Floxuridine (Monograph)

Drug class: Antineoplastic Agents
VA class: AN300
Chemical name: 2′-Deoxy-5-fluorouridine
Molecular formula: C₉H₁₁FN₂O₅
CAS number: 50-91-9

Medically reviewed by Drugs.com on Jul 24, 2023. Written by ASHP.

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

• 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

• Poor nutritional state.

• Depressed bone marrow function (leukocyte count ≤5000/mm³ and/or a platelet count ≤100,000/mm³).

• 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

Drug Compatibility

Actions

• Inhibits DNA synthesis and, to a lesser extent, RNA formation.

• Active metabolite FUDR-MP inhibits thymidylate synthetase (thus inhibiting methylation of deoxyuridylic acid to thymidylic acid), resulting in inhibition of DNA synthesis.

• 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

• Risk of severe adverse hematologic (e.g., anemia, leukopenia, thrombocytopenia) and GI effects (e.g., vomiting, diarrhea, stomatitis, esophagopharyngitis).

• Risk of transient alopecia.

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• 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.

• 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

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