Fluorouracil 2.5% | Salicylic Acid 20%

Route: Topical application to lesional skin only.

Apply precisely to targeted lesions (actinic keratoses, warts, hyperkeratotic lesions) using the applicator provided. Avoid application to surrounding normal skin where possible; surrounding normal skin may be protected with petrolatum or zinc paste if needed. Occluding the lesion (e.g., with tape) after application may enhance penetration of both agents as directed by the prescriber. Wear gloves when applying. Wash hands thoroughly after application. Avoid contact with eyes, nostrils, and mucous membranes.

Application frequency, occlusion requirements, and treatment duration are individualized by the prescribing clinician. General principles based on clinical literature:

• Apply once or twice daily to the lesion(s), with or without occlusion, as directed.
• Treatment duration for actinic keratoses may range from 2–12 weeks depending on lesion severity and response.
• For warts, treatment cycles of several weeks with periodic debridement may be prescribed.
• Prescribers should inspect lesions and reassess response regularly during treatment.

• Fluorouracil (2.5%): 5-FU is a fluorinated pyrimidine analogue that is converted intracellularly to active metabolites (FdUMP, FUTP). FdUMP irreversibly inhibits thymidylate synthase, blocking thymidine nucleotide synthesis, impairing DNA replication, and causing strand breaks in rapidly dividing dysplastic cells. FUTP is incorporated into RNA, disrupting RNA processing and function. These actions selectively destroy actively proliferating atypical keratinocytes (AK cells) and virally transformed epidermal cells while relatively sparing quiescent normal cells.
• Salicylic Acid (20%): A beta-hydroxy acid that penetrates the follicular/intercellular lipid pathways; at 20% concentration, it powerfully disrupts the corneodesmosomes holding stratum corneum keratinocytes together, causing dissolution and physical removal of the hyperkeratotic stratum corneum overlying the lesion. This keratolytic action removes the physical barrier that would otherwise limit 5-FU's access to living atypical keratinocytes, dramatically enhancing 5-FU penetration and efficacy. Salicylic acid also has mild direct cytolytic activity on hyperkeratotic tissue.

Clinical Context: This compounded topical combination is used in prescriber-directed management of:

• Actinic keratoses (AKs): Particularly hyperkeratotic AKs that may be resistant to lower-concentration 5-FU monotherapy or where keratolytic pre-treatment is required to allow drug penetration.
• Cutaneous warts (verrucae): Where salicylic acid's keratolytic activity disrupts wart-associated hyperkeratosis, enabling 5-FU to reach virally infected basal keratinocytes.
• Other hyperkeratotic lesions as determined by the prescribing dermatologist.

Monitoring Considerations:

• Inspect treated lesions every 2–4 weeks. Significant erythema, erosion, and crusting are expected as treatment markers of efficacy for AKs; prescribers should distinguish expected therapeutic reactions from infection or excessive reaction requiring dose reduction.
• If treatment area is large (field therapy), monitor for systemic 5-FU toxicity, though topical absorption at this concentration is low.
• Lesions not responding after the prescribed treatment course should be biopsied to exclude invasive carcinoma.

Contraindications:

• Known hypersensitivity to fluorouracil, salicylic acid, or any excipient.
• Pregnancy: fluorouracil is teratogenic and embryotoxic; contraindicated in pregnancy. Women of childbearing potential should use effective contraception during treatment.
• Known DPD (dihydropyrimidine dehydrogenase) deficiency: rare enzyme deficiency causing severe 5-FU toxicity even from topical application; screen if indicated.
• Application to mucous membranes or periorbital skin.

Warnings & Precautions:

• Avoid application to surrounding uninvolved skin at 20% salicylic acid, which can cause significant chemical burns on normal skin.
• Avoid ocular or mucosal contact with either agent.
• Significant inflammation, erosion, and ulceration of treated lesions are expected with effective treatment; do not discontinue prematurely due to expected local reaction unless severe.
• Protect treated areas from UV exposure; photosensitivity is increased.
• Limit treatment area to avoid excessive systemic salicylate absorption (salicylism) — monitor in elderly or renally impaired patients.

Drug Interactions:

• Systemic fluorouracil or other antimetabolites: additive myelosuppressive and gastrointestinal toxicity risk if used concurrently; contraindicated with systemic 5-FU chemotherapy.
• Systemic salicylates (aspirin): additive salicylate burden; caution with large-area high-SA topical use.
• Topical agents that increase skin permeability (AHAs, urea, retinoids) may enhance penetration of both agents; coordinate prescribing accordingly.

Common Side Effects: Local: erythema, burning, stinging, pruritus, erosion, ulceration, crusting of treated lesions — these are expected treatment responses, particularly for AKs. Hyperpigmentation or hypopigmentation post-treatment. Rare: allergic contact dermatitis.

Store at controlled room temperature (20–25°C / 68–77°F). Protect from heat and direct light. Keep tightly capped. Do not freeze. Keep out of reach of children and pregnant women. Use before the BUD assigned by Genesis Compounding on the prescription label.

Why is salicylic acid at such a high concentration (20%) in this preparation?

Actinic keratoses and warts are covered by a thickened layer of keratin. Salicylic acid at 20% is a potent keratolytic that physically dissolves this barrier, allowing fluorouracil to penetrate to the underlying abnormal cells where it exerts its cytotoxic effect. Without keratolysis, the dense keratin layer would significantly limit 5-FU's reach.

How much skin reaction should I expect?

Significant local reaction — redness, irritation, erosion, and crusting — is a normal and expected sign that the treatment is working against actinic keratoses. Your prescriber will explain what level of reaction is within the expected therapeutic range versus a sign to reduce treatment.

Can I apply this to surrounding normal skin?

No. At 20% salicylic acid, this preparation can cause significant chemical irritation and burns on normal, non-lesional skin. Apply precisely to the targeted lesion only. Protect surrounding skin with petrolatum if directed by your prescriber.

Is this FDA-approved?

No. This is a prescription-only 503A compounded preparation made by Genesis Compounding. Fluorouracil and salicylic acid individually have FDA-approved commercial products, but this specific combination at these concentrations is a compounded formulation that has not been FDA-reviewed as a finished combination product.

Are there any systemic concerns with this topical preparation?

Topical 5-FU absorption is generally minimal with lesion-directed use. High-concentration salicylic acid applied to large body surface areas can cause systemic salicylism; limit the application area to lesions only as directed by your prescriber.