Methotrexate (MTX)

==General information==
Class/mechanism: Folate analog, antimetabolite, interferes with DNA synthesis. Methotrexate inhibits dihydrofolic acid reductase, which catalyzes reactions that produce tetrahydrofolates, which are used in purine nucleotide and thymidylate synthesis.Methotrexate (MTX) tablet package insertMethotrexate (MTX) tablet package insert (locally hosted backup)Methotrexate (MTX) injection package insertMethotrexate (MTX) injection package insert (locally hosted backup)Methotrexate (Otrexup) subcutaneous injection package insertMethotrexate (Otrexup) subcutaneous injection package insert (locally hosted backup)Otrexup manufacturer's website
Route: IV, PO, IM, IT, SC, intraarterial
Extravasation: inflammitant
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information. 
==Toxicity==
===Monitoring of plasma levels===
# Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA. Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med. 1977 Sep 22;297(12):630-4. link to original article EuroPMC
===Reversal agents===
*Glucarpidase (Voraxaze) can be used to treat toxic plasma methotrexate concentrations (greater than 1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function
==Diseases for which it is established (work in progress)==
*Osteosarcoma
*Peripheral T-cell lymphoma
==Diseases for which it is used==
*Acute lymphoblastic leukemia, infant
*Acute myeloid leukemia
*Acute promyelocytic leukemia
*B-cell acute lymphoblastic leukemia
*Breast cancer
*CNS leukemia
*Desmoid tumors
*Gestational trophoblastic neoplasia
*Head and neck cancer
*Hemophagocytic lymphohistiocytosis
*Langerhans cell histiocytosis
*Large granular lymphocytic leukemia
*Medulloblastoma
*Non-Hodgkin lymphoma
**Adult T-cell leukemia-lymphoma
**Burkitt lymphoma
**CNS lymphoma
**Cutaneous T-cell lymphoma
**Diffuse large B-cell lymphoma
**Extranodal NK- and T-cell lymphoma, nasal type
**HIV-associated lymphoma
**Mantle cell lymphoma
**NK- and T-cell lymphoma
*Penile cancer
*Testicular cancer
*T-cell acute lymphoblastic leukemia
*Urothelial carcinoma
**Bladder cancer
==Diseases for which it was used==
*Colon cancer
*Follicular lymphoma
*Gastric cancer
*Hodgkin lymphoma
*Non-small cell lung cancer
*Ovarian cancer
*Prostate cancer
*Small cell lung cancer
==Patient drug information==
*Methotrexate (Otrexup) subcutaneous injection package insert
*Methotrexate (MTX) patient drug information (Chemocare)Methotrexate (MTX) patient drug information (Chemocare)
*Methotrexate (MTX) patient drug information (UpToDate)Methotrexate (MTX) patient drug information (UpToDate)
==History of changes in FDA indication==
* 1953-12-07: Initial FDA approval
* Uncertain date: Methotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. (No supporting studies are cited)
*Uncertain date: In acute lymphocytic leukemia, methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. (No supporting studies are cited)
*Uncertain date: Methotrexate is also indicated in the treatment of meningeal leukemia. (No supporting studies are cited)
*Uncertain date: Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma), and lung cancer, particularly squamous cell and small cell types. (No supporting studies are cited)
*Uncertain date: Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas. (No supporting studies are cited)
*Uncertain date: Methotrexate in high doses followed by leucovorin rescue in combination with other chemotherapeutic agents is effective in prolonging relapse-free survival in patients with non- metastatic osteosarcoma who have undergone surgical resection or amputation for the primary tumor. (No supporting studies are cited)
==History of changes in EMA indication==
*1962-01-01: EURD
==Also known as==
*Generic names: amethopterin, MTX
*Brand names:
Synonyms 	Synonyms 	Synonyms 	Synonyms 	Synonyms 	Synonyms 	Synonyms 	Synonyms
Abitrexate 	Alltrex 	Antifolan 	Artrait 	Biometrox 	Biotrexate 	Caditrex 	Cytotrexate
Ebetrexat 	Emthexat 	Emthexate 	Ervemin 	Farmitrexat 	Fauldmetro 	Folex PFS 	Folitrax
Hextrate 	Ifamet 	Imutrex 	Jylamvo 	Ledertrexate	Ledertrexato 	Lumexon 	Matrex
Maxtrex 	Medsatrexate	Merex 	Metex 	Methobax 	Methoblastin 	Methorex 	Methotrexaat
Methotrexat	Methotrexato	Methotrexatum	Meticil 	Metolate 	Metotressato 	Metotrexate	Metotrexato
Metotrexol 	Metrex 	Metrexan 	Metrexato 	Metrotex 	Mexate 	Miantrex CS	Neometho
Neotrexate 	Nordimet 	Novatrex 	Oncotrex 	O Trexat 	Pharmatrexate	Remtrex 	Reumatrex
Rextop 	Rheumatrex 	Tecnomet 	Texate 	Texorate 	Tratoben 	Tremetex 	Trexall
Trexan 	Trexeron 	Trixilem 	Unitrexate	Xatmep 	Zexate 	 	
==References==
Category:Drugs
Category:Intramuscular medications
Category:Intrathecal medications
Category:Intravenous medications
Category:Oral medications
Category:Subcutaneous medications
Category:Inflammitant
Category:Antimetabolites
Category:Antifolates
Category:Immunosuppressants
Category:Acute lymphoblastic leukemia, infant medications
Category:Acute myeloid leukemia medications
Category:Acute promyelocytic leukemia medications
Category:Adult T-cell leukemia-lymphoma medications
Category:B-cell acute lymphoblastic leukemia medications
Category:Bladder cancer medications
Category:Breast cancer medications
Category:Burkitt lymphoma medications
Category:CNS lymphoma medications
Category:CNS leukemia medications
Category:Cutaneous T-cell lymphoma medications
Category:Desmoid tumor medications
Category:Diffuse large B-cell lymphoma medications
Category:Extranodal NK- and T-cell lymphoma, nasal type medications
Category:Gestational trophoblastic neoplasia medications
Category:Head and neck cancer medications
Category:Hemophagocytic lymphohistiocytosis medications
Category:HIV-associated lymphoma medications
Category:Langerhans cell histiocytosis medications
Category:Large granular lymphocytic leukemia medications
Category:Mantle cell lymphoma medications
Category:Medulloblastoma medications
Category:NK- and T-cell lymphoma medications
Category:Osteosarcoma medications
Category:Penile cancer medications 
Category:Peripheral T-cell lymphoma medications
Category:Testicular cancer medications
Category:T-cell acute lymphoblastic leukemia medications
Category:Urothelial carcinoma medications
Category:Colon cancer medications (historic)
Category:Follicular lymphoma medications (historic)
Category:Gastric cancer medications (historic)
Category:Classical Hodgkin lymphoma medications (historic)
Category:Non-small cell lung cancer medications (historic)
Category:Ovarian cancer medications (historic)
Category:Prostate cancer medications (historic)
Category:Small cell lung cancer medications (historic)
Category:FDA approved in 1953
Category:EMA approved in 1962
Category:WHO Essential Cancer Medicine