Fluorouracil (5-FU) is a fluorinated pyrimidine antimetabolite and a cornerstone of chemotherapy, primarily used in the treatment of various solid tumors. It is a cell cycle-specific agent, active in the S-phase. In the Indian context, it is widely available as an injection for intravenous administration and as a topical cream for certain skin conditions. Its use requires careful monitoring due to a narrow therapeutic index and significant toxicity profile.
Adult: Dosing is HIGHLY REGIMEN-SPECIFIC and based on Body Surface Area (BSA). Common regimens: 1. **Bolus (Mayo Clinic regimen)**: 425 mg/m² IV daily for 5 days, repeated every 4-5 weeks, combined with leucovorin. 2. **Infusional (de Gramont regimen)**: 400 mg/m² IV bolus followed by 600 mg/m² continuous IV infusion over 22 hours on days 1 and 2, repeated every 2 weeks, with leucovorin. 3. **Weekly Bolus**: 500-600 mg/m² IV once weekly. The 500mg vial strength is used as part of these calculated doses.
Note: **For IV use only.** Must be administered by healthcare professionals trained in cytotoxic drug handling. Reconstitute 500mg vial with provided diluent or sterile water for injection. Can be given as a slow IV push over 1-5 minutes or diluted in compatible IV solutions (e.g., 0.9% NaCl, 5% Dextrose) for infusion. Extravasation can cause severe local tissue damage. Monitor infusion site closely.
Fluorouracil is a prodrug that requires intracellular activation to exert cytotoxic effects. Its primary mechanism is the inhibition of thymidylate synthase (TS), a key enzyme for de novo synthesis of thymidine, which is essential for DNA replication and repair. It also gets misincorporated into RNA and DNA, disrupting normal nucleic acid function.
Pregnancy: **FDA Pregnancy Category D (Indian 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 in pregnancy unless the potential benefit justifies the potential risk to the fetus. Effective contraception is required during and for at least 6 months after therapy.
Driving: May cause dizziness, cerebellar ataxia, or visual disturbances. Patients should be cautioned against driving or operating machinery, especially during and shortly after treatment.
| Leucovorin (Folinic Acid) | Potentiates the cytotoxicity and toxicity of fluorouracil by stabilizing the ternary complex with thymidylate synthase. | Major |
| Cimetidine | May increase plasma concentrations of fluorouracil by inhibiting its metabolism, potentially increasing toxicity. | Moderate |
| Metronidazole | May increase toxicity of fluorouracil; mechanism unclear (possible reduced clearance). | Moderate |
| Warfarin | Fluorouracil may potentiate 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., MMR, Varicella, Yellow Fever) | Risk of disseminated infection due to immunosuppression. Contraindicated during treatment. | Major |