Solage

Solage

CLINICAL PHARMACOLOGY

Solar lentigines are localized, pigmented, macular lesions of the skin on the areas of the body which have been chronically exposed to sunlight. Biopsy specimens of solar lentigines were collected in a clinical study with Solagé at baseline, at the end of a 24 week treatment period, and at the end of a subsequent 24 week, no treatment, follow-up period. The end of treatment specimens showed a decrease in melanin pigmentation in both melanocytes and keratinocytes, and an increased lymphocytic infiltration, which may have been the result of irritation or an immunologic reaction. The end of follow-up period specimens showed repigmentation of the melanocytes and keratinocytes to a state similar to the baseline specimens. These results indicate that there is no assurance that any improvement obtained would persist upon discontinuation of drug therapy.

Mechanism of Action

The mechanism of action of mequinol is unknown. Although mequinol is a substrate for the enzyme tyrosinase and acts as a competitive inhibitor of the formation of melanin precursors, the clinical significance of these findings is unknown. The mechanism of action of tretinoin as a depigmenting agent also is unknown.

Pharmacokinetics

The percutaneous absorption of tretinoin and the systemic exposure to tretinoin and mequinol were assessed in healthy subjects (n=8) following two weeks of twice daily topical treatment of Solagé. Approximately 0.8 mL of Solagé was applied to a 400 cm2 area of the back, corresponding to a dose of 37.3 g/cm2 for mequinol and 0.23 g/cm2 for tretinoin. The percutaneous absorption of tretinoin was approximately 4.4%, and systemic concentrations did not increase over endogenous levels. The mean Cmax for mequinol was 9.92 ng/mL (range 4.22 to 23.62 ng/mL) and the Tmax was 2 hours (range 1 to 2 hours).

Clinical Studies

Two adequate and well-controlled trials evaluated changes in treated hyperpigmented lesions on the face, forearms/back of hands in 421 patients treated with Solagé, 422 patients treated with tretinoin topical solution, 209 patients treated with mequinol topical solution and 107 patients treated with vehicle for up to 24 weeks. In these studies, patients were to avoid sun exposure and use protective clothing, and use of suncreens was prohibited. Patients were allowed to apply Moisturel® Lotion 30 minutes after application of Solagé. Physicians assessed the extent of improvement or worsening of all the treated lesions from the baseline condition on a 7 point scale. The results of these evaluations are shown below.

  Face Forearms/Back of Hands
Solagé Solution Vehicle Solagé Solution Vehicle
Moderate Improvement or greater1 57% 15% 54% 14%
Slight Improvement 28% 36% 26% 33%
No Change2 15 % 49% 20% 53%
1 Includes the following grades: Moderate Improvement, Marked Improvement, Almost Clear, Completely Clear. Moderate Improvement or greater was considered clinically meaningful.
2 Includes the following grades: No Change, Worse (less than 1% of patients treated with Solagé were rated as worse).

Improvement (lightening) of the solar lentigines occurred gradually over time during the 24 week treatment period. At 24 weeks of treatment, 57% and 54% of patients experienced moderate improvement or greater, and 3% and 1% of patients were completely clear of all treated lesions for the face and forearms/back of hands, respectively. It should be noted that approximately 9% of patients, from both treatment areas in these studies, with moderate improvement or greater also experienced hypopigmentation of the skin surrounding at least one treated lesion. There are no vehicle-controlled effectiveness data on the course of lesions treated beyond 24 weeks.

After 24 weeks of treatment, for the forearm/back of hands treatment site, the percentage of patients treated with tretinoin topical solution with moderate improvement or greater, slight improvement, or no change, were 38%, 37%, and 26%, respectively, and for mequinol topical solution were 24%, 40%, and 36%, respectively. For the face treatment site, the percentage of patients treated with tretinoin topical solution with moderate improvement or greater, slight improvement, or no change, were 46%, 33%, and 21%, respectively, and for mequinol topical solution were 33%, 30%, and 37% respectively.

The duration of effect was investigated during a period of up to 24 weeks following the discontinuation of treatment. Results from these studies showed that patients may maintain the level of clinical improvement of their treated lesions from the end of treatment through the 24 week follow-up period. However, some degree of repigmentation of treated lesions was observed over time, demonstrating reversibility of the depigmenting action of Solagé.

In the pivotal clinical trials of 24 weeks duration, some patients experienced temporary hypopigmentation of treated lesions (5%) or of the skin surrounding treated lesions (7%). Hypopigmentation of the skin surrounding treated lesions occurs even in the setting of proper application of the drug within the lesion border. The majority (94/106 - 89%) resolved upon discontinuation of treatment to the lesion, and/or re-instruction on proper application to the lesion only. Another 8% (9/106) of patients with hypopigmentation events had resolution within 120 days after the end of treatment.

Three of the 106 patients (2.8%) had persistence of hypopigmentation beyond 120 days. This further demonstrates the reversibility of the depigmenting action of Solagé.

Over 150 patients used Solagé twice daily for 52 weeks in an open label clinical study. The safety profile for Solagé in this long-term study was similar to that seen in the 24 week studies although burning/stinging/tingling, desquamation, pruritis, and irritation of the skin occurred at lower rates and halo hypopigmentation and hypopigmentation occurred at a slightly greater rate.

Over 90 patients used Solagé twice daily and a concomitant sunscreen (PreSun® 29) daily for up to 24 weeks in an open label clinical study. The safety profile for Solagé in this study was similar to that seen in studies which prohibited sunscreen use although desquamation, pruritis, and halo hypopigmentation occurred at slightly lower rates.

The initial clinical trials for Solagé included 1794 individuals of Skin Type I-V, 94.5% of whom were Caucasian. The trials also included 5% of individuals who were Asian/Pacific Islander (1.2%), African-American (0.8%), and Hispanic/Latino (3.5%). An additional open label study was conducted in 259 patients in the Asian (24.3%), Hispanic/Latino (62.2%), and African American (13.5%) ethnic groups with skin types II to V. This number reflects approximately three times as many subjects in this population as were represented in the initial clinical trials. In this study, as in the earlier studies, Solagé was used twice daily for a period of 24 weeks. The overall safety profile in this study was generally consistent with the initial clinical trials although erythema, desquamation, and pruritis occurred at lower rates and halo hypopigmentation occurred at a higher rate (7.7% versus 6.2%). The safety of Solagé in women of childbearing potential has not been established (see CONTRAINDICATIONS).

Last reviewed on RxList: 1/19/2010
This monograph has been modified to include the generic and brand name in many instances.

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