Drug Interaction Report

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: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

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. Although the interaction has not been specifically studied, the possibility of an additive or potentiating effect with central nervous system (CNS) depressants such as alcohol, barbiturates, opiates, anxiolytics, sedatives, and anesthetics should be considered. Additive hypotensive effects and orthostasis may also occur with some CNS depressants and other agents that have these effects, particularly during initial dosing and/or parenteral administration.

MANAGEMENT: Patients receiving topical alpha-2 adrenergic receptor agonists in combination with agents that can cause CNS depression should be made aware of the potential for increased adverse effects such as drowsiness, dizziness, lightheadedness and confusion, 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.