New Gel Formulation of Acne Drugs Is Effective for Adolescents

Kathleen Louden

July 20, 2007

July 20, 2007 (Chicago) -- A gel that combines topical 1.2% clindamycin and 0.025% tretinoin treats acne vulgaris in children aged 12 to 18 years as or more effectively than either of its active ingredients alone, a study presented at the Society for Pediatric Dermatology (SPD) 33rd Annual Meeting shows.

The novel antibiotic-retinoid gel ( Ziana, Medicis), which has been on the market since early this year, also was found in 2 other studies conducted by the same group to be tolerable and have long-term safety in patients aged 12 to 36 years.

The pediatric study was done in a large subgroup (n = 1710) of patients aged 12 to 18 years who participated in 2 pivotal trials of the study drug. Presenter Mitchell Wortzman, PhD, executive vice president and chief scientific officer of Medicis in Scottsdale, Arizona, and coauthors studied the efficacy of clindamycin-tretinoin (n = 572) during 12 weeks' treatment compared with 0.25% tretinoin gel (n = 560), 1.2% clindamycin (n = 284), or vehicle (n = 294).

At week 12 the combination medication showed significantly better ( P < .001) reductions in both inflammatory and noninflammatory acne lesions and total lesions compared with tretinoin or vehicle and in noninflammatory and total lesions compared with clindamycin. For inflammatory lesions there was no statistically significant difference in efficacy between the study drug and clindamycin. Results applied to all baseline severities of acne (from mild to severe).

In the tolerability study, the authors treated 45 children and adults (mean age, 24.6 years) with clindamycin-tretinoin once daily on 1 side of the face for 21 days. They randomly selected patients to receive either 0.1% adapalene gel (22 patients) or 0.1% tretinoin microsphere gel (23 patients) on the opposite side. The evaluator was blinded to the treatment schedule and used a standard 4-point scale to assess erythema and skin scaling.

Cumulative erythema and skin scaling as well as patient-reported burning, itching, and stinging were significantly less with clindamycin-tretinoin than with 0.1% tretinoin microsphere gel ( P not given). At day 22, less than 20% of patients had erythema or scaling using the study drug, whereas more than 60% of those receiving tretinoin had erythema and greater than 50% had scaling, the authors reported. Adapalene also had higher cumulative erythema (38.4% of patients) and scaling (53.8%) than clindamycin-tretinoin (25.7% and 35.3%, respectively), but the difference was not statistically significant.

"You get very little skin irritation," Dr. Wortzman said of the combination medication, which the US Food and Drug Administration approved last November.

Dr. Wortzman proposed several reasons why the new formulation may be more tolerable than 0.1% tretinoin microsphere gel. The vehicle has an alcohol-free water base, he told Medscape, and the tretinoin is in a crystalline form designed to slowly dispense the drug to the skin. Also, the combination drug has a lower concentration of tretinoin than 0.1% tretinoin microsphere gel, he noted. Tretinoin microsphere gel is also available in a 0.04% formulation, although this formulation was not included in this study.

"You would expect to get more irritation with [the higher strength of tretinoin]," said Robert Silverman, MD, a pediatric dermatologist in private practice in Fairfax, Virginia, and a past president of SPD. Dr. Silverman was not involved in the study.

"But the combination of clindamycin and tretinoin does potentially simplify treatment of standard comedonal and inflammatory acne," Dr. Silverman added, "and, as such, should improve patient compliance."

However, compliance was not evaluated in either of these studies.

In the safety study, a 52-week open-label trial, Dr. Wortzman and colleagues reported clindamycin-tretinoin gel to be safeand well tolerated in 655 patients (mean age, 20 years). These patients had acne vulgaris ranging from mild to severe and were a subgroup of patients from phase 3, randomized, double-blind, vehicle-controlled, multicenter clinical trials. Because it was a long-term safety study, Dr. Wortzman said patients were allowed to use concomitant medications, but only 30% did so.

More than 90% of patients treated with clindamycin-tretinoin gel reported no burning, stinging, or itching during the 12-month study, according to the abstract. Furthermore, the discontinuation rate resulting from adverse events was less than 1%.

The study did not screen for antibiotic-resistant organisms, according to Dr. Wortzman. He told Medscape, "If one is concerned about resistance, one can add the use of benzoyl peroxide."

Noting that the new drug is expensive, Dr. Silverman told Medscape it is too soon to tell whether it will change clinical practice.

The studies were funded by Medicis. Dr. Wortzman works for Medicis, the manufacturer of Ziana. Dr. Silverman reports no relevant financial relationship with Medicis.

Society for Pediatric Dermatology 33rd Annual Meeting: Posters 2, 3, and 4. Presented July 13-14, 2007.


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