renal tubular clearance. Use Caution/Monitor.safinamidesafinamide 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.sapropterinmethotrexate decreases levels of sapropterin by Other (see comment). Use Caution/Monitor. Comment: Mechanism: Inhibition of dihydropteridine reductase (DHPR).sarecyclinesarecycline 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.siponimodsiponimod 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-Tmethotrexate decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.sirolimusmethotrexate and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.sofosbuvir/velpatasvirsofosbuvir/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.stiripentolstiripentol 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.streptozocinmethotrexate and streptozocin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.tacrolimusmethotrexate and tacrolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.tafamidistafamidis will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.tafamidis megluminetafamidis meglumine will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.temsirolimusmethotrexate and temsirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.tetanus toxoid adsorbed or fluidmethotrexate decreases effects of tetanus toxoid adsorbed or fluid by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.tetracyclinetetracycline 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.theophyllinemethotrexate increases levels of theophylline by unknown mechanism. Use Caution/Monitor. Methotrexate may decrease the clearance of theophylline. Theophylline levels should be monitored when used concomitantly with methotrexate.ticarcillinticarcillin 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.trastuzumabtrastuzumab, methotrexate. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .trastuzumab deruxtecantrastuzumab deruxtecan, methotrexate. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .tretinoinmethotrexate, tretinoin. 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.trimethoprimtrimethoprim increases toxicity of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may increase risk of methotrexate-induced bone marrow suppression and megaloblastic anemia. If this drug combination cannot be avoided, closely monitor for signs of hematologic toxicity.tucatinibtucatinib will increase the level or effect of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.typhoid polysaccharide vaccinemethotrexate decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant administration of methotrexate can decrease the immunological response of vaccines.ublituximabublituximab and methotrexate both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministeredustekinumabmethotrexate and ustekinumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.ustekinumab, methotrexate. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.valoctocogene roxaparvovecmethotrexate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.vancomycinvancomycin decreases levels of methotrexate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Recent exposure to vancomycin, in the absence of overt renal impairment, may adversely affect methotrexate excretion and increase risk of toxicity. Assess renal function, so appropriate methotrexate dose modifications can be made. .voclosporinvoclosporin, methotrexate. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.warfarinmethotrexate increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.willow barkwillow bark will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.zidovudinemethotrexate, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of myelosuppression.zoster vaccine recombinantmethotrexate decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant.Minor (10)adalimumabmethotrexate decreases levels of adalimumab by decreasing renal clearance. Minor/Significance Unknown. Methotrexate reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44%, respectively. Dosage adjustment is not needed.colestipolcolestipol 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.folic acidfolic 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.golimumabgolimumab, methotrexate. Other (see comment). Minor/Significance Unknown. Comment: Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.hydrochlorothiazidehydrochlorothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.L-methylfolateL-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.maitakemaitake increases effects of methotrexate by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).methyclothiazidemethyclothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.rituximab-hyaluronidasemethotrexate and rituximab-hyaluronidase both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.voclosporinvoclosporin will increase the level or effect of methotrexate by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.acalabrutinibMonitor Closely (2)acalabrutinib 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.acitretinContraindicated (1)acitretin, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of additive hepatotoxicity.activated charcoalMonitor Closely (1)activated 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.adalimumabMinor (1)methotrexate decreases levels of adalimumab by decreasing renal clearance. Minor/Significance Unknown. Methotrexate reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44%, respectively. Dosage adjustment is not needed.adenovirus types 4 and 7 live, oralSerious - Use Alternative (1)methotrexate decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressants also increase risk of infection with concomitant live vaccines.aldesleukinMonitor Closely (1)aldesleukin increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. May increase myelosupression and hepatotoxicity.allopurinolMonitor Closely (1)allopurinol decreases effects of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression.aminohippurate sodiumMonitor Closely (1)aminohippurate sodium will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.amoxicillinMonitor Closely (1)amoxicillin 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.ampicillinMonitor Closely (1)ampicillin 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.anthrax vaccineSerious - Use Alternative (1)methotrexate decreases effects of anthrax vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.apalutamideMonitor Closely (1)apalutamide 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.aspirinSerious - Use Alternative (1)aspirin 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.aspirin rectalMonitor Closely (1)aspirin rectal will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)aspirin rectal 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).aspirin/citric acid/sodium bicarbonateMonitor Closely (1)aspirin/citric acid/sodium bicarbonate will increase the level or effect of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)aspirin/citric acid/sodium bicarbonate 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.astragalusMonitor Closely (1)methotrexate increases and astragalus decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.axicabtagene ciloleucelSerious - Use Alternative (1)methotrexate, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.bacitracinSerious - Use Alternative (1)methotrexate and bacitracin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug. Avoid concurrent use of bacitracin with other nephrotoxic drugsBCG intravesical liveSerious - Use Alternative (1)methotrexate decreases effects of BCG intravesical live by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressants also increase risk of infection with concomitant live vaccines.belataceptMonitor Closely (1)belatacept and methotrexate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.berotralstatMonitor Closely (1)berotralstat 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.bosutinibMonitor Closely (1)bosutinib increases levels of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.bremelanotideSerious - Use Alternative (1)bremelanotide will decrease the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces