Fluorouracil (5-FU) is a fluorinated pyrimidine antimetabolite and a cornerstone chemotherapeutic agent. It is a cell cycle-specific agent, primarily active in the S-phase, used extensively in the treatment of various solid tumors. In the Indian context, it is a widely available, cost-effective chemotherapy option, often used in combination regimens for gastrointestinal, breast, and head & neck cancers. Its mechanism involves inhibition of thymidylate synthase and incorporation into RNA and DNA, leading to faulty nucleic acid synthesis and cell death.
Adult: Dose varies drastically based on regimen, cancer type, and combination therapy. Common regimens: 1) Bolus: 370-425 mg/m² IV daily for 5 days, repeated every 4-5 weeks. 2) Continuous Infusion (common in India for GI cancers): 1000 mg/m²/day IV as a continuous infusion over 24 hours for 4-5 days, repeated every 3-4 weeks. 3) Weekly Bolus: 500-600 mg/m² IV once weekly. Dose MUST be calculated using Body Surface Area (BSA).
Note: For 250mg vial: Reconstitute with sterile water for injection or other specified diluent as per manufacturer's instructions. Administer as a slow intravenous push (bolus) over 1-5 minutes or dilute in compatible IV fluid (e.g., 0.9% NaCl, 5% Dextrose) for infusion as per protocol. EXTRAVASATION CAN CAUSE SEVERE LOCAL TISSUE DAMAGE. Ensure patent IV line. Continuous infusion requires a central venous line or a well-secured peripheral line with an infusion pump. NEVER administer intrathecally - FATAL.
Fluorouracil is a prodrug that requires intracellular activation to exert its cytotoxic effects. Its primary mechanism is the inhibition of thymidylate synthase (TS) by its active metabolite, fluorodeoxyuridine monophosphate (FdUMP), in the presence of a folate cofactor (5,10-methylenetetrahydrofolate). This inhibition blocks the conversion of deoxyuridylic acid (dUMP) to deoxythymidylic acid (dTMP), thereby depleting intracellular thymidine triphosphate (dTTP) pools, which is essential for DNA synthesis and repair. Additionally, fluorouracil is metabolized to fluorouridine triphosphate (FUTP), which is incorporated into RNA, disrupting normal RNA processing and function. A third metabolite, fluorodeoxyuridine triphosphate (FdUTP), can be misincorporated into DNA, leading to DNA strand breaks and cell death.
Pregnancy: FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. Can cause fetal harm. Contraindicated, especially in first trimester. Effective contraception is required for both males and females during and for at least 6 months after therapy.
Driving: May cause dizziness, confusion, or cerebellar ataxia (neurotoxicity). Patients should be cautioned against driving or operating machinery, especially if such symptoms occur.
| Leucovorin (Calcium Folinate) | Potentiates the cytotoxicity and toxicity of fluorouracil by stabilizing the ternary complex with thymidylate synthase. Requires careful dose monitoring. | Major |
| Cimetidine | May increase plasma concentrations of fluorouracil by inhibiting its metabolism, potentially increasing toxicity. | Moderate |
| Metronidazole | May increase toxicity of fluorouracil by reducing its clearance. Avoid combination. | Major |
| Warfarin | Fluorouracil may enhance the anticoagulant effect of warfarin, increasing INR and risk of bleeding. Monitor INR closely. | Major |
| Phenytoin | Fluorouracil may decrease phenytoin levels, potentially leading to loss of seizure control. | Moderate |
| Live Vaccines (e.g., BCG, MMR, Varicella) | Risk of disseminated infection due to immunosuppression. Contraindicated. | Major |
| Other Myelosuppressive Agents (e.g., Clozapine, Azathioprine) | Additive risk of severe bone marrow suppression. | Major |
Same composition (Fluorouracil (250mg)), different brands: