Fluorouracil and Calcipotriol - A new treatment for sun damaged skin

Day 7                                                                                         Day 14

Day 7 Day 14

Sun damaged skin is extremely prevalent in North Queensland. It is very common to see faces, arms, balding scalps, noses and ears covered with pink scaly spots. These are called solar keratosis and whilst they can be unsightly and bothersome the more concerning feature is they are considered precancerous with the potential to progress to a skin cancer called squamous cell carcinoma (SCC). It is for this reason that treatment of these lesions is advised.

Over the past 30 years there have been a number of creams used to treat sun damage, all with varying degrees of success. Most treatments involve a month’s worth of application and result in a large reaction. A recent study combining  creams fluorouracil (Efudix) and calcipotriol (Daivonex) has produced very impressive results with a much shorter duration and better tolerated course of treatment. (1)

Fluorouracil was first approved for use in Australia to treat solar keratosis in 1991 but the treatment was first used in the 1960s. The prescribed treatment is usually once to twice daily for 28 days. A large inflammatory reaction has usually developed by the end of the first week which then becomes worse over the course and results in crust, swelling and excoriation with symptoms of itch, burning and stinging. It can remain for a few weeks following the completion of treatment. Clearance rates of solar keratoses have been reported at a range of 59-94%. (2)

Calcipotriol was first approved for use in Australia for the treatment of psoriasis in 1994. In small amounts it is generally well tolerated although if used for longer than a few weeks in can cause skin irritation. It is a vitamin D derivative and part of its action is an immune response. It stimulates the body’s own immune system to make antibodies to attack the damaged cells

By combining the two creams there are two differing modes of action. There is the inflammatory response of the fluorouracil and an immune response of the calcipotriol. This results in a much reduced course of treatment of twice daily for 4 days for the face, scalp, ears and decolletage and 6 days for the forearms and backs of hands.  Similar to the fluorouracil there is still a resultant reaction but the degree is much reduced. The reaction is contained to the sun damaged cells and normal skin is spared. So the cream is applied to the entire body part. 

The face has a more pronounced reaction than the arms. Usually by day 3-4 there is some redness developing with the reaction peaking at day 5 and 6. On these days the redness is quite marked and sometimes there will be some crusting, scale or even a peel. Some symptoms may include stinging and burning. This can be relieved by moisturiser or an after sun gel.

From day 7 the reaction begins to improve and normally by day 10-14 it has fully resolved. The end result is a large clearance of solar keratosis resulting in clearer smoother skin. But more importantly, studies have shown a reduced rate of squamous cell carcinoma ongoing for at least 3 years. (3) No other treatment has been able to achieve this. The clearance rates of solar keratoses were at least as good as fluorouracil by itself with 87.8% on the face, 76.4% scalp and 79% on the arm. (1) As earlier stated fluorouracil by itself has been reported to have clearance rates ranging from 59-94%. (2) Of course the advantage of the combination cream is a much shorter duration of treatment and reduced reaction.

The combination is not available commercially so will need to be compounded by a compounding pharmacist. It costs about $60 for a 12g tube which should treat a scalp, face and forearms. Being a new treatment it currently does not have approval by the therapeutic goods administration however both creams individually have been used for over 30 years in Australia. If you would like some more information on this treatment it would be advised to book with one of our skin cancer doctors for a skin check. If they think it is an appropriate treatment they will issue you with a prescription. 


  1. Cunningham TJ, Tabacchi M, Eliane JP, Tuchayi SM, Manivasagam S, Mirzaalian H, Turkoz A, Kopan R, Schaffer A, Saavedra AP, Wallendorf M, Cornelius LA, Demehri S. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106–16.

  2. Sinclair, R., Baker, C., Spelman, L., Supranowicz, M. and MacMahon, B. (2021), A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies. Australas J Dermatol.

  3. Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;