Methotrexate

"Amethopterin" redirects here. Not to be confused with Aminopterin.

Methotrexate
Clinical data
Pronunciation/ˌmɛθəˈtrɛkˌseɪt, ˌmiː-, -θoʊ-/ ⓘ[1][2][3]
Trade namesTrexall, Rheumatrex, Otrexup, others[4]
Other namesMTX, amethopterin
AHFS/Drugs.comMonograph
MedlinePlusa682019
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth, intravenous, intramuscular, subcutaneous, intrathecal
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)
  • US: WARNING[5]Rx-only
  • EU: Rx-only[6]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability60% at lower doses, less at higher doses.[7]
Protein binding35–50% (parent drug),[7] 91–93% (7-hydroxymethotrexate)[8]
MetabolismHepatic and intracellular[7]
Elimination half-life3–10 hours (lower doses), 8–15 hours (higher doses)[7]
ExcretionUrine (80–100%), feces (small amounts)[7][8]
Identifiers
  • (2S)-2-[(4-{[(2,4-Diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)amino]pentanedioic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.000.376 Edit this at Wikidata
Chemical and physical data
FormulaC20H22N8O5
Molar mass454.447 g·mol−1
3D model (JSmol)
  • O=C([C@H](CCC(O)=O)NC(C1=CC=C(N(CC2=CN=C(N=C(N)N=C3N)C3=N2)C)C=C1)=O)O
  • InChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1 checkY
  • Key:FBOZXECLQNJBKD-ZDUSSCGKSA-N checkY
  (verify)

Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant.[4] It is used to treat cancer, autoimmune diseases, and ectopic pregnancies.[4] Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma.[4] Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease.[4] It can be given by mouth or by injection.[4]

Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth.[4] Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes.[4] People on long-term treatment should be regularly checked for side effects.[4] It is not safe during breastfeeding.[4] In those with kidney problems, lower doses may be needed.[4] It acts by blocking the body's use of folic acid.[4]

Methotrexate was first made in 1947 and initially was used to treat cancer, as it was less toxic than the then-current treatments.[9] In 1956 it provided the first cures of a metastatic cancer.[10] It is on the World Health Organization's List of Essential Medicines.[11] Methotrexate is available as a generic medication.[4] In 2022, it was the 132nd most commonly prescribed medication in the United States, with more than 4 million prescriptions.[12][13]

A photoswitchable analog of methotrexate has been developed (phototrexate) for photoactivated chemotherapy with localized illumination and reduced adverse effects.[14] Using proteasome-targeting technology, the MTX-PROTAC versortrexate (VSTX) selectively degrades dihydrofolate reductase (DHFR), the primary target of MTX. [15]

  1. ^ "methotrexate – definition of methotrexate in English from the Oxford dictionary". OxfordDictionaries.com. Archived from the original on 22 October 2012. Retrieved 20 January 2016.
  2. ^ "methotrexate". Merriam-Webster.com Dictionary. Merriam-Webster.
  3. ^ "methotrexate". Dictionary.com Unabridged (Online). n.d.
  4. ^ a b c d e f g h i j k l m "Methotrexate". The American Society of Health-System Pharmacists. Archived from the original on 8 October 2016. Retrieved 22 August 2016.
  5. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  6. ^ "Jylamvo EPAR". European Medicines Agency. 29 March 2017. Retrieved 25 June 2024.
  7. ^ a b c d e "Trexall, Rheumatrex (methotrexate) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 8 February 2014. Retrieved 12 April 2014.
  8. ^ a b Bannwarth B, Labat L, Moride Y, Schaeverbeke T (January 1994). "Methotrexate in rheumatoid arthritis. An update". Drugs. 47 (1): 25–50. doi:10.2165/00003495-199447010-00003. PMID 7510620. S2CID 46974070.
  9. ^ Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 251. ISBN 9780470015520. Archived from the original on 16 February 2017.
  10. ^ "Today's anti-cancer tools are ever better wielded". The Economist. 14 September 2017. Retrieved 16 September 2017.
  11. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  12. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  13. ^ "Methotrexate Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  14. ^ Matera C, Gomila AM, Camarero N, Libergoli M, Soler C, Gorostiza P (November 2018). "Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy". Journal of the American Chemical Society. 140 (46): 15764–15773. doi:10.1021/jacs.8b08249. hdl:2445/126377. PMID 30346152.
  15. ^ Rana, S., Dranchak, P., Dahlin, J.L., Lamy, L., Li, W., Oliphant, E., et al. (2024). "Methotrexate-based PROTACs as DHFR-specific chemical probes". Cell Chem Biol. 31 (2): 221–33. doi:10.1016/j.chembiol.2023.09.014. PMID 37875111.