Adapalene 0.1%/Benzoyl Peroxide 2.5% Gel
Adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo™, Tactuo™) is the only fixed-dose combination product available that combines a topical retinoid with benzoyl peroxide; it targets three of the four main pathophysiologic factors in acne. This article reviews the therapeutic efficacy and tolerability of topical adapalene 0.1%/benzoyl peroxide 2.5% gel in the treatment of patients aged ≥ 12 years with acne vulgaris, as well as summarizing its pharmacologic properties.
In three 12-week trials in patients aged ≥12 years with moderate acne, success rates were significantly higher with adapalene 0.1%/benzoyl peroxide 2.5% gel than with adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone, and combination therapy had an earlier onset of action. In addition, significantly greater reductions in total, inflammatory, and noninflammatory lesion counts were seen in patients receiving adapalene 0.1%/benzoyl peroxide 2.5% gel than in those receiving adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone.
Adapalene 0.1%/benzoyl peroxide 2.5% gel did not significantly differ from clindamycin 1%/benzoyl peroxide 5% gel in terms of the reduction in the inflammatory, noninflammatory, or total lesion counts in patients with mild to moderate acne, according to the results of a 12-week trial.
Twelve-week studies showed that topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral lymecycline was more effective than oral lymecycline alone in patients with moderate to severe acne, and topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral doxycycline hyclate was more effective than oral doxycycline hyclate alone in patients with severe acne.
In patients with severe acne who responded to 12 weeks’ therapy with topical adapalene 0.1%/benzoyl peroxide 2.5% gel plus oral doxycycline hyclate or oral doxycycline hyclate alone, an additional 6 months’ therapy with adapalene 0.1%/benzoyl peroxide 2.5% gel was more effective than vehicle gel at maintaining response, with further improvement seen in adapalene 0.1%/benzoyl peroxide 2.5% gel recipients. A noncomparative study also demonstrated the efficacy of 12 months’ therapy with adapalene 0.1%/benzoyl peroxide 2.5% gel in patients with acne vulgaris.
Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in patients with acne. In 12-week trials, the most commonly occurring treatment-related adverse events included erythema, scaling, dryness, and stinging/burning; these dermatologic treatment-related adverse events were usually of mild to moderate severity, occurred early in the course of treatment, and resolved without residual effects. Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in the longer term, with dry skin being the most commonly occurring treatment-related adverse event over 12 months of treatment.
In conclusion, adapalene 0.1%/benzoyl peroxide 2.5% gel is a valuable agent for the first-line treatment of acne vulgaris.
- 2.Yentzer BA, Hick J, Reese EL, et al. Acne vulgaris in the United States: a descriptive epidemiology. Cutis 2010 Aug; 86 (2): 94–9Google Scholar
- 4.Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009 May; 60 (5 Suppl.): S1–50Google Scholar
- 5.Zaenglein AL, Thiboutot DM. Expert committee recommendations for acne management. Pediatrics 2006 Sep; 118 (3): 1188–99Google Scholar
- 6.Zuliani T, Khammari A, Chaussy H, et al. Ex vivo demonstration of a synergistic effect of adapalene and benzoyl peroxide on inflammatory acne lesions. Exp Dermatol. Epub 2011 Jul 2Google Scholar
- 7.Tan J, Gollnick HP, Loesche C, et al. Synergistic efficacy of adapalene 0.1%-benzoyl peroxide 2.5% in the treatment of 3855 acne vulgaris patients. J Dermatolog Treat 2011 Aug; 22 (4): 197–205Google Scholar
- 8.Ghali F, Kang S, Leyden J, et al. Changing the face of acne therapy. Cutis 2009 Feb; 83 (2 Suppl.): 4–15Google Scholar
- 9.Galderma Laboratories. Epiduo® (adapalene and benzoyl peroxide) gel 0.1%/2.5% for topical use: US prescribing information [online]. Available from URL: (http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022320s001lbl.pdf) [Accessed 2011 Jun 14]
- 10.Galderma (UK) Ltd. Epiduo 0.1%/2.5% gel: UK summary of product characteristics [online]. Available from URL: (http://www.medicines.org.uk/EMC/medicine/22679/SPC/Epiduo+0.1++2.5++Gel/) [Accessed 2011 Jun 14]
- 12.Layton AM, Eady EA. Benzoyl peroxide and adapalene fixed combination: a novel agent for acne. Br J Dermatol 2009 Nov; 161 (5): 971–6Google Scholar
- 13.Tan JKL. Adapalene 0.1%and benzoyl peroxide 2.5%: a novel combination for treatment of acne vulgaris. Skin Therapy Lett 2009 Jul/Aug; 14 (6): 4–5Google Scholar
- 14.Bikowski JB. Mechanisms of the comedolytic and anti-inflammatory properties of topical retinoids. J Drugs Dermatol 2005 Jan/Feb; 4 (1): 41–7Google Scholar
- 16.Asselineau D, Cavey M-T, Shroot B, et al. Control of epidermal differentiation by a retinoid analogue unable to bind to cytosolic retinoic acid-binding proteins (CRABP). J Invest Dermatol 1992 Feb; 98 (2): 128–34Google Scholar
- 17.Shroot B, Michel S. Pharmacology and chemistry of adapalene. J Am Acad Dermatol 1997 Jun; 36 (6 Pt 2): S96–103Google Scholar
- 18.Shroot B. Pharmacodynamics and pharmacokinetics of topical adapalene. J Am Acad Dermatol 1998 Aug; 39 (2 Pt 3): S17–24Google Scholar
- 22.Tenaud I, Khammari A, Dreno B. In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol 2007 Jun; 16 (6): 500–6Google Scholar
- 23.Vega B, Jomard A, Michel S. Regulation of humanmonocyte Toll-like receptor 2 (TLR2) expression by adapalene [abstract no. P1-39]. J Eur Acad Dermatol Venerol 2002 Oct; 16 Suppl. 1: 123–4Google Scholar
- 24.Michel S, Jomard A, Démarchez M. Pharmacology of adapalene. Br J Dermatol 1998 Oct; 139 Suppl. 52: 3–7Google Scholar
- 25.Center for Drug Evaluation and Research. Application number: 22-320: pharmacology review(s) [online]. Available from URL: (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022320s000_PharmR.pdf) [Accessed 2011 Jun 14]
- 26.Mills OH, Kligman AM, Pochi P, et al. Comparing 2.5%, 5%, and 10%benzoyl peroxide on inflammatory acne vulgaris. Int J Dermatol 1986 Dec; 25 (10): 664–7Google Scholar
- 28.Cove JH, Holland KT. The effect of benzoyl peroxide on cutaneous microorganisms in vitro. J Appl Bacteriol 1983 Jun; 54 (3): 379–82Google Scholar
- 29.Bojar RA, Cunliffe WJ, Holland KT. The short-term treatment of acne vulgaris with benzoyl peroxide: effects on the surface and follicular cutaneous microflora. Br J Dermatol 1995 Feb; 132 (2): 204–8Google Scholar
- 31.Leyden JJ, Preston N, Osborn C, et al. In-vivo effectiveness of adapalene 0.1%/benzoyl peroxide 2.5% gel on antibiotic-sensitive and resistant Propionibacterium acnes. J Clin Aesthet Dermatol 2011 May; 4 (5): 22–6Google Scholar
- 32.Caron D, Clucas A, Dunsire JP, et al. Radiolabelled adapalene is poorly absorbed after topical application of adapelene 0.1% gel [abstract no. P384]. J Eur Acad Dermatol Venerol 1998 Sep; 11 Suppl. 2: S275–6Google Scholar
- 33.Allec J, Chatelus A, Wagner N. Skin distribution and pharmaceutical aspects of adapalene gel. J Am Acad Dermatol 1997 Jun; 36 (6 Pt 2): S119–125Google Scholar
- 34.Center forDrug Evaluation andResearch. Application number 22-320: clinical pharmacology and biopharmaceutics review(s) [online]. Available from URL: (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022320s000_ClinPharmR.pdf) [Accessed 2011 Jun 14]
- 35.Nacht S, Yeung D, Beasley JN, et al. Benzoyl peroxide: percutaneous penetration and metabolic disposition. J Am Acad Dermatol 1981 Jan; 4 (1): 31–7Google Scholar
- 36.Gollnick HPM, Draelos Z, Glenn MJ, et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients. Br J Dermatol 2009 Nov; 161 (5): 1180–9Google Scholar
- 37.Stein Gold L, Tan J, Cruz-Santana A, et al. A North American study of adapalene-benzoyl peroxide combination gel in the treatment of acne. Cutis 2009 Aug; 84 (2): 110–6Google Scholar
- 38.Thiboutot DM, Weiss J, Bucko A, et al. Adapalene-benzoyl peroxide, a fixeddose combination for the treatment of acne vulgaris: results of a multicenter, randomized double-blind, controlled study. J Am Acad Dermatol 2007 Nov; 57 (5): 791–9Google Scholar
- 39.Eichenfield LF, Jorizzo JL, Dirschka T, et al. Treatment of 2,453 acne vulgaris patients aged 12-17 years with the fixed-dose adapalene-benzoyl peroxide combination topical gel: efficacy and safety. J Drugs Dermatol 2010 Nov; 9 (11): 1395–401Google Scholar
- 40.Feldman SR, Tan J, Poulin Y, et al. The efficacy of adapalene-benzoyl peroxide combination increases with number of acne lesions. J Am Acad Dermatol 2011 Jun; 64 (6): 1085–91Google Scholar
- 41.Zouboulis CC, Fischer TC, Wohlrab J, et al. Study of the efficacy, tolerability, and safety of 2 fixed-dose combination gels in the management of acne vulgaris. Cutis 2009 Oct; 84 (4): 223–9Google Scholar
- 42.Dréno B, Kaufmann R, Talarico S, et al. Combination therapy with adapalenebenzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicenter, randomised, double-blind controlled study. Br J Dermatol 2011 Aug; 165 (2): 383–90Google Scholar
- 43.Stein Gold L, Cruz A, Eichenfield L, et al. Effective and safe combination therapy for severe acne vulgaris: a randomized, vehicle-controlled, doubleblind study of adapalene 0.1%-benzoyl peroxide 2.5% fixed-dose combination gel with doxycycline hyclate 100 mg. Cutis 2010 Feb; 85 (2): 94–104Google Scholar
- 44.Poulin Y, Sanchez NP, Bucko A, et al. A 6-month maintenance therapy with adapalene-benzoyl peroxide gel prevents relapse and continuously improves efficacy among patients with severe acne vulgaris: results of a randomized controlled trial. Br J Dermatol 2011 Jun; 164 (6): 1376–82Google Scholar
- 45.Troielli PA, Asis B, Bermejo A, et al. Community study of fixed-combination adapalene 0.1% and benzoyl peroxide 2.5% in acne. Skinmed 2010 Jan/Feb; 8 (1): 17–22Google Scholar
- 46.Pariser DM, Westmoreland P, Morris A, et al. Long-termsafety and efficacy of a unique fixed-dose combination gel of adapalene 0.1% and benzoyl peroxide 2.5% for the treatment of acne vulgaris. J Drugs Dermatol 2007 Sep; 6 (9): 899–905Google Scholar
- 47.Callender VD, Preston N, Osborn C, et al. A meta-analysis to investigate the relation between Fitzpatrick skin types and tolerability of adapalene-benzoyl peroxide topical gel in subjects with mild or moderate acne. J Clin Aesthet Dermatol 2010 Aug; 3 (8): 15–9Google Scholar
- 48.Loesche C, Pernin C, Poncet M. Adapalene 0.1%and benzoyl peroxide 2.5%as a fixed-dose combination gel is as well tolerated as the individual components alone in terms of cumulative irritancy. Eur J Dermatol 2008 Sep-Oct; 18 (5): 524–6Google Scholar
- 49.Leyden JJ, Nighland M, Rossi AB, et al. Irritation potential of tretinoin gel microsphere pump versus adapalene plus benzoyl peroxide gel. J Drugs Dermatol 2010 Aug; 9 (8): 998–1003Google Scholar
- 50.Andres P, Pernin C, Poncet M. Adapalene-benzoyl peroxide once-daily, fixeddose combination gel for the treatment of acne vulgaris: a randomized, bilateral (split-face), dose-assessment study of cutaneous tolerability in healthy participants. Cutis 2008 Mar; 81 (3): 278–84Google Scholar
- 51.Webster GF. Evidence-based review: fixed-combination therapy and topical retinoids in the treatment of acne. J Drugs Dermatol 2011 Jun; 10 (6): 636–44Google Scholar
- 52.Dréno B, Thiboutot D, Gollnick H, et al. Large-scale worldwide observational study of adherence with acne therapy. Int J Dermatol 2010 Apr; 49 (4): 448–56Google Scholar
- 53.Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol 2007 Apr; 56 (4): 651–63Google Scholar
- 54.Ortho Dermatologics. Retin-A Micro® (tretinoin) gel microsphere 0.1% and 0.04%: US prescribing information [online]. Available from URL: (http://www.retinamicro.com/sites/default/files/RetinAMicro.pdf#zoom=200) [Accessed 2011 Jun 17]
- 55.Mylan Pharmaceuticals Inc. Avita® (tretinoin) gel 0.025%: US prescribing information [online]. Available from URL: (http://www.drugs.com/pro/avita.html?printable=1) [Accessed 2011 Jun 21]