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 inactivatedMonitor Closely (1)methotrexate decreases effects of hepatitis A vaccine inactivated by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.hepatitis a/b vaccineMonitor Closely (1)methotrexate decreases effects of hepatitis a/b vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.hepatitis b vaccineMonitor Closely (1)methotrexate decreases effects of hepatitis b vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.human papillomavirus vaccine, nonavalentSerious - Use Alternative (1)methotrexate 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)methotrexate 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.hydrochlorothiazideMinor (1)hydrochlorothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.hydroxychloroquine sulfateMonitor Closely (1)hydroxychloroquine sulfate decreases levels of methotrexate by unknown mechanism. Use Caution/Monitor. Hydroxychloroquine may reduce the renal clearance of methotrexate; the exact mechanism of this interaction is unknown. .hydroxyureaMonitor Closely (1)methotrexate, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression.ibuprofenSerious - Use Alternative (1)ibuprofen increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .ibuprofen IVMonitor Closely (1)ibuprofen IV will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)ibuprofen IV increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .idecabtagene vicleucelSerious - Use Alternative (1)methotrexate, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.ifosfamideMonitor Closely (1)ifosfamide, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with ifosfamide may increase the risk of immunosuppression and myelosuppression.indomethacinSerious - Use Alternative (1)indomethacin increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .influenza A (H5N1) vaccineMonitor Closely (1)methotrexate decreases effects of influenza A (H5N1) vaccine by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce immune response to H5N1 vaccine.influenza virus vaccine (H5N1), adjuvantedMonitor Closely (1)methotrexate decreases effects of influenza virus vaccine (H5N1), adjuvanted by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce immune response to H5N1 vaccine.influenza virus vaccine quadrivalentMonitor Closely (1)methotrexate decreases effects of influenza virus vaccine quadrivalent by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.influenza virus vaccine quadrivalent, adjuvantedSerious - Use Alternative (1)methotrexate 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-culturedMonitor Closely (1)methotrexate decreases effects of influenza virus vaccine quadrivalent, cell-cultured by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.influenza virus vaccine quadrivalent, intranasalContraindicated (1)methotrexate decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.influenza virus vaccine quadrivalent, recombinantMonitor Closely (1)methotrexate 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 trivalentMonitor Closely (1)methotrexate decreases effects of influenza virus vaccine trivalent by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.influenza virus vaccine trivalent, adjuvantedSerious - Use Alternative (1)methotrexate 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)methotrexate decreases effects of influenza virus vaccine trivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.ioversolMonitor Closely (1)ioversol and methotrexate both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.isavuconazonium sulfateMonitor Closely (1)methotrexate and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.isotretinoinMonitor Closely (1)methotrexate, isotretinoin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Patients receiving other agents that may cause hepatotoxicity, including systemic retinoids, could be at increased risk of liver-related side effects of methotrexate and such patients should be monitored closely during methotrexate therapy.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.Japanese encephalitis virus vaccineMonitor Closely (1)methotrexate decreases effects of Japanese encephalitis virus vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.ketoprofenSerious - Use Alternative (1)ketoprofen increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .ketorolacSerious - Use Alternative (1)ketorolac increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .ketorolac intranasalMonitor Closely (1)ketorolac intranasal will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)ketorolac intranasal increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. The relative risk of interaction of different NSAIDs w/methotrexate is not established. Selective COX 2 inhibitors are believed to have minimal interaction. Greater risk in pts. with renal impairment. Greater toxicity with high dose methotrexate (e.g., anti neoplastic regimen).L-methylfolateMonitor Closely (1)methotrexate decreases effects of L-methylfolate by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Folic acid antagonists may interfere with folic acid utilization.Minor (3)L-methylfolate decreases levels of methotrexate by increasing metabolism. Minor/Significance Unknown. Folic acid antagonists may interfere with folic acid utilization. L-methylfolate decreases levels of methotrexate by pharmacodynamic antagonism. Minor/Significance Unknown. methotrexate decreases levels of L-methylfolate by altering metabolism. Minor/Significance Unknown.lansoprazoleMonitor Closely (1)lansoprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.lasmiditanSerious - Use Alternative (1)lasmiditan increases levels of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates.leflunomideMonitor 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.leniolisibSerious - Use Alternative (1)leniolisib will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP, OATP1B1, and OATP1B3 inhibitor, may increase systemic exposure of these substratesletermovirMonitor Closely (1)letermovir increases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.lisocabtagene maraleucelSerious - Use Alternative (1)methotrexate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.lomitapideMonitor Closely (1)lomitapide increases levels of methotrexate by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.lomustineMonitor Closely (1)lomustine, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with lomustine may increase the risk of immunosuppression and myelosuppression.lonafarnibMonitor Closely (1)lonafarnib will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.maitakeMonitor Closely (1)methotrexate increases and maitake decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)maitake increases effects of methotrexate by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).measles mumps and rubella vaccine, liveContraindicated (1)methotrexate decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.measles, mumps, rubella and varicella vaccine, liveContraindicated (1)methotrexate decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.meclofenamateMonitor Closely (1)meclofenamate will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)meclofenamate increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .mefenamic acidSerious - Use Alternative (1)mefenamic acid increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .meloxicamSerious - Use Alternative (1)meloxicam increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .meningococcal A C Y and W-135 polysaccharide vaccine combinedMonitor Closely (1)methotrexate decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.meningococcal group B vaccineMonitor Closely (1)methotrexate 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.methyclothiazideMonitor Closely (1)methyclothiazide will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Minor (1)methyclothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.minocyclineMonitor Closely (1)minocycline increases levels of methotrexate by decreasing elimination. Use Caution/Monitor. If tetracyclines cannot be avoided in patients receiving high-dose methotrexate, closely monitor methotrexate plasma concentrations and patients for signs and symptoms of toxicity.mipomersenMonitor Closely (1)mipomersen, methotrexate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.muromonab CD3Monitor Closely (1)methotrexate and muromonab CD3 both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.mycophenolateMonitor Closely (1)mycophenolate, methotrexate. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Infections may occur.nabumetoneSerious - Use Alternative (1)nabumetone increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .nafcillinMonitor Closely (1)nafcillin increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with concurrent administration of high or