Floxuridine: Drug information
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(For additional information see "Floxuridine: Patient drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
ALERT: US 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.

Brand Names: Canada
  • FUDR®
Pharmacologic Category
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)
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: 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).

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).

Dosage Forms

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

Solution Reconstituted, Injection:

Generic: 0.5 g (1 ea)

Generic Equivalent Available (US)

Yes

Administration

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

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving, a gown, and (if dosage form allows) CSTDs are required during administration (NIOSH 2016).

Use

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Floxuridine may be confused with Fludara, fludarabine, fluorouracil

FUDR may be confused with Fludara

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

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%, 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

Contraindications

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

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.

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.

Metabolism/Transport Effects

Inhibits CYP2C9 (strong)

Drug Interactions

(For additional information: Launch drug interactions program)

Alitretinoin (Systemic): CYP2C9 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP2C9 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP2C9 inhibitor. Risk D: Consider therapy modification

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

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: 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. Risk C: Monitor therapy

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

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

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

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

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

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

CYP2C9 Substrates (High risk with Inhibitors): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

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

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: 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. Risk D: Consider therapy modification

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

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

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

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

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

Lacosamide: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Lacosamide. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

Lornoxicam: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Lornoxicam. Risk C: Monitor therapy

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

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

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

Ospemifene: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Risk C: 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. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Risk C: Monitor therapy

Tetrahydrocannabinol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Risk C: 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. Risk D: Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: 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. Risk D: 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. Risk X: Avoid combination

Pregnancy Risk Factor

D (show table)

Pregnancy Implications

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.

Breast-Feeding Considerations

It is not known if floxuridine is excreted in human milk; the manufacturer recommends against breast-feeding during floxuridine treatment.

Monitoring Parameters

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

Mechanism of Action

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

Pharmacodynamics/Kinetics

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])

Pricing: US

Solution (reconstituted) (Floxuridine Injection)

0.5 g (1): $142.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • FUDR (CA)
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REFERENCES

  1. Allen-Mersh TG, Earlam S, Fordy C, et al. Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet. 1994;344(8932):1255-1260. [PubMed 7526096]
  2. Davidson BS, Izzo F, Chase JL, et al, “Alternating Floxuridine and 5-Fluorouracil Hepatic Arterial Chemotherapy for Colorectal Liver Metastases Minimizes Biliary Toxicity,” Am J Surg, 1996, 172(3):244-7. [PubMed 8862076]
  3. de Takats PG, Kerr DJ, Poole CJ, et al, “Hepatic Arterial Chemotherapy for Metastatic Colorectal Carcinoma,” Br J Cancer, 1994, 69(2):372-8. [PubMed 8297738]
  4. Floyd J, Mirza I, Sachs B, et al, "Hepatotoxicity of Chemotherapy," Semin Oncol, 2006, 33(1):50-67. [PubMed 16473644]
  5. Fudr (floxuridine) [prescribing information]. Bedford, OH: Bedford Laboratories; February 2000.
  6. Griggs JJ, Mangu PB, Anderson H, et al, “Appropriate Chemotherapy Dosing For Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline,” J Clin Oncol, 2012, 30(13):1553-61. [PubMed 22473167]
  7. Kemeny N, Seiter K, Conti JA, et al, Hepatic Arterial Floxuridine and Leucovorin for Unresectable Liver Metastases From Colorectal Carcinoma. New Dose Schedules and Survival Update,” Cancer, 1994, 73(4):1134-42.
  8. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.
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