FUDR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FUDR (FUDR).
FUDR (floxuridine) is a fluoropyrimidine antimetabolite that inhibits thymidylate synthase after conversion to 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), thereby blocking DNA synthesis. It also incorporates into RNA and DNA, causing cytotoxicity.
| Metabolism | Hepatic metabolism via dihydropyrimidine dehydrogenase (DPD) to 5-fluorouracil (5-FU), which is further catabolized; also directly phosphorylated to active nucleotides. |
| Excretion | Primarily hepatic metabolism; <10% excreted unchanged in urine. Biliary/fecal elimination accounts for approximately 40-60% of metabolites. |
| Half-life | Terminal half-life is approximately 25-30 hours (range 20-40 h) after intravenous administration, prolonged in hepatic impairment. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.5-0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral: negligible (<10%) due to extensive first-pass metabolism; IV: 100%. |
| Onset of Action | Intravenous: within 1-2 hours after bolus; continuous infusion: steady state achieved in 4-6 hours. |
| Duration of Action | Intravenous: effects persist for 24-48 hours; continuous infusion: sustained for duration of infusion plus 24-48 hours post-infusion. |
0.1 to 0.6 mg/kg/day via continuous intra-arterial infusion (hepatic artery infusion) for 14 days followed by 7 days rest, repeated every 21 days. Alternatively, 0.5 to 1 mg/kg/day via continuous intravenous infusion for 5 days every 28 days.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose modifications established. Use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation. Consider dose reduction of 50%. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 25-50%. Child-Pugh C: Contraindicated or use with extreme caution and reduce dose by ≥50%. |
| Pediatric use | Safety and efficacy not established. No standard dosing recommendations. Use only in clinical trial settings. |
| Geriatric use | No specific dose adjustments recommended. Monitor renal and hepatic function closely. Elderly patients may have increased sensitivity to 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 FUDR (FUDR).
| Breastfeeding | Contraindicated during breastfeeding. Floxuridine is excreted into breast milk; M/P ratio not reported. Risk of severe infant toxicity including immunosuppression and growth impairment. |
| Teratogenic Risk | FUDR (floxuridine) is a pregnancy category D drug. First trimester exposure is associated with teratogenicity including neural tube defects, skeletal anomalies, and growth restriction due to antimetabolite action inhibiting DNA synthesis. Second and third trimester use increases risk of fetal myelosuppression, IUGR, and preterm birth. |
■ FDA Black Box Warning
Must be administered by or under the supervision of a physician experienced in cancer chemotherapy and in a facility with adequate diagnostic and therapeutic resources to manage drug toxicity.
| Serious Effects |
Hypersensitivity to floxuridine or any component, severe bone marrow depression, active infection, and pregnancy.
| Precautions | Hepatotoxicity, biliary sclerosis (especially with hepatic arterial infusion), gastrointestinal toxicity (stomatitis, diarrhea), myelosuppression, cardiopulmonary toxicity (chest pain, dyspnea), renal impairment, and increased risk with DPD deficiency. |
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| Fetal Monitoring |
| Monitor complete blood counts (CBC) with differential weekly, hepatic function (AST/ALT, bilirubin), renal function (serum creatinine, BUN). Fetal ultrasound for growth and anatomy at 18-20 weeks and monthly thereafter. Non-stress test or biophysical profile in third trimester. |
| Fertility Effects | Floxuridine can cause gonadal suppression in both sexes leading to amenorrhea, oligospermia, or azoospermia. Fertility may be impaired during treatment and may be irreversible depending on cumulative dose and age. |