FLAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLAC (FLAC).
FLAC (Fluorouracil) is a pyrimidine analog that inhibits thymidylate synthase, blocking DNA synthesis. It is converted to active metabolites (FdUMP, FUTP) that disrupt RNA function and DNA replication.
| Metabolism | Hepatic via dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil; further catabolized to urea and CO2. DPD deficiency leads to severe toxicity. |
| Excretion | Renal: 70% unchanged; Fecal: 20%; Biliary: 10% |
| Half-life | 2-4 hours; prolonged in renal impairment (up to 12 hours) |
| Protein binding | 75-80% bound to albumin |
| Volume of Distribution | 0.5-0.8 L/kg; indicates moderate tissue distribution |
| Bioavailability | Oral: 60-70% (first-pass metabolism) |
| Onset of Action | Oral: 30-60 minutes; IV: immediate |
| Duration of Action | 4-6 hours; extended with higher doses or renal impairment |
Adults: 40 mg orally twice daily.
| Dosage form | OIL/DROPS |
| Renal impairment | GFR 30-59 mL/min: 20 mg twice daily; GFR 15-29 mL/min: 20 mg once daily; GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 20 mg twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Children 2-12 years: 1 mg/kg orally twice daily, max 40 mg/day; Children 12-18 years: adult dosing. |
| Geriatric use | No specific adjustment; monitor renal function and consider lower starting dose in frail elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FLAC (FLAC).
| Breastfeeding | FLAC is excreted in breast milk with an M/P ratio of 0.8. Avoid breastfeeding due to potential adverse effects on infant CNS, including irritability and poor feeding. If unavoidable, monitor infant for sedation and respiratory depression. |
| Teratogenic Risk | First trimester: Associated with increased risk of neural tube defects and orofacial clefts. Second/third trimester: Risk of fetal growth restriction, preterm birth, and neonatal adaptation syndrome. Late third trimester/neonatal period: Risk of persistent pulmonary hypertension and withdrawal symptoms. |
■ FDA Black Box Warning
Should be administered under supervision of physicians experienced in cancer chemotherapy. May cause severe myelosuppression, gastrointestinal toxicity, and neurotoxicity. Not recommended in patients with poor nutritional status or severe infections.
| Serious Effects |
Hypersensitivity to fluorouracil, dihydropyrimidine dehydrogenase (DPD) deficiency, severe bone marrow suppression, serious infections, pregnancy, breastfeeding.
| Precautions | Monitor complete blood counts; dose reduction for toxicity. Caution in DPD deficiency, liver/renal impairment, and elderly. Avoid in pregnancy (teratogenic). Use with leucovorin increases toxicity. |
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| Fetal Monitoring |
| Monitor maternal blood pressure, blood glucose, and renal function. Serial fetal growth ultrasounds and nonstress tests starting at 28 weeks. Evaluate for signs of preterm labor. |
| Fertility Effects | FLAC may reduce fertility in both sexes. In males, reversible oligospermia and abnormal sperm motility. In females, menstrual irregularities and anovulation. Discontinuation typically restores fertility. |