literature.

MANAGEMENT: Patients receiving brimonidine in combination with MAOIs should be made aware of the potential for increased adverse effects, and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should also avoid rising abruptly from a sitting or recumbent position and notify their physician if they experience orthostasis or tachycardia. Blood pressure should be monitored closely.

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