The short answer
- How: mix equal amounts of 5-fluorouracil 5% (Efudex/Efudix) and calcipotriene 0.005% (Dovonex), or use a pharmacy-prepared mix, and apply a thin layer to the treatment area twice daily for 4 days.
- What to expect: redness and irritation from about day 3–4, peaking in the following days, then crusting and healing over 1–2 weeks.
- Aftercare: gentle cleanser, plain petroleum jelly, strict sun protection; no other actives until healed.
Why combine 5-FU with calcipotriene?
Actinic keratoses (solar keratoses) are rough, scaly spots on sun-damaged skin. A small proportion can progress to squamous cell carcinoma, so dermatologists often treat a whole area (“field treatment”) rather than individual spots. 5-fluorouracil cream destroys rapidly dividing abnormal cells, but used alone it usually needs 2–4 weeks of application with a long, uncomfortable reaction.
Calcipotriene (called calcipotriol outside the US), the vitamin D analogue used for psoriasis, triggers the skin to express a signal (TSLP) that recruits immune T cells. In a randomised trial published in 2017, the combination applied twice daily for just 4 days cleared many more actinic keratoses than 5-FU with petroleum jelly, and a follow-up analysis suggested fewer squamous cell carcinomas in treated areas over the next few years. It’s now a widely used regimen, prescribed off-label.
How to apply it
- Wash the area with a gentle cleanser and pat dry. Wait 10–15 minutes.
- Mix the creams as instructed (often equal amounts) on a clean surface, or use the pre-mixed jar from your pharmacy.
- Apply a thin layer to the whole treatment area (face, scalp, forearms or hands, as prescribed), avoiding eyes, nostrils and lips.
- Wash your hands well.
- Repeat in the evening. Continue for 4 days, or as directed, then stop even if little reaction is visible.
Safety: 5-fluorouracil must not be used in pregnancy. People with a rare enzyme deficiency (DPD deficiency) can react severely; tell your doctor if you’ve ever had a severe reaction to fluorouracil or capecitabine chemotherapy. Keep the cream away from pets: 5-FU is highly toxic to dogs and cats if licked or swallowed.
Day-by-day: what to expect
| Days |
Typical skin reaction |
| 1–2 |
Little or no change; maybe mild tingling |
| 3–5 |
Redness appears, especially over keratoses; burning or itch |
| 5–8 |
Peak: redness, swelling, scaling, sometimes crusting or weeping |
| 8–14 |
Crusts lift, pink new skin; most people look close to normal |
| 2–4 weeks |
Residual pinkness fades |
The reaction is generally shorter and milder than with a full course of 5-FU alone, though it varies with how much sun damage there is. The redness is the treatment working, not an allergy.
Aftercare
- Wash gently with lukewarm water; pat dry.
- Apply plain petroleum jelly or a bland ointment several times a day once you’ve stopped the creams.
- Avoid retinoids, acids, scrubs and fragranced products until fully healed.
- Stay out of the sun and use a broad-spectrum sunscreen once the skin isn’t raw; a hat for the scalp.
- Take paracetamol if it’s sore. Your doctor may suggest a mild steroid cream after the course if irritation is intense.
Other skin treatments, including steroid strengths and retinoids, are explained in the skin treatments guide.
When to contact your dermatologist
Call if you notice pus, increasing pain, fever, spreading redness beyond the treated area, blisters on the eyelids or lips, or if a spot hasn’t healed after a month. Any lesion that bleeds, grows or stays tender should be checked for skin cancer.
Frequently asked questions
Is there a 14-day version of the treatment?
Plain 5-fluorouracil is often used for 2–4 weeks. The calcipotriene combination is usually 4 days; some dermatologists adjust the length for the scalp, arms or hands. Follow your own prescription.
What does “SM1 fluorouracil 5% / 0.005% calcipotriene” mean on the label?
It’s a pharmacy-compounded mix of both creams in one jar. Use it exactly as the label says, usually twice daily for 4 days.
Can I wear makeup during treatment?
It’s best not to during the 4 days and the peak reaction. Once the skin has healed and isn’t raw, gentle mineral makeup is usually fine.
Sources and further reading
CanforaMedicine Guide
