METHOTREXATE SODIUM INJECTION USP SOLUTION

Land: Canada

Taal: Engels

Bron: Health Canada

Werkstoffen:

METHOTREXATE (METHOTREXATE SODIUM)

Beschikbaar vanaf:

PFIZER CANADA ULC

ATC-code:

L01BA01

INN (Algemene Internationale Benaming):

METHOTREXATE

Dosering:

25MG

farmaceutische vorm:

SOLUTION

Samenstelling:

METHOTREXATE (METHOTREXATE SODIUM) 25MG

Toedieningsweg:

INTRA-ARTERIAL

Eenheden in pakket:

2/20ML VIAL

Prescription-type:

Prescription

Therapeutisch gebied:

ANTINEOPLASTIC AGENTS

Product samenvatting:

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

Autorisatie-status:

CANCELLED POST MARKET

Autorisatie datum:

2006-08-02

Productkenmerken

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