Floxuridine (Monograph)
Drug class: Antineoplastic Agents
VA class: AN300
Chemical name: 2′-Deoxy-5-fluorouridine
Molecular formula: C9H11FN2O5
CAS number: 50-91-9
Warning
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Only for administration by, or under the supervision of, a clinician experienced in cancer chemotherapy (including the use of antimetabolites) and in intra-arterial drug therapy.
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Severe toxic reactions are possible; hospitalize patient during initial course of treatment.
Introduction
Pyrimidine antagonist; antimetabolite; antineoplastic agent.
Uses for Floxuridine
GI Adenocarcinoma
Palliative management of GI adenocarcinoma that has metastasized to the liver and is considered incurable by surgery or other means of cancer therapy.
Not intended for use as adjuvant to surgery.
In patients with carcinoma extending beyond area capable of being infused via a single artery, consider using other systemic chemotherapeutic agents.
Liver Cancer
Palliative management of liver cancer† [off-label]; usually administered by hepatic intra-arterial infusion.
Floxuridine Dosage and Administration
General
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Consult specialized references for procedures for proper handling and disposal of antineoplastics.
Administration
Intra-arterial Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer by continuous regional intra-arterial infusion via a catheter inserted into the arterial blood supply of the tumor.
Use an appropriate infusion pump to overcome pressure in large arteries and to ensure uniform rate of infusion.
Sterile water for injection may be infused between courses to keep catheter open.
Reconstitution
Reconstitute vial containing 500 mg of floxuridine with 5 mL of sterile water for injection to provide a solution containing 100 mg/mL.
Dilution
Dilute calculated daily dose with 5% dextrose or 0.9% sodium chloride injection to a volume appropriate for infusion apparatus used.
Dosage
Adults
GI Adenocarcinoma
Intra-arterial
0.1–0.6 mg/kg daily.
For hepatic artery infusion, use higher dosages (0.4–0.6 mg/kg daily); the liver metabolizes the drug, thus reducing risk of systemic toxicity.
Continue therapy until toxicity occurs (see General Precautions under Cautions); 1–6 weeks of continuous administration generally adequate. Maintain therapy as long as response continues.
Cautions for Floxuridine
Contraindications
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Poor nutritional state.
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Depressed bone marrow function (leukocyte count ≤5000/mm3 and/or a platelet count ≤100,000/mm3).
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Potentially serious infections.
Warnings/Precautions
Warnings
Prior Use of Irradiation Therapy or Alkylating Agents
Use with extreme caution in patients who have previously received high-dose pelvic irradiation therapy or alkylating agents.
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; teratogenicity demonstrated in animals.
Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.
Toxicity Potentiation with Concomitant Therapy
Increased risk of toxicity if used with any form of therapy that adds to the stress of the patient, interferes with nutrition, or depresses bone marrow function.
Sensitivity Reactions
Localized erythema, alopecia, dermatitis, rash, edema, excoriation, maceration, pruritus, ulceration, and nonspecific skin reactions reported.
Anaphylaxis, generalized allergic reactions, and photosensitivity reported with fluorouracil; potential for similar sensitivity reactions with floxuridine due to pharmacologic similarity with fluorouracil.
General Precautions
Toxicity
Toxic effects following intra-arterial infusion generally related to the drug-infused area; however, systemic toxicity has been reported.
Floxuridine is metabolized to fluorouracil, but the full spectrum of fluorouracil toxicity is not expected due to regional administration of the drug. Consider the possibility of typical adverse effects of fluorouracil during floxuridine therapy.
May produce severe hematologic toxicity, GI hemorrhage, and even death.
Adequate Patient Evaluation and Monitoring
Therapeutic response is not likely to occur without some evidence of toxicity (e.g., adverse hematologic or GI effects). (See Toxicity under Cautions.)
Severe toxicity more likely to occur in poor-risk patients (e.g., poor nutritional state, depressed bone marrow function, concurrent serious infections) (see Contraindications); however, possible death (despite careful patient selection and dosage adjustment) even in patients in relatively good condition.
Monitor patients carefully due to narrow margin of safety.
Hematologic Effects
Anemia, leukopenia, and thrombocytopenia reported. Carefully monitor WBC and platelet counts.
Discontinue promptly for leukopenia (WBC <3500/mm3) or if WBC decreases rapidly.
Discontinue promptly for thrombocytopenia (platelets <100,000/mm3).
Discontinue promptly for hemorrhage at any site.
May resume therapy when manifestations have resolved.
GI Effects
Nausea, vomiting, diarrhea, enteritis, stomatitis, duodenal ulcer, duodenitis, gastritis, GI bleeding, gastroenteritis, glossitis, pharyngitis, anorexia, cramps, and abdominal pain reported.
Discontinue promptly for stomatitis or esophagopharyngitis.
Discontinue promptly for intractable vomiting.
Discontinue promptly for GI ulceration and bleeding.
May resume therapy when manifestations have resolved.
Cardiovascular Effects
Discontinue promptly if myocardial ischemia occurs. May resume therapy when manifestations have resolved.
Hepatic Effects
Acalculus cholecystitis and elevations in serum alkaline phosphatase, aminotransferase, bilirubin, and LDH concentrations reported.
With hepatic arterial infusion, possible intra- and/or extrahepatic biliary sclerosis and liver cirrhosis.
Local and Regional Effects
Arterial aneurysm, arterial ischemia, arterial thrombosis, bleeding at catheter site, blocked/displaced/leaking catheter, embolism, fibromyositis, infection at catheter site, hepatic necrosis, abscesses, and thrombophlebitis reported. Inaccurate catheter placement and contamination of infusion assembly also reported.
Specific Populations
Pregnancy
Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether floxuridine is distributed into milk. Discontinue nursing.
Pediatric Use
Safety and efficacy not established.
Hepatic Impairment
Use with extreme caution.
Renal Impairment
Use with extreme caution.
Common Adverse Effects
Nausea, vomiting, diarrhea, enteritis, stomatitis, localized erythema, anemia, leukopenia, thrombocytopenia, elevated hepatic enzyme concentrations.
Drug Interactions
Increased risk of toxicity if used with any form of therapy that adds to the stress of the patient, interferes with nutrition, or depresses bone marrow function.
Floxuridine Pharmacokinetics
Elimination
Metabolism
Following continuous intra-arterial infusion, floxuridine is anabolized to active metabolite floxuridine-monophosphate (FUDR-MP). Following rapid intra-arterial injection, the drug is catabolized to fluorouracil.
Metabolized in the liver. Less metabolic degradation following intra-arterial continuous infusion than following rapid injection.
Elimination Route
Excreted intact in urine as urea, fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-alanine; also excreted as respiratory carbon dioxide.
Stability
Storage
Parenteral
Powder for Injection
15–30°C.
Reconstituted solution: 2–8°C for ≤2 weeks.
Compatibility
Parenteral
Solution Compatibility105
Compatible |
---|
Dextrose 5% |
Sodium chloride 0.9% |
Drug Compatibility
Compatible |
---|
Carboplatin |
Cisplatin |
Cisplatin with etoposide |
Cisplatin with leucovorin calcium |
Etoposide |
Fluorouracil |
Leucovorin calcium |
Compatible |
---|
Amifostine |
Aztreonam |
Etoposide phosphate |
Filgrastim |
Fludarabine phosphate |
Gemcitabine HCl |
Granisetron HCl |
Melphalan HCl |
Ondansetron HCl |
Paclitaxel |
Piperacillin sodium–tazobactam sodium |
Sargramostim |
Teniposide |
Thiotepa |
Vinorelbine tartrate |
Incompatible |
Allopurinol sodium |
Cefepime HCl |
Actions
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Inhibits DNA synthesis and, to a lesser extent, RNA formation.
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Active metabolite FUDR-MP inhibits thymidylate synthetase (thus inhibiting methylation of deoxyuridylic acid to thymidylic acid), resulting in inhibition of DNA synthesis.
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Produces the same antimetabolic effects as fluorouracil (i.e., blocks uracil riboside phosphorylase, thus inhibiting utilization of preformed uracil in RNA synthesis). Metabolites of fluorouracil become incorporated to a small extent into RNA, producing fraudulent RNA.
Advice to Patients
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Risk of severe adverse hematologic (e.g., anemia, leukopenia, thrombocytopenia) and GI effects (e.g., vomiting, diarrhea, stomatitis, esophagopharyngitis).
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Risk of transient alopecia.
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Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
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Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. Necessity for clinicians to advise women to avoid pregnancy during therapy; advise pregnant women of risk to the fetus.
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Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
For injection, for intra-arterial infusion only |
500 mg* |
Floxuridine for Injection |
Abraxis |
FUDR |
Mayne |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
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