"The U.S. Food and Drug Administration today approved Differin Gel 0.1% (adapalene), a once-daily topical gel for the over-the-counter (OTC) treatment of acne. Differin Gel 0.1% is approved for use in people 12 years of age and older.
Mechanism of Action
Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedone formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
In an open-label study of 17 patients with moderate-to-severe acne vulgaris, topical administration of approximately 3 grams of VELTIN (clindamycin phosphate and tretinoin gel) Gel once daily for 5 days, clindamycin concentrations were quantifiable in all 17 patients starting from 1 hour post dose. All plasma clindamycin concentrations were ≤ 5.56 ng/mL on day 5, with the exception of one subject who had a maximum clindamycin concentration of 8.73 ng/mL at 4 hours post-dose. There was no appreciable increase in systemic exposure to tretinoin, as compared to the baseline value. The average tretinoin concentration across all sampling times on day 5 ranged from 1.19 to 1.23 ng/mL compared with the corresponding baseline mean tretinoin concentration range of 1.16 to 1.30 ng/mL.
No microbiology studies were conducted in the clinical trials with this product.
Mechanism of Action
Clindamycin binds to the SOS ribosomal subunit of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with VELTIN™ (clindamycin phosphate and tretinoin gel) Gel. P. acnes resistance to clindamycin has been documented.
Inducible Clindamycin Resistance
The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.
Resistance to clindamycin is often associated with resistance to erythromycin.
The safety and efficacy of VELTIN (clindamycin phosphate and tretinoin gel) Gel, applied once daily for the treatment of acne vulgaris, was evaluated in 12-week multicenter, randomized, blinded studies in subjects 12 years and older.
Treatment response was defined as the percent of subjects who had a two grade improvement from baseline to Week 12 based on the Investigator's Global Assessment (IGA) and a mean absolute change from baseline to Week 12 in two out of three (total, inflammatory and non-inflammatory) lesion counts. The IGA scoring scale used in all the clinical trials for VELTIN (clindamycin phosphate and tretinoin gel) Gel is as follows:
|0||Clear||Normal, clear skin with no evidence of acne vulgaris.|
|1||Almost Clear||Skin almost clear; rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be nyperpigmented, though not pink-red) requiring no further treatment in the Investigator's opinion.|
|2||Mild||Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only, no nodulo-cystic lesions).|
|3||Moderate||Non-inflammatory lesions predominate, with multiple inflammatory lesions evident; several to many comedones and papules/pustules, and there may or may not be 1 small nodulo-cystic lesion.|
|4||Severe||Inflammatory lesions are more apparent; many comedones and papules/pustules, there may or may not be a few nodulo-cystic lesions.|
|5||Very Severe||Highly inflammatory lesions predominate; variable numbers of comedones, many papules/pustules and nodulo-cystic lesions.|
In Study 1, 1649 subjects were randomized to VELTIN (clindamycin phosphate and tretinoin gel) Gel, Clindamycin gel, Tretinoin gel, and vehicle gel. The median age of subjects was 17 years old and 58% were females. At baseline, subjects had an average of 71 total lesions of which the mean number of inflammatory lesions was 25.5 lesions and the mean number of non-inflammatory lesions was 45.1 lesions. The majority of subjects enrolled with a baseline IGA score of 3. The efficacy results at week 12 are presented in Table 3.
Table 3: Efficacy Results at Week 12
|Study 1|| VELTIN Gel
| Clindamycin Gel
| Tretinoin Gel
| Vehicle Gel
|Investigator's Global Assessment|
|Percentage of subjects achieving Two Grade Improvement||36.3%||26.6%||26.1%||20.2%|
|Percentage of subjects achieving an IGA of 0 or 1 with a Two Grade Improvement||33.2%||24.0%||22.6%||17.8%|
|Mean absolute reduction||15.5||14.5||13.9||11.1|
|Mean percentage (%) reduction||60.4%||56.5%||54.5%||43.3%|
|Mean absolute reduction||23.2||19.5||22.1||17.0|
|Mean percentage (%) reduction||51.0%||42.9%||47.3%||36.0%|
|Mean absolute reduction||38.7||34.0||36.0||28.1|
|Mean percentage (%) reduction||55.0%||49.0%||50.5%||39.1%|
The safety and efficacy of clindamycin-tretinoin gel was also evaluated in two additional 12-week, multi-centered, randomized, blinded, studies in patients 12 years and older. A total of 2219 subjects with mild-to-moderate acne vulgaris were treated once daily for 12 weeks. Of the 2219 subjects, 634 subjects were treated with clindamycin-tretinoin gel. These studies demonstrated consistent outcomes.
Last reviewed on RxList: 11/16/2016
This monograph has been modified to include the generic and brand name in many instances.
Additional Veltin Information
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