Basic Profile / Key Facts
Drug Category
- Antineoplastics
- antimetabolites
- Antimetabolites
Dosage Forms
- Powder for solution (500mg vial)
Indications
For palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means.
Pharmacology
Floxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Floxuridine is an anti-metabolite. Anti-metabolites masquerade as pyramidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Flurouracil (the end-product of catabolism of floxuridine) blacks an enzyme which converts cytosine nucleosides into the deoxy derivative. In addition, DNA synthesis is further inhibited because fluoruracil blocks the incorporation of the thymdine nucleotide into the DNA strand.
Mechanism of Action
Floxuridine is rapidly catabolized to 5-fluorouracil which is the active form of the drug. Fluorouracil inhibits thymydilate synthase leading to inhibition of DNA synthesis, RNA synthesis and cell death.
Absorption
Not Available
Toxicity
Oral, rat LD50: 215 mg/kg. Signs of overdose include nausea, vomiting, diarrhea, gastrointestinal ulceration and bleeding, and bone marrow depression (including thrombocytopenia, leukopenia and agranulocytosis).
Biotrnasformation / Drug Metabolism
Hepatic.
Contraindications
FUDR therapy is contraindicated for patients in a poor nutritional state, those with depressed bone marrow
function or those with potentially serious infections.
Drug Interactions
Combination Therapy: Any form of therapy which adds to the stress of the patient, interferes with nutrition or depresses bone marrow function will increase the toxicity of Floxuridine.
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