Clinical experience results with clindamycin 1% benzoyl peroxide 5% gel as monotherapy and in combination

Journal of Drugs in Dermatology, March-April, 2005 by Joseph B. Bikowski

Abstract

This article will examine various clinical experiences with acne patients successfully treated with topical clindamycin 1% benzoyl peroxide 5% gel (Duac[R]) alone and in combination with other acne treatments. Clindamycin 1% benzoyl peroxide 5%, the only once-daily prescription topical aqueous gel combining a benzoyl peroxide and an antibiotic, has demonstrated excellent tolerability and efficacy and is stable when used concomitantly with other therapies. A regimen of topical clindamycin 1% benzoyl peroxide 5% gel, oral doxycycline hyclate (Doryx[R]), and adapalene gel (Differin[R]) seems especially advantageous from a theoretical and practical perspective. Improvement is noted by means of photographic, physician, and/or patient assessments at baseline and follow-up visits.

**********

Introduction

Acne has a multifactorial pathogenesis involving sebaceous gland hyperplasia, follicular hyperkeratinization, microbial proliferation, immune reactions, and inflammation. (1) The combination of high sebum production and follicular hyperkeratinization causes an obstruction in the sebaceous follicles. This blockage creates an environment for the proliferation of Propionibacterium acnes (P. acnes), (1) which releases chemotactic factors and proinflammatory mediators that may lead to inflammation. (2,3) P. acnes can also induce follicular keratinocytes to release interleukin-1, which leads to their proliferation and the formation of preclinical microcomedones. (4)

There are a variety of therapeutic agents available for the treatment of acne, including topical and systemic retinoids and antibiotics, and antibacterials, such as benzoyl peroxide (BP). The use of topical antibiotics, most commonly erythromycin, (5) is associated with the development of resistant strains of P. acnes, which decreases their effectiveness as monotherapy, but combination therapy with a topical antibiotic and BP may minimize the emergence of resistant strains. (6-9) The multifactorial nature of the pathogenesis of acne necessitates the use of a combination of different classes of therapeutic agents that act upon different areas of pathophysiology. For example, topical antibiotics reduce the population of P. acnes in the pilosebaceous duct, (10) while the addition of a topical retinoid normalizes desquamation of the follicular epithelium. (10,11) Furthermore, the combination of a retinoid plus BP combination product can promote faster resolution of existing acne lesions than the individual agents alone, and can also prevent the development of new lesions. (1)

Several combination products are available that combine either erythromycin or clindamycin with BP, which have demonstrated greater efficacy than either ingredient alone. (12-14) The efficacy and tolerability of 2 of these products, clindamycin 1% BP 5% gel and erythromycin 3% BP 5% gel (Benzamycin[R]) were assessed with BP 5% in a randomized, 10-week, multicenter, single-blind trial in 492 patients. (15) Results showed a nonsignificant trend for greater efficacy of clindamycin 1% BP 5% versus erythromycin 3% BP 5%, but overall, these combination agents were similarly efficacious. All 3 therapies demonstrated similar tolerability, with dry skin being the most frequent (< or = 7.3%) adverse event with all 3 therapies. These results mirror numerous other studies that have shown that all topical therapies cause some degree of irritation, especially BP, which can cause skin irritation and drying, and can cause contact allergy in up to 1% of patients. (10)

Although these combination products have demonstrated similar efficacy and tolerability, one drawback of erythromycin/BP combination products is that they require compounding by the pharmacist or patient, and require subsequent refrigeration. (16) Clindamycin 1% BP 5% gel, however, confers an advantage in that it is a uniform, aqueous gel that is manufactured under stringent US Food and Drug Administration (FDA) Good Manufacturing Practices and controls, which assure product consistency. (17) Since clindamycin 1% BP 5% is premixed, the manufacturing inconsistencies often encountered with human mixing and compounding do not occur. Additionally, the active ingredients have been shown to be stable for 60 days at 20[degrees] to 25[degrees]C (68[degrees]-77[degrees] F), so that neither the patient nor the physician ever need to store this gel in the refrigerator. (11,17) When kept at 2[degrees] to 8[degrees]C, the product is stable for 2 years. (17)

In addition to the stability and convenience of clindamycin 1% BP 5% gel, this product contains dimethicone and glycerin to moisturize and soften the skin. Dimethicone is an occlusive moisturizer that is hypoallergenic and lacks a strong odor. Occlusives condition the skin by impairing evaporation of water into the atmosphere. (18) Glycerin is a humectant moisturizer that attracts water from the viable skin layers to the stratum corneum. (18) An ideal formulation is one that combines occlusive and humectant ingredients to provide optimal rehydration, as products that contain only humectants actually increase transepidermal water loss. (18) The synergistic moisturizing properties of dimethicone and glycerin not only have the potential to enhance patient compliance and maximize the therapeutic benefits of clindamycin 1% BP 5% gel, but can preclude the need for supplemental moisturizers.