Abic ltd, Pharmacia and upjohn co, Hospira inc, App pharmaceuticals llc, Abraxis pharmaceutical products, Bedford laboratories div ben venue laboratories inc, Norbrook laboratories ltd, Pharmachemie usa inc, Bioniche pharma usa llc, Ebewe pharma ges mbh nfg kg, Pharmachemie bv, Bristol laboratories inc div bristol myers co, Bristol myers co, Bristol myers squibb, Barr laboratories inc, Dava pharmaceuticals inc, Duramed pharmaceuticals inc sub barr laboratories inc, Mylan pharmaceuticals inc, Roxane laboratories inc • Methotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis. Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis. Other formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma. It is also used in the maintenance of acute lymphocytic leukemia. Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma.
Methotrexate is an antineoplastic agent used the treatment of a wide variety of cancers as well as severe psoriasis, severe rheumatoid arthritis, and juvenile rheumatoid arthritis.
Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate. Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase. Inhibtion of nucleotide synthesis prevents cell division. In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate. This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.
