Fluorouracil (5-FU, 5-fluorouracil), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, p and is also administered systemically for cancers of the breast, pancreas in combination regimens, and head and neck malignancies; topical formulations are used for actinic keratoses and certain superficial skin cancers. Chemically it is a fluorinated pyrimidine analogue that is taken up by proliferating cells and converted intracellularly to active metabolites including FdUMP and FUTP. FdUMP forms a stable complex with thymidylate synthase and 5,10-methylenetetrahydrofolate, leading to thymidine nucleotide depletion and disruption of DNA synthesis, while FUTP incorporation into RNA impairs RNA processing and function. Clinical administration routes include bolus intravenous injections, continuous infusions and topical application, with dosing modified for renal or hepatic impairment and for patients with dihydropyrimidine dehydrogenase deficiency which markedly increases systemic exposure and risk of severe toxicity.
Parent: Fluorouracil
Parent: Fluorouracil
Pharmaceutical quality specifications for fluorouracil control both known related compounds and unspecified impurities; typical control ranges used by manufacturers and pharmacopeias require individual related organic impurities to be low, commonly in the range of 0.1 to 0.5 percent by weight and total related compounds generally limited to around 1.0 to 2.0 percent by weight, with exact limits set by the registered drug master file and regulatory filings. Known related compounds and process or degradation impurities that are routinely monitored include uracil, dihydrouracil, 5-fluoro-5,6-dihydrouracil, 5-fluoro-2-prime-deoxyuridine, deaminated or chlorinated derivatives arising from synthesis, and trace levels of starting material or solvents; residual solvents and elemental impurities are controlled to international guidelines such as ICH Q3C and Q3D. Final product release and stability testing use validated chromatographic and spectroscopic methods to ensure impurity profiles remain within approved acceptance criteria.
Fluorouracil is used to treat a variety of cancers including colorectal, oesophageal, stomach, breast, pancreatic and head and neck cancers when given systemically, and is applied topically for actinic keratoses and certain superficial skin malignancies; it is often used in combination with other cytotoxic agents or radiotherapy.
Fluorouracil is a potent antimetabolite chemotherapy agent with dose dependent myelosuppressive, gastrointestinal and mucocutaneous toxicities; whether it is considered strong depends on regimen, dose intensity and combination partners, but it is widely regarded as a cornerstone cytotoxic drug with significant systemic effects.
Common adverse effects include myelosuppression with neutropenia, mucositis, stomatitis, diarrhea, nausea, hand foot syndrome and alopecia; severe toxicities can occur in patients with dihydropyrimidine dehydrogenase deficiency leading to life threatening myelosuppression, neurotoxicity and cardiac events, and other risks include local infusion reactions and cumulative mucocutaneous toxicity with continuous infusions.
Fluorouracil is metabolised intracellularly to FdUMP which inhibits thymidylate synthase causing depletion of dTMP and impaired DNA synthesis, and to FUTP which is incorporated into RNA disrupting RNA processing; the combination of thymidylate synthase inhibition and RNA misincorporation leads to cytotoxicity preferentially in rapidly dividing cells.
