Drug Interactions between etrasimod and Triavil

MONITOR CLOSELY: Due to the risk of bradycardia and atrioventricular (AV) block, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of etrasimod treatment in patients receiving drugs that prolong the QT interval. Etrasimod may cause a transient decrease in heart rate during initiation of therapy, in the randomized placebo-controlled studies UC-1 and UC-2, following an initial dose of 2 mg, the greatest mean decrease from baseline in heart rate of 7.2 bpm occurred at hour 2 (UC-2) and hour 3 (UC-1) on day 1. In studies UC-2 and UC-3, bradycardia was reported on day 1 in 2.9% of patients on etrasimod compared to none in the placebo group. On Day 2, bradycardia was reported in 1 patient (0.3%) treated with etrasimod compared to none in the placebo group. Overall, subjects who experienced bradycardia were generally asymptomatic. Few subjects experienced symptoms such as dizziness, and these symptoms resolved without intervention. Initiation of etrasimod treatment has also resulted in transient AV conduction delays. In the UC-1 study, after 2 mg of etrasimod on day 1 of treatment, first- or second-degree Mobitz type I AV blocks were observed in 0.7% of etrasimod- treated subjects compared to none in the placebo group. In studies UC-2 and UC-3, Mobitz type I AV blocks were observed in 0.8% of etrasimod-treated subjects compared to none in the placebo group. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, advice from a cardiologist should be sought if treatment with etrasimod is considered in patients with significant QT prolongation (QTcF greater than 450 msec in males or 470 msec in females), patients on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction, or in patients with arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic agents.

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MONITOR CLOSELY: Due to the risk of bradycardia and atrioventricular (AV) block, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of etrasimod treatment in patients receiving drugs that prolong the QT interval. Etrasimod may cause a transient decrease in heart rate during initiation of therapy, in the randomized placebo-controlled studies UC-1 and UC-2, following an initial dose of 2 mg, the greatest mean decrease from baseline in heart rate of 7.2 bpm occurred at hour 2 (UC-2) and hour 3 (UC-1) on day 1. In studies UC-2 and UC-3, bradycardia was reported on day 1 in 2.9% of patients on etrasimod compared to none in the placebo group. On Day 2, bradycardia was reported in 1 patient (0.3%) treated with etrasimod compared to none in the placebo group. Overall, subjects who experienced bradycardia were generally asymptomatic. Few subjects experienced symptoms such as dizziness, and these symptoms resolved without intervention. Initiation of etrasimod treatment has also resulted in transient AV conduction delays. In the UC-1 study, after 2 mg of etrasimod on day 1 of treatment, first- or second-degree Mobitz type I AV blocks were observed in 0.7% of etrasimod- treated subjects compared to none in the placebo group. In studies UC-2 and UC-3, Mobitz type I AV blocks were observed in 0.8% of etrasimod-treated subjects compared to none in the placebo group. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, advice from a cardiologist should be sought if treatment with etrasimod is considered in patients with significant QT prolongation (QTcF greater than 450 msec in males or 470 msec in females), patients on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction, or in patients with arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic agents.

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MONITOR: Coadministration of a phenothiazine with a tricyclic antidepressant (TCA) may result in elevated plasma concentrations of one or both drugs as well as additive adverse effects. Most phenothiazines and TCAs have been found to undergo metabolism by CYP450 2D6, thus competitive inhibition of the enzyme may occur when more than one of these agents are administered. Although these drugs have been used together clinically, the possibility of increased risk of serious adverse effects such as central nervous system depression, tardive dyskinesia, hypotension, and prolongation of the QT interval should be considered, as many of these agents alone can and have produced these effects. In addition, excessive anticholinergic effects may occur in combination use, which can result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.

MANAGEMENT: Concurrent use of phenothiazines and TCAs should be approached with caution, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication (e.g., abdominal pain, fever, heat intolerance, blurred vision, confusion, hallucinations) or cardiovascular toxicity (e.g., dizziness, palpitations, arrhythmias, syncope). Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A dosage reduction in one or both drugs may be necessary if excessive adverse effects develop.

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