prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .pneumococcal vaccine 13-valentmethotrexate decreases effects of pneumococcal vaccine 13-valent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.pretomanidpretomanid 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.probenecidprobenecid 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.ropeginterferon alfa 2bropeginterferon 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.salicylates (non-asa)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.salsalatesalsalate 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.sotorasibsotorasib 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.sparsentansparsentan 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. sulfadiazinesulfadiazine increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug.sulfamethoxazolesulfamethoxazole 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).sulfasalazinesulfasalazine increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug.sulfisoxazolesulfisoxazole increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug.sulindacsulindac 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. .tepotinibtepotinib will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.tisagenlecleucelmethotrexate, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tocilizumabtocilizumab and methotrexate both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tofacitinibmethotrexate, tofacitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tolmetintolmetin 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. .tongkat alimethotrexate and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tretinoin topicalmethotrexate, tretinoin topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive hepatotoxicity.trimethoprimtrimethoprim, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Due to an additive antifolate effect, trimethoprim has been shown to rarely increase bone marrow suppression in patients receiving methotrexate.trofinetidetrofinetide will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.Monitor Closely (148)acalabrutinibacalabrutinib increases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.acalabrutinib, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.activated charcoalactivated charcoal will decrease the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Charcoal can reduce absorption of methotrexate and remove it from systemic circulation. Depending on the clinical situation, this will reduce the effectiveness or toxicity of methotrexate.aldesleukinaldesleukin increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. May increase myelosupression and hepatotoxicity.allopurinolallopurinol decreases effects of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression.aminohippurate sodiumaminohippurate sodium will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.amoxicillinamoxicillin 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.ampicillinampicillin 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.apalutamideapalutamide will decrease the level or effect of methotrexate by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and OATP1B1 and may decrease systemic exposure of drugs that are substrates of both BCRP and OATP1B1.aspirin rectalaspirin rectal will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.aspirin/citric acid/sodium bicarbonateaspirin/citric acid/sodium bicarbonate will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.astragalusmethotrexate increases and astragalus decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.belataceptbelatacept and methotrexate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.berotralstatberotralstat will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.bosutinibbosutinib increases levels of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.caffeinecaffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.carboplatincarboplatin and methotrexate both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.chlorpropamidechlorpropamide will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor. Methotrexate is partially bound to plasma proteins, and drugs that can displace methotrexate from these proteins, such as oral sulfonylureas, could cause methotrexate-induced toxicity.cholera vaccinemethotrexate 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.cholestyraminecholestyramine decreases levels of methotrexate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4-6 hours after the administration of cholestyramine.choline magnesium trisalicylatecholine magnesium trisalicylate will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.cidofovircidofovir and methotrexate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor. May increase myelosupression.ciprofloxacinciprofloxacin will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Renal tubular transport of methotrexate may be inhibited by coadministration of ciprofloxacin, potentially leading to increased methotrexate plasma levels and toxicity.cisplatincisplatin and methotrexate both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.crofelemercrofelemer increases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Crofelemer has the potential to inhibit transporters MRP2 and OATP1A2 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.cyclosporinecyclosporine, methotrexate. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Close monitoring of cyclosporine and methotrexate concentrations, renal function, and liver enzymes is recommended during concurrent therapy. .dapsonedapsone, methotrexate. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of hematologic toxicity.demeclocyclinedemeclocycline increases levels of methotrexate by decreasing elimination. Use Caution/Monitor. Tetracyclines may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria.dengue vaccinemethotrexate 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.denosumabmethotrexate, 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.dexlansoprazoledexlansoprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.dicloxacillindicloxacillin 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.digoxinmethotrexate decreases levels of digoxin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Serum levels of digoxin may be reduced and actions may be decreased. Monitor patient for signs of reduction in pharmacologic effect of digoxin and increase digoxin dose if necessary. Serum level monitoring may facilitate tailoring dosage.diphtheria & tetanus toxoidsmethotrexate decreases effects of diphtheria & tetanus toxoids by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.diphtheria & tetanus toxoids/ acellular pertussis vaccinemethotrexate decreases effects of diphtheria & tetanus toxoids/ acellular pertussis vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccinemethotrexate decreases effects of diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressants also increase risk of infection with concomitant live vaccines.doxycyclinedoxycycline increases levels of methotrexate by decreasing elimination. Use Caution/Monitor. Tetracyclines may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria.echinaceamethotrexate increases and echinacea decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.elacestrantelacestrant will increase the level or effect of methotrexate by Other (see comment). Modify Therapy/Monitor Closely. Elacestrant (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations. elagolixelagolix will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.eliglustateliglustat increases levels of methotrexate by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.eltrombopageltrombopag increases levels of methotrexate by decreasing metabolism. Use Caution/Monitor. OATP transporter protein inhibition.eluxadolineeluxadoline increases levels of methotrexate by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.elvitegravir/cobicistat/emtricitabine/tenofovir DFmethotrexate and elvitegravir/cobicistat/emtricitabine/tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.encorafenibencorafenib will increase the level or effect of methotrexate by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled. esomeprazoleesomeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.ferric maltolferric maltol, methotrexate. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether