INDICATIONS AND USAGE 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.

WARNINGS 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 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, thrombo-cytopenia 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.