Diclofenac Gel 3% for Actinic Keratosis

Composition and Mechanism

Diclofenac 3% in a 2.5% hyaluronic acid gel is approved for twice-daily application over 60-90 days and can be used as a lesion- or field-based treatment 1
The mechanism of action in actinic keratosis is not fully understood, but may be related to the inhibition of the cyclooxygenase pathway, leading to reduced prostaglandin E2 synthesis 1

In clinical studies, Diclofenac Gel 3% showed a clearance rate of 70% of target lesions in actinic keratosis after an average treatment duration of 60 days, compared to 44% in patients using the vehicle only 1
In a second study with 90-day treatment, 50% of patients achieved complete clearance, compared to 20% using the vehicle alone (P < 0.001) 1
Extension of treatment from 90 to 180 days resulted in an additional 5% complete clearance, without significant change in adverse effects 1

Diclofenac Gel generally causes less intense local skin reactions than 5-FU or Imiquimod 5% cream 1
Reduction in adverse effects is associated with reduced efficacy when comparing Diclofenac Gel and 5-FU 5%, but both achieve high patient satisfaction rates (73% vs. 77%) 1
In a three-arm randomized controlled study comparing Diclofenac 3%, Imiquimod 5% cream, and base cream, complete clearance rates at the end of treatment were 19.1%, 20%, and 0% 2

Diclofenac may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal 3
Patients with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk 3
Topical Diclofenac has a more favorable safety profile compared to oral NSAIDs, making it particularly beneficial for older patients 4

Diclofenac 3% in hyaluronic acid gel is applied twice daily for 60-90 days 1, 2
Treatment can be used as a lesion- or field-based therapy 1
When used as field treatment, the size of the field should be defined with the patient to anticipate and tolerate adverse effects 1

Diclofenac 3% gel should be used only for the treatment of actinic keratosis when first‑line topical agents such as 5‑fluorouracil or imiquimod are contraindicated or poorly tolerated, as recommended by the American Academy of Dermatology. 5

In head‑to‑head studies, diclofenac 3% gel achieved complete clearance of actinic keratosis in ≈ 50 % of patients after 60–90 days of twice‑daily application, compared with ≈ 55 % clearance for 5‑fluorouracil/salicylic acid; however, the diclofenac formulation produced less intense local skin reactions. 6