Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses

Harrison P. Nguyen, BA; Jason K. Rivers, MD, FRCPC, FAAD


Skin Therapy Letter. 2016;21(3) 

In This Article

Abstract and Introduction


Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall− for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm2, which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.


Actinic keratosis (AK) is a lesion considered to be on a continuum with squamous cell carcinoma (SCC).[1,2,3,4,5,6] Invasive disease occurs in up to 10% of cases over time, which highlights the need for early recognition and adequate treatment of all AKs, including subclinical lesions.[7] Although many AKs never progress to SCC, their treatment has been recommended to preempt this eventuality.

Treatment options can generally be stratified based on whether only discrete lesions are treated, or whether subclinical lesions are also targeted, which is referred to as eld-directed therapy. Lesion-directed therapy has historically consisted of ablative and/or surgical procedures. However, several topical agents have emerged as attractive alternatives in the treatment of AKs. Examples of topical agents available in Canada and/or the United States include 5- fluorouracil (5-FU), imiquimod (2.5%, 3.75%, and 5% formulations), diclofenac 3%, methylaminolevulinate/aminolevulinic acid (for photodynamic therapy), and ingenol mebutate.[8]

In one controlled clinical trial, topical 5-FU applied to AKs resulted in 96% clearance after 4 weeks of twice daily application.[9] However, high rates of severe localized tissue reactions with 5-FU have led to reduced patient compliance, and this, in part, may explain why the long-term clearance of AKs in clinical practice is around 50%.[8] This problem has resulted in a search for therapeutic agents less likely to induce skin irritation.[10] In 2011, a topical formulation combining 0.5% 5-FU with 10% salicylic acid (5-FU-SA) was introduced to the European market under the trade name Actikerall™ for the topical treatment of grade I/II AKs (slightly palpable and/or moderately thick hyperkeratotic lesions) in immunocompetent adult patients.[11,12] This preparation is not novel as the same agent has been used in Europe for more than 30 years in the treatment of plantar warts (Verrumal®).

Functionally, 5-FU is a pyrimidine analogue that inhibits nucleic acid synthesis and its efficacy is thought to be enhanced by the addition of salicylic acid, a keratolytic agent that facilitates penetration of 5-FU into AKs.[13] In this brief review, we present some of the clinical data to support the use of 5-FU-SA in patient-directed* management of AKs and we summarize the salient information that the provider should be aware of when prescribing this product.

*Health Canada has elected to classify Actikerall™ as neither lesion-directed nor field-directed. This was done to support the individual needs of patients; the locational distribution of a patient's lesions will dictate whether a lesion-directed versus a field-directed approach is preferred.