Negara: Kanada
Bahasa: Inggris
Sumber: Health Canada
FLUOROURACIL
SANDOZ CANADA INCORPORATED
L01BC02
FLUOROURACIL
50MG
SOLUTION
FLUOROURACIL 50MG
INTRAVENOUS
10ML
Prescription
ANTINEOPLASTIC AGENTS
Active ingredient group (AIG) number: 0107505001; AHFS:
APPROVED
2005-06-01
_Fluorouracil Injection _ _Page 1 of 19 _ _ _ PRODUCT MONOGRAPH FLUOROURACIL INJECTION 5-fluorouracil Ph.Eur. 50 mg/mL Injection USP Antineoplastic Agent Sandoz Canada Inc. Date of Revision: April 3, 2012 145 Jules-Léger Boucherville, QC J4B 7K8 Submission Control No: 145218 _ _ _Fluorouracil Injection _ _Page 2 of 19 _ Fluorouracil Injection (5-fluorouracil Ph.Eur.) THERAPEUTIC CLASSIFICATION Antineoplastic CAUTION: FLUOROURACIL (5-FLUOROURACIL) IS A POTENT DRUG AND SHOULD BE PRESCRIBED ONLY BY PHYSICIANS EXPERIENCED WITH CANCER CHEMOTHERAPEUTIC DRUGS (SEE WARNINGS AND PRECAUTIONS). BLOOD COUNTS AS WELL AS RENAL AND HEPATIC FUNCTION TESTS SHOULD BE PERFORMED REGULARLY. DISCONTINUE THE DRUG IF THERE IS SIGNIFICANT LEUKOPENIA (UNDER 3 000/mm 3 ) OR GRANULOCYTOPENIA (UNDER 1 500/mm 3 ). ACTIONS AND CLINICAL PHARMACOLOGY Fluorouracil (5-fluorouracil) is a fluorinated pyrimidine antimetabolite which is structurally similar to uracil, one of the necessary building blocks in cellular division and growth. Figure 1 Its usefulness is based on uracil being utilized preferentially for nucleic acid biosynthesis in some tumors. 5-fluorouracil is metabolized to 5-fluorouridine triphosphate (F-UTP), 2-deoxyfluorouridine monophosphate (Fd-UMP), and 2-deoxyfluorouridine triphosphate (Fd-UTP) in cells to concentrations that result in both DNA-directed and RNA-directed cytotoxicities (see Figure 1). Fd-UMP is the intracellular cytotoxic form of 5-fluorouracil. It competes with the natural substrate d-UMP (deoxyuridine monophosphate) for the catalytic site _ _ _Fluorouracil Injection _ _Page 3 of 19 _ on thymidylate synthetase (a key enzyme in DNA synthesis), forming a covalent complex with the enzyme that is unable to undergo the normal catalytic reaction of converting d-UMP to d-TMP. The presence of a reduced folate cofactor is required for tight binding of Fd-UMP to thymidylate synthetase. Folinic acid (leucovorin), which is metabolized to 5,10-methylene- tetrahydropteroylglutamine (a reduced folate), is able to modulate the ant Baca dokumen lengkapnya