Methotrexate

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methotrexate is a drug that blocks the body’s ability to use folic acid, which is needed by growing cells such as those making up the skin, blood, digestive tract, and the cells that protect the body against infection and disease. Methotrexate is used to treat some types of cancer, arthritis, and severe skin disorders. It belongs to the group of drugs called antimetabolites.

Information about Methotrexate

Methotrexate is an antineoplastic and immunosuppressive agent widely used in the therapy of leukemia, lymphoma, solid tumors, psoriasis and rheumatoid arthritis. 

Liver safety of Methotrexate

When given in high intravenous doses, methotrexate can cause acute elevations in serum enzymes, and long term methotrexate therapy has been associated with frequent but mild elevations in serum liver enzymes and, more importantly, with development of chronic liver injury, progressive fibrosis, cirrhosis and portal hypertension. 

Mechanism of action of Methotrexate

Methotrexate (meth" oh trex' ate) is an antifolate and antimetabolite that is used extensively in the therapy of leukemia, lymphoma and several solid organ tumors.  It also has potent activity against psoriasis and has immunomodulatory activity against inflammatory bowel disease and the inflammatory arthritidies.  Methotrexate is considered a disease modifying antirheumatic drug (DMARD) and used widely in rheumatoid arthritis and other autoimmune diseases.  Methotrexate acts by inhibition of folate metabolism, blocking dihydrofolic acid reductase, thereby inhibiting synthesis of purines and pyrimidines and decreasing DNA and RNA synthesis.  Recent results suggest that methotrexate also leads to increase and release of adenosine, which may mediate its immunosuppressive activity. 

FDA approval information for Methotrexate

Folic acid antagonists (aminopterin) were developed in the late 1940s and introduced into clinical medicine shortly thereafter.  Aminopterin was later replaced by methotrexate because of its better tolerance and lower rate of toxicity.  Methotrexate was approved for use in cancer in the United States in 1955, for psoriasis in 1972 and rheumatoid arthritis in 1988 and is still widely used for these indications. 

Dosage and administration for Methotrexate

Methotrexate is available in generic forms and under the brand names of Rheumatrex and Trexall in tablets of 2.5, 5, 7.5, 10 and 15 mg, and in both powdered and liquid-for-injection forms in vials of various strengths for intravenous, intramuscular or intrathecal injection.  The dose regimen varies by indication; high, short term doses being used in treatment of cancer and chronic, lower doses for autoimmune conditions.  The typical maintenance dose used to treat psoriasis and rheumatoid arthritis is 7.5 to 25 mg once weekly either orally or by injection. 

Side effects of Methotrexate

side effects are mostly dose related and include stomatitis, oral ulcers, hair loss, fatigue, headache, gastrointestinal upset, nausea, diarrhea and bone marrow suppression.   

Antineoplastic Agents

Alkylating Agents - Altretamine, Bendamustine, Busulfan, Carmustine, Chlorambucil, Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine, Mechlorethamine, Melphalan, Procarbazine, Streptozocin, Temozolomide, Thiotepa, Trabectedin

Platinum Coordination Complexes - Carboplatin, Cisplatin, Oxaliplatin

Antibiotics Cytotoxic - Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitomycin, Mitoxantrone, Plicamycin, Mithramycin, Valrubicin

Antimetabolites Antifolates - Methotrexate, Pemetrexed, Pralatrexate, Trimetrexate

Purine Analogues - Azathioprine, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Nelarabine, Pentostatin, Thioguanine

Pyrimidine Analogues - Azacitidine, Capecitabine, Cytarabine, Decitabine, Floxuridine, Fluorouracil, Gemcitabine, Trifluridine/Tipracil

Biologic Response Modifiers - Aldesleukin (IL-2), Denileukin Diftitox, Interferon gamma

Histone Deacetylase Inhibitors - Belinostat, Panobinostat, Romidepsin, Vorinostat

Hormonal Agents Antiandrogens - Abiraterone, Bicalutamide, Cyproterone, Enzalutamide, Flutamide, Nilutamide

Antiestrogens (including Aromatase Inhibitors) - Anastrozole, Exemestane, Fulvestrant, Letrozole

Selective Estrogen Receptor Modulators - Raloxifene, Tamoxifen, Toremifene

Gonadotropin Releasing Hormone Analogues - Degarelix, Goserelin, Histrelin, Leuprolide, Triptorelin

Peptide Hormones - Lanreotide, Octreotide, Pasireotide

Monoclonal Antibodies - Alemtuzumab, Atezolizumab, Avelumab, Bevacizumab, Blinatumomab, Brentuximab, Cetuximab, Daratumumab, Dinutuximab, Durvalumab, Elotuzumab, Gemtuzumab, Inotuzumab Ozogamicin, Ipilimumab, Necitumumab, Nivolumab, Ofatumumab, Olaratumab, Panitumumab, Pembrolizumab, Pertuzumab, Ramucirumab, Rituximab, Tositumomab, Trastuzumab

Protein Kinase Inhibitors - Abemaciclib, Acalabrutinib, Afatinib, Alectinib, Axitinib, Bortezomib, Bosutinib, Brigatinib, Cabozantinib, Carfilzomib, Ceritinib, Cobimetinib, Copanlisib, Crizotinib, Dabrafenib, Dasatinib, Enasidenib, Erlotinib, Gefitinib, Ibrutinib, Idelalisib, Imatinib, Ivosidenib, Ixazomib, Lapatinib, Lenvatinib, Neratinib, Nilotinib, Niraparib, Olaparib, Osimertinib, Palbociclib, Pazopanib, Ponatinib, Regorafenib, Ribociclib, Rucaparib, Ruxolitinib, Sonidegib, Sorafenib, Sunitinib, Trametinib, Vandetanib, Vemurafenib, Vismodegib

Taxanes - Cabazitaxel, Docetaxel, Paclitaxel

Topoisomerase Inhibitors - Etoposide, Irinotecan, Teniposide, Topotecan

Tyrosine Kinase Receptor Inhibitors See Protein Kinase Inhibitors

Vinca Alkaloids - Vinblastine, Vincristine, Vinorelbine

Miscellaneous - Asparaginase (Pegaspargase), Bexarotene, Eribulin, Everolimus, Hydroxyurea, Ixabepilone, Lenalidomide, Mitotane, Omacetaxine, Pomalidomide, Temsirolimus, Thalidomide, Venetoclax


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