Fluorouracil (5-FU)
- Uracil analog
- Numerous active metabolites in cell: fluorodeoxyuridine monophosphate or triphosphate, fluorouridine triphosphate
- Metabolism via dihydropyrimidine dehydrogenase (DPD): 5-FU to dihydrofluorouracil (DHFU)
- 1-6% absorbed systemically in healthy skin (no systemic adverse effects) compared to 15-75x more in diseased/ulcerated skin
- Pregnancy Category X
- Topical
- Solutions:
- 1%; 2%; 5%
- Creams:
- 0.5%, 1%, 4%, 5%
- with salicylic acid (Actikerall)
- Antimetabolite
- Irreversibly inhibits thymidylate synthetase preventing DNA synthesis
- Incorporates in RNA disrupting RNA synthesis
FDA
- Actinic keratosis:
- Face – twice a day x 2 weeks;
- Trunk/arms – twice a day x 4-6 weeks
- Superficial Basal Cell Carcinoma (multiple lesions, not surgical candidate, difficult anatomy location for surgery): twice a day x 3-6 weeks, may continue for up to 12 weeks (only Efudex approved)
Off-label
- Squamous Cell carcinoma (SCC) in situ – twice a day x 8 weeks, SCC, keratoacanthoma (if no response, biopsy to rule out SCC), actinic cheilitis, porokeratosis, Darier disease, extramammary Paget disease, warts…
- Pregnancy & lactation
- Type I hypersensitivity
- Dihydropyrimidine dehydrogenase deficiency
- Inflammatory reaction (expected): 5-10 days after beginning treatment = Erythema +/- edema or oozing then crusted erosions then re-epithelialization
- Burning, pruritus
- Allergic contact dermatitis
- post-inflammatory hyperpigmentation
- Photosensitivity
- Rare systemic effects (very low systemic absorption)
* For further reading refer to a pharmacology source
- If minimal reaction, continue for 1-2 weeks
- If severe inflammatory reactions:
- decrease strength / frequency 5-FU
- topical corticosteroids during 5-FU treatment & 1-2 weeks after treatment (no impact on 5-FU efficacy)
- Topical antibiotics for superinfection
- Topical calcipotriol with 5-FU reported efficacious for actinic keratosis when applied twice a day for 4 consecutive days