Diclofenac Gel for the Treatment of Actinic Keratosis
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Diclofenac gel for the treatment of actinic keratosis (AK) is reaching the market several months after it received FDA approval. The gel combines the anti-inflamatory diclofenac with hyaluronate sodium for the topical treatment of these common skin lesions. SkyePharma has licensed the marketing rights for the United States, Canada, and Mexico to Bioglan Pharma. Diclofenac gel will be marketed under the trade name Solaraze.
Diclofenac gel is indicated for the topical treatment of AK.
Diclofenac gel is applied to lesion areas twice daily. The amount should be enough to cover each lesion adequately. The recommended duration of therapy is from 60 to 90 days. One-half gram of gel will cover about 25 cm2 of lesion. Diclofenac gel is supplied in tubes of 25 g and 50 g at a strength of 30 mg/g (3% w/w). Patients should avoid exposure to sunlight or sunlamps.
Diclofenac gel provides an alternative to other topical treatments such as masoprocol and 5-fluorouracil and may be better tolerated in terms of local adverse events.
Common side effects compared to vehicle are contact dermatitis (19% vs 4%), rash (35% vs 20%), and dry skin (27% vs 12%). About 18% of patients discontinue treatment due to side effects compared to 4% for the vehicle.1 Optimal therapeutic effect may not be evident for up to 30 days. Due to some systemic absorption, albeit low, diclofenac gel should be used with caution in patients with active gastrointestinal ulcers, or bleeding, or severe renal or hepatic impairment. Also, concomitant administration of NSAIDs should be minimized.1
Diclofenac is a cyclooxygenase inhibitor used widely in the oral from for the treatment of pain and inflammation. It is also used as a topical ophthalmic drop for post cataract surgery and prior to corneal refractive surgery. In the topical formulation, diclofenac is formulated with hyaluronate sodium. Hyaluronate has been reported to enhance drug delivery to pathogical sites.2 The mechanism of action of diclofenac in AK is not known, but it has been proposed that the inhibition of antiangiogensis may be a mechanism of action.2 In clinical trials reported by the manufacturer, diclofenac gel had a success rate of 18-47% compared to 10-20% for the vehicle.1 Success was defined as complete clearance of AK lesions 30 days after a treatment regimen. Statistical differences were demonstrated for lesions on the forehead and face but not on the scalp, arm/forearm, and the back of the hand, although numerical advantage was reported for these body locations.
Diclofenac may be better tolerated but currently there are no comparative studies with 5-fluorouracil or masoprocol. Cost is currently not available.
AK is a common premalignant inflammatory skin lesion involving areas of the body exposed to the sun. The prevalence of the disease is believed to be about 25% in the Western Hemisphere and more prevalent in individuals with fair complexion and older than the age of 50 years.3,4 Left untreated, AK may progress to squamous cell carcinoma. Treatment ranges from topical application of 5-fluorouracil or masoprocol to excisional surgery, Mohs surgery, cyrosurgery, or radiotherapy, but each has its limitations. Diclofenac gel offers another, perhaps better-tolerated option for treatment of these common skin lesions.
1. Solaraze Product Information. SkyePharma. October 2000.
2. Seed MP, et al. Cancer Res. 1997;57(9):1625-1629.
3. Peters DC, RH Foster. Drugs & Aging. 1999;14:
4. Frost CA, Green AC. Br J Dermatol. 1994;131:455-464.