Overview
DESCRIPTION Floxuridine for Injection, USP, an antineoplastic antimetabolite, is available as a sterile, nonpyrogenic, lyophilized powder for reconstitution. Each vial contains 500 mg of floxuridine which is to be reconstituted with 5 mL of sterile water for injection. An appropriate amount of reconstituted solution is then diluted with a parenteral solution for intra-arterial infusion (see...
Mechanism of Action
CLINICAL PHARMACOLOGY When floxuridine is given by rapid intra-arterial injection it is apparently rapidly catabolized to 5-fluorouracil. Thus, rapid injection of floxuridine produces the same toxic and antimetabolic effects as does 5-fluorouracil. The primary effect is to interfere with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibit the formation of ribonucleic acid (RNA). However, when floxuridine is given by continuous intra-arterial infusion its direct anabolism to floxuridine-monophosphate is enhanced, thus increasing the inhibition of DNA. Floxuridine is metabolized in the liver.
Indications
- INDICATIONS AND USAGE Floxuridine for Injection, USP is effective in the 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. Patients with known disease extending beyond an area capable of infusion via a single artery should, except in unusual circumstances, be considered for systemic therapy with other chemotherapeutic agents.
Common Doses
- 5 mL
- 100 mg
- 0.6 mg
Dosage
DOSAGE AND ADMINISTRATION Each vial must be reconstituted with 5 mL of sterile water for injection to yield a solution containing approximately 100 mg of floxuridine/mL. The calculated daily dose(s) of the drug is then diluted with 5% dextrose or 0.9% sodium chloride injection to a volume appropriate for the infusion apparatus to be used. The administration of floxuridine is best achieved with the use of an appropriate pump to overcome pressure in large arteries and to ensure a uniform rate of infusion.
Black Box Warning
WARNING It is recommended that floxuridine be given only by or under the supervision of a qualified physician who is experienced in cancer chemotherapy and intra-arterial drug therapy and is well versed in the use of potent antimetabolites. Because of the possibility of severe toxic reactions, all patients should be hospitalized for initiation of the first course of therapy.
Contraindications
- CONTRAINDICATIONS Floxuridine therapy is contraindicated for patients in a poor nutritional state, those with depressed bone marrow function or those with potentially serious infections.
Side Effects
- ADVERSE REACTIONS Adverse reactions to the arterial infusion of floxuridine are generally related to the procedural complications of regional arterial infusion. The more common adverse reactions to the drug are nausea, vomiting, diarrhea, enteritis, stomatitis and localized erythema. The more common laboratory abnormalities are anemia, leukopenia, thrombo-cytopenia and elevations of alkaline phosphatase, serum transaminase, serum bilirubin and lactic dehydrogenase.
Interactions
- Drug Interactions See WARNINGS section.