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

Dosing and Administration

Actikerall™ is a transparent, colorless to slightly orange-white solution packaged in 25 mL glass bottles, accompanied by a nylon brush that allows for easy application. 5-FU-SA is recommended for application 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 (Table 1). However, if the patient has lesions in areas with thin epidermis, the solution may be applied less frequently (e.g., 3 times per week). To avoid excess application, the brush can be wiped on the neck of the bottle. The solution should be allowed to dry on the skin but prior to re-application on subsequent days, the existing film should be peeled off, which can be facilitated by using warm water.

As noted, significant reduction in the lesion count is usually observed within 6 weeks of starting treatment, and patients most likely to benefit from the full 12-week course are those who have failed previous therapy with other modalities.[16] Patients should be advised that lesions may continue to regress for up to 8 weeks after cessation of therapy.

The use of 5-FU-SA in areas other than the face and scalp has only been reported in the setting of small case series. In one publication,[21] two patients with multiple AKs on the dorsal aspect of the hands achieved complete clearance after sequential treatment with diclofenac 3% gel and 5-FU-SA. A notable observation has been a lower therapeutic response of AKs located on the upper extremities compared to lesions on the face and scalp.[16] This finding has also been observed with photodynamic therapy, ingenol mebutate and other topical agents used to treat AKs. Although the reason for this observation remains poorly understood, one hypothesis is that increased skin thickness in the upper extremities restricts drug absorption, thus limiting its therapeutic efficacy.[22]

5-FU-SA is contraindicated for use during lactation or pregnancy. Other contraindications include renal insufficiency and concurrent usage of brivudine, sorivudine, or similar analogues. The latter consideration is related to the ability of these agents to inhibit the enzyme dihydropyrimidine dehydrogenase, which plays a critical role in breakdown of fluorouracil.[23] Of note, although these agents are structurally similar to acyclovir, the latter drug does not inhibit dihydropyrimidine dehydrogenase to any significant extent and is therefore safe to administer concurrently with 5-FU-SA. Additionally, instances of phenytoin toxicity related to the concurrent use of topical 5-FU-SA have been reported, so these patients should be tested at monthly intervals for plasma levels of phenytoin when this combination of therapies exists.[11] 5-FU-SA should not be applied on bleeding lesions and has not been evaluated for the treatment of recurrent lesions. With regards to user experience and safety, the patient should be educated on the solution's flammability, propensity to desiccate quickly (the bottle needs to be closed tightly after use and it should be discarded if crystallization occurs), and ability to cause permanent stains on textiles and acrylics

Cipher Pharmaceuticals, which owns the rights to Actikerall™ in Canada, has indicated that each bottle will be sold for a wholesale price of $36.25.[24] Commercial availability commenced in February 2016.