METHOTREXATE SODIUM INJECTION USP SOLUTION

Nazione: Canada

Lingua: inglese

Fonte: Health Canada

Principio attivo:

METHOTREXATE (METHOTREXATE SODIUM)

Commercializzato da:

PFIZER CANADA ULC

Codice ATC:

L01BA01

INN (Nome Internazionale):

METHOTREXATE

Dosaggio:

25MG

Forma farmaceutica:

SOLUTION

Composizione:

METHOTREXATE (METHOTREXATE SODIUM) 25MG

Via di somministrazione:

INTRA-ARTERIAL

Confezione:

2/20ML VIAL

Tipo di ricetta:

Prescription

Area terapeutica:

ANTINEOPLASTIC AGENTS

Dettagli prodotto:

Active ingredient group (AIG) number: 0107545002; AHFS:

Stato dell'autorizzazione:

CANCELLED POST MARKET

Data dell'autorizzazione:

2006-08-02

Scheda tecnica

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