QuickView for Methotrexate (compound)

Summary
General Info

PubChem

PubChem Compound 126941

Name:	Methotrexate
PubChem Compound ID:	126941
Description:	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.
Molecular formula:	C₂₀H₂₂N₈O₅
Molecular weight:	454.44 g/mol
Synonyms:	SPBio_001094; 59-05-2; KBio2_002338; AIDS-006948; MTX; SPBio_002149; KBio1_000114; N-(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)-L-glutamic acid; CHEBI:6837; Methotrexate. show more » SPBio_001094; 59-05-2; KBio2_002338; AIDS-006948; MTX; SPBio_002149; KBio1_000114; N-(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)-L-glutamic acid; CHEBI:6837; Methotrexate; Methotrexate (JP15/USP); AIDS214679; folic acid antagonist; Tocris-1230; Amethopterin; Prestwick_322; 4-amino-N(10)-methylpteroylglutamic acid; 4-Amino-10-methylfolic acid; Bio1_000975; KBioGR_001172; Bio1_001464; Prestwick0_000135; MLS000049968; KBio2_007474; KBioSS_002341; AIDS006948; CL14377; N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid; AIDS-214679; N-[4-[[(2,4-Diamino-6-pteridinyl)methyl] methylamino]benzoyl]-L-glutamic acid;; C01937; Spectrum2_001077; NCGC00025060-01; Bio1_000486; Spectrum4_000616; SMR000112001; NSC740; Prestwick1_000135; KBio2_004906; EU-0100020; DivK1c_000114; D00142; Spectrum3_000497; NCIMech_000767; Spectrum_001836; Mexate (TN); KBio3_001493; NINDS_000114; Mexate show less «

DrugBank

Identification

Name:	Methotrexate
Name (isomeric):	DB00563
Drug Type:	small molecule
Description:	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.
Synonyms:	MTX; HDMTX; Methotrexate Sodium; Amethopterine; Methylaminopterinum; N-Bismethylpteroylglutamic Acid; Methylaminopterin; Methotrexat; Methopterin; Methotextrate. show more » MTX; HDMTX; Methotrexate Sodium; Amethopterine; Methylaminopterinum; N-Bismethylpteroylglutamic Acid; Methylaminopterin; Methotrexat; Methopterin; Methotextrate; Amethopterin; L-Amethopterin show less «
Brand:	Metatrexan, Trexall, Rheumatrex, Mexate, Abitrexate, Folex, Methotrate, Ledertrexate, Arbitrexate, Emtexate, Antifolan
Category:	Antimetabolites, Antimetabolites, Antineoplastic, Antineoplastic Agents, Abortifacient Agents, Enzyme Inhibitors, Abortifacient Agents, Nonsteroidal, Folic Acid Antagonists, Antirheumatic Agents, Immunosuppressive Agents, Dermatologic Agents, Nucleic Acid Synthesis Inhibitors
CAS number:	59-05-2

Pharmacology

Indication:	For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis.
Pharmacology:	Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is respon... show more » Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis. show less «
Mechanism of Action:	Methotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known.
Absorption:	Generally well absorbed with a mean bioavailability of about 60%.
Protein binding:	50%, primarily to albumin
Biotransformation:	Hepatic.
Route of elimination:	With IV administration, 80% to 90% of the administered dose is excreted unchanged in the urine within 24 hours. There is limited biliary excretion amounting to 10% or less of the administered dose.
Half Life:	Low doses: 3 to 10 hours; High doses: 8 to 15 hours.
Toxicity:	Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD₅₀=43mg/kg(orally in rat).
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals. Limit caffeine intake.

Milk appears to reduce its absorption.

Drug interaction:

Diclofenac	The NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Sulfathiazole	The sulfamide increases the toxicity of methotrexate
Amoxicillin	The penicillin increases the effect and toxicity of methotrexate
Clavulanate	The penicillin increases the effect and toxicity of methotrexate
Omeprazole	Omeprazole increases the levels of methotrexate

Diclofenac	The NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Sulfathiazole	The sulfamide increases the toxicity of methotrexate
Amoxicillin	The penicillin increases the effect and toxicity of methotrexate
Clavulanate	The penicillin increases the effect and toxicity of methotrexate
Omeprazole	Omeprazole increases the levels of methotrexate
Pivampicillin	The penicillin increases the effect and toxicity of methotrexate
Methicillin Acyl-Serine	The penicillin increases the effect and toxicity of methotrexate
Nabumetone	The NSAID, nabumetone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Tolmetin	Tolmetin may decrease the renal excretion of Methotrexate. Alternate therapy should be considered. Otherwise, monitor for hemotologic and renal toxicities.
Acitretin	Acitretin/etretinate increases the effect and toxicity of methotrexate
Sulfadimethoxine	The sulfamide increases the toxicity of methotrexate
Salsalate	The salicylate, salsalate, increases the effect and toxicity of methotrexate.
Fosphenytoin	The antineoplasic agent decreases the effect of hydantoin
Cisplatin	Cisplatin increases methotrexate toxicity
Ketoprofen	The NSAID, ketoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Fenoprofen	The NSAID, fenoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Ampicillin	The penicillin increases the effect and toxicity of methotrexate
Mephenytoin	The antineoplasic agent decreases the effect of hydantoin
Flucloxacillin	The penicillin increases the effect and toxicity of methotrexate
Meclofenamic acid	The NSAID, meclofenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Dicloxacillin	The penicillin increases the effect and toxicity of methotrexate
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Tiaprofenic acid	Tiaprofenic acid may decrease renal excretion of methotrexate. Consider alternate therapy or monitor for methotrexate toxicity.
Piperacillin	The penicillin increases the effect and toxicity of methotrexate
Ibuprofen	The NSAID, ibuprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Doxycycline	The tetracycline, doxycycline, may increase methotrexate toxicity.
Phenytoin	The antineoplasic agent decreases the effect of hydantoin
Sulfacytine	The sulfamide increases the toxicity of methotrexate
Piroxicam	The NSAID, piroxicam, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Sulfamethizole	The sulfamide increases the toxicity of methotrexate
Ketorolac	The NSAID, ketorolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Procarbazine	Increased nephrotoxicity with this combination
Carbenicillin	The penicillin increases the effect and toxicity of methotrexate
Sulindac	The NSAID, sulindac, may decrease the clearance methotrexate. Consider alternate therapy, especially in patients receiving high antineoplastic doses of methotrexate. Otherwise, monitor for hematologic and renal toxicities.
Sulfapyridine	The sulfamide increases the toxicity of methotrexate
Probenecid	Probenecid increases the effect and toxicity of methotrexate
Oxaprozin	The NSAID, oxaprozin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Rofecoxib	Rofecoxib increases the levels of methotrexate
Mezlocillin	The penicillin increases the effect and toxicity of methotrexate
Hydroxychloroquine	Hydroxychloroquine increases the effect and toxicity of methotrexate
Mefenamic acid	The NSAID, mefenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Naproxen	The NSAID, naproxen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Tetracycline	Tetracycline may increase methotrexate toxicity.
Trisalicylate-choline	The salicylate, trisalicylate-choline, increases the effect and toxicity of methotrexate.
Ticarcillin	The penicillin increases the effect and toxicity of methotrexate
Phenylbutazone	The NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Nafcillin	The penicillin increases the effect and toxicity of methotrexate
Diflunisal	The NSAID, diflunisal, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Trimethoprim	Trimethoprim may increase the adverse/toxic effects of Methotrexate (e.g. bone marrow suppression). Concomitant use should be avoided or closely monitored for Methotrexate toxicity.
Acetylsalicylic acid	Acetylsalicylic acid increases the effect and toxicity of methotrexate.
Etodolac	The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Sulfamethazine	The sulfamide increases the toxicity of methotrexate
Sulfamerazine	The sulfamide increases the toxicity of methotrexate
Sulfadoxine	The sulfamide increases the toxicity of methotrexate
Indomethacin	The NSAID, indomethacin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Salicylate-sodium	The salicylate, salicylate-sodium, increases the effect and toxicity of methotrexate.
Flurbiprofen	The NSAID, flurbiprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Sulfisoxazole	The sulfamide increases the toxicity of methotrexate
Magnesium salicylate	The salicylate, magnesium salicylate, increases the effect and toxicity of methotrexate.
Etretinate	Acitretin/etretinate increases the effect and toxicity of methotrexate
Cyclosporine	Cyclosporine may increase the effect and toxicity of methotrexate.
Bacampicillin	The penicillin increases the effect and toxicity of methotrexate
Penicillin G	The penicillin increases the effect and toxicity of methotrexate
Penicillin V	The penicillin increases the effect and toxicity of methotrexate
Cholestyramine	Decreased levels of methotrexate
Tenoxicam	Tenoxicam may increase the serum concentration of Methotrexate by reducing renal tubular secretion of Methotrexate. Monitor for changes in Methotrexate therapeutic and adverse effects if Tenoxicam is initiated, discontinued or dose changed.
Ciprofloxacin	Ciprofloxacine may decrease the metabolism of methotrexate. Monitor for changes adverse effects of methotrexate if ciprofloxacin is initiated.
Ethotoin	The antineoplasic agent decreases the effect of hydantoin
Sulfamethoxazole	The sulfamide increases the toxicity of methotrexate
Digoxin	The antineoplasic agent decreases the effect of digoxin
Sulfadiazine	The sulfamide increases the toxicity of methotrexate
Bismuth Subsalicylate	The salicylate, bismuth subsalicylate, increases the effect and toxicity of methotrexate.
Cloxacillin	The penicillin increases the effect and toxicity of methotrexate