Страна: Канада
Язык: английский
Источник: Health Canada
METHOTREXATE (METHOTREXATE SODIUM)
PFIZER CANADA ULC
L01BA01
METHOTREXATE
25MG
SOLUTION
METHOTREXATE (METHOTREXATE SODIUM) 25MG
INTRA-ARTERIAL
2/20ML VIAL
Prescription
ANTINEOPLASTIC AGENTS
Active ingredient group (AIG) number: 0107545002; AHFS:
CANCELLED POST MARKET
2006-08-02
PRODUCT MONOGRAPH METHOTREXATE SODIUM INJECTION USP 25 mg/ mL methotrexate (2 mL and 20 mL vials) ANTIMETABOLITE Pfizer Canada Inc Date of Preparation: 17,300 Trans-Canada Highway October 15, 2003 Kirkland, Quebec H9J 2M5 Control No. 087271 © Pfizer Canada Inc 2003 PRODUCT MONOGRAPH 2 METHOTREXATE SODIUM INJECTION USP 25 mg / mL methotrexate (2 mL and 20 mL vials) ANTIMETABOLITE CAUTION: METHOTREXATE SODIUM INJECTION USP (MTX) IS A POTENT CHEMOTHERAPEUTIC AGENT WHICH SHOULD BE USED ONLY BY PHYSICIANS WHO ARE FAMILIAR WITH THE DRUG, ITS ACTION, AND ITS SIDE EFFECTS. ACTION AND CLINICAL PHARMACOLOGY Methotrexate (MTX), the 3-amino N 10 - methyl analog of folic acid, is a potent folate antagonist, and is cell cycle specific in the S-phase. MTX blocks the reduction of dihydrofolate to the active tetrahydrofolate (FH 4 ) which functions as a cofactor in one-carbon (C 1 ) transfer reactions (carrier), crucial for the synthesis of purine nucleotides and thymidylate. MTX competes with folate, and acts as an antimetabolite by relatively irreversible intracellular binding to the enzyme dihydrofolate reductase (DHFR). Inhibition of the formation of FH 4 produces an acute intracellular deficiency of folate coenzymes and a vast accumulation of the toxic substrate FH 2 polyglutamates. The C 1 carrier reactions cease, subsequently interrupting the synthesis of DNA and RNA. Polyglutamate derivatives, increasing as a function of drug 3 concentration and time of exposure, occur through extensive intracellular metabolism of MTX, extending the cytotoxicity of MTX to the cells in the S-phase. Protein synthesis is also inhibited, since reduced folates are cofactors in the conversion of glycine to serine, and homocysteine to methionine. Decreased ability to synthesize MTX polyglutamates, DHFR gene amplification leading to overproduction of the target enzyme, decreased or impaired membrane transport of MTX into cells, and decreased affinity for the MTX binding site due to production of altered forms of DHFR, are the four biochemical ma Прочитать полный документ