enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.anakinraSerious - Use Alternative (1)anakinra and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.anthrax vaccineSerious - Use Alternative (1)leflunomide decreases effects of anthrax vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.antithymocyte globulin equineSerious - Use Alternative (1)antithymocyte globulin equine and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.antithymocyte globulin rabbitSerious - Use Alternative (1)antithymocyte globulin rabbit and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.apalutamideMonitor Closely (1)apalutamide will decrease the level or effect of leflunomide by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.astragalusMonitor Closely (1)leflunomide increases and astragalus decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.axicabtagene ciloleucelSerious - Use Alternative (1)leflunomide, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.azathioprineSerious - Use Alternative (1)azathioprine and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.basiliximabSerious - Use Alternative (1)basiliximab and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.BCG vaccine liveSerious - Use Alternative (1)leflunomide decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.beclomethasone, inhaledSerious - Use Alternative (1)beclomethasone, inhaled increases toxicity of leflunomide by unspecified interaction mechanism. Avoid or Use Alternate Drug. May increase risk of hematologic toxicities; should monitor for bone marrow suppression at least monthly throughout duration of concurrent therapy when leflunomide is given with another immunosuppressants.belataceptMonitor Closely (1)belatacept and leflunomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.bosentanMinor (1)leflunomide will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.brexucabtagene autoleucelSerious - Use Alternative (1)leflunomide, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.canakinumabSerious - Use Alternative (1)canakinumab and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.carvedilolMonitor Closely (1)leflunomide will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.celecoxibMinor (1)leflunomide will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.cholera vaccineMonitor Closely (1)leflunomide decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.cholestyramineMonitor Closely (1)cholestyramine decreases levels of leflunomide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.ciltacabtagene autoleucelSerious - Use Alternative (1)leflunomide, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.cyclosporineSerious - Use Alternative (1)cyclosporine and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.darolutamideSerious - Use Alternative (1)darolutamide will increase the level or effect of leflunomide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).dengue vaccineMonitor Closely (1)leflunomide decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.denosumabMonitor Closely (1)leflunomide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.dichlorphenamideMonitor Closely (1)dichlorphenamide and leflunomide both decrease serum potassium. Use Caution/Monitor.diclofenacMinor (1)leflunomide will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.diphtheria & tetanus toxoidsSerious - Use Alternative (1)leflunomide decreases effects of diphtheria & tetanus toxoids by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.diphtheria & tetanus toxoids/ acellular pertussis vaccineSerious - Use Alternative (1)leflunomide decreases effects of diphtheria & tetanus toxoids/ acellular pertussis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccineSerious - Use Alternative (1)leflunomide decreases effects of diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.echinaceaMonitor Closely (1)leflunomide increases and echinacea decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.eltrombopagMonitor Closely (1)leflunomide will increase the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.eluxadolineMonitor Closely (1)eluxadoline increases levels of leflunomide by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.encorafenibMonitor Closely (1)encorafenib will increase the level or effect of leflunomide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.etanerceptSerious - Use Alternative (1)etanercept and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.ethotoinMonitor Closely (1)leflunomide will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.etravirineMonitor Closely (1)leflunomide will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.everolimusSerious - Use Alternative (1)everolimus and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.fingolimodMonitor Closely (1)leflunomide increases effects of fingolimod by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects. .flurbiprofenMinor (1)leflunomide will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.fluvastatinMinor (1)leflunomide will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.fosphenytoinMonitor Closely (1)leflunomide will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.fostamatinibMonitor Closely (1)fostamatinib will increase the level or effect of leflunomide by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.fostemsavirMonitor Closely (1)fostemsavir will increase the level or effect of leflunomide by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir.glatiramerSerious - Use Alternative (1)glatiramer and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.glecaprevir/pibrentasvirMonitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of leflunomide by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.golimumabSerious - Use Alternative (1)golimumab and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.haemophilus influenzae type b vaccineMonitor Closely (1)leflunomide decreases effects of haemophilus influenzae type b vaccine 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. .hepatitis A vaccine inactivatedSerious - Use Alternative (1)leflunomide decreases effects of hepatitis A vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.hepatitis a/b vaccineSerious - Use Alternative (1)leflunomide decreases effects of hepatitis a/b vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.hepatitis a/typhoid vaccineSerious - Use Alternative (1)leflunomide decreases effects of hepatitis a/typhoid vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.hepatitis b vaccineSerious - Use Alternative (1)leflunomide decreases effects of hepatitis b vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.human papillomavirus vaccine, nonavalentSerious - Use Alternative (1)leflunomide decreases effects of human papillomavirus vaccine, nonavalent by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.human papillomavirus vaccine, quadrivalentSerious - Use Alternative (1)leflunomide decreases effects of human papillomavirus vaccine, quadrivalent by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.hydroxychloroquine sulfateSerious - Use Alternative (1)hydroxychloroquine sulfate and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.hydroxyureaMonitor Closely (1)hydroxyurea, leflunomide. Other (see comment). Use Caution/Monitor. Comment: Combination therapy may lead to increased risk of infection.ibuprofenMinor (1)leflunomide will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.ibuprofen IVMinor (1)leflunomide will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.idecabtagene vicleucelSerious - Use Alternative (1)leflunomide, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.ifosfamideMonitor Closely (1)ifosfamide increases toxicity of leflunomide by Other (see comment). Use Caution/Monitor. Comment: 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.infliximabSerious - Use Alternative (1)infliximab and leflunomide both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.influenza virus vaccine quadrivalentSerious - Use Alternative (1)leflunomide decreases effects of influenza virus vaccine quadrivalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.influenza virus vaccine quadrivalent, adjuvantedSerious - Use Alternative (1)leflunomide decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.influenza virus vaccine quadrivalent, cell-culturedSerious - Use Alternative (1)leflunomide decreases effects of influenza virus vaccine quadrivalent, cell-cultured by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.influenza virus vaccine quadrivalent, intranasalSerious - Use Alternative (1)leflunomide decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.influenza virus vaccine quadrivalent, recombinantMonitor Closely (1)leflunomide decreases effects of influenza virus vaccine quadrivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.influenza virus vaccine trivalentSerious - Use Alternative (1)leflunomide decreases effects of influenza virus vaccine trivalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.influenza virus vaccine trivalent, adjuvantedSerious - Use Alternative (1)leflunomide decreases effects of influenza virus vaccine trivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.influenza virus vaccine trivalent, recombinantMonitor Closely (1)leflunomide decreases effects of influenza virus vaccine trivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.isavuconazonium sulfateMonitor Closely (1)leflunomide and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.Japanese encephalitis virus vaccineSerious - Use Alternative (1)leflunomide decreases effects of Japanese encephalitis virus vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.lasmiditanSerious - Use Alternative (1)lasmiditan increases levels of leflunomide by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates.leniolisibSerious - Use Alternative (1)leniolisib will increase the level or effect of leflunomide by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrateslisocabtagene maraleucelSerious - Use Alternative (1)leflunomide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.lomustineMonitor Closely (1)lomustine 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.losartanMonitor Closely (2)leflunomide will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage. leflunomide decreases effects of losartan by decreasing metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.maitakeMonitor Closely (1)leflunomide increases and maitake decreases immunosuppressive effects;