Drug Interactions between etrasimod and Mepergan

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 in patients with ulcerative colitis UC-1 and UC-2, following an initial dose of 2 mg on day 1, the greatest mean decrease from baseline in heart rate of 7.2 bpm occurred at hour 2 (UC-2) and hour 3 (UC-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 with arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic agents, or in 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. Temporary interruption of anti-arrhythmic therapy may be required prior to initiation of etrasimod, depending on the patient's resting heart rate. Some authorities state that treatment with an anti-arrhythmic agent may be initiated in patients who have been stabilized on etrasimod therapy for at least 7 consecutive days. The manufacturer's product labeling or local treatment protocols should also be consulted for additional guidance.

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.