the drug is an immediate or extended release product).fingolimodmethotrexate 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. .foodfood decreases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Food may delay the absorption and reduce the peak concentration of methotrexate.fosphenytoinfosphenytoin increases toxicity of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by certain drugs.fostamatinibfostamatinib will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp/BCRP substrate drugs. Monitor for toxicities of P-gp/BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.fostemsavirfostemsavir will increase the level or effect of methotrexate by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 and BCRP transporters. If possible, avoid coadministration or modify dose of OATP1B1/3 or BCRP substrates coadministered with fostemsavir.glecaprevir/pibrentasvirglecaprevir/pibrentasvir will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of OATP1B1/OATP1B3, P-gp and BCRP substrates.haemophilus influenzae type b vaccinemethotrexate 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 inactivatedmethotrexate 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 vaccinemethotrexate 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 vaccinemethotrexate decreases effects of hepatitis b vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.hydroxychloroquine sulfatehydroxychloroquine 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. .hydroxyureamethotrexate, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression.ibuprofen IVibuprofen IV will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.ifosfamideifosfamide, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with ifosfamide may increase the risk of immunosuppression and myelosuppression.influenza A (H5N1) vaccinemethotrexate 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), adjuvantedmethotrexate 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 quadrivalentmethotrexate 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, cell-culturedmethotrexate 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, recombinantmethotrexate 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 trivalentmethotrexate 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, recombinantmethotrexate decreases effects of influenza virus vaccine trivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.ioversolioversol and methotrexate both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.isavuconazonium sulfatemethotrexate and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.isotretinoinmethotrexate, 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.istradefyllineistradefylline 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 vaccinemethotrexate decreases effects of Japanese encephalitis virus vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.ketorolac intranasalketorolac intranasal will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.L-methylfolatemethotrexate decreases effects of L-methylfolate by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Folic acid antagonists may interfere with folic acid utilization.lansoprazolelansoprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.leflunomideleflunomide 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.letermovirletermovir 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.lomitapidelomitapide increases levels of methotrexate by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.lomustinelomustine, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with lomustine may increase the risk of immunosuppression and myelosuppression.lonafarniblonafarnib 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.maitakemethotrexate increases and maitake decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.meclofenamatemeclofenamate will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.meningococcal A C Y and W-135 polysaccharide vaccine combinedmethotrexate 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 vaccinemethotrexate 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.methyclothiazidemethyclothiazide will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.minocyclineminocycline 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.mipomersenmipomersen, 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 CD3methotrexate and muromonab CD3 both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.mycophenolatemycophenolate, methotrexate. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Infections may occur.nafcillinnafcillin 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 low doses of methotrexate and penicillins.neomycin POneomycin PO decreases levels of methotrexate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Neomycin may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria.ocrelizumabmethotrexate and ocrelizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration of ocrelizumab with immunosuppessants is expected to increase the risk of immunosuppression.ofatumumab SCofatumumab SC, methotrexate. Either decreases toxicity 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.olaparibmethotrexate 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. omeprazoleomeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Temporary withdrawal of PPI may be considered in some patients.osimertinibosimertinib will increase the level or effect of methotrexate by Other (see comment). Modify Therapy/Monitor Closely. Osimertinib is an inhibitor of BCRP transport. Caution if coadministered with sensitive BCRP substrates.oteseconazoleoteseconazole will increase the level or effect of methotrexate 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.oxaliplatinmethotrexate and oxaliplatin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.oxaliplatin, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Combination may increase risk of myelosuppression.ozanimodozanimod, methotrexate. 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.pantoprazolepantoprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.paromomycinparomomycin decreases levels of methotrexate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Paromomycin may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria.pegaspargasepegaspargase decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor. It is recommended to give pegaspargase at least 10-14 days prior to methotrexate or shortly after methotrexate administration.phenytoinphenytoin increases toxicity of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by certain drugs, such as phenytoin.pirtobrutinibpirtobrutinib will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Pirtobrutinib (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase the risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations. pneumococcal vaccine polyvalentmethotrexate decreases effects of pneumococcal vaccine polyvalent by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.poliovirus vaccine inactivatedmethotrexate 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. .ponatinibponatinib increases levels of methotrexate by Other (see comment). Use Caution/Monitor.ponesimodponesimod and methotrexate 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.probenecidprobenecid will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Methotrexate plasma levels, therapeutic effects, and toxicity may be enhanced. Monitor methotrexate concentrations and adjust dose accordingly.procarbazineprocarbazine, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of immunosupression.rabeprazolerabeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.rabies vaccinemethotrexate decreases effects of rabies vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.regorafenibregorafenib will increase the level or effect of methotrexate 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.rilonaceptmethotrexate and rilonacept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.rolapitantrolapitant will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Oral rolapitant (BCRP inhibitor) may increase plasma concentrations of BCRP substrates and may result in potential adverse reactions. Monitor possible adverse reactions if concomitant use of BCRP substrates and rolapitant can not be avoided.rose hipsrose hips will increase the level or effect of methotrexate by acidic (anionic) drug competition for