Drug Interactions between etrasimod and glasdegib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration of etrasimod with antineoplastic, immunosuppressive, or other immune-modulating therapies may increase the risk of unintended additive immunosuppressive effects. Etrasimod causes reversible sequestration of lymphocytes in lymphoid tissues. When administered daily for 52 weeks, etrasimod produced a mean reduction in peripheral blood lymphocyte count to 45% of baseline values, which may increase the risk of infections. Life-threatening and rare fatal infections have occurred in association with other sphingosine 1-phosphate (S1P) receptor modulators. Decreased lymphocyte counts persist during chronic daily dosing and generally return to normal within 4 to 5 weeks after stopping the medication.

MANAGEMENT: The safety and efficacy of etrasimod in combination with antineoplastic, immunosuppressive, or immune-modulating agents have not been evaluated. Because its pharmacodynamic effects may persist for up to 5 weeks after treatment discontinuation, concomitant use during and within 5 weeks following the last dose of etrasimod with antineoplastic, immunosuppressive, or immune-modulating agents should generally be avoided. If concomitant use within this period is considered necessary, patients should be monitored for infectious complications during this extended period. When switching from drugs with prolonged immune effects to etrasimod, the half-life and mode of action of these drugs must also be considered to avoid unintended additive immunosuppressive effects.

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.