Methotrexate

Combined use of methotrexate and acitretin is contraindicated due to increased risk of hepatitis.

Should not be used concomitantly with natalizumab due to potential increased risk of PML and other infections.

Should not be used concomitantly with natalizumab due to increased risk of PML and other infections in Crohn's disease patients.

Anesthetic that potentiates methotrexate effects on folate-dependent metabolic pathways, increasing risk of severe adverse reactions. Avoid use in methotrexate-treated patients.

NSAIDs should not be administered prior to or concomitantly with high-dose methotrexate. Concomitant administration has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.

DHFR inhibitor that may reduce sepiapterin metabolism to tetrahydrobiopterin (BH4). Avoid concomitant use.

Sulfonamides displace methotrexate from plasma protein binding and compete with renal transport, increasing free methotrexate concentrations.

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti- inflammatory drugs Hepatotoxic products Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.

May increase methotrexate plasma concentrations and risk of severe adverse reactions. Monitor closely for methotrexate adverse reactions.

NSAID that may increase methotrexate plasma concentrations, increasing risk of severe adverse reactions and potentially reducing clinical effectiveness.

Salicylate inhibits renal clearance of methotrexate, leading to bone marrow toxicity, especially in elderly or renal impaired patients.

Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in elderly or renally impaired patients.

Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in elderly or renal impaired patients.

Patients receiving concomitant therapy with methotrexate and azathioprine should be closely monitored for possible increased risk of hepatotoxicity.

Aspirin causes bone marrow toxicity and blood dyscrasias by displacing from binding sites and reducing its excretion.

Caution must be exercised if high-dose methotrexate is administered in combination with cisplatin due to potential nephrotoxicity of both agents.

When coadministered with cyclosporine in rheumatoid arthritis patients, the AUC of methotrexate was significantly increased.

Antifolate drug that may increase methotrexate plasma concentrations, increasing risk of severe adverse reactions and potentially reducing clinical effectiveness.

Concomitant use may elevate and prolong serum concentrations of methotrexate and hydroxymethotrexate, possibly leading to toxicities, particularly at high doses.

Concomitant use is not recommended as dichlorphenamide inhibits OAT1 transporters, increasing methotrexate plasma exposure.

NSAIDs may competitively inhibit methotrexate accumulation and enhance methotrexate toxicity. Caution advised with concomitant use.

Concomitant use with high-dose methotrexate may elevate and prolong serum methotrexate and hydroxymethotrexate levels, possibly leading to toxicity. Use caution with high-dose methotrexate.

Concomitant use may elevate and prolong serum concentrations of methotrexate and metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Concomitant use may elevate and prolong serum concentrations of methotrexate and its metabolite, possibly leading to methotrexate toxicities.

Concomitant use may elevate and prolong serum concentrations of methotrexate and its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Etodolac may cause elevated serum levels and increased toxicity of methotrexate. Should not be administered prior to or concomitantly with high-dose methotrexate.

Methotrexate interferes with folate metabolism, resulting in folate deficiency.

Concomitant use should be avoided due to additive nephrotoxicity and renal impairment risk.

Drugs undergoing significant renal tubular secretion like methotrexate may reduce furosemide effect. High-dose treatment may elevate serum levels and potentiate toxicity.

Combined use has not been studied and may increase the incidence of adverse effects.

NSAIDs competitively inhibit methotrexate accumulation and may enhance methotrexate toxicity. Caution should be used when administered concomitantly.

NSAIDs may competitively inhibit methotrexate accumulation and enhance methotrexate toxicity. Use with caution when administering concomitantly.

Imatinib mesylate delays clearance of methotrexate and results in sustained methotrexate concentrations when used at high doses (>500 mg/m²).

Ketoprofen may alter methotrexate elimination leading to elevated serum levels and increased toxicity. NSAIDs may competitively inhibit methotrexate accumulation.

Concomitant use with lansoprazole may elevate and prolong serum concentrations of methotrexate and its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Concomitant use may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to methotrexate toxicities.

Oral or intravenous sulfonamides may increase methotrexate plasma concentrations and are highly protein-bound, increasing risk of severe adverse reactions.

May increase methotrexate plasma concentrations, increasing risk of severe adverse reactions and potentially reducing clinical effectiveness.

Meloxicam may reduce methotrexate elimination, thereby enhancing methotrexate toxicity.

May increase methotrexate plasma concentrations, increasing risk of severe adverse reactions. Monitor closely for methotrexate adverse reactions.

NSAIDs may competitively inhibit methotrexate accumulation and enhance its toxicity. Caution should be used when administering nabumetone concomitantly with methotrexate.

NSAIDs may reduce tubular secretion of methotrexate and enhance its toxicity. Caution advised with concomitant use.

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti- inflammatory drugs Hepatotoxic products Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.

Concomitant use with omeprazole may elevate and prolong serum concentrations of methotrexate and/or metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Concomitant use may elevate and prolong serum concentrations of methotrexate and metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Concomitant use, especially at high dose, may elevate and prolong serum concentrations of methotrexate and hydroxymethotrexate, possibly leading to methotrexate toxicities.

Highly protein-bound drug that may increase methotrexate plasma concentrations, increasing risk of severe adverse reactions and potentially reducing clinical effectiveness.

Aspirin may enhance serious side effects and toxicity of methotrexate through protein binding displacement.

Concomitant use of pantoprazole with methotrexate, particularly at high dose, may elevate and prolong serum concentrations of methotrexate and its metabolite hydroxymethotrexate, leading to toxicities.

Concomitant use may elevate and prolong serum concentrations of methotrexate and/or hydroxymethotrexate, possibly leading to methotrexate toxicities, particularly at high doses.

Concomitant use of pantoprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and metabolite, possibly leading to toxicities.

Concomitant use may elevate and prolong serum concentrations of methotrexate and hydroxymethotrexate, possibly leading to toxicities, especially at high doses.

Concomitant use of pantoprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations, possibly leading to methotrexate toxicities.

Antifolate drug that may increase methotrexate plasma concentrations, increasing risk of severe adverse reactions and potentially reducing clinical effectiveness.

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti- inflammatory drugs Hepatotoxic products Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.

Penicillin G benzathine may reduce the renal excretion of methotrexate, causing a potential increase in its toxicity.

May increase methotrexate toxicity by displacing the drug from serum albumin binding.

May increase methotrexate toxicity by displacing the drug from serum albumin binding.

Probenecid increases plasma concentrations of methotrexate in animals and humans.

Probenecid increases plasma concentrations of methotrexate in animals and humans.

Concomitant use may increase risk of bone marrow suppression and folate deficiency.

Concomitant use with rabeprazole may elevate and prolong serum levels of methotrexate and its metabolite, possibly leading to methotrexate toxicities.

Concomitant use may elevate and prolong serum levels of methotrexate and its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities.

Patients receiving concomitant therapy with methotrexate and retinoids should be closely monitored for possible increased risk of hepatotoxicity.

Caution should be used when salicylates are administered concomitantly with methotrexate. These drugs reduce tubular secretion of methotrexate and may displace it from serum albumin binding, enhancing toxicity.

Salicylate decreases tubular reabsorption of methotrexate, which can result in clinical toxicity.

Salicylate decreases tubular reabsorption of methotrexate, resulting in clinical toxicity.

NSAIDs may competitively inhibit methotrexate accumulation and enhance methotrexate toxicity. Caution should be used when administered concomitantly.

BCRP substrate whose exposure may be altered by velpatasvir and voxilaprevir inhibition. Coadministration is not recommended.

Patients receiving concomitant therapy with methotrexate and sulfasalazine should be closely monitored for possible increased risk of hepatotoxicity.

Highly protein-bound drug that may increase methotrexate plasma concentrations, increasing risk of severe adverse reactions.

Naproxen increases methotrexate plasma levels, potentially increasing methotrexate toxicity.

Highly protein-bound drug that may increase methotrexate plasma concentrations, increasing risk of severe adverse reactions and potentially reducing clinical effectiveness.

Methotrexate increases theophylline plasma concentrations, increasing risk of theophylline adverse reactions. Monitor theophylline levels and adjust dosage accordingly.

NSAIDs competitively inhibit methotrexate accumulation and may enhance methotrexate toxicity. Caution should be used when administering concomitantly.

MTX reduces apparent adalimumab clearance but no dose adjustment needed for either drug.

MTX reduces apparent clearance of adalimumab, but no dose adjustment needed for either drug.

Methotrexate reduces apparent clearance of adalimumab but does not require dose adjustment of either drug.

Methotrexate reduced apparent adalimumab clearance, but no dose adjustment needed for either YUSIMRY or MTX based on available data.

MTX reduces apparent clearance of adalimumab but no dose adjustment needed for either AMJEVITA or MTX.

MTX reduces apparent adalimumab clearance but no dose adjustment needed for either drug.

MTX reduces apparent clearance of adalimumab but no dose adjustment needed for either drug. Monitoring recommended.

Folic acid may decrease patient response to methotrexate therapy.

Oral antibiotics like chloramphenicol may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation.

Co-administration requires caution; ciprofloxacin may inhibit methotrexate elimination.

Ciprofloxacin may inhibit methotrexate elimination. Use with caution and monitor therapy.

Co-administration requires caution and monitoring.

High-dose methotrexate is hepatotoxic and may impair liver function, increasing risk of daunorubicin toxicity. Dosage reduction may be required.

Monitor patients for methotrexate toxicity during concomitant use.

Monitor patients for methotrexate toxicity during concomitant use.

May affect valproate clearance. Monitoring of valproate concentrations is recommended.

Folic acid may decrease a patient's response to methotrexate.

BCRP substrate; eltrombopag may increase exposure. Monitor closely for signs of excessive exposure.

BCRP substrate; monitor for excessive exposure and consider dose reduction if appropriate.

Decreases clinical effectiveness of methotrexate in neoplastic diseases. Should be used only as directed by healthcare provider.

May decrease phenytoin serum levels; dose adjustment may be required.

Methotrexate and other drugs undergoing significant renal tubular secretion may reduce the effect of furosemide and furosemide may decrease renal elimination of these drugs, potentially causing toxicity.

MultiHance may compete for MOAT transporter and prolong systemic exposure of methotrexate.

Concomitant methotrexate decreases golimumab clearance by approximately 9% and reduces antibody development to golimumab.

Concomitant use may increase the incidence of adverse reactions.

Concomitant methotrexate use may decrease anti-drug antibody production and increase infliximab concentrations.

Concomitant methotrexate use may decrease anti-drug antibody production and increase infliximab concentrations; monitoring recommended.

Exposure to methotrexate may be increased when coadministered with leflunomide. Monitor and adjust dose as required.

Exposure of methotrexate may be increased in patients taking leflunomide. Monitor and adjust dose as required.

High doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate.

NSAIDs may competitively inhibit methotrexate accumulation and could enhance methotrexate toxicity. Caution should be used with concomitant administration.

NSAIDs may competitively inhibit methotrexate accumulation and enhance methotrexate toxicity. Caution should be used with concomitant administration.

Meloxicam may increase methotrexate plasma levels. Monitor for increases in methotrexate levels.

Folic acid may decrease patient response to methotrexate therapy.

Oral neomycin inhibits gastrointestinal absorption of methotrexate.

Nitisinone is an inhibitor of OAT1/OAT3 that increases exposure of methotrexate. Monitor for potential adverse reactions.

Co-administration of methotrexate with pegloticase may increase pegloticase concentration compared to pegloticase alone.

May decrease phenytoin serum levels; monitoring of phenytoin levels recommended.

Concurrent use of pivmecillinam may reduce clearance of methotrexate from the body. Consider alternative therapy where possible.

Folic acid may decrease a patient's response to methotrexate.

OAT3 substrate. Pretomanid inhibits OAT3 transporter, potentially increasing methotrexate concentrations and adverse reactions. Monitor and consider dose reduction.

BCRP substrate whose plasma concentrations increase with regorafenib; monitor for exposure-related toxicity.

Increased plasma concentrations may result in potential adverse reactions. Monitor for adverse reactions if use cannot be avoided.

May decrease endogenous BH4 levels by inhibiting dihydrofolate reductase, potentially increasing phenylalanine levels.

DIACOMIT may inhibit BCRP transport of methotrexate; consider dose reduction if adverse reactions occur.

Sulfonamides may increase the effect of methotrexate, probably by displacement from plasma albumin binding sites.

Probenecid inhibits OAT1/3, increasing methotrexate plasma concentrations. Monitor frequently for adverse reactions if concomitant use cannot be avoided.

Tafamidis inhibits BCRP, increasing methotrexate exposure and toxicity risk. Monitor for toxicities and adjust dosage if needed.

Tedizolid inhibits BCRP, increasing plasma concentrations of orally administered methotrexate. Monitor for adverse reactions; consider interrupting methotrexate during tedizolid treatment due to narrow therapeutic index.

Teriflunomide may increase exposure of methotrexate via OAT3 and OATP inhibition. Monitor patients and adjust dose as required.

May elevate and prolong serum methotrexate levels and increase toxicity; can be continued or reduced gradually in responding patients.

Immunomodulator used concomitantly; in psoriatic arthritis trials, concomitant use did not influence safety or efficacy of ustekinumab.

Concomitant use in psoriatic arthritis did not appear to influence safety or efficacy. In Crohn's disease and ulcerative colitis, use with immunomodulators including MTX did not influence overall safety or efficacy.

Concomitant MTX use did not appear to influence safety or efficacy of ustekinumab in psoriatic arthritis and Crohn's disease/ulcerative colitis trials. Monitor for therapeutic effect.

Concomitant use in psoriatic arthritis did not appear to influence safety or efficacy of ustekinumab; also used in ~30% of CD/UC subjects without affecting overall safety or efficacy.

Concomitant use did not appear to influence safety or efficacy of ustekinumab in psoriatic arthritis and inflammatory bowel disease trials; monitoring recommended.

Concomitant MTX use did not appear to influence safety or efficacy of ustekinumab in psoriatic arthritis trials; monitor for any unexpected effects.

Concomitant MTX use did not appear to influence safety or efficacy of ustekinumab in psoriatic arthritis trials; monitor concomitant use.

Methotrexate reduces apparent adalimumab clearance but no dose adjustment needed for either drug.

Administered concomitantly in clinical trials without evidence of clinically meaningful effect on belimumab pharmacokinetics.

Intravenous ondansetron does not increase blood levels of high-dose methotrexate in pediatric patients.

Intravenous ondansetron did not increase blood levels of high-dose methotrexate in pediatric patients.

Concomitant administration of methotrexate did not alter the pharmacokinetics of rituximab in clinical trials of RA patients.

Population pharmacokinetic analyses did not detect any effect of methotrexate on sarilumab clearance.

Concomitant administration with tocilizumab had no clinically significant effect on methotrexate exposure.

Concomitant administration with tocilizumab had no clinically significant effect on methotrexate exposure.

Concomitant administration of methotrexate did not alter the pharmacokinetics of rituximab in RA patients.

Trimethoprim/sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving methotrexate, probably by decreased tubular secretion and/or an additive antifolate effect. Trimethoprim/sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving methotrexate, probably by decreased tubular secretion and/or an additive antifolate effect.