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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Floxuridine may be confused with Fludara®, fludarabine
FUDR® may be confused with Fludara®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Pronunciation
(floks YOOR i deen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Management of hepatic metastases of colorectal and gastric cancers
Pregnancy Risk Factor
D
Lactation
Excretion in breast milk unknown/contraindicated
Contraindications
Hypersensitivity to floxuridine, fluorouracil, or any component of the formulation; pregnancy
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
• Initiation of therapy: See “Other warnings/precautions” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Toxicity: Discontinue if intractable vomiting, diarrhea, precipitous fall in leukocyte or platelet counts, myocardial ischemia, hemorrhage, gastrointestinal ulcer, or stomatitis occur.
Disease-related concerns:
• Bone marrow suppression: Use with caution in patients with depressed (leukocyte count <5000/mm3 or platelet count <100,000/mm3) bone marrow function.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Infection: Use with caution in patients with potentially serious infections.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Alkylating agents: Use with caution in patients who have had previous use of alkylating agents.
Special populations:
• Pelvic radiation recipients: Use with caution in patients who have had high-dose pelvic radiation.
• Poor nutritional status: Use with caution in patients with poor nutritional status.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• Initiation of therapy: [U.S. Boxed Warning]: Patients should be hospitalized for initiation of the first course of therapy due to the risk for severe toxic reactions.
Adverse Reactions
>10%:
Gastrointestinal: Stomatitis, diarrhea; may be dose limiting
Hematologic: Myelosuppression, may be dose limiting; leukopenia, thrombocytopenia, anemia
Onset: 4-7 days
Nadir: 5-9 days
Recovery: 21 days
1% to 10%:
Dermatologic: Alopecia, photosensitivity, hyperpigmentation of the skin, localized erythema, dermatitis
Gastrointestinal: Anorexia
Hepatic: Biliary sclerosis, cholecystitis, jaundice
<1%: Nausea, vomiting, intrahepatic abscess
Drug Interactions
Cardiac Glycosides: Antineoplastic Agents may decrease the absorption of Cardiac Glycosides. This may only affect digoxin tablets. Exceptions: Digitoxin. 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
CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
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
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Phenytoin: Floxuridine may increase the serum concentration of Phenytoin. 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). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live virus vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Antineoplastic Agents may enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to GI irritation).
Storage
Store intact vials at room temperature of 15°C to 30°C (59°F to 86°F). Reconstituted vials are stable for up to 2 weeks under refrigeration at 2°C to 8°C (36°C to 46°C). Further dilution in 500-1000 mL D5W or NS is stable for 2 weeks at room temperature. Solutions in 0.9% sodium chloride are stable in some ambulatory infusion pumps for up to 21 days.
Reconstitution
Reconstitute with 5 mL SWI for a final concentration of 100 mg/mL. Further dilute in 500-1000 mL D5W or NS for I.V. infusion.
Compatibility
Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Amifostine, aztreonam, etoposide phosphate, filgrastim, fludarabine, gemcitabine, granisetron, melphalan, ondansetron, paclitaxel, piperacillin/tazobactam, sargramostim, teniposide, thiotepa, vinorelbine. Incompatible: Allopurinol, cefepime.
Compatibility when admixed: Compatible: Carboplatin, cisplatin, cisplatin with etoposide, cisplatin with leucovorin, etoposide, fluorouracil, leucovorin.
Mechanism of Action
Mechanism of action and pharmacokinetics are very similar to fluorouracil; floxuridine is the deoxyribonucleotide of fluorouracil. Floxuridine is a fluorinated pyrimidine antagonist which inhibits DNA and RNA synthesis and methylation of deoxyuridylic acid to thymidylic acid.
Pharmacodynamics/Kinetics
Metabolism: Hepatic; Active metabolites: Floxuridine monophosphate (FUDR-MP) and fluorouracil; Inactive metabolites: Urea, CO2, ?-fluoro-?-alanine, ?-fluoro-?-guanidopropionic acid, ?-fluoro-?-ureidopropionic acid, and dihydrofluorouracil
Excretion: Urine: Fluorouracil, urea, ?-fluoro-?-alanine, ?-fluoro-?-guanidopropionic acid, ?-fluoro-?-ureidopropionic acid, and dihydrofluorouracil; exhaled gases (CO2)
Dosage
Refer to individual protocols.
Intra-arterial:
0.1-0.6 mg/kg/day
4-20 mg/day
I.V. (unlabeled use):
0.15 mg/kg/day for 7-14 days
0.5-1 mg/kg/day for 6-15 days
30 mg/kg/day for 5 days, then 15 mg/kg/day every other day, up to 11 days
Dosage adjustment in renal impairment: The FDA-approved labeling does not contain dosing adjustment guidelines; use with extreme caution.
Dosage adjustment in hepatic impairment: The FDA-approved labeling does not contain dosing adjustment guidelines; use with extreme caution. The following guidelines have been used by some clinicians (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
Administration: I.V.
Continuous intra-arterial or I.V. infusion (unlabeled use)
Administration: I.V. Detail
pH: 4.0-5.5
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This drug can only be administered by infusion. Follow instructions of prescriber for care of implantable pump. Avoid alcohol. It is important to maintain adequate hydration unless instructed to restrict fluid intake, and nutrition (small, frequent meals may help). You will be more susceptible to infection (avoid crowds and exposure to infection and do not have any vaccinations without consulting prescriber). May cause nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); loss of hair (reversible); diarrhea; mouth sores (use a soft toothbrush or cotton swabs for oral care); or sterility. Increased emotional or physical stress will adversely affect the response to this medication. Notify prescriber if you are experiencing unusual or elevated levels of stress. Report extreme fatigue; pain or numbness in extremities; severe GI upset or diarrhea; bleeding or bruising; fever, chills, or sore throat; vaginal discharge; or signs of fluid retention (eg, swelling extremities, respiratory difficulty, unusual weight gain). Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication and for 1 month following therapy. Consult prescriber for appropriate barrier contraceptives. Do not breast-feed.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Use caution with impaired liver or kidney function. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking. See Administration for infusion specifics. Assess results of laboratory tests, therapeutic effectiveness, and adverse response (eg, CNS changes, acute gastrointestinal reactions [intractable vomiting or diarrhea may be dose limiting]) on a regular basis throughout therapy. Teach patient (caregiver) use and care of implantable pump, possible side effects/appropriate interventions, and adverse symptoms to report.
Oncology: Vesicant
May be an irritant
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg
References
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.
DeConti RC, Kaplan SR, Papac RJ, et al, “Continuous Infusions of 5-Fluoro-2-Deoxyuridine in the Treatment of Solid Tumors,” Cancer, 1973, 31(4):894-8.
de Takats PG, Kerr DJ, Poole CJ, et al, “Hepatic Arterial Chemotherapy for Metastatic Colorectal Carcinoma,” Br J Cancer, 1994, 69(2):372-8.
Floyd J, Mirza I, Sachs B, et al, "Hepatotoxicity of Chemotherapy," Semin Oncol, 2006, 33(1):50-67.
Hrushesky WJ, von Roemeling R, Lanning RM, et al, “Circadian-Shaped Infusions of Floxuridine for Progressive Metastatic Renal Cell Carcinoma,” J Clin Oncol, 1990, 8(9):1504-13.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2009
Content last modified October 2009
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