Pharmaceutical Approval Update: Clindamycin Phosphate 1.2% and Tretinoin 0.025% (Ziana) Gel

Posted by James

Manufacturer: Medicis, Scottsdale, AZ

Indication: The gel is indicated for the topical treatment of acne vulgaris in patients 12 years of age or older.

Drug Class: The gel combines a lincosamide antibiotic and a retinoid.

Uniqueness of Drug: The product contains two active ingredients. Generic clindamycin phosphate is a water-soluble ester of the semisynthetic antibiotic, produced by a 7(S)-chloro­substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin.

Warnings and Precautions:

Colitis: Clindamycin can cause severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of clindamycin. The gel should be discontinued if significant diarrhea occurs.

Ultraviolet Light and Environmental Exposure: Patients should avoid exposure to sunlight and sunlamps and should wear sunscreen daily.

Contraindications: The gel is contraindicated in patients with regional enteritis, ulcerative colitis, or a history of antibiotic-associated colitis.

Dosage and Administration: Each gram of the product contains, as dispensed, 10 mg (1%) clindamycin as phosphate and 0.25 mg (0.025%) tretinoin in an aqueous-based gel.

At bedtime, the patient should squeeze a pea-sized amount of medication onto one fingertip, dot onto the chin, cheeks, nose, and forehead, then gently rub over the entire face. The gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes. The gel is not indicated for oral, ophthalmic, or intravaginal use.

Commentary: Acne is a common, recurring disease. Treatment can be complex, often requiring aggressive combination therapy of oral antibiotics and medication applied directly to the skin. Sometimes a long-term strategy is also necessary.

Patients who first received an oral antibiotic and topical gel for acne were often able to maintain their clearer skin by using topical agents alone. Because acne can return after successful treatment, maintenance therapy may be necessary. However, because of a reduced sensitivity of acne to some antibiotics, it has been recommended that antibiotic use be limited to three months. Topical retinoids, medications derived from vitamin A, have been identified as a choice for maintenance therapy.

Three 12-week clinical studies showed that the combination gel was more effective than canadian clindamycin or tretinoin alone for achieving “clear” or “almost clear” status: 21% with Ziana, 16% with clindamycin, 14% with tretinoin, and 8% with the vehicle (the alcohol-free aqueous-based gel) alone.

The combination gel was more effective in reducing inflammatory lesion counts: 48% with Ziana, 42% with clin-damycin, 39% with tretinoin, and 26% with the vehicle alone.

Ziana also reduced non-inflammatory lesion counts from the baseline evaluation: 36% with Ziana; with clindamycin, 31% with tretinoin, and 16% with placebo (the vehicle gel).

Another study, involving 2,010 patients, further confirmed the improved efficacy of clindamycin/tretinoin gel over clin-damycin for (1) achieving clear or almost clear status (41% with Ziana, 34% with clindamycin); (2) decreasing inflammatory lesion counts (61% with Ziana, 55% with clindamycin); and (3) decreasing non-inflammatory lesion counts from baseline (50% with Ziana, 41% with clindamycin).

The major caveat with Ziana is that longer-term clinical studies are needed to determine the possibility of the development of resistance.