Peringatan Keamanan

The oral LD50 in rats is 135mg/kg and in mice is 146mg/kg.L7204

Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding.L7180 In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase.L7180

Methotrexate

DB00563

small molecule approved

Deskripsi

Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis.A180322 This inhibition leads to suppression of inflammation as well as prevention of cell division.A180322 Because of these effects, methotrexate is often used to treat inflammation caused by arthritis or to control cell division in neoplastic diseases such as breast cancer and non-Hodgkin's lymphoma.A180322,L7144,L7147,L7150,L7180

Due to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments.L7180

Methotrexate was granted FDA approval on 7 December 1953.L7198

Struktur Molekul 2D

Berat 454.4393
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half life of low dose methotrexate is 3 to 10 hours in adults.[L7144] The half life for high dose methotrexate is 8 to 15 hours.[L7147] Pediatric patients taking methotrexate for acute lymphoblastic anemia experience a terminal half life of 0.7 to 5.8 hours.[L7144] Pediatric patients taking methotrexate for juvenile idiopathic arthritis experience a half life of 0.9 to 2.3 hours.[L7144]
Volume Distribusi The volume of distribution of methotrexate at steady state is approximately 1L/kg.[A180322]
Klirens (Clearance) Methotrexate clearance varies widely between patients and decreases with increasing doses.[A180400] Currently, predicting clearance of methotrexate is difficult and exceedingly high serum levels of methotrexate can still occur when all precautions are taken.[A180400]

Absorpsi

Methotrexate has a bioavailability of 64-90%, though this decreases at oral doses above 25mg due to saturation of the carrier mediated transport of methotrexate.A180322. Methotrexate has a Tmax of 1 to 2 hours.A180322 oral doses of 10-15µg reach serum levels of 0.01-0.1µM.A180322

Metabolisme

Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues.A180322,L7180 Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate.A180322,L7180 A small amount of methotrexate is also converted to 7-hydroxymethotrexate.A180322,L7180

Rute Eliminasi

Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite.A180322 Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile.A180322

Farmakogenomik

2 Varian
ABCC2 (None)

Patients with this genotype have increased risk of toxicity with methotrexate.

MTHFR (rs1801133)

Patients with this genotype have increased risk of toxicity with methotrexate.

Interaksi Makanan

5 Data
  • 1. Avoid alcohol.
  • 2. Avoid milk and dairy products. Milk and dairy products reduce absorption.
  • 3. Exercise caution with St. John's Wort.
  • 4. Limit caffeine intake. Caffeine may reduce the effectiveness of methotrexate.
  • 5. Take with or without food.

Interaksi Obat

1773 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Methotrexate.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Methotrexate.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Methotrexate.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Methotrexate.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Methotrexate.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Methotrexate.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Methotrexate.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Methotrexate.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Methotrexate.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Methotrexate.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Methotrexate.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Methotrexate.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Methotrexate.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Methotrexate.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Methotrexate.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Methotrexate.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Methotrexate.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Methotrexate.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Methotrexate.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Methotrexate.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Methotrexate.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Methotrexate.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Methotrexate.
Cladribine Methotrexate may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Methotrexate.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Methotrexate.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Methotrexate.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Methotrexate.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Methotrexate.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Methotrexate.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Methotrexate.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Methotrexate.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Methotrexate.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Methotrexate.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Methotrexate.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Methotrexate.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Methotrexate.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Methotrexate.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Methotrexate.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Methotrexate.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Methotrexate.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Methotrexate.
Oxaliplatin The risk or severity of nephrotoxicity can be increased when Oxaliplatin is combined with Methotrexate.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Methotrexate.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Methotrexate.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Methotrexate.
Linezolid The risk or severity of adverse effects can be increased when Methotrexate is combined with Linezolid.
Clofarabine The risk or severity of adverse effects can be increased when Methotrexate is combined with Clofarabine.
Fludrocortisone The risk or severity of adverse effects can be increased when Methotrexate is combined with Fludrocortisone.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Methotrexate is combined with Mycophenolate mofetil.
Irinotecan The risk or severity of adverse effects can be increased when Methotrexate is combined with Irinotecan.
Dacarbazine The risk or severity of adverse effects can be increased when Methotrexate is combined with Dacarbazine.
Temozolomide The risk or severity of adverse effects can be increased when Methotrexate is combined with Temozolomide.
Penicillamine The risk or severity of adverse effects can be increased when Methotrexate is combined with Penicillamine.
Mechlorethamine The risk or severity of adverse effects can be increased when Methotrexate is combined with Mechlorethamine.
Azacitidine The risk or severity of adverse effects can be increased when Methotrexate is combined with Azacitidine.
Carboplatin The risk or severity of adverse effects can be increased when Methotrexate is combined with Carboplatin.
Dactinomycin The risk or severity of adverse effects can be increased when Methotrexate is combined with Dactinomycin.
Cytarabine The risk or severity of adverse effects can be increased when Methotrexate is combined with Cytarabine.
Hydroxyurea The risk or severity of adverse effects can be increased when Methotrexate is combined with Hydroxyurea.
Mycophenolic acid The risk or severity of adverse effects can be increased when Methotrexate is combined with Mycophenolic acid.
Thalidomide The metabolism of Methotrexate can be increased when combined with Thalidomide.
Melphalan The risk or severity of adverse effects can be increased when Methotrexate is combined with Melphalan.
Fludarabine The risk or severity of adverse effects can be increased when Methotrexate is combined with Fludarabine.
Trilostane The risk or severity of adverse effects can be increased when Methotrexate is combined with Trilostane.
Procarbazine The risk or severity of adverse effects can be increased when Methotrexate is combined with Procarbazine.
Arsenic trioxide The risk or severity of adverse effects can be increased when Methotrexate is combined with Arsenic trioxide.
Idarubicin The risk or severity of adverse effects can be increased when Methotrexate is combined with Idarubicin.
Estramustine The risk or severity of adverse effects can be increased when Methotrexate is combined with Estramustine.
Lomustine The risk or severity of adverse effects can be increased when Methotrexate is combined with Lomustine.
Eculizumab The risk or severity of adverse effects can be increased when Methotrexate is combined with Eculizumab.
Decitabine The risk or severity of adverse effects can be increased when Methotrexate is combined with Decitabine.
Nelarabine The risk or severity of adverse effects can be increased when Nelarabine is combined with Methotrexate.
Stepronin The risk or severity of adverse effects can be increased when Methotrexate is combined with Stepronin.
Castanospermine The risk or severity of adverse effects can be increased when Methotrexate is combined with Castanospermine.
Vorinostat The risk or severity of adverse effects can be increased when Methotrexate is combined with Vorinostat.
2-Methoxyethanol The risk or severity of adverse effects can be increased when Methotrexate is combined with 2-Methoxyethanol.
Brequinar The risk or severity of adverse effects can be increased when Methotrexate is combined with Brequinar.
Thiotepa The risk or severity of adverse effects can be increased when Methotrexate is combined with Thiotepa.
Aldosterone The risk or severity of adverse effects can be increased when Methotrexate is combined with Aldosterone.
Pirfenidone The risk or severity of adverse effects can be increased when Methotrexate is combined with Pirfenidone.
Belinostat The risk or severity of adverse effects can be increased when Methotrexate is combined with Belinostat.
Trabectedin The risk or severity of adverse effects can be increased when Methotrexate is combined with Trabectedin.
Interferon alfa The risk or severity of adverse effects can be increased when Methotrexate is combined with Interferon alfa.
Glatiramer The risk or severity of adverse effects can be increased when Methotrexate is combined with Glatiramer.
Briakinumab The risk or severity of adverse effects can be increased when Methotrexate is combined with Briakinumab.
Human interferon omega-1 The risk or severity of adverse effects can be increased when Methotrexate is combined with Human interferon omega-1.
Panobinostat The risk or severity of adverse effects can be increased when Methotrexate is combined with Panobinostat.
Mepolizumab The risk or severity of adverse effects can be increased when Methotrexate is combined with Mepolizumab.
Abetimus The risk or severity of adverse effects can be increased when Methotrexate is combined with Abetimus.
Belatacept The risk or severity of adverse effects can be increased when Methotrexate is combined with Belatacept.
Cabazitaxel The risk or severity of adverse effects can be increased when Methotrexate is combined with Cabazitaxel.
Pralatrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Pralatrexate.
Wortmannin The risk or severity of adverse effects can be increased when Methotrexate is combined with Wortmannin.
Eribulin The risk or severity of adverse effects can be increased when Methotrexate is combined with Eribulin.
Ruxolitinib The risk or severity of adverse effects can be increased when Methotrexate is combined with Ruxolitinib.
Belimumab The risk or severity of adverse effects can be increased when Methotrexate is combined with Belimumab.
Carfilzomib The risk or severity of adverse effects can be increased when Methotrexate is combined with Carfilzomib.
Tofacitinib The risk or severity of adverse effects can be increased when Methotrexate is combined with Tofacitinib.
Ponatinib The risk or severity of adverse effects can be increased when Methotrexate is combined with Ponatinib.

Target Protein

Thymidylate synthase TYMS
Reduced folate transporter SLC19A1
Proton-coupled folate transporter SLC46A1
Bifunctional purine biosynthesis protein ATIC ATIC
Dihydrofolate reductase DHFR

Referensi & Sumber

Artikel (PubMed)
  • PMID: 24284432
    Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26.
  • PMID: 17242415
    Przekop PR Jr, Tulgan H, Przekop AA, Glantz M: Adverse drug reaction to methotrexate: pharmacogenetic origin. J Am Osteopath Assoc. 2006 Dec;106(12):706-7.
  • PMID: 27210722
    Muhrez K, Benz-de Bretagne I, Nadal-Desbarats L, Blasco H, Gyan E, Choquet S, Montigny F, Emond P, Barin-Le Guellec C: Endogenous metabolites that are substrates of organic anion transporter's (OATs) predict methotrexate clearance. Pharmacol Res. 2017 Apr;118:121-132. doi: 10.1016/j.phrs.2016.05.021. Epub 2016 May 19.

Contoh Produk & Brand

Produk: 317 • International brands: 16
Produk
  • Ach-methotrexate
    Tablet • 2.5 mg • Oral • Canada • Generic • Approved
  • Apo-methotrexate
    Tablet • 2.5 mg • Oral • Canada • Generic • Approved
  • Auro-methotrexate
    Tablet • 2.5 mg • Oral • Canada • Generic • Approved
  • Eugia-methotrexate
    Tablet • 2.5 mg • Oral • Canada • Approved
  • Jamp-methotrexate
    Solution • 25 mg / mL • Intra-arterial; Intramuscular; Intrathecal; Intravenous • Canada • Generic • Approved
  • Jylamvo
    Solution • 2 mg/1mL • Oral • US • Approved
  • Jylamvo
    Solution • 2 mg/ml • Oral • EU • Approved
  • M-methotrexate
    Tablet • 2.5 mg • Oral • Canada • Approved
Menampilkan 8 dari 317 produk.
International Brands
  • Abitrexate — Teva
  • Alltrex — Naprod
  • Artrait — TRB
  • Atrexel — Schering-Plough
  • Bendatrexat — Bendalis
  • Carditrex — Cadila
  • Dermotrex — East West
  • Ebetrex — Ebewe
  • Emtexate
  • Ledertrexate — Biodim

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul