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 Solagé) 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.


CONCLUSIONS
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.
Fleischer
A B
AB
Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Schwartzel
E H
EH
Colby
S I
SI
Altman
D J
DJ
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000840:Anisoles / Q000008:administration & dosage* / Q000009:adverse effects; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D001132:Arm; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005148:Facial Dermatoses / Q000188:drug therapy; D005260:Female; D006229:Hand Dermatoses / Q000188:drug therapy; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy; D007641:Keratolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007911:Lentigo / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects
D000840:Anisoles; D000975:Antioxidants; D007641:Keratolytic Agents; D014212:Tretinoin; C009760:mequinol