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Floxuridine

Pronunciation

(floks YOOR i deen)

Index Terms

  • 5-FUDR
  • FdUrD
  • Floxuridin
  • Fluorodeoxyuridine
  • FUDR

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Generic: 0.5 g (1 ea)

Pharmacologic Category

  • Antineoplastic Agent, Antimetabolite
  • Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)

Pharmacology

Floxuridine is catabolized to fluorouracil after intra-arterial administration, resulting in activity similar to fluorouracil; inhibits thymidylate synthetase and disrupts DNA and RNA synthesis.

Metabolism

Hepatic; Active metabolites: Floxuridine monophosphate (FUDR-MP) and fluorouracil; Inactive metabolites: Urea, CO2, α-fluoro-β-alanine, α-fluoro-β-guanidopropionic acid, α-fluoro-β-ureidopropionic acid, and dihydrofluorouracil

Excretion

Urine: As fluorouracil, urea, α-fluoro-β-alanine, α-fluoro-β-guanidopropionic acid, α-fluoro-β-ureidopropionic acid, and dihydrofluorouracil; Respiratory (as exhaled gases [CO2])

Use: Labeled Indications

Colorectal cancer, hepatic metastases: Palliative management of hepatic metastases of colorectal cancer (administered by continuous regional intra-arterial infusion) in select patients considered incurable by surgical resection or other means.

Contraindications

Poor nutritional states; depressed bone marrow function; potentially serious infections

Dosing: Adult

Colorectal cancer, hepatic metastases: Intra-arterial: 0.1-0.6 mg/kg/day as a continuous infusion; continue until intolerable toxicity

Dosing: Renal Impairment

No dosage adjustment provided in the manufacturer’s labeling; use with extreme caution.

Dosing: Hepatic Impairment

No dosage adjustment provided in the manufacturer’s labeling; use with extreme caution. The following adjustments have been recommended (Floyd, 2006):

Serum bilirubin 1.2 times ULN or alkaline phosphatase 1.2 times ULN: Administer 80% of dose

Serum bilirubin 1.5 times ULN; transaminases 3 times baseline or alkaline phosphatase 1.5 times ULN: Administer 50% of dose

Serum bilirubin 2 times ULN; transaminases >3 times baseline or alkaline phosphatase 2 times ULN: No recommendation is available

Dosing: Adjustment for Toxicity

Hematologic: Discontinue if white blood count <3500/mm3 (or is falling rapidly) or if platelet count <100,000/mm3.

Nonhematologic toxicity: Discontinue for myocardial ischemia, stomatitis/esophagopharyngitis, vomiting (intractable), diarrhea, gastrointestinal ulceration/bleeding, hemorrhage (from any site).

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Reconstitute with 5 mL SWFI for a final concentration of 100 mg/mL. Further dilute in D5W or NS to a volume appropriate for intra-arterial administration.

Administration

Administer as a continuous intra-arterial infusion using an infusion pump.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Compatibility

Stable in D5W, NS, SWFI.

Y-site administration: Incompatible with allopurinol, cefepime.

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F). Reconstituted vials are stable for up to 2 weeks under refrigeration at 2°C to 8°C (36°F to 46°F).

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Cannabis: May increase the serum concentration of CYP2C9 Inhibitors (Strong). More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cimetidine: May increase serum concentrations of the active metabolite(s) of Floxuridine. Specifically, concentrations of fluorouracil may be increased. Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

CYP2C9 Substrates: CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates. Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Diclofenac (Systemic): CYP2C9 Inhibitors (Strong) may increase the serum concentration of Diclofenac (Systemic). Management: Consider using a lower dose of diclofenac when used together with a strong CYP2C9 inhibitor. Arthrotec (diclofenac and misoprostol) labeling specifically recommends limiting the total daily dose to a maximum of 50 mg twice/day. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Dronabinol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosphenytoin: Floxuridine may increase the serum concentration of Fosphenytoin. Consider therapy modification

Gimeracil: May increase serum concentrations of the active metabolite(s) of Floxuridine. Specifically, gimeracil may increase concentrations of fluorouracil. Avoid combination

Lacosamide: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Lacosamide. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ospemifene: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Monitor therapy

Parecoxib: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Monitor therapy

Phenytoin: Floxuridine may increase the serum concentration of Phenytoin. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Ramelteon: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tetrahydrocannabinol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

>10%:

Gastrointestinal: Diarrhea (may be dose limiting), stomatitis

Hematologic & oncologic: Anemia, bone marrow depression (nadir: 7-10 days; may be dose limiting), leukopenia, thrombocytopenia

1% to 10%:

Dermatologic: Alopecia, dermatitis, localized erythema, skin hyperpigmentation, skin photosensitivity

Gastrointestinal: Anorexia, biliary sclerosis, cholecystitis

Hepatic: Jaundice

<1% (Limited to important or life-threatening): BSP abnormality, change in prothrombin time, decreased erythrocyte sedimentation rate, decreased serum total protein, duodenal ulcer, duodenitis, enteritis, gastritis, gastroenteritis, gastrointestinal hemorrhage, gastrointestinal ulcer, glossitis, hemorrhage, hepatic abscess, increased erythrocyte sedimentation rate, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum bilirubin, increased serum total protein, increased serum transaminases, infusion related reaction (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), ischemic heart disease, pharyngitis

ALERT: U.S. Boxed Warning

Experienced physician:

It is recommended that floxuridine be given only by or under the supervision of a qualified health care provider who is experienced in cancer chemotherapy and intraarterial drug therapy, and is well versed in the use of potent antimetabolites.

Appropriate use:

Because of the possibility of severe toxic reactions, hospitalize all patients for initiation of the first course of therapy.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: May cause severe hematologic toxicity (anemia, leukopenia, and thrombocytopenia). Discontinue if white blood count <3500/mm3 (or is falling rapidly) or if platelet count <100,000/mm3.

• Cardiovascular toxicity: Myocardial ischemia has been reported; discontinue if occurs.

• Gastrointestinal toxicity: May cause gastrointestinal toxicity. Discontinue at the first sign of stomatitis or esophagopharyngitis; discontinue for intractable vomiting, diarrhea, or gastrointestinal ulceration/bleeding.

• Hemorrhage: Bleeding may occur; discontinue if hemorrhage (from any site) occurs.

• Toxicity: Toxicities may occur; monitor closely. Severe toxicities are more likely to occur in high risk patients, patients with prior pelvic irradiation, or in those who have received prior alkylating agents.

Disease-related concerns:

• Hepatic impairment: Use with extreme caution in patients with hepatic impairment.

• Renal impairment: Use with extreme caution in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Other warnings/precautions:

• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of a physician experienced in cancer chemotherapy and in intra-arterial treatment.

• Appropriate use: [U.S. Boxed Warning]: Due to the risk for severe toxic reactions, the manufacturer recommends that patients be hospitalized for initiation of the first treatment course. Not intended for use as an adjuvant to surgery or in patients with known disease extending beyond an area of single-artery infusion.

Monitoring Parameters

CBC with differential and platelet count; liver function; signs/symptoms of stomatitis/esophagopharyngitis, gastrointestinal ulceration/bleeding, hemorrhage, vomiting, and diarrhea

Pregnancy Risk Factor

D

Pregnancy Considerations

Teratogenic effects have been observed in animal reproduction studies. Medications that inhibit DNA synthesis are known to be teratogenic in humans. Women of childbearing potential should avoid pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience alopecia or lack of appetite. Have patient report immediately to prescriber signs of infection, angina, stomatitis, significant diarrhea, severe nausea, signs of hemorrhaging, urine discoloration, jaundice, intolerable asthenia, or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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