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.

Author(s): Fleischer AB Jr, Schwartzel EH, Colby SI, Altman DJ

Affiliation(s): Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Publication date & source: 2000-03, J Am Acad Dermatol., 42(3):459-67.

Publication type: Clinical Trial; Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial

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 hands 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 </=.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.