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: Concomitant use of asparaginase with other hepatotoxic agents may potentiate the risk of liver injury. Asparaginase-associated hepatotoxicity has been reported more commonly in adults than in children and has been strongly associated with obesity. Hepatomegaly, acute severe hepatotoxicity, and fatal liver failure have been reported with asparaginase treatment in adults. Also, asparaginase may increase the toxicity of drugs bound to plasma proteins or metabolized by the liver.

MANAGEMENT: The risk of additive hepatotoxicity should be considered when asparaginase is used with other hepatotoxic agents (e.g., alcohol, androgens, antituberculosis agents, azole antifungal agents, ACE inhibitors, macrolide antibiotics, nonsteroidal anti-inflammatory agents, nucleoside reverse transcriptase inhibitors, sulfonamides, thiazolidinediones, and statins). Liver function tests should be monitored at regular intervals during asparaginase treatment with or without other hepatotoxic drugs. Patients should be advised to seek medical attention if they experience potential symptoms of hepatotoxicity such as right upper quadrant pain, increasing abdominal size, fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, dark urine, pale stools, and jaundice.