Floxuridine

Pronunciation: (flox-YOUR-ih-deen)
Class: Pyrimidine antimetabolite

Trade Names

FUDR
- Powder for injection 500 mg
- Solution for injection 100 mg/mL

Pharmacology

The primary effect is to interfere with the synthesis of DNA and to a lesser extent inhibit the formation of RNA.

Pharmacokinetics

Metabolism

When given by rapid intra-arterial injection, floxuridine is rapidly catabolized to 5-fluorouracil. When given by continuous intra-arterial infusion, direct anabolism to floxuridine-monophosphate is enhanced. Floxuridine is metabolized in the liver.

Elimination

The drug is excreted intact as urea, fluorouracil, alpha-fluoro-beta-ureidopropionic acid, dihydrofluorouracil, alpha-fluoro-beta-guanidopropionic acid, and alpha-fluoro-beta alanine in the urine. It also is expired as respiratory carbon dioxide.

Indications and Usage

Palliative management of GI adenocarcinoma metastatic to the liver administered by continuous regional intra-arterial infusion as long as cancer does not extend beyond area perfused by a single artery.

Unlabeled Uses

Tumors of the liver, gallbladder, bile ducts, or kidneys.

Contraindications

Patients in a poor nutritional state, those with depressed bone marrow function or those with potentially serious infections.

Dosage and Administration

Hepatic Artery Infusion
Adults

Implantable pump Using an implantable pump, administer 0.1 to 0.6 mg/kg/day for 1 to 6 wk, followed by a 14-day rest period between courses. Repeat cycles as long as response continues.

Solid Tumors
Adults

IV infusion 0.5 to 1 mg/kg/day for 6 to 15 days or until toxicity occurs.

Drug Interactions

Cimetidine

Cimetidine may increase the bioavailability of floxuridine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Arterial aneurysm; ischemia; thrombosis; embolism; fibromyositis.

Dermatologic

Localized erythema; alopecia; rash.

GI

Nausea and vomiting; diarrhea; enteritis; mucositis; duodenal ulcers; elevated LFTs; hepatic necrosis; hepatic abscesses; intra- and extrahepatic biliary sclerosis; acalculous cholecystitis.

Hematologic

Bone marrow suppression, nadir at 9 to 14 days; bleeding at the catheter site.

Miscellaneous

Fever and malaise; infection of the catheter site.

Precautions

Warnings

Hospitalization recommended for first course of therapy because of possibility of severe toxic reactions.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Special Risk Patients

Use with extreme caution in poor-risk patients who have had high-dose pelvic irradiation or previous use of alkylating agents, who have wide-spread involvement of bone marrow by metastatic tumors, or impaired hepatic or renal function.

Discontinue use

According to product labeling, promptly discontinue floxuridine if any of the following occur: myocardial ischemia, mucositis or esophagopharyngitis, leukopenia with WBC less than 3,500/mm ³ , intractable vomiting, frequent diarrhea, GI ulcer or bleeding, thrombocytopenia with platelets less than 100,000/mm ³ , or hemorrhage from any site.

Extravasation

Local irritation or phlebitis may occur. Refer to your institution-specific protocol.

Overdosage

Symptoms

Nausea, vomiting, diarrhea, GI ulceration and bleeding, bone marrow depression (eg, thrombocytopenia, leukopenia, agranulocytosis).

Patient Information

Contraceptive measures are recommended for men and women during therapy.
Notify health care provider if chills, nausea, vomiting, unusual bleeding or bruising, yellowing of skin or eyes, abdominal pain, flank or joint pain, or swelling of feet or legs occurs.
Notify health care provider if the following become pronounced: diarrhea, fever, weakness
Drink plenty of liquids while taking this drug.
Inform patients of expected toxic effects, particularly oral manifestations.
Alert patient to the possibility of alopecia as a result of therapy, and inform patient that alopecia is usually a transient effect.