Drug Interactions between escitalopram and Ticlid

MONITOR: Coadministration with inhibitors of CYP450 2C19 including ticlopidine may increase the plasma concentrations of escitalopram, which is primarily metabolized by the isoenzyme. The interaction has been studied with omeprazole, a potent CYP450 2C19 inhibitor. In study subjects, administration of a single 20 mg dose of escitalopram on day 5 of treatment with omeprazole 30 mg once daily for 6 days resulted in increases of escitalopram peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 10% and 50%, respectively. High plasma levels of escitalopram may increase the risk of serious side effects such as QT prolongation, which may lead to arrhythmias including torsade de pointes and sudden death, as well as serotonin syndrome, which is a rare but potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MONITOR: Serotonin reuptake inhibitors (SRIs) including escitalopram may potentiate the risk of bleeding in patients treated with agents that affect hemostasis such as ticlopidine. Serotonin release by platelets plays an important role in hemostasis, thus SRIs may alter platelet function and induce bleeding. Published case reports have documented the occurrence of bleeding episodes in patients treated with psychotropic agents that interfere with serotonin reuptake. Bleeding events related to SRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Additional epidemiological studies have confirmed the association between use of these agents and the occurrence of upper gastrointestinal bleeding.

MANAGEMENT: Caution is advised if escitalopram must be used in combination with CYP450 2C19 inhibitors including ticlopidine. Pharmacologic response to escitalopram should be monitored more closely whenever ticlopidine is added to or withdrawn from therapy, and the escitalopram dosage adjusted as necessary. This may be particularly important in patients receiving escitalopram at the upper end of the dosage range. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heartbeat, shortness of breath, or syncope. Patients should also be closely monitored for symptoms of the serotonin syndrome and potential bleeding complications during treatment.