The combination of 2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double-blind multicenter clinical studies

Background: Solar lentigines are a chronic condition of,the-aging population resulting from years of cumulative sun exposure. A topical treatment that is both safe and effective would be welcome and useful. Combinations of therapeutic agents are often used and allow:synergy of mechanisms with tolerability. A tyrosinase inhibitor in use in Europe, 4-hydroxyanisole (Mequinol), and the retinoid tretinoin have been used singly as depigmenting agents. Objective: The efficacy and safety of the combination product of 2% 4-hydroxyanisole (4HA [mequinol])/0.01% tretinoin solution (tradename Solage) were evaluated in two phase III, randomized, controlled, double-blind trials. Methods: Subjects were randomized to treatment with: 4HA/tretinoin solution, one of the active components (4HA or tretinoin), or vehicle. Subjects applied the test solution with a wand applicator twice daily to all solar lentigines and related hyperpigmented lesions:on the face, forearms, and backs of bands for up to 24 weeks. Trial 1 had a 24-week no-treatment regression phase and trial 2 had a 4-week no-treatment regression phase. Information collected included clinical assessments of Target Lesion Pigmentation, Physician's Global Assessment of Improvement/Worsening, an Assessment of Overall Cosmetic Effect, and a Subject's Self-Assessment Questionnaire. Results: The 4HA-/tretinoin combination was clinically superior to each of its active components and to the vehicle in the treatment of solar lentigines. At the end of treatment, in: trial 1 and trial 2, 4HA/tretinoin was statistically superior to each of its active components and vehicle on the forearms and face (P less than or equal to .03), except versus tretinoin on the face in trial 2 (P = .2). In trial 2, a trend toward greater efficacy of 4HA/tretinoin over tretinoin on the face was demonstrated at the end of treatment (P = .2), which was also increasingly evident at the end of the 4-week follow-up (P = .06). Most skin-related adverse events were mild and were similar for both the 4HA/tretinoin and tretinoin treatment groups. Conclusion: For the treatment of solar lentigines and related hyperpigmented lesions, the topical combination product containing 2% 4HA/0.01% tretinoin solution is well tolerated and superior to either active component.