Pharmacotherapy Update: Managing Truncal Acne Vulgaris - James Q. Del Rosso, D.O., F.A.O.C.D., and Joseph Bikowski, M.D. Focus on combination therapy with clindamycin 1% foam and benzoyl peroxide cleanser. C lindamycin phosphate 1% is an effective topical agent for managing acne vulgaris, including truncal involvement (acneiform folliculitis). This antibiotic exhibits marked antistaphylococcal activity and may be of benefit topically for superficial bacterial folliculitis. A novel foam vehicle of clindamycin phosphate 1% (Evoclin) approved for treatment of acne vulgaris allows for rapid cutaneous penetration and widespread application. This article will discuss the pharmacokinetic properties of this formulation and report observational experience with clindamycin phosphate 1% foam for treatment of truncal acne vulgaris. In addition, an evaluation will be presented of a subset population of patients who underwent treatment with clindamycin phosphate 1% foam for truncal or lower extremity bacterial folliculitis. The history of topical Clindamycin in Treating Acne Clindamycin, a synthetic lincosamide antibiotic, has a long established track record of more than 25 years as an effective and safe topical agent used for the treatment of acne vulgaris.1-3 The efficacy of topical clindamycin phosphate for acne vulgaris has been demonstrated in studies evaluating both monotherapy, and in combination with other topical agents (for example, benzoyl peroxide and topical retinoids).2-7 Comparative trials have demonstrated equal or superior reduction of inflammatory acne lesions with use of topical clindamycin phosphate as compared to oral tetracycline (500 mg to 1 gram daily).4,5,8 As with topical erythromycin, the original topical formulations of clindamycin were extemporaneously compounded into solution. Subsequently, proprietary topical 1% formulations were developed, including solution, lotion and gel vehicles, with FDA approval for acne vulgaris designated initially in 1980. Twice daily application was recommended with older formulations based on dosage frequency used in clinical trials for acne vulgaris; newer formulations of topical clindamycin 1% including a foam and aqueous gel are FDA approved for once daily use. Based on microbiologic assays and clinical data from systemic use of clindamycin, this agent is highly active against Staphylococcus aureus, streptococci, some anaerobes and Propionibacterium acnes.1,9 Although monotherapy trials in patients with acne vulgaris have effectively demonstrated improvement with topical clindamycin use, it is recommended that topical or systemic antibiotics be used in combination with the other topical agents, such as retinoids and benzoyl peroxide.10,11 Antibiotic use in combination with benzoyl peroxide has been shown to be of significance as the latter reduces the development of antibiotic-resistant P. acnes and suppresses the further emergence of already resistant strains.11 Topical Clindamycin in a Patented Foam Formulation Clinical results. Recently, topical clindamycin phosphate 1% (clindamycin 1%) has been formulated in a patented foam vehicle, and has received FDA approval for treatment of acne vulgaris. In 12-week, double-blind, randomized, parallel multicenter trials inclusive of 1,026 patients, clindamycin 1% foam demonstrated statistically significant superiority over clindamycin 1% gel (p=0.0014) and both vehicle foam and gel (p<0.001) with regard to mean percent reduction in total acne lesion counts.12 The clindamycin 1% foam was well tolerated. Formulation Characteristics. Estab-lished advantages of the foam vehicle include rapid penetration into skin, lack of residue, easy spreadability, applicability to multiple body locations, ease of application to widespread body surfaces and favorable patient preference.13 The foam formulation of clindamycin differs slightly from that which is currently used to formulate the topical corticosteroids, betamethasone valerate 0.12% and clobetasol propionate 0.05%. The skin temperature “break” characteristics after application of the topical corticosteroid foams allow for immediate dissolution onto the skin surface (“quick-break” foam) followed by rapid cutaneous penetration. The clindamycin foam exhibits “slower break” characteristics, dissolving at approximately 5 degrees higher skin temperature exposure.14 As a result, a mound of applied foam may sit longer on the skin, with penetration occurring rapidly when the foam is gently spread across the skin’s surface. Gentle spreading of the foam into the skin’s surface allows for rapid penetration in a manner similar to that observed with the corticosteroid foams. The advantage of the “slower break” property is greater control of application and ease of spreading the clindamycin foam over large body surface areas, such as the chest and back. Systemic Absorption Assays. The systemic absorption of clindamycin was compared after application of clindamycin 1% foam vs. aqueous gel in an open study (n=24 / age >= 12 years). Each patient self-administered 4g of study drug to the face and other sites affected with acne (for example, neck and upper trunk) daily for 5 days. Minimal systemic absorption was observed with no statistically significant differences in mean plasma levels of clindamycin observed between the foam (Cmax = 1.70 ng/ml) and aqueous gel (Cmax = 2.22 ng/ml).14 Interestingly, in vitro 24-hour permeation studies using split thickness human skin have demonstrated more rapid rate of delivery and a greater quantity of drug delivered into skin with clindamycin 1% foam as compared to the aqueous gel.14 The use of clindamycin foam for truncal acne vulgaris and folliculitis was evaluated in an ambulatory dermatology setting in three private practice offices.1,15 The results are reported below. Study Methods Used in the Truncal Acne Patient Group Male and female patients with truncal acne vulgaris involving the chest, shoulders and/or back (n=40) were included. All cases were graded as moderate severity, defined as the presence of non-inflammatory lesions (comedones) with multiple inflammatory lesions (papules, pustules) and few or no deep inflammatory lesions. These patients were required to be off of all topical acne therapy used on the trunk for at least 4 weeks. (See Tables 1 and 2 for study details.) Analyzing the Results At final follow-up (week 8), efficacy was rated by the investigator based on percent reduction in total lesion count. Ratings were defined as completely clear (no lesions observed), almost clear (>75% reduction), markedly improved (>50 to 75% reduction), moderately improved (>25 to 50% reduction), minimally improved (<25% reduction), no improvement (total count unchanged from baseline +/- 5 lesions) or worsening (lesion count >5 above baseline). (Responses are summarized in Table 3.) Superficial Folliculitis Patient Group Patients with culture-confirmed superficial staphylococcal (S. aureus) folliculitis involving the trunk (n=4) or legs (n=2) were included in another study. In this study, patients presented with multiple follicular papules and pustules without the presence of deep inflammatory lesions or abscesses on the trunk (n=4 males) or legs (n=2 females). Methicillin-sensitive S. aureus was confirmed by culture obtained prior to initiation of therapy in all six cases of superficial folliculitis. Repeat culture was performed if inflammatory lesions were observed at follow-up. All six patients were treated with topical clindamycin 1% foam once daily for 2 weeks and followed up at 2 to 3 weeks after therapy started and again 4 weeks later. None of the patients had undergone previous therapy for their disorder. Before After Photographs 1A and 1B illustrate a patient treated once daily with clindamycin 1% foam (Evoclin) and benzoyl peroxide 8% creamy wash (Brevoxyl). Superficial Folliculitis Patient Group All six patients demonstrated clearance of superficial staphylococcal folliculitis with use of clindamycin 1% foam applied once daily for 2 weeks. At follow-up, 2 patients (1 on trunk, 1 on legs) demonstrated scattered foci of macular follicular erythema determined to be residual change at sites of clearance. No palpable inflammatory lesions were present for culture assessment at follow-up. At final follow-up 4 to 5 weeks post-therapy, no relapses or new episodes of folliculitis were observed. Assessing Safety and Tolerability None of the patients in either treatment group (n=46 total) experienced any systemic adverse reactions. All patients were queried at each visit regarding new onset of signs (ie. dryness, scaling, erythema) and symptoms (ie. stinging, burning, itching) of local tolerability reactions potentially related to therapy. Reported application site reactions included dryness (n=6), transient stinging or burning after foam application, which resolved within 1 to 2 minutes (n=5), and mild erythema (n=7). In all six cases, dryness resolved after use of a non-fragranced, branded, noncomedogenic moisturizer cream or lotion. Points to Remember • Clindamycin 1% foam is a novel formulation that may be used effectively in combination with a benzoyl peroxide wash/cleanser (8% or 9%) once daily for truncal acne vulgaris of moderate severity. • In patients with truncal acne vulgaris treated once daily with a combination of clindamycin 1% foam and a benzoyl peroxide wash/cleanser (8% or 9%), 60% were at least markedly improved and 92.5% were moderately improved to completely clear at study endpoint. • Overall favorable tolerability was observed with use of clindamycin 1% foam once daily, either in combination with a benzoyl peroxide wash/cleanser (n=40) or as monotherapy for superficial bacterial folliculitis (n=6). • Although data are limited, clindamycin 1% foam applied once daily for 2 weeks proved to be effective for treatment of superficial folliculitis caused by methicillin-sensitive S. aureus in a small subset of adult patients with truncal or leg involvement. References: 1. Hsu S, Quan LT. Topical antibacterial agents. In: Wolverton S (Ed). Comprehensive Dermatology Drug Therapy, 1st Edition. WB Saunders (Philadelphia) 2001, p. 481-483. 2. Becker LE, Bergstresser PR, Whiting DA, et al. Topical clindamycin therapy for acne vulgaris : a cooperative clinical study. Arch Dermatol. 1981;117:482-485. 3. Ellis CN, Gammon WR, Stone DZ, et al. A comparison of clindamycin solution, clindamycin gel, and placebo in the treatment of acne vulgaris. Cutis. 1988;42:245-247. 4. Braathen LR. Topical clindamycin versus oral tetracycline and placebo in acne vulgaris. Scand J Infect Dis (Suppl). 1984;43:71-75. 5. Stoughton RB, Cornell RC, Gange RW, et al. Double-blind comparison of topical 1 percent clindamycin phosphate and oral tetracycline 500 mg/day in the treatment of acne vulgaris. Cutis. 1980;26:424-425. 6. Tucker SB, Tausend R, Cochran R, et al. Comparison of topical clindamycin phosphate, benzoyl peroxide, and a combination of the two for the treatment of acne vulgaris. Br J Dermatol. 1984;110:487-492. 7. Lookingbill DP, Chalker DK, Lindholm JS, et al. Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations. J Am Acad Dermatol. 1997;37:590-595. 8. Katsambas A, Towansky AA, Stratigos J. Topical clindamycin phosphate compared with oral tetracycline in the treatment of acne vulgaris. Br J Dermatol. 1987;116:387-391. 9. Nishijima S, Kurokawa I, Kawabata S. Sensitivity of Propionibacterium acnes isolated from acne patients: a comparative study of antimicrobial agents. Acta Derm Venereol. 1996;24:473-477. 10. Bershad S. Developments in topical retinoid therapy for acne. Sem Cut Med Surg. 2001;20:154-161. 11. Leyden JJ. The evolving role of Propionibacterium acnes in acne. Sem Cut Med Surg. 2001;20:139-143. 12. Shalita AR, Myers JA, Krochmal L, Yaroshinsky A; Clindamycin Foam Study Group. The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris. J Drugs Dermatol. 2005 Jan-Feb;4(1):48-56. 13. Housman TS, Mellen BG, Rapp SR, et al. Patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. Cutis 2002;70:327-332. 14. Data on file. Connetics Corporation. Palo Alto, California, 2005. 15. Rosen T, Waisman M. Topically administered clindamycin in the treatment of acne vulgaris and other dermatologic disorders. Pharmacotherapy. 1981;1:201-205. Skin & Aging - ISSN: 1096-0120 - Volume 13 - Issue 8_2005 - August 2005 - Pages: 66 - 70