Antineoplastic, pyrimidine analogue (5-FU)
ATC code: L01BC02 (Fluorouracil)
Brand names
Adrucil, Efudex (topical)
After intracellular activation to fluorodeoxyuridine monophosphate, inhibits thymidylate synthase – the enzyme synthesising dTMP needed for DNA replication. Metabolites also incorporate into RNA and DNA and disrupt their function. Catabolised by dihydropyrimidine dehydrogenase (DPD): patients with DPD deficiency (3-5% of population) experience fatal toxicity even at standard doses. Plasma half-life 8-20 minutes.
First line
5-Fluorouracil is first-line antineoplastic in colorectal, breast, gastric and pancreatic cancer. ESMO 2024 includes 5-FU in FOLFOX, FOLFIRI, FOLFIRINOX regimens for metastatic colorectal cancer. DPD deficiency testing is mandatory before starting (-required since 2020).
Sources
ICD-10: C18-C20
3 pairs found. Sorted from critical to minor.
Mechanism
Brivudine irreversibly inhibits dihydropyrimidine dehydrogenase (DPD) – the enzyme degrading 5-FU. After 5-FU, toxicity escalates manifold: myelosuppression, severe mucositis, neurotoxicity. reported fatal cases. Effect persists 18+ days after brivudine withdrawal – 4-week washout required.
Symptoms
Severe myelosuppression with agranulocytosis, mucositis, diarrhoea, neurological disturbance within 5-10 days.
Management
Combination contraindicated. At least 4 weeks between brivudine and starting 5-FU/capecitabine. After accidental co-administration – uridine triacetate (Vistogard) within 96 hours as antidote.
Mechanism
5-FU inhibits CYP2C9 (S-warfarin metabolism) and impairs vitamin K-dependent clotting factor synthesis through direct myelotoxicity. INR rises 2-4 fold within 5-10 days. Fatal bleeding cases reported.
Symptoms
Gum/nose bleeding, haematuria, bloody stool within 5-10 days. INR above 5.0.
Management
If possible – switch warfarin to LMWH during chemotherapy. If warfarin needed – reduce by 30-50% with weekly INR.
Mechanism
5-FU inhibits CYP2C9 – phenytoin rises 2-fold. Toxicity with ataxia, nystagmus.
Symptoms
Nystagmus, ataxia, drowsiness after 7-14 days.
Management
Check phenytoin level on day 7. Reduce dose 25-50%.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Strictly contraindicated. Use only in life-threatening tumour by multidisciplinary decision. Contraception in men and women 6 months after withdrawal.
Breastfeeding contraindicated.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Fluorouracil is evaluated for the following indications with varying evidence strength: Colorectal cancer (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Fluorouracil (≥ 1 in 100): Mucositis and stomatitis, Nausea, vomiting, diarrhoea, Myelosuppression, Hand-foot syndrome (especially with continuous infusion). See the Safety section for uncommon and serious reactions.
FDA category D. Strictly contraindicated. Use only in life-threatening tumour by multidisciplinary decision. Contraception in men and women 6 months after withdrawal.
Breastfeeding contraindicated.
Fluorouracil is contraindicated in: Complete DPD deficiency (fatal toxicity); Combination with brivudine, sorivudine (fatal DPD inhibition); Severe bone marrow depression; Pregnancy. Full list in the Safety section.