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.¹⁰⁵

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.^{102 105}

Not intended for use as adjuvant to surgery.¹⁰⁵

In patients with carcinoma extending beyond area capable of being infused via a single artery, consider using other systemic chemotherapeutic agents.¹⁰⁵

Liver Cancer

Palliative management of liver cancer^{† [off-label]}; usually administered by hepatic intra-arterial infusion.¹⁰²

Floxuridine Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.¹⁰⁵

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.^{105 a}

Use an appropriate infusion pump to overcome pressure in large arteries and to ensure uniform rate of infusion.¹⁰⁵

Sterile water for injection may be infused between courses to keep catheter open.^a

Reconstitution

Reconstitute vial containing 500 mg of floxuridine with 5 mL of sterile water for injection to provide a solution containing 100 mg/mL.¹⁰⁵

Dilution

Dilute calculated daily dose with 5% dextrose or 0.9% sodium chloride injection to a volume appropriate for infusion apparatus used.¹⁰⁵

Dosage

Adults

GI Adenocarcinoma

Intra-arterial

0.1–0.6 mg/kg daily.¹⁰⁵

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.¹⁰⁵

Continue therapy until toxicity occurs (see General Precautions under Cautions);¹⁰⁵ 1–6 weeks of continuous administration generally adequate.^a Maintain therapy as long as response continues.¹⁰⁵

Cautions for Floxuridine

Contraindications

• Poor nutritional state.¹⁰⁵

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

• Potentially serious infections.^a

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.¹⁰⁵

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals.¹⁰⁵

Avoid pregnancy during therapy.¹⁰⁵ If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹⁰⁵

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.¹⁰⁵

Sensitivity Reactions

Localized erythema, alopecia, dermatitis, rash, edema, excoriation, maceration, pruritus, ulceration, and nonspecific skin reactions reported.^{105 106}

Anaphylaxis, generalized allergic reactions, and photosensitivity reported with fluorouracil; potential for similar sensitivity reactions with floxuridine due to pharmacologic similarity with fluorouracil.¹⁰⁵

General Precautions

Toxicity

Toxic effects following intra-arterial infusion generally related to the drug-infused area;¹⁰⁵ however, systemic toxicity has been reported.¹⁰⁵

Floxuridine is metabolized to fluorouracil, but the full spectrum of fluorouracil toxicity is not expected due to regional administration of the drug.¹⁰⁵ Consider the possibility of typical adverse effects of fluorouracil during floxuridine therapy.¹⁰⁵

May produce severe hematologic toxicity, GI hemorrhage, and even death.¹⁰⁵

Adequate Patient Evaluation and Monitoring

Therapeutic response is not likely to occur without some evidence of toxicity (e.g., adverse hematologic or GI effects).¹⁰⁵ (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.¹⁰⁵

Monitor patients carefully due to narrow margin of safety.¹⁰⁵

Hematologic Effects

Anemia, leukopenia, and thrombocytopenia reported.¹⁰⁵ Carefully monitor WBC and platelet counts.¹⁰⁵

Discontinue promptly for leukopenia (WBC <3500/mm³) or if WBC decreases rapidly.¹⁰⁵

Discontinue promptly for thrombocytopenia (platelets <100,000/mm³).¹⁰⁵

Discontinue promptly for hemorrhage at any site.¹⁰⁵

May resume therapy when manifestations have resolved.¹⁰⁵

GI Effects

Nausea, vomiting, diarrhea, enteritis, stomatitis, duodenal ulcer, duodenitis, gastritis, GI bleeding, gastroenteritis, glossitis, pharyngitis, anorexia, cramps, and abdominal pain reported.¹⁰⁵

Discontinue promptly for stomatitis or esophagopharyngitis.^a

Discontinue promptly for intractable vomiting.¹⁰⁵

Discontinue promptly for GI ulceration and bleeding.¹⁰⁵

May resume therapy when manifestations have resolved.¹⁰⁵

Cardiovascular Effects

Discontinue promptly if myocardial ischemia occurs.¹⁰⁵ May resume therapy when manifestations have resolved.¹⁰⁵

Hepatic Effects

Acalculus cholecystitis and elevations in serum alkaline phosphatase, aminotransferase, bilirubin, and LDH concentrations reported.¹⁰⁵

With hepatic arterial infusion, possible intra- and/or extrahepatic biliary sclerosis^{100 101 103 104 105} and liver cirrhosis.^{101 103}

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.¹⁰⁵ Inaccurate catheter placement and contamination of infusion assembly also reported.¹⁰

Specific Populations

Pregnancy

Category D.¹⁰⁵ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether floxuridine is distributed into milk.¹⁰⁵ Discontinue nursing.¹⁰⁵

Pediatric Use

Safety and efficacy not established.¹⁰⁵

Hepatic Impairment

Use with extreme caution.¹⁰⁵

Renal Impairment

Use with extreme caution.¹⁰⁵

Common Adverse Effects

Nausea, vomiting, diarrhea, enteritis, stomatitis, localized erythema, anemia, leukopenia, thrombocytopenia, elevated hepatic enzyme concentrations.¹⁰⁵

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.¹⁰⁵

Floxuridine Pharmacokinetics

Elimination

Metabolism

Following continuous intra-arterial infusion, floxuridine is anabolized to active metabolite floxuridine-monophosphate (FUDR-MP).¹⁰⁵ Following rapid intra-arterial injection, the drug is catabolized to fluorouracil.¹⁰⁵

Metabolized in the liver.¹⁰⁵ Less metabolic degradation following intra-arterial continuous infusion than following rapid injection.^a

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.¹⁰⁵

Stability

Storage

Parenteral

Powder for Injection

15–30°C.¹⁰⁵

Reconstituted solution: 2–8°C for ≤2 weeks.¹⁰⁵

Compatibility

Parenteral

Solution Compatibility105

Drug Compatibility

Actions

• Inhibits DNA synthesis and, to a lesser extent, RNA formation.¹⁰⁵

• Active metabolite FUDR-MP inhibits thymidylate synthetase (thus inhibiting methylation of deoxyuridylic acid to thymidylic acid),^a resulting in inhibition of DNA synthesis.¹⁰⁵

• Produces the same antimetabolic effects as fluorouracil¹⁰⁵ (i.e., blocks uracil riboside phosphorylase, thus inhibiting utilization of preformed uracil in RNA synthesis).^a Metabolites of fluorouracil become incorporated to a small extent into RNA, producing fraudulent RNA.^a

Advice to Patients

• Risk of severe adverse hematologic (e.g., anemia, leukopenia, thrombocytopenia) and GI effects (e.g., vomiting, diarrhea, stomatitis, esophagopharyngitis).¹⁰⁵

• Risk of transient alopecia.¹⁰⁵

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹⁰⁵

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹⁰⁵ Necessity for clinicians to advise women to avoid pregnancy during therapy; advise pregnant women of risk to the fetus.¹⁰⁵

• 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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