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Methotrexate

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"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]

Medical uses

[edit]

Chemotherapy

[edit]

Methotrexate was originally developed and continues to be used for chemotherapy, either alone or in combination with other agents. It is effective for the treatment of a number of cancers, including solid tumours of breast, head and neck, lung, bladder, as well as acute lymphocytic leukemias, non-Hodgkin's lymphoma, osteosarcoma, and choriocarcinoma and other trophoblastic neoplasms. It is also used in the treatment of aggressive fibromatosis (desmoid tumor).[4][16][17]

Autoimmune disorders

[edit]

Although originally designed as a chemotherapy drug, in lower doses methotrexate is a generally safe and well-tolerated drug in the treatment of certain autoimmune diseases.

Methotrexate is used as a disease-modifying treatment for a number of autoimmune diseases in adults, including rheumatoid arthritis,[18] psoriasis and psoriatic arthritis, reactive arthritis, enteropathic arthritis, myositis, systemic sclerosis, lupus, sarcoidosis, Crohn's disease,[19][20] and many forms of vasculitis. In children, it can be used for juvenile dermatomyositis, juvenile idiopathic arthritis, uveitis and localised scleroderma.[21][22][23]

Methotrexate is one of the first-line therapies for the treatment of rheumatoid arthritis. Weekly doses of 5 to 25mg were found by a Cochrane review to be beneficial for 12–52 weeks duration of therapy, though it is used longer-term in clinical practice. Discontinuation rates are as high as 16% due to adverse effects.[24][21][25][26]

Use of low doses of methotrexate together with NSAIDs such as aspirin or analgesics such as paracetamol is relatively safe in people being treated for rheumatoid arthritis, with appropriate monitoring.[27] Methotrexate is also sometimes used in combination with other conventional DMARDs, such as sulfasalazine and hydroxychloroquine.[28]

Studies and reviews have found that most rheumatoid arthritis patients treated with methotrexate for up to one year had less pain, functioned better, had fewer swollen and tender joints, and had less disease activity overall as reported by themselves and their doctors.[citation needed] X-rays also showed that the progress of the disease slowed or stopped in many people receiving methotrexate, with the progression being completely halted in about 30% of those receiving the drug.[29] Those individuals with rheumatoid arthritis treated with methotrexate have been found to have a lower risk of cardiovascular events such as myocardial infarctions and strokes.[30]

Results of a systematic review exploring the comparative effectiveness of treatments of early rheumatoid arthritis show that treatment efficacy can be improved with combination therapy with anti-TNF or other biologic medications, compared with methotrexate monotherapy.[18][31]

Likewise, a 2016 study found the use of methotrexate, in combination with anti-TNF agents, has been shown to be effective for the treatment of ulcerative colitis.[32]

Methotrexate has also been used for multiple sclerosis[4] and is used occasionally in systemic lupus erythematosus, with tentative evidence to support such use.[33]

Atopic dermatitis

[edit]

Along with other immunosuppressants, methotrexate is used to treat severe atopic dermatitis (eczema).[34][35][36]

During pregnancy

[edit]

Methotrexate is an abortifacient and is used to treat ectopic pregnancies, provided the fallopian tube has not ruptured.[4][37] Methotrexate with dilation and curettage is used to treat molar pregnancy. Rarely, it is used in combination with misoprostol to abort intrauterine pregnancies.[38]

Administration

[edit]

Methotrexate can be given by mouth or by injection (intramuscular, intravenous, subcutaneous, or intrathecal).[4] Doses are usually taken weekly, not daily, to limit toxicity.[4] Routine monitoring of the complete blood count, liver function tests, and creatinine are recommended.[4] Measurements of creatinine are recommended at least every two months.[4]

Folic acid is commonly co-prescribed with methotrexate to minimise the risk of adverse effects.[23]

Adverse effects

[edit]

The most common adverse effects include hepatotoxicity, stomatitis, blood abnormalities (leukopenia, anaemia and thrombocytopenia), increased risk of infection, hair loss, nausea, reduced appetite, abdominal pain, diarrhea, fatigue, fever, dizziness, drowsiness, headache, acute pneumonitis and renal impairment.[4][21][39][16] Methotrexate can also cause mucositis.[40]

Methotrexate pneumonitis is a rare complication of therapy, and appears to be reducing in frequency in most recent rheumatoid arthritis treatment trials.[41] In the context of rheumatoid arthritis interstitial lung disease, methotrexate treatment may be associated with a lower incidence of ILD over time.[citation needed]

Methotrexate is teratogenic and it is advised stop taking it at least 4 weeks before becoming pregnant and it should be avoided during pregnancy (pregnancy category X) and while breastfeeding.[42] Guidelines have been updated to state that it is safe for a male partner to take at any point while trying to conceive.[43]

Central nervous system reactions to methotrexate have been reported, especially when given via the intrathecal route (directly into the cerebrospinal fluid), which include myelopathies and leukoencephalopathies. It has a variety of cutaneous side effects, particularly when administered in high doses.[44]

Another little-understood but serious possible adverse effect of methotrexate is neurological damage and memory loss.[45] Neurotoxicity may result from the drug crossing the blood–brain barrier and damaging neurons in the cerebral cortex. People with cancer who receive the medication often nickname these effects "chemo brain" or "chemo fog".[45]

Drug interactions

[edit]

Penicillins may decrease the elimination of methotrexate, so increase the risk of toxicity.[4] While they may be used together, increased monitoring is recommended.[4] The aminoglycosides neomycin and paromomycin have been found to reduce gastrointestinal (GI) absorption of methotrexate.[46] Probenecid inhibits methotrexate excretion, which increases the risk of methotrexate toxicity.[46] Likewise, retinoids and trimethoprim have been known to interact with methotrexate to produce additive hepatotoxicity and haematotoxicity, respectively.[46]

Other immunosuppressants like cyclosporins may potentiate methotrexate's haematologic effects, hence potentially leading to toxicity.[46] NSAIDs have also been found to fatally interact with methotrexate in numerous case reports.[46] Nitrous oxide potentiating the haematological toxicity of methotrexate has also been documented.[46]

Proton-pump inhibitors such as omeprazole and the anticonvulsant valproate have been found to increase the plasma concentrations of methotrexate, as have nephrotoxic agents such as cisplatin, the GI drug colestyramine, and dantrolene.[46]

Vaccine interactions

[edit]
Methotrexate might reduce the effectiveness of COVID-19 vaccines.

Taking methotrexate can reduce the effectiveness of vaccinations against various diseases, such as influenza and hepatitis A. It does this by blunting the immune response of the body to the vaccine.[47][48]

Methotrexate also dampens the immune response to COVID-19 vaccines, making them less effective.[49][50] Pausing methotrexate for two weeks following COVID-19 vaccination may result in improved immunity. Not taking the medicine for two weeks might result in a minor increase of inflammatory disease flares in some people.[47][51][52]

Mechanism of action

[edit]
The chemical structures of folic acid and methotrexate highlighting the differences between these two substances (amidation of pyrimidone and methylation of secondary amine)
The coenzyme folic acid (top) and the anticancer drug methotrexate (bottom) are very similar in structure. As a result, methotrexate is a competitive inhibitor of many enzymes that use folates.
Methotrexate (green) complexed into the active site of DHFR (blue)

Methotrexate is an antimetabolite of the antifolate type. It is thought to affect cancer and rheumatoid arthritis by two different pathways. For cancer, methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis.[53][54] The affinity of methotrexate for DHFR is about 1000-fold that of dihydrofolate. DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate.[53] Tetrahydrofolate is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis.[53] Also, folate is essential for de-novo purine base biosynthesis, so synthesis will be inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins.[53]

For the treatment of rheumatoid arthritis, inhibition of DHFR is not thought to be the main mechanism, but rather multiple mechanisms appear to be involved, including the inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine; inhibition of T cell activation and suppression of intercellular adhesion molecule expression by T cells; selective down-regulation of B cells; increasing CD95 sensitivity of activated T cells; and inhibition of methyltransferase activity, leading to deactivation of enzyme activity relevant to immune system function.[55][56] Another mechanism of MTX is the inhibition of the binding of interleukin 1-beta to its cell surface receptor.[57] Thereby, it acts as anticytokine.

History

[edit]
See also: History of cancer chemotherapy
Image shows open bottle of methotrexate drug—one of the first chemotherapeutic drugs used in the early 1950s

In 1947, a team of researchers led by Sidney Farber showed aminopterin, a chemical analogue of folic acid developed by Yellapragada Subbarao of Lederle, could induce remission in children with acute lymphoblastic leukemia. The development of folic acid analogues had been prompted by the discovery that the administration of folic acid worsened leukemia, and that a diet deficient in folic acid could, conversely, produce improvement; the mechanism of action behind these effects was still unknown at the time.[58] Other analogues of folic acid were in development, and by 1950, methotrexate (then known as amethopterin) was being proposed as a treatment for leukemia.[59] Animal studies published in 1956 showed the therapeutic index of methotrexate was better than that of aminopterin, and clinical use of aminopterin was thus abandoned in favor of methotrexate.[citation needed]

In 1951, Jane C. Wright demonstrated the use of methotrexate in solid tumors, showing remission in breast cancer.[60] Wright's group was the first to demonstrate use of the drug in solid tumors, as opposed to leukemias, which are a cancer of the marrow. Min Chiu Li and his collaborators then demonstrated complete remission in women with choriocarcinoma and chorioadenoma in 1956,[61] and in 1960 Wright et al. produced remissions in mycosis fungoides.[62][63]

References

[edit]
  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 n o p q r s t u v w "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.
  16. ^ a b "Methotrexate 2.5 mg Tablets - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Retrieved 19 February 2023.
  17. ^ Lee YS, Joo MW, Shin SH, Hong S, Chung YG (January 2024). "Current Treatment Concepts for Extra-Abdominal Desmoid-Type Fibromatosis: A Narrative Review". Cancers. 16 (2): 273. doi:10.3390/cancers16020273. PMC 10813957. PMID 38254764.
  18. ^ a b Donahue KE, Gartlehner G, Schulman ER, Jonas B, Coker-Schwimmer E, Patel SV, et al. (2018). Drug Therapy for Early Rheumatoid Arthritis: A Systematic Review Update. AHRQ Comparative Effectiveness Reviews. Rockville (MD): Agency for Healthcare Research and Quality (US). PMID 30199187.
  19. ^ Herfarth HH, Long MD, Isaacs KL (2012). "Methotrexate: underused and ignored?". Digestive Diseases. 30 (Suppl 3): 112–8. doi:10.1159/000342735. PMC 4629813. PMID 23295701.
  20. ^ Boehm IB, Boehm GA, Bauer R (1998). "Management of cutaneous lupus erythematosus with low-dose methotrexate: indication for modulation of inflammatory mechanisms". Rheumatol Int. 18 (2): 59–62. doi:10.1515/cclm.1993.31.10.667. PMID 9782534. S2CID 25311594.
  21. ^ a b c Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  22. ^ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
  23. ^ a b "Methotrexate". Versus Arthritis. Retrieved 19 February 2023.
  24. ^ Lopez-Olivo MA, Siddhanamatha HR, Shea B, Tugwell P, Wells GA, Suarez-Almazor ME (June 2014). "Methotrexate for treating rheumatoid arthritis". The Cochrane Database of Systematic Reviews. 2014 (6): CD000957. doi:10.1002/14651858.CD000957.pub2. PMC 7047041. PMID 24916606.
  25. ^ Cronstein BN (June 2005). "Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis". Pharmacological Reviews. 57 (2): 163–72. doi:10.1124/pr.57.2.3. PMID 15914465. S2CID 1643606.
  26. ^ American Rheumatoid Arthritis Guidelines (February 2002). "Guidelines for the management of rheumatoid arthritis: 2002 Update". Arthritis and Rheumatism. 46 (2): 328–46. doi:10.1002/art.10148. PMID 11840435.
  27. ^ Colebatch AN, Marks JL, Edwards CJ (November 2011). "Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)". The Cochrane Database of Systematic Reviews (11): CD008872. doi:10.1002/14651858.CD008872.pub2. PMID 22071858.
  28. ^ "Methotrexate and its use in rheumatoid arthritis (RA)". NRAS. Retrieved 19 February 2023.
  29. ^ Weinblatt ME (2013). "Methotrexate in rheumatoid arthritis: a quarter century of development". Transactions of the American Clinical and Climatological Association. 124: 16–25. PMC 3715949. PMID 23874006.
  30. ^ Marks JL, Edwards CJ (June 2012). "Protective effect of methotrexate in patients with rheumatoid arthritis and cardiovascular comorbidity". Therapeutic Advances in Musculoskeletal Disease. 4 (3): 149–57. doi:10.1177/1759720X11436239. PMC 3400102. PMID 22850632.
  31. ^ Donahue KE, Schulman ER, Gartlehner G, Jonas BL, Coker-Schwimmer E, Patel SV, et al. (October 2019). "Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis". Journal of General Internal Medicine. 34 (10): 2232–2245. doi:10.1007/s11606-019-05230-0. PMC 6816735. PMID 31388915.
  32. ^ Herfarth HH (1 January 2016). "Methotrexate for Inflammatory Bowel Diseases - New Developments". Digestive Diseases. 34 (1–2): 140–6. doi:10.1159/000443129. PMC 4820247. PMID 26981630.
  33. ^ Tsang-A-Sjoe MW, Bultink IE (2015). "Systemic lupus erythematosus: review of synthetic drugs". Expert Opinion on Pharmacotherapy. 16 (18): 2793–806. doi:10.1517/14656566.2015.1101448. PMID 26479437. S2CID 36049926. ] To date, three small [86–88] RCTs in SLE patients have been published, including in total 76 patients in the active arm
  34. ^ Paolino A, Alexander H, Broderick C, Flohr C (May 2023). "Non-biologic systemic treatments for atopic dermatitis: Current state of the art and future directions". Clinical and Experimental Allergy. 53 (5): 495–510. doi:10.1111/cea.14301. PMID 36949024.
  35. ^ Flohr C, Rosala-Hallas A, Jones AP, Beattie P, Baron S, Browne F, et al. (November 2023). "Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial". The British Journal of Dermatology. 189 (6): 674–684. doi:10.1093/bjd/ljad281. PMID 37722926.
  36. ^ Eczema in children: uncertainties addressed (Report). NIHR Evidence. 19 March 2024. doi:10.3310/nihrevidence_62438.
  37. ^ Mol F, Mol BW, Ankum WM, van der Veen F, Hajenius PJ (2008). "Current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal ectopic pregnancy: a systematic review and meta-analysis". Human Reproduction Update. 14 (4): 309–19. doi:10.1093/humupd/dmn012. PMID 18522946.
  38. ^ "Medical abortion". Mayo Clinic. Retrieved 10 July 2022.
  39. ^ "BNF is only available in the UK". NICE. Retrieved 19 February 2023.
  40. ^ Oliff A, Bleyer WA, Poplack DG (1 September 1979). "Methotrexate-induced oral mucositis and salivary methotrexate concentrations". Cancer Chemotherapy and Pharmacology. 2 (3): 225–226. doi:10.1007/BF00258300. PMID 313282. S2CID 6273303.
  41. ^ Fragoulis GE, Nikiphorou E, Larsen J, Korsten P, Conway R (2019). "Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment". Frontiers in Medicine. 6: 238. doi:10.3389/fmed.2019.00238. PMC 6819370. PMID 31709258.
  42. ^ Gromnica-Ihle E, Krüger K (1 September 2010). "Use of methotrexate in young patients with respect to the reproductive system". Clinical and Experimental Rheumatology. 28 (5 Suppl 61): S80-4. PMID 21044438.
  43. ^ Russell MD, Dey M, Flint J, Davie P, Allen A, Crossley A, et al. (BSR Standards, Audit and Guidelines Working Group) (November 2022). "Executive Summary: British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids". Rheumatology. 62 (4): 1370–1387. doi:10.1093/rheumatology/keac558. PMC 10070067. PMID 36318965.
  44. ^ Scheinfeld N (December 2006). "Three cases of toxic skin eruptions associated with methotrexate and a compilation of methotrexate-induced skin eruptions". Dermatology Online Journal. 12 (7): 15. doi:10.5070/D30NQ2C0BX. PMID 17459301.
  45. ^ a b Hafner DL (August 2009). "Lost in the fog: understanding "chemo brain"". Nursing. 39 (8): 42–5. doi:10.1097/01.nurse.0000358574.56241.2f. PMID 19633502. S2CID 9456346.
  46. ^ a b c d e f g Brayfield A, ed. (6 January 2014). "Methotrexate". Martindale: The Complete Drug Reference. Pharmaceutical Press. Retrieved 12 April 2014.
  47. ^ a b Wroński J, Ciechomska M, Kuca-Warnawin E (September 2023). "Impact of methotrexate treatment on vaccines immunogenicity in adult rheumatological patients - Lessons learned from the COVID-19 pandemic". Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 165: 115254. doi:10.1016/j.biopha.2023.115254. PMID 37542854.
  48. ^ Bass AR, Chakravarty E, Akl EA, Bingham CO, Calabrese L, Cappelli LC, et al. (March 2023). "2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases". Arthritis Care & Research. 75 (3): 449–464. doi:10.1002/acr.25045. PMC 10291822. PMID 36597813.
  49. ^ Al-Haideri MT, Mannani R, Kaboli R, Gharebakhshi F, Darvishzadehdeldari S, Tahmasebi S, et al. (August 2023). "The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence". Transplant Immunology. 79: 101858. doi:10.1016/j.trim.2023.101858. PMC 10205646. PMID 37236514.
  50. ^ "A pause in methotrexate treatment boosted the immune response to the COVID-19 vaccine". NIHR Evidence. National Institute for Health and Care Research. 26 January 2023. doi:10.3310/nihrevidence_56391.
  51. ^ Imran M, Ali S, Ibrahim AA, Amjad A, Tanveer A, Khalil S, et al. (July 2024). "Effect of methotrexate hold on COVID-19 vaccine response in the patients with autoimmune inflammatory disorders: a systematic review and meta-analysis". Clinical Rheumatology. 43 (7): 2203–2214. doi:10.1007/s10067-024-07013-3. PMID 38802670.
  52. ^ Abhishek A, Peckham N, Pade C, Gibbons JM, Cureton L, Francis A, et al. (February 2024). "Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial". The Lancet. Rheumatology. 6 (2): e92–e104. doi:10.1016/S2665-9913(23)00298-9. PMID 38267107.
  53. ^ a b c d Rajagopalan PT, Zhang Z, McCourt L, Dwyer M, Benkovic SJ, Hammes GG (October 2002). "Interaction of dihydrofolate reductase with methotrexate: ensemble and single-molecule kinetics". Proceedings of the National Academy of Sciences of the United States of America. 99 (21): 13481–6. Bibcode:2002PNAS...9913481R. doi:10.1073/pnas.172501499. PMC 129699. PMID 12359872.
  54. ^ Goodsell DS (August 1999). "The molecular perspective: methotrexate". The Oncologist. 4 (4): 340–1. doi:10.1634/theoncologist.4-4-340. PMID 10476546.
  55. ^ Wessels JA, Huizinga TW, Guchelaar HJ (March 2008). "Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis". Rheumatology. 47 (3): 249–55. doi:10.1093/rheumatology/kem279. PMID 18045808.
  56. ^ Böhm I (June 2004). "Increased peripheral blood B-cells expressing the CD5 molecules in association to autoantibodies in patients with lupus erythematosus and evidence to selectively down-modulate them". Biomedicine & Pharmacotherapy. 58 (5): 338–43. doi:10.1016/j.biopha.2004.04.010. PMID 15194170.
  57. ^ Brody M, Böhm I, Bauer R (October 1993). "Mechanism of action of methotrexate: experimental evidence that methotrexate blocks the binding of interleukin 1 beta to the interleukin 1 receptor on target cells". European Journal of Clinical Chemistry and Clinical Biochemistry. 31 (10): 667–74. CiteSeerX 10.1.1.633.8921. doi:10.1515/cclm.1993.31.10.667. PMID 8292668. S2CID 25311594.
  58. ^ Bertino JR (2000). "Methotrexate: historical aspects". In Cronstein BN, Bertino JR (eds.). Methotrexate. Basel: Birkhäuser. ISBN 978-3-7643-5959-1.[page needed]
  59. ^ Meyer LM, Miller FR, Rowen MJ, Bock G, Rutzky J (September 1950). "Treatment of acute leukemia with amethopterin (4-amino, 10-methyl pteroyl glutamic acid)". Acta Haematologica. 4 (3): 157–67. doi:10.1159/000203749. PMID 14777272.
  60. ^ Wright JC, Prigot A, Wright B, Weintraub S, Wright LT (July 1951). "An evaluation of folic acid antagonists in adults with neoplastic diseases: a study of 93 patients with incurable neoplasms". Journal of the National Medical Association. 43 (4): 211–40. PMC 2616951. PMID 14850976.
  61. ^ Hertz R, Li MC, Spencer DB (November 1956). "Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma". Proceedings of the Society for Experimental Biology and Medicine. 93 (2): 361–6. doi:10.3181/00379727-93-22757. PMID 13379512. S2CID 22939197.
  62. ^ Wright JC, Gumport SL, Golomb FM (November 1960). "Remissions produced with the use of Methotrexate in patients with mycosis fungoides". Cancer Chemotherapy Reports. 9: 11–20. PMID 13786791.
  63. ^ Wright JC, Lyons MM, Walker DG, Golomb FM, Gumport SL, Medrek TJ (August 1964). "Observations on the Use of Cancer Chemotherapeutic Agents in Patients With Mycosis Fungoides". Cancer. 17 (8): 1045–62. doi:10.1002/1097-0142(196408)17:8<1045::AID-CNCR2820170811>3.0.CO;2-S. PMID 14202592.
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