Drug Interaction Report

MONITOR CLOSELY: Coadministration of ponesimod with antineoplastic, immunosuppressive, or other immune-modulating therapies may increase the risk of unintended additive immunosuppressive effects. Ponesimod causes reversible sequestration of lymphocytes in lymphoid tissues. When administered daily, ponesimod produces a dose-dependent reduction in peripheral lymphocyte count to 30% to 40% of baseline values, which may increase the risk of infections. Life-threatening and rare fatal infections have been reported in association with sphingosine 1-phosphate (S1P) receptor modulators. Decreased lymphocyte counts persist during chronic daily dosing and generally return to normal within 1 week after stopping the medication. Because residual pharmacodynamic effects, such as decreased peripheral lymphocytes, may persist for 1 to 2 weeks after the last dose, use of immunosuppressants during this time may also lead to additive immune effects.

MANAGEMENT: The safety and efficacy of ponesimod in combination with antineoplastic, immunosuppressive, or immune-modulating agents have not been evaluated. Caution is advised during coadministration and for 1 to 2 weeks after the last dose of ponesimod. When switching from drugs with prolonged immune effects to ponesimod, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of umbralisib. When a single oral dose of umbralisib was administered with a high-fat, high-calorie meal (approximately 917 calories; 171 calories from protein, 232 calories from carbohydrate, 502 calories from fat) in healthy subjects, umbralisib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 115% and 61%, respectively, compared to administration under fasted conditions.

MANAGEMENT: Umbralisib should be administered with food at approximately the same time each day.