FLOXURIDINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLOXURIDINE (FLOXURIDINE).
FLOXURIDINE is an antimetabolite that inhibits thymidylate synthetase, thereby blocking DNA synthesis. It is converted to 5-fluorouracil (5-FU) in the body, which is further metabolized to active nucleotides that incorporate into RNA and inhibit thymidylate synthase.
| Metabolism | FLOXURIDINE is rapidly metabolized to 5-fluorouracil (5-FU) by thymidine phosphorylase. 5-FU is further catabolized by dihydropyrimidine dehydrogenase (DPD) in the liver and other tissues. |
| Excretion | Primarily hepatic metabolism to inactive metabolites; renal excretion accounts for <10% of unchanged drug; biliary/fecal excretion is minor. |
| Half-life | Terminal half-life is approximately 20 minutes; clinical context: rapid clearance necessitates continuous IV infusion for sustained antineoplastic effect. |
| Protein binding | <10% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.3-0.6 L/kg; clinical meaning: distributes primarily into total body water and extracellular fluid. |
| Bioavailability | Not available for oral route; only administered intravenously; no oral formulation exists. |
| Onset of Action | Onset of action is immediate via continuous IV infusion; clinical effect (antitumor activity) typically observed within days to weeks. |
| Duration of Action | Duration of action is short-lived due to rapid metabolism; clinical effect requires continuous infusion; antineoplastic activity persists for days after discontinuation due to incorporation into DNA. |
0.1 to 0.6 mg/kg/day via continuous intra-arterial infusion for 14 days, then 7-day rest; typical dose 0.3 mg/kg/day.
| Dosage form | Injectable |
| Renal impairment | No specific guidelines; use with caution in renal impairment. Monitor for toxicity. Consider dose reduction if GFR < 30 mL/min. |
| Liver impairment | Contraindicated in patients with severe hepatic dysfunction (Child-Pugh class C). For mild to moderate (Child-Pugh A or B), consider dose reduction and monitor hepatic function. |
| Pediatric use | Safety and efficacy not established; no standard pediatric dosing recommendations. |
| Geriatric use | Use caution due to increased sensitivity; monitor for myelosuppression, mucositis, and hepatic toxicity. Consider starting at lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FLOXURIDINE (FLOXURIDINE).
| Breastfeeding | No data available on excretion into human milk. Due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression, gastrointestinal toxicity), breastfeeding is contraindicated during therapy and for 2 weeks after last dose. |
| Teratogenic Risk | FLOXURIDINE is a fluoropyrimidine antimetabolite. Based on its mechanism of action and animal studies, it is expected to cause fetal harm if administered during pregnancy. First trimester exposure is associated with increased risk of major malformations (e.g., craniofacial, skeletal, cardiovascular). Second and third trimester exposure may cause fetal growth restriction, myelosuppression, and neurodevelopmental deficits. Use is contraindicated in pregnancy. |
■ FDA Black Box Warning
FLOXURIDINE should be administered only by or under the supervision of a qualified physician experienced in cancer chemotherapy and with access to adequate laboratory and supportive resources. Severe toxicities including myelosuppression, gastrointestinal toxicity, and hepatotoxicity may occur.
| Serious Effects |
Hypersensitivity to floxuridine or 5-FU; severe bone marrow suppression; serious infection; history of severe toxicity from fluoropyrimidine therapy; DPD deficiency (relative); pregnancy; lactation.
| Precautions | Hepatotoxicity, especially with intra-arterial infusion; biliary sclerosis; gastrointestinal toxicity (stomatitis, diarrhea); myelosuppression (leukopenia, thrombocytopenia); photosensitivity; hand-foot syndrome; neurological toxicity; renal impairment; pregnancy category D; lactation; risk of bleeding; infection. |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests, renal function, and electrolytes. Assess for signs of infection, bleeding, and diarrhea. Fetal monitoring: ultrasound for growth and anatomy if inadvertent exposure occurs. |
| Fertility Effects | FLOXURIDINE may impair fertility in both males and females. In males, it may cause oligospermia, azoospermia, and testicular atrophy. In females, it may cause amenorrhea and ovarian failure. Effects may be irreversible. |