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Adapalene

A Review of its Use in the Treatment of Acne Vulgaris

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Summary

Abstract

Adapalene (Differin®) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a rolein the first-line treatment of acne vulgaris.

Pharmacological Properties

Adapalene is a chemically stable derivative of naphthoic acid that binds selectively to the nuclear retinoic acid receptor (RAR) subtypes RARγ (found mainly in the epidermis) and RARβ (found in dermal fibroblasts), activating genes responsible for cellular differentiation; it does not bind to cytosolic retinoic acid binding proteins. Adapalene is thought to modulate keratinisation, differentiation and inflammation of follicular epithelial cells. This results in a reduction in microcomedones, the precursors of acne lesions.

Absorption of 0.1% adapalene gel through human skin is low. Adapalene was not detected in plasma in volunteers after topical application of either the gel or cream, nor was it detected in urine, faeces or skin. In animals, metabolism is via O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route. There are no known interactions with other drugs and, because of the low absorption through the skin, interaction with systemic drugs is unlikely.

Therapeutic Efficacy

Across several endpoints (including the mean percentage reduction in the number of inflammatory and noninflammatory lesions), 0.1% adapalene gel had similar efficacy to 0.025% tretinoin gel, 0.05% tretinoin cream and 0.05% isotretinoin cream as well as the newer 0.1% tretinoin microsphere gel formulation in the treatment of mild-to-moderate acne vulgaris. Data were from predominantly multicentre, randomised, single- or double-blind, parallel-group trials. After 8–12 weeks’ treatment, the percentage reductions in lesion counts were 47–75% and 38–73% for adapalene and 0.025% tretinoin gel treatment groups (inflammatory lesions), respectively, and 46–83% and 33%–83% (noninflammatory lesions). The similar efficacy of these two treatments was confirmed by two meta-analyses. The onset of action with 0.1% adapalene gel is rapid and generally appears to be similar to that with tretinoin formulations.

In two randomised, double-blind, parallel-group studies, patients with mild-tomoderate acne vulgaris receiving 0.1% tazarotene gel once daily had significantly greater reductions in inflammatory and noninflammatory lesions than 0.1% adapalene recipients. The same dosage of 0.1% adapalene gel showed similar efficacy to that of 0.1% tazarotene gel once every two days (dosage reduced to improve tolerability) in another trial of the same design.

Data indicate that 0.1% adapalene gel is effective in combination with topical clindamycin or benzoyl peroxide or oral cyclines (lymecycline, minocycline) in reducing the number of inflammatory and noninflammatory lesions in patients with mild-to-moderate or moderate to moderately severe acne vulgaris. Furthermore, 0.1% adapalene gel was effective as maintenance treatment following treatment with clindamycin plus adapalene.

Tolerability

Adapalene was generally better tolerated than comparators, particularly in the first 4 weeks of treatment. The most commonly reported adverse events in both adapalene and comparator recipients were erythema, dry skin, pruritus, desquamation and stinging/burning sensations. These were generally less severe in adapalene recipients than in the recipients of other topical retinoids.

Several randomised, intraindividual patch studies in healthy volunteers found 0.1% adapalene gel was the least irritating acne treatment when compared with various concentrations of tretinoin gel, cream, the new formulation of tretinoin (0.1% and 0.04% tretinoin microsphere gel) or with tazarotene gel.

When used as adjunctive therapy with topical clindamycin or oral lymecycline, 0.1% adapalene gel was generally well tolerated compared with gel vehicle plus the respective antibacterial agent. Overall, local cutaneous adverse events were mild in intensity.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    John Waugh, Stuart Noble & Lesley J. Scott

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  1. John Waugh
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  2. Stuart Noble
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Correspondence to John Waugh.

Additional information

Various sections of the manuscript reviewed by: N. Auffret, Hopital Europeen Georges Pompidou, Paris, France; S. Bershad, Department of Dermatology, The Mount Sinai School of Medicine, New York, New York, USA; P. Coates, Department of Dermatology, The General Infirmary at Leeds, Leeds, United Kingdom; B. Dreno, Clinique Dermatologique, Centre Hospitalier Regional University De Nantes, Nantes, France; A.M. Layton, Harrogate District Hospital, Harrogate, United Kingdom; J.C. Shaw, Division of Dermatology, University of Toronto, Toronto, Canada.

Data Selection

Sources: medical literature published in any language since 1997 on adapalene, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘adapalene’ or ‘CD-271’. EMBASE search terms were ‘adapalene’ or ‘CD 271’. AdisBase search terms were ‘adapalene’ or ‘CD271’. Searches were last updated 10 May 2004.

Selection: Studies in patients with acne vulgaris who received adapalene. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Adapalene, acne vulgaris, pharmacodynamics, pharmacokinetics, therapeutic efficacy, tolerability.

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Waugh, J., Noble, S. & Scott, L.J. Adapalene. Drugs 64, 1465–1478 (2004). https://doi.org/10.2165/00003495-200464130-00005

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