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5-Fluorouracil is a pyrimidine analogue that disrupts DNA and RNA synthesis in rapidly dividing cells by inhibiting thymidylate synthase. Applied topically, it selectively destroys sun-damaged and precancerous cells while sparing normal tissue.
Commercial 5-FU (Efudex, Carac) is available at 0.5%, 2%, and 5%. Compounding allows intermediate concentrations, combinations with tretinoin or salicylic acid to enhance penetration, and formulations for subungual warts.
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5-Fluorouracil (5-FU) has been used topically for over 50 years to treat actinic keratoses — the most common precancerous skin lesion in fair-skinned individuals. It is also effective for superficial basal cell carcinoma, Bowen's disease (squamous cell carcinoma in situ), and refractory viral warts.
Compounded 5-FU allows combination with tretinoin for field treatment of severe sun damage and combination with DMSO or salicylic acid for improved penetration in wart protocols not achievable with commercial formulations.
Thymidylate Synthase Inhibition
5-Fluorouracil is a pyrimidine analog that is metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP), which irreversibly inhibits thymidylate synthase — blocking the conversion of dUMP to thTMP. This depletes the cellular pool of thymidine necessary for DNA synthesis, causing cell death in rapidly dividing cells.
Selective Toxicity to Pre-cancerous Cells
Sun-damaged keratinocytes and actinic keratosis cells divide more rapidly than normal skin and preferentially accumulate 5-FU, resulting in selective cytotoxicity to pre-cancerous and cancerous cells while relatively sparing normal slowly-dividing tissue.
Actinic keratosis (AK), superficial basal cell carcinoma, Bowen's disease (squamous cell carcinoma in situ), viral warts (plantar, periungual), skin field cancerization treatment
Superficial basal cell carcinoma (alternative to surgery for low-risk lesions), Bowen's disease (squamous cell carcinoma in situ), plantar and periungual warts (off-label), skin field cancerization treatment, erythroplasia of Queyrat
Actinic keratosis: 5% cream applied 1–2x daily for 2–4 weeks
Superficial BCC: 5% cream twice daily for 3–6 weeks
Low-dose pulsed (Carac protocol): 0.5% cream once daily for 4 weeks
Warts: Custom concentration under occlusion nightly
There is no dose titration — the prescribed concentration is applied consistently throughout the treatment course. For patients concerned about reaction intensity, prescribers may use the Carac protocol (0.5% once daily for 4 weeks) as a gentler alternative to the classic Efudex regimen. Applying a thin layer of petrolatum around the eyes and lips before application protects sensitive areas.
Topical Cream 5% — standard concentration for actinic keratosis and superficial BCC; most evidence-based
Topical Cream 0.5% — lower concentration for pulsed therapy protocols; less intense reaction; longer treatment course
Combination with Tretinoin — tretinoin enhances skin penetration of 5-FU; used for thick lesions or poor-penetration areas
DMSO-based Formula — DMSO carrier dramatically increases penetration; used for subungual and plantar warts resistant to standard treatments
Custom Concentration — intermediate strengths (e.g., 1%, 2%) for patients with sensitive skin or specific prescriber protocols
Intense inflammatory reaction (erythema, erosion, crusting, ulceration) is expected and indicates efficacy. Pain and burning during treatment course. Post-treatment hypopigmentation possible. Avoid sunlight during treatment. Not for use near eyes or mucous membranes. Contraindicated in pregnancy.
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