risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.measles (rubeola) vaccineSerious - Use Alternative (1)leflunomide decreases effects of measles (rubeola) vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.measles mumps and rubella vaccine, liveSerious - Use Alternative (1)leflunomide decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.measles, mumps, rubella and varicella vaccine, liveSerious - Use Alternative (1)leflunomide decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.mechlorethamineMonitor Closely (1)mechlorethamine increases toxicity of leflunomide by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Monitor for bone marrow suppression at least monthly in patients concomitantly using leflunomide and another immunosuppressant.meloxicamMinor (1)leflunomide will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.melphalanMonitor Closely (1)melphalan, leflunomide. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Monitor for bone marrow suppression at least monthly in patients concomitantly using leflunomide and another immunosuppressant.meningococcal A C Y and W-135 polysaccharide vaccine combinedSerious - Use Alternative (1)leflunomide decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.meningococcal group B vaccineMonitor Closely (1)leflunomide decreases effects of meningococcal group B vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Individuals with altered immunocompetence may have reduced immune responses to the vaccine.mercaptopurineMonitor Closely (1)leflunomide and mercaptopurine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.methotrexateMonitor Closely (1)leflunomide increases levels of methotrexate by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Additive hepatotoxicity, pancytopenia. If leflunomide and methotrexate are given concomitantly, monitor liver toxicity with ALT, AST, and serum albumin testing. Also, monitor platelets, WBC count, hemoglobin, or hematocrit at baseline and monthly for 6 months following initiation and every 6-8 weeks thereafter.muromonab CD3Serious - Use Alternative (1)leflunomide and muromonab CD3 both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.mycophenolateSerious - Use Alternative (1)leflunomide and mycophenolate both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.nateglinideMonitor Closely (1)leflunomide will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.ocrelizumabMonitor Closely (1)ocrelizumab increases toxicity of leflunomide by unknown mechanism. Modify Therapy/Monitor Closely. Coadminstration of leflunomide and ocrelizumab may cause increased risk of infections, pancytopenia, agranulocytosis and thrombocytopenia.ofatumumab SCMonitor Closely (1)ofatumumab SC, leflunomide. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.olaparibMonitor Closely (1)leflunomide and olaparib both increase pharmacodynamic synergism. Use Caution/Monitor. Coadministration with other other myelosuppressive anticancer agents, including DNA damaging agents, may potentiate and prolongate the myelosuppressive toxicity. oteseconazoleMonitor Closely (1)oteseconazole will increase the level or effect of leflunomide by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.oxaliplatinMonitor Closely (1)oxaliplatin increases toxicity of leflunomide by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Monitor for bone marrow suppression at least monthly in patients concomitantly using leflunomide and another immunosuppressant.ozanimodMonitor Closely (1)ozanimod, leflunomide. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration with immunosuppressive therapies may increase the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs in order to avoid unintended additive immunosuppressive effects.parecoxibMonitor Closely (1)leflunomide will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.phenytoinMonitor Closely (1)leflunomide will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.piroxicamMinor (1)leflunomide will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.pneumococcal vaccine 13-valentSerious - Use Alternative (1)leflunomide decreases effects of pneumococcal vaccine 13-valent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.pneumococcal vaccine heptavalentSerious - Use Alternative (1)leflunomide decreases effects of pneumococcal vaccine heptavalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.pneumococcal vaccine polyvalentSerious - Use Alternative (1)leflunomide decreases effects of pneumococcal vaccine polyvalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.poliovirus vaccine inactivatedMonitor Closely (1)leflunomide decreases effects of poliovirus vaccine inactivated by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .ponatinibMonitor Closely (1)ponatinib increases levels of leflunomide by Other (see comment). Use Caution/Monitor.ponesimodMonitor Closely (1)ponesimod and leflunomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.procarbazineMonitor Closely (1)procarbazine increases toxicity of leflunomide by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Monitor for bone marrow suppression at least monthly in patients concomitantly using leflunomide and another immunosuppressant.rabies vaccineSerious - Use Alternative (1)leflunomide decreases effects of rabies vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants may interfere with development of active immunity.rabies vaccine chick embryo cell derivedSerious - Use Alternative (1)leflunomide decreases effects of rabies vaccine chick embryo cell derived by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.ramelteonMinor (1)leflunomide will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.regorafenibMonitor Closely (1)regorafenib will increase the level or effect of leflunomide by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.rifampinMinor (1)rifampin increases effects of leflunomide by increasing metabolism. Minor/Significance Unknown. Leflunomide's effects due to its active metabolite.rilonaceptSerious - Use Alternative (1)leflunomide and rilonacept both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.rotavirus oral vaccine, liveSerious - Use Alternative (1)leflunomide decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.rubella vaccineSerious - Use Alternative (1)leflunomide decreases effects of rubella vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.safinamideMonitor Closely (1)safinamide will increase the level or effect of leflunomide by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.selinexorSerious - Use Alternative (1)selinexor, leflunomide. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.shark cartilageMinor (1)leflunomide, shark cartilage. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Enhanced anti angiogenesis (theoretical interaction).siponimodMonitor Closely (1)siponimod and leflunomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.sipuleucel-TMonitor Closely (1)leflunomide decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.sirolimusSerious - Use Alternative (1)leflunomide and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.smallpox (vaccinia) vaccine, liveSerious - Use Alternative (1)leflunomide decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.sofosbuvir/velpatasvirMonitor Closely (1)sofosbuvir/velpatasvir will increase the level or effect of leflunomide by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.stiripentolMonitor Closely (1)stiripentol will increase the level or effect of leflunomide by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.sulfamethoxazoleMinor (1)leflunomide will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.tacrolimusSerious - Use Alternative (1)leflunomide and tacrolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tafamidisMonitor Closely (1)tafamidis will increase the level or effect of leflunomide by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.tafamidis meglumineMonitor Closely (1)tafamidis meglumine will increase the level or effect of leflunomide by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.tamoxifenMonitor Closely (1)leflunomide, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. CYP2C9/10 inhibition decreases tamoxifen metabolism to active metabolites.temsirolimusSerious - Use Alternative (1)leflunomide and temsirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tetanus toxoid adsorbed or fluidSerious - Use Alternative (1)leflunomide decreases effects of tetanus toxoid adsorbed or fluid by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.tick-borne encephalitis vaccineSerious - Use Alternative (1)leflunomide decreases effects of tick-borne encephalitis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.tisagenlecleucelSerious - Use Alternative (1)leflunomide, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tocilizumabSerious - Use Alternative (1)tocilizumab and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tofacitinibSerious - Use Alternative (1)leflunomide, tofacitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tolbutamideMinor (1)leflunomide will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.tongkat aliSerious - Use Alternative (1)leflunomide and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.trastuzumabMonitor Closely (1)trastuzumab, leflunomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .trastuzumab deruxtecanMonitor Closely (1)trastuzumab deruxtecan, leflunomide. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .travelers diarrhea and cholera vaccine inactivatedSerious - Use Alternative (1)leflunomide decreases effects of travelers diarrhea and cholera vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.typhoid polysaccharide vaccineSerious - Use Alternative (1)leflunomide decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.typhoid vaccine liveSerious - Use Alternative (1)leflunomide decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.ublituximabMonitor Closely (1)ublituximab and leflunomide both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministeredustekinumabSerious - Use Alternative (1)leflunomide and ustekinumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.varicella virus vaccine liveSerious - Use Alternative (1)leflunomide decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.voriconazoleMinor (1)leflunomide will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.warfarinMonitor Closely (1)leflunomide increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.yellow fever vaccineSerious - Use Alternative (1)leflunomide decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.zoster vaccine liveSerious - Use Alternative (1)leflunomide decreases effects of zoster vaccine live by pharmacodynamic antagonism.