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.
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 such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Toxicity

Monitoring of plasma levels

1. 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 PubMed

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 (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
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	Zexate