Drug Interaction Report

MONITOR CLOSELY: Coadministration of siponimod with antineoplastic, immunosuppressive, or other immune-modulating therapies may result in additive immune system effects and increased risk of infections. Siponimod causes reversible sequestration of lymphocytes in lymphoid tissues. When administered daily, siponimod produces a dose-dependent reduction in peripheral lymphocyte count to 20% to 30% of baseline values, which may increase the risk of infections. Life-threatening and rare fatal infections have occurred in association with siponimod. Decreased lymphocyte counts persist during chronic daily dosing and generally return to normal within 10 days after stopping the medication. However, residual pharmacodynamic effects, such as decreased peripheral lymphocytes, may persist for up to 3 to 4 weeks after the last dose. Use of other myelo- or immunosuppressive drugs during this time may lead to unintended additive effects on the immune system.

MANAGEMENT: The safety and efficacy of siponimod in combination with antineoplastic, immunosuppressive, or other immune-modulating agents have not been evaluated. Close monitoring for signs and symptoms of infection is advised during coadministration and for 3 to 4 weeks after the last dose of siponimod. When switching from drugs with prolonged immune effects to siponimod, 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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ruxolitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with ruxolitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ruxolitinib may be administered with or without food.