Introduction
Efudex (fluorouracil) is a topical antineoplastic agent belonging to the antimetabolite class. It is primarily used in dermatology for the treatment of various precancerous and cancerous skin conditions. First approved by the FDA in 1970, Efudex remains a cornerstone therapy for actinic keratosis and superficial basal cell carcinoma.
Mechanism of Action
Fluorouracil is a pyrimidine analog that interferes with DNA synthesis by inhibiting thymidylate synthase, ultimately disrupting RNA processing and function. The drug is incorporated into RNA in place of uracil, producing fraudulent RNA that interferes with normal protein synthesis. This dual mechanism creates cytotoxic effects preferentially in rapidly dividing cells, particularly actinic keratoses and malignant cells.
Indications
- Treatment of multiple actinic keratoses
- Superficial basal cell carcinoma when conventional methods are impractical
- Off-label uses include treatment of Bowen's disease, squamous cell carcinoma in situ, and genital warts (though not FDA-approved for these indications)
Dosage and Administration
Actinic Keratosis:- Apply twice daily for 2-4 weeks
- Apply sufficient quantity to cover lesions
- Apply twice daily for 3-6 weeks
- Apply sufficient quantity to cover lesions (typically 1 cm beyond lesion borders)
- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: Use with caution
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Minimal systemic absorption (typically <10% of applied dose) Distribution: Primarily local tissue distribution with minimal systemic distribution Metabolism: Undergoes extensive hepatic metabolism via dihydropyrimidine dehydrogenase (DPD) Elimination: Primarily renal elimination (80-90%) with respiratory elimination of CO₂ Half-life: 10-20 minutes (systemic)Contraindications
- Hypersensitivity to fluorouracil or any component of the formulation
- Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency
- Pregnancy (Category X)
- Breastfeeding
Warnings and Precautions
- Photosensitivity: Patients should avoid excessive sunlight exposure during treatment
- Inflammatory reactions: Expected therapeutic response includes erythema, scaling, and crusting
- Systemic absorption: May occur with application to large areas, broken skin, or under occlusive dressings
- DPD deficiency screening: Consider testing for DPD deficiency in patients requiring extensive application
- Ocular exposure: Avoid contact with eyes and mucous membranes
Drug Interactions
- Cimetidine: May increase fluorouracil concentrations
- Leucovorin: Enhances fluorouracil toxicity (systemic administration)
- Warfarin: May potentiate anticoagulant effect
- Photosensitizing agents: Increased risk of phototoxicity
- Live vaccines: Avoid concurrent administration
Adverse Effects
Common (>10%):- Application site reactions (erythema, dryness, scaling, crusting)
- Pruritus
- Burning sensation
- Hyperpigmentation
- Dermatitis
- Severe inflammatory reactions
- Ulceration
- Scarring
- Systemic effects (with extensive application): nausea, vomiting, diarrhea, bone marrow suppression
- Anaphylaxis (rare)
Monitoring Parameters
- Clinical response: Assess therapeutic effect and local reactions
- Skin integrity: Monitor for excessive inflammation or ulceration
- Systemic symptoms: Watch for nausea, vomiting, or diarrhea (indicating possible systemic absorption)
- Complete blood count: If applying to large body surface areas or compromised skin
- Renal and hepatic function: In patients with pre-existing conditions
Patient Education
- Apply with finger cot or glove to prevent application to unaffected areas
- Wash hands thoroughly after application
- Avoid sunlight and UV exposure during treatment; use protective clothing and sunscreen
- Expect redness, scaling, and crusting - this indicates the medication is working
- Do not cover treated areas with occlusive dressings unless directed by physician
- Contact healthcare provider if severe pain, ulceration, or signs of infection develop
- Treatment response may continue for 1-2 months after discontinuation
- Inform all healthcare providers about Efudex use before any procedures
References
1. FDA Prescribing Information: Efudex (fluorouracil) cream. Revised 2022. 2. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier; 2021. 3. Lexicomp Online. Fluorouracil (Topical). Wolters Kluwer Clinical Drug Information; 2023. 4. Stockfleth E, et al. J Eur Acad Dermatol Venereol. 2015;29(2):345-353. 5. Drew PJ, et al. Br J Dermatol. 2017;176(2):299-306. 6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 2.2023. 7. American Academy of Dermatology. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021;85(4):e209-e229.
Note: This monograph is for educational purposes only. Always consult current prescribing information and clinical guidelines before making treatment decisions.