low doses of methotrexate and penicillins.naproxenSerious - Use Alternative (1)naproxen 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.neomycin POMonitor Closely (1)neomycin 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.ocrelizumabMonitor Closely (1)methotrexate 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 SCMonitor Closely (1)ofatumumab 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.olaparibMonitor Closely (1)methotrexate 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. omeprazoleMonitor Closely (1)omeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Temporary withdrawal of PPI may be considered in some patients.osimertinibMonitor Closely (1)osimertinib 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.oteseconazoleMonitor Closely (1)oteseconazole 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.oxaliplatinMonitor Closely (2)methotrexate 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.oxaprozinSerious - Use Alternative (1)oxaprozin 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. .ozanimodMonitor Closely (1)ozanimod, 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.pacritinibSerious - Use Alternative (1)pacritinib will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (BCRP inhibitor) with BCRP substrates may increase the plasma concentrations of these substrates.paliferminSerious - Use Alternative (1)palifermin increases toxicity of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hrbefore, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.pantoprazoleMonitor Closely (1)pantoprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.paromomycinMonitor Closely (1)paromomycin 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.pegaspargaseMonitor Closely (1)pegaspargase 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.pexidartinibSerious - Use Alternative (1)methotrexate and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.phenytoinMonitor Closely (1)phenytoin 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.piroxicamSerious - Use Alternative (1)piroxicam 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. .pirtobrutinibMonitor Closely (1)pirtobrutinib 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 13-valentSerious - Use Alternative (1)methotrexate decreases effects of pneumococcal vaccine 13-valent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.pneumococcal vaccine polyvalentMonitor Closely (1)methotrexate 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 inactivatedMonitor Closely (1)methotrexate 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 methotrexate by Other (see comment). Use Caution/Monitor.ponesimodMonitor Closely (1)ponesimod 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.pretomanidSerious - Use Alternative (2)pretomanid will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. In vitro studies demonstrated that pretomanid significantly inhibits OAT3; monitor for increased adverse effects and consider dosage reduction for OAT3 substrates. methotrexate, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.probenecidMonitor Closely (1)probenecid 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.Serious - Use Alternative (1)probenecid increases levels of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. If combination must be used, decrease methotrexate dose; also, methotrexate increases uric acid production and risk for uric acid neuropathy.procarbazineMonitor Closely (1)procarbazine, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of immunosupression.rabeprazoleMonitor Closely (1)rabeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.rabies vaccineMonitor Closely (1)methotrexate decreases effects of rabies vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.regorafenibMonitor Closely (1)regorafenib 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.rilonaceptMonitor Closely (1)methotrexate and rilonacept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.rituximab-hyaluronidaseMinor (1)methotrexate and rituximab-hyaluronidase both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.rolapitantMonitor Closely (1)rolapitant 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.ropeginterferon alfa 2bSerious - Use Alternative (1)ropeginterferon alfa 2b, methotrexate. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.rose hipsMonitor Closely (1)rose hips will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.rotavirus oral vaccine, liveContraindicated (1)methotrexate decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.safinamideMonitor Closely (1)safinamide will increase the level or effect of methotrexate 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.salicylates (non-asa)Serious - Use Alternative (1)salicylates (non-asa) increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.salsalateSerious - Use Alternative (1)salsalate increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.sapropterinMonitor Closely (1)methotrexate decreases levels of sapropterin by Other (see comment). Use Caution/Monitor. Comment: Mechanism: Inhibition of dihydropteridine reductase (DHPR).sarecyclineMonitor Closely (1)sarecycline will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.siponimodMonitor Closely (1)siponimod 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.sipuleucel-TMonitor Closely (1)methotrexate decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.sirolimusMonitor Closely (1)methotrexate and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.smallpox (vaccinia) vaccine, liveContraindicated (1)methotrexate decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.sofosbuvir/velpatasvirMonitor Closely (1)sofosbuvir/velpatasvir will increase the level or effect of methotrexate 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.sotorasibSerious - Use Alternative (1)sotorasib will decrease the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.sparsentanSerious - Use Alternative (1)sparsentan will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Sparsentan (a BCRP inhibitor) may increase exposure of sensitive BCRP substrates and the risk of these substrates toxicities. stiripentolMonitor Closely (2)stiripentol will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol. stiripentol will increase the level or effect of methotrexate 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.streptozocinMonitor Closely (1)methotrexate and streptozocin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.sulfadiazineSerious - Use Alternative (1)sulfadiazine increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug.sulfamethoxazoleSerious - Use Alternative (1)sulfamethoxazole increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug. Methotrexate concentrations may be elevated, increasing the risk of toxicity (eg, bone marrow suppression).sulfasalazineSerious - Use Alternative (1)sulfasalazine increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug.sulfisoxazoleSerious - Use Alternative (1)sulfisoxazole increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug.sulindacSerious - Use Alternative (1)sulindac increases levels of methotrexate by decreasing renal clearance.