FOR INTRA-ARTERIAL INFUSION ONLY

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 DOSAGE AND ADMINISTRATION).

Floxuridine is a fluorinated pyrimidine. Chemically, floxuridine is 2’-deoxy-5-fluorouridine.  It is a white to off-white odorless solid which is freely soluble in water.  The 2% aqueous solution has a pH of between 4.0 and 5.5.

The structural formula is:

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.  The drug is excreted intact and as urea, fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid and α-fluoro-β-alanine in the urine; it is also expired as respiratory carbon dioxide.  Pharmacokinetic data on intra-arterial infusion of floxuridine are not available.

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.

Floxuridine therapy is contraindicated for patients in a poor nutritional state, those with depressed bone marrow function or those with potentially serious infections.

BECAUSE OF THE POSSIBILITY OF SEVERE TOXIC REACTIONS, ALL PATIENTS SHOULD BE HOSPITALIZED FOR THE FIRST COURSE OF THERAPY.

Floxuridine should be used with extreme caution in poor risk patients with impaired hepatic or renal function or a history of high-dose pelvic irradiation or previous use of alkylating agents.  The drug is not intended as an adjuvant to surgery.

Floxuridine may cause fetal harm when administered to a pregnant woman.  It has been shown to be teratogenic in the chick embryo, mouse (at doses of 2.5 to 100 mg/kg) and rat (at doses of 75 to 150 mg/kg).  Malformations included cleft palates; skeletal defects; and deformed appendages, paws and tails.  The dosages which were teratogenic in animals are 4.2 to 125 times the recommended human therapeutic dose.

There are no adequate and well-controlled studies with floxuridine in pregnant women.  If this drug is used during pregnancy or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus.  Women of childbearing potential should be advised to avoid becoming pregnant.

Combination Therapy

Any form of therapy which adds to the stress of the patient, interferes with nutrition or depresses bone marrow function will increase the toxicity of floxuridine.

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, thrombocytopenia and elevations of alkaline phosphatase, serum transaminase, serum bilirubin and lactic dehydrogenase.

Other adverse reactions are:

Gastrointestinal: duodenal ulcer, duodenitis, gastritis, bleeding, gastroenteritis, glossitis, pharyngitis, anorexia, cramps, abdominal pain; possible intra- and extrahepatic biliary sclerosis, as well as acalculous cholecystitis.

Dermatologic: alopecia, dermatitis, nonspecific skin toxicity, rash.

Cardiovascular: myocardial ischemia.

Miscellaneous Clinical Reactions: fever, lethargy, malaise, weakness.

Laboratory Abnormalities: BSP, prothrombin, total proteins, sedimentation rate and thrombopenia.

Procedural Complications of Regional Arterial Infusion: arterial aneurysm; arterial ischemia; arterial thrombosis; embolism; fibromyositis; thrombophlebitis; hepatic necrosis; abscesses; infection at catheter site; bleeding at catheter site; catheter blocked, displaced or leaking.

The following adverse reactions have not been reported with floxuridine but have been noted following the administration of 5-fluorouracil.  While the possibility of these occurring following floxuridine therapy is remote because of its regional administration, one should be alert for these reactions following the administration of floxuridine because of the pharmacological similarity of these two drugs: pancytopenia, agranulocytosis, myocardial ischemia, angina, anaphylaxis, generalized allergic reactions, acute cerebellar syndrome, nystagmus, headache, dry skin, fissuring, photosensitivity, pruritic maculopapular rash, increased pigmentation of the skin, vein pigmentation, lacrimal duct stenosis, visual changes, lacrimation, photophobia, disorientation, confusion, euphoria, epistaxis and nail changes, including loss of nails.

The possibility of overdosage with floxuridine is unlikely in view of the mode of administration.  Nevertheless, the anticipated manifestations would be nausea, vomiting, diarrhea, gastrointestinal ulceration and bleeding, bone marrow depression (including thrombocytopenia, leukopenia and agranulocytosis).  No specific antidotal therapy exists.  Patients who have been exposed to an overdosage of floxuridine should be monitored hematologically for at least 4 weeks.  Should abnormalities appear, appropriate therapy should be utilized. 
    The acute intravenous toxicity of floxuridine is as follows:

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.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

The recommended therapeutic dosage schedule of floxuridine by continuous arterial infusion is 0.1 to 0.6 mg/kg/day.  The higher dosage ranges (0.4 to 0.6 mg) are usually employed for hepatic artery infusion because the liver metabolizes the drug, thus reducing the potential for systemic toxicity.  Therapy can be given until adverse reactions appear.  (See PRECAUTIONS).  When these side effects have subsided, therapy may be resumed.  The patients should be maintained on therapy as long as response to floxuridine continues.

Procedures for proper handling and disposal of anticancer drugs should be considered.  Several guidelines on this subject have been published.1-7  There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

The container closure is not made with natural rubber latex.

The sterile powder should be stored at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].  Reconstituted vials should be stored under refrigeration 2° to 8°C (36° to 46°F) for not more than 2 weeks.

1. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC, US Government Printing Office NIH publication 83-2621.
2. AMA Council Report. Guidelines for handling parenteral antineoplastics. JAMA. Mar 15, 1985, 253:1590-1592.
3. National Study Commission on Cytotoxic Exposure: Recommendations for handling cytotoxic agents. Available from Louis P. Jeffrey, ScD, Director of Pharmacy Services, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02902.
4. Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. Apr 30, 1983, 1:426-428.
5. Jones, RB, Frank R, Mass T: Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA. Sept-Oct, 1983, 33:258-263.
6. ASHP technical assistance bulletin on handling cytotoxic drugs in hospitals. AM J Hosp Pharm. Jan, 1985, 42:131-137.
7. OSHA Work-Practice Guidelines for Personnel Dealing with Cytotoxic (Antineoplastic) Drugs. Am J Hosp Pharm. 1986; 43:1193-1204.

www.fresenius-kabi.us

45914D

Revised: August 2016

PACKAGE LABEL - PRINCIPAL DISPLAY - Floxuridine 500 mg Vial Label
Floxuridine for Injection, USP
500 mg per vial
For intra-arterial use only.
Powder for reconstitution of parenteral solutions.
Rx only 

 

 

PACKAGE LABEL - PRINCIPAL DISPLAY - Floxuridine 500 mg Vial Carton Panel
Floxuridine for Injection, USP
500 mg per vial
For intra-arterial use only.
Powder for reconstitution of parenteral solutions.
Rx only