the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.brexucabtagene autoleucelSerious - Use Alternative (1)methotrexate, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.caffeineMonitor Closely (1)caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.carboplatinMonitor Closely (1)carboplatin and methotrexate both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.celecoxibSerious - Use Alternative (1)celecoxib 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. .chlorpropamideMonitor Closely (1)chlorpropamide 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 vaccineMonitor Closely (1)methotrexate 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 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 trisalicylateMonitor Closely (1)choline magnesium trisalicylate will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)choline magnesium trisalicylate 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).cidofovirMonitor Closely (1)cidofovir and methotrexate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor. May increase myelosupression.ciltacabtagene autoleucelSerious - Use Alternative (1)methotrexate, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.ciprofloxacinMonitor Closely (1)ciprofloxacin 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.cisplatinMonitor Closely (1)cisplatin and methotrexate both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.colestipolMinor (1)colestipol decreases levels of methotrexate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Patients should take other drugs at least 1 hour before or 4 hours after colestipol to avoid impeding their absorption.crofelemerMonitor Closely (1)crofelemer 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.cyclosporineMonitor Closely (1)cyclosporine, 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. .dapsoneMonitor Closely (1)dapsone, methotrexate. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of hematologic toxicity.darolutamideSerious - Use Alternative (1)darolutamide will increase the level or effect of methotrexate 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).deferiproneSerious - Use Alternative (1)deferiprone, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.demeclocyclineMonitor Closely (1)demeclocycline 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 vaccineMonitor Closely (1)methotrexate 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)methotrexate, 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.dexlansoprazoleMonitor Closely (1)dexlansoprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.diclofenacSerious - Use Alternative (1)diclofenac 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. .dicloxacillinMonitor Closely (1)dicloxacillin 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.diflunisalSerious - Use Alternative (1)diflunisal 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. .digoxinMonitor Closely (1)methotrexate 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 toxoidsMonitor Closely (1)methotrexate 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 vaccineMonitor Closely (1)methotrexate 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 vaccineMonitor Closely (1)methotrexate 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.divalproex sodiumSerious - Use Alternative (1)methotrexate will decrease the level or effect of divalproex sodium by unspecified interaction mechanism. Avoid or Use Alternate Drug. may potentially result in increased frequency of seizures or bipolar symptoms; monitor serum valproate concentrations and clinical response when adding or discontinuing methotrexate and adjust valproate dosagedoxycyclineMonitor Closely (1)doxycycline 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.echinaceaMonitor Closely (1)methotrexate increases and echinacea decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.elacestrantMonitor Closely (1)elacestrant 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. elagolixMonitor Closely (1)elagolix will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.eliglustatMonitor Closely (1)eliglustat 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.eltrombopagMonitor Closely (1)eltrombopag increases levels of methotrexate by decreasing metabolism. Use Caution/Monitor. OATP transporter protein inhibition.eluxadolineMonitor Closely (1)eluxadoline increases levels of methotrexate by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.elvitegravir/cobicistat/emtricitabine/tenofovir DFMonitor Closely (1)methotrexate and elvitegravir/cobicistat/emtricitabine/tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.encorafenibMonitor Closely (1)encorafenib 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. erdafitinibSerious - Use Alternative (1)erdafitinib will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.esomeprazoleMonitor Closely (1)esomeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.ethanolSerious - Use Alternative (1)methotrexate, ethanol. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Ethanol (alcohol) may increase the risk for liver-related side effects of methotrexate. Patients should be advised to avoid intake of alcoholic beverages during methotrexate therapy. Patients who are noncompliant with alcohol restrictions (e.g., alcoholism) should not receive methotrexate.etodolacSerious - Use Alternative (1)etodolac 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. .fenoprofenSerious - Use Alternative (1)fenoprofen 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. .ferric maltolMonitor Closely (1)ferric 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 the drug is an immediate or extended release product).fingolimodMonitor Closely (1)methotrexate 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. .flurbiprofenSerious - Use Alternative (1)flurbiprofen 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. .folic acidMinor (1)folic acid decreases effects of methotrexate by pharmacodynamic antagonism. Minor/Significance Unknown. Vitamin preparations containing folic acid or its derivatives may decrease responses to systemically administered methotrexate.foodMonitor Closely (1)food decreases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Food may delay the absorption and reduce the peak concentration of methotrexate.fosphenytoinMonitor Closely (1)fosphenytoin 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.fostamatinibMonitor Closely (1)fostamatinib 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.fostemsavirMonitor Closely (1)fostemsavir 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/pibrentasvirMonitor Closely (1)glecaprevir/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.golimumabMinor (1)golimumab, methotrexate. Other (see comment). Minor/Significance Unknown. Comment: Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.haemophilus influenzae type b vaccineMonitor Closely (1)methotrexate decreases effects of haemophilus influenzae type b vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor