Drug Interactions between apraclonidine ophthalmic and Zoloft

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.

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.