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.

MONITOR: Smoking during treatment with abrocitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies. During abrocitinib clinical studies, current or past smokers had an additional increased risk of overall malignancies. Also, abrocitinib may increase patients' risk of MACE, including myocardial infarction, stroke, and cardiovascular death.

Administration of abrocitinib with high-fat, high-calorie food increased abrocitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 29% and 26%, respectively, and prolonged the time to reach Cmax by 2 hours. These changes are not considered clinically relevant.

MANAGEMENT: Caution is advised if abrocitinib is prescribed to current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. The manufacturer recommends discontinuing abrocitinib in patients that have experienced a myocardial infarction or stroke. Abrocitinib may be taken with or without food.