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Floxuridine

Medically reviewed by Drugs.com. Last updated on Oct 27, 2020.

Pronunciation

(floks YOOR i deen)

Index Terms

  • 5-FUDR
  • FdUrD
  • Floxuridin
  • Fluorodeoxyuridine
  • Fluorouridine deoxyribose
  • FUDF
  • 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 hepatic intra-arterial infusion) in select patients considered incurable by surgical resection or other means.

Limitation of use: Patients with known disease extending beyond an area capable of a single artery infusion should (in most cases) be considered for systemic chemotherapy with other agents.

Contraindications

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

Dosing: Adult

Colorectal cancer, hepatic metastases: Hepatic intra-arterial (off-label combination): 0.25 mg/kg/day (with dexamethasone and heparin) continuous infusion for 14 days during a 5-week cycle for 6 cycles (in combination with 6 cycles of fluorouracil and leucovorin; begin floxuridine 2 weeks after the fluorouracil and leucovorin cycle) (Kemeny 1999).

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. Range: 0.1 to 0.6 mg/kg/day as a continuous infusion; Usual dose: 0.4 to 0.6 mg/kg/day as a continuous infusion; continue until intolerable toxicity.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Adjustment for Toxicity

Withhold therapy for adverse reactions; may resume if adverse reaction subsides.

Hematologic: Discontinue for white blood count <3,500/mm3 (or is falling rapidly) or for platelet count <100,000/mm3.

Nonhematologic toxicity: Discontinue for myocardial ischemia, stomatitis/esophagopharyngitis, vomiting (intractable), diarrhea (or frequent/watery stools), 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

Reconstitute each 500 mg vial with 5 mL SWFI to a final concentration of 100 mg/mL. Further dilute in D5W or NS to a volume appropriate for intra-arterial administration. Floxuridine has been reported to be mixed with dexamethasone and heparin to a total volume of 50 mL in NS (Kemeny 1999).

Administration

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

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). Follow USP 797 recommendations for beyond use dates based on the level of risk for preparation.

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

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

Brivudine [INT]: May enhance the adverse/toxic effect of Fluorouracil Products. Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cimetidine: May increase the serum concentration of Fluorouracil Products. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

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

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

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

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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. 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

Folic Acid: May enhance the adverse/toxic effect of Fluorouracil Products. Monitor therapy

Fosphenytoin-Phenytoin: CYP2C9 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Monitor therapy

Gimeracil: May increase the serum concentration of Fluorouracil Products. Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Leucovorin Calcium-Levoleucovorin: May enhance the adverse/toxic effect of Fluorouracil Products. Monitor therapy

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

MetroNIDAZOLE (Systemic): May increase the serum concentration of Fluorouracil Products. Monitor therapy

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. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

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

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

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

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

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

TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or 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

Vitamin K Antagonists (eg, warfarin): Fluorouracil Products may increase the serum concentration of Vitamin K Antagonists. Management: Monitor INR and for signs/symptoms of bleeding closely when a fluorouracil product is combined with a vitamin K antagonist (eg, warfarin). Anticoagulant dose adjustment will likely be necessary. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>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%, postmarketing, and/or case reports: Abdominal cramps, abdominal pain, BSP abnormality, change in prothrombin time, decreased erythrocyte sedimentation rate, decreased serum total protein, duodenal ulcer, duodenitis, enteritis, fever, 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, lethargy, malaise, nausea, pharyngitis, skin rash, vomiting, weakness

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 intra-arterial drug therapy, and is well versed in the use of potent antimetabolites.

Appropriate use:

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

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Floxuridine may cause severe hematologic toxicity; anemia, leukopenia, and thrombocytopenia commonly occur. The nadir is usually at 7 to 10 days (Perry 2012). Leukopenia or thrombocytopenia may require therapy discontinuation.

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

Other warnings/precautions:

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

• Appropriate use: [US 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.

Monitoring Parameters

Monitor CBC with differential and platelet count; liver function (bilirubin, alkaline phosphatase, and transaminases); monitor for signs/symptoms of stomatitis/esophagopharyngitis, gastrointestinal ulceration/bleeding, hemorrhage, vomiting, and/or diarrhea

Reproductive Considerations

Females of reproductive potential should avoid pregnancy during floxuridine treatment.

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse effects have been observed in animal reproduction studies. Floxuridine may cause fetal harm if administered during pregnancy. Medications that inhibit DNA synthesis are known to be teratogenic in humans.

Patient Education

What is this drug used for?

• It is used to treat cancers which have spread.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hair loss

• Sore throat

• Abdominal cramps

• Lack of appetite

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Chest pain

• Mouth irritation

• Mouth sores

• Diarrhea

• Severe nausea

• Vomiting

• Severe abdominal pain

• Dark urine

• Yellow skin

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.