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Class: Skin and Mucous Membrane Agents, Miscellaneous
VA Class: DE752
Chemical Name: 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid
Molecular Formula: C28H28O3
CAS Number: 106685-40-9
Brands: Differin

Medically reviewed by Last updated on Jan 22, 2020.


Retinoid; synthetic naphthoic acid-derivative.7 8 10 11 12 13 14 15 16 17 18 19 20 22

Uses for Adapalene

Acne Vulgaris

Treatment of acne vulgaris.1 4 5 6 7 11 12 13 14 16 17 18 19 20 21 22 31 32

Adapalene Dosage and Administration


Topical Administration

Apply a thin film to skin as a cream, gel, or solution.1 4 5 7 11 12 13 16 17 18 19 20 21 22 31 32

Cleanse and dry the affected areas prior to application.1 31 32

Do not apply to eye(s), lips, angles of nose, or mucous membranes.1 31 32

A transient feeling of pruritus or burning may occur immediately after application.1 12 31 32 If increased sensitivity or irritation occurs, reduce frequency of application or, depending on the severity, discontinue use.1 31 32

Apparent exacerbation of acne that may occur during early weeks of therapy is attributable to the drug’s action on previously unseen lesions; do not discontinue.1 31 32

Excessive use does not increase therapeutic effects and may produce marked erythema, peeling, and discomfort.1 31 32


Remove single-use pledget applicators from foil immediately before use, use once, and then discard; do not use if seal is broken.31


Pediatric Patients

Acne Vulgaris

Children and adolescents ≥12 years of age: Apply once daily in the evening at bedtime.1 12 31 32

Improvement usually detectable within 8–12 weeks.1 31 32


Acne Vulgaris

Apply once daily in the evening at bedtime.1 12 31 32

Improvement usually detectable within 8–12 weeks.1 31 32

Prescribing Limits

Pediatric Patients

Acne Vulgaris

Children and adolescents ≥12 years of age: most reported experience to date has been for treatment periods that did not exceed 12 weeks.4 5 6 12 22


Acne Vulgaris

Most reported experience to date has been for treatment periods that did not exceed 12 weeks.4 5 6 12 22

Cautions for Adapalene


  • Known hypersensitivity to adapalene or any ingredient in the formulation.1 31 32


Sensitivity Reactions


Increased risk for sunburn; minimize exposure to sunlight or artificial UV irradiation sources (e.g., sunlamps).1 31 32

Use caution in patients subjected to considerable occupational sun exposure or with inherent sun sensitivity; use of sunscreen products (SPF 15 or greater) and protective clothing over treated areas recommended when exposure cannot be avoided.1 31 32

Avoid concomitant use of photosensitizing agents.33 (See Interactions.)

Use not recommended in patients with sunburn until full recovery occurs.1 31

Other Sensitivity Reactions

Discontinue therapy if sensitivity reaction or chemical irritation occurs.1 31 32

General Precautions

Dermatologic Effects

Erythema, dryness, scaling, burning, or pruritus may occur.1 31 32 If increased sensitivity or irritation occurs, use less frequently or, depending on the severity of the reaction, discontinue.1 31 32

Do not apply to cuts, abrasions, or eczematous or sunburned skin.1 31 32 (See Photosensitivity under Cautions.)

Facial Cleansing

Use of mild or soapless cleanser is recommended; use medicated or drying soaps and abrasive soaps and cleansers with caution.1 31 32

Cosmetic Agents or Processes

Avoid use of irritating cosmetics, other preparations, or processes (e.g., electrolysis) that might dry or irritate the skin.33 (See Interactions.)

Environmental Stimuli

Possible increased skin irritation in patients exposed to environmental extremes (e.g., wind, cold).1 31 32

Dry Skin

Use moisturizers if necessary; avoid preparations containing alpha hydroxy or glycolic acids.32

Specific Populations


Category C.1 31 32


Not known whether adapalene is distributed into milk.1 31 32 Use caution.1 31 32

Pediatric Use

Safety and efficacy not established in children <12 years of age.1 31 32

Geriatric Use

Insufficient experience in controlled clinical studies in patients ≥65 years of age to determine whether geriatric patients respond differently to adapalene than younger adults.32 However, clinical experience generally has not revealed age-related differences.32

Common Adverse Effects

Erythema, scaling, dryness, pruritus, burning/stinging.1 31 32

Interactions for Adapalene

Specific Drugs




Keratolytic agents (e.g., resorcinol, salicylic acid, sulfur)

Possible additive effects1 31 32

Allow sufficient time for the effects of the keratolytic agent to subside before initiating adapalene1 31 32

Photosensitizing agents (e.g., fluoroquinolone anti-infectives, phenothiazines, sulfonamides, thiazide diuretics)

Possible increased phototoxicity33

Avoid concomitant use33

Other Topical Preparations

Potential pharmacodynamic interaction (increased skin irritation).1 31 32 Avoid concurrent use of topical preparations with high concentrations of alcohol, menthol, spices, or lime (e.g., lotions, astringents, perfume); irritating cosmetics (e.g., toners, peeling [desquamating] agents); permanent wave solutions; or hair depilatories or waxes.1 31 32 33

Adapalene Pharmacokinetics



Minimally absorbed following topical application.1 31 32


Elimination Route

Eliminated principally by biliary excretion.1 31 32




Cream, Gel, Solution

20–25°C.1 31 32

Protect cream from freezing.32

Store solution upright in tight container.31


  • Actions similar to those of other retinoids (e.g., isotretinoin, tretinoin) but more potent anti-inflammatory activity in vitro and in vivo.1 4 5 6 9 13 15 16 17 19 23 24 31

  • Relatively selective affinity for specific nuclear retinoic acid receptor (RAR) proteins (e.g., RARβ, RARγ) that appear to enhance gene transcription.5 6 7 23 24

  • Exact mechanism(s) of action not elucidated.1 4 5 6 9 13 15 16 17 19 31 Appears to affect expression of genes that modulate follicular keratinization5 19 22 and cell (e.g., epithelial) differentiation,1 4 5 6 9 10 13 15 19 22 23 31 which result in inhibition of corneocyte accumulation and cohesion and reduction in inflammatory and noninflammatory acne lesions.1 6 11 12 22 23 24 31

Advice to Patients

  • Importance of clinicians instructing patients about proper use of the drug.1 31 32

  • Importance of continuing therapy in early weeks, even if acne initially appears to worsen.1 31 32

  • Risk of photosensitivity; importance of using sunscreens and wearing protective clothing over treated areas.1 31 32

  • Importance of avoiding contact with eyes, lips, angles of nose, or mucous membranes.1 31 32

  • Importance of not applying adapalene to cuts, abrasions, or eczematous or sunburned skin.1 31 32

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1 31 32

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 31 32

  • Importance of informing patients of other important precautionary information.1 31 32 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.



Dosage Forms


Brand Names





Differin (with parabens)




Differin (with methylparaben and propylene glycol)


Pledgets (saturated with solution)


Differin (with SD alcohol 40-B 30% w/v)




Differin (with SD alcohol 40-B 30% w/v)


AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 1, 2005. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Galderma. Differin (adapalene) gel 0.1% prescribing information. Fort Worth, TX; 1996 May.

2. Hurwitz S. Acne vulgaris: current concepts of pathogenesis and treatment. Am J Dis Child. 1979; 133:536-44.

3. Chandraratna RAS. Tazarotene—first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996; 135:18-25.

4. Verschoore M, Langner A, Wolska H et al. Efficacy and safety of CD 271 alcoholic gels in the topical treatment of acne vulgaris. Br J Dermatol. 1991; 124:368-71.

5. Shalita A, Weiss JS, Chalker DK et al. A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial. J Am Acad Dermatol. 1996; 34:482-5.

6. Bernard BA. Adapalene, a new chemical entity with retinoid activity. Skin Pharmacol. 1993; 6(Suppl 1):61-9.

7. Griffiths CEM, Elder JT, Bernard BA et al. Comparison of CD271 (Adapalene) and all- trans retinoic acid in human skin: dissociation of epidermal effects and CRABP-II mRNA expression. J Invest Dermatol. 1993; 101:325-28.

8. Jamoulle JC, Grandjean L, Lamaud E et al. Follicular penetration and distribution of topically applied CD 271, a new naphthoic acid derivative intended for topical acne treatment. J Invest Dermatol. 1990; 94:731-2.

9. Hensby C, Cavey D, Bouclier M et al. The in vivo and in vitro anti- inflammatory activity of CD271: a new retinoid-like modulator of cell differentiation. Agents Actions. 1990; 29:56-8.

10. Bernerd F, Ortonne JP, Bouclier M et al. The rhino mouse model: the effects of topically applied all-trans retinoic acid and CD271 on the fine structure of the epidermis and utricle wall of pseudocomedones. Arch Dermatol Res. 1991; 283:100-7.

11. Leyden JJ. Therapy for acne vulgaris. N Engl J Med. 1997; 336:1156-62.

12. Brogden RN, Goa KL. Adapalene: a review of its pharmacological properties and clinical potential in the management of mild to moderate acne. Drugs. 1997; 53:511-9.

13. Verschoore M. Adapalene: a novel topical retinoid receptor agonist for acne—overview. J Am Acad Dermatol. 1997; 36:S91.

14. Kligman AM. The treatment of acne with topical retinoids: one man’s opinions. J Am Acad Dermatol. 1997; 36:S92-5.

15. Shroot B, Michel S. Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997; 36:S96-103.

16. Verschoore M, Poncet M, Czernielewski J et al. Adapalene 0.1% gel has low skin- irritation potential. J Am Acad Dermatol. 1997; 36:S104-9.

17. Caron D, Sorba V, Kerrouche N et al. Split-face comparison of adapalene 0.1% gel and tretinoin 0.025% gel in acne patients. J Am Acad Dermatol. 1997; 36:S110-12.

18. Caron D, Sorba V, Clucas A et al. Skin tolerance of adapalene 0.1% gel in combination with other topical antiacne treatments. J Am Acad Dermatol. 1997; 36:S113-5.

19. Clucas A, Verschoore M, Sorba V et al. Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients. J Am Acad Dermatol. 1997; 36:S116-8.

20. Allec J, Chatelus A, Wagner N. Skin distribution and pharmaceutical aspects of adapalene gel. J Am Acad Dermatol. 1997; 36:S119-25.

21. Cunliffe WJ, Caputo R, Dreno B et al. Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials. J Am Acad Dermatol. 1997; 36:S126-34.

22. Anon. Adapalene for acne. Med Lett Drugs Ther. 1997; 39:19-20.

23. Thiboutot DM. Acne: an overview of clinical research findings. Dermatol Clin. 1997; 15:97-109.

24. Gibson JR. Rationale for the development of new topical treatments for acne vulgaris. Cutis. 1996; 57:13-9.

25. Anon. Update on birth defects with isotretinoin. FDA Drug Bull. 1984; 14:15-6.

26. Benke PJ. The isotretinoin teratogen syndrome. JAMA. 1984; 251:3267-9.

27. de la Cruz E, Sun S, Vangvanichyakorn K et al. Multiple congenital malformations associated with maternal isotretinoin therapy. Pediatrics. 1984; 74:428-30.

28. Lammer EJ, Chen DT, Hoar RM et al. Retinoic acid embryopathy. N Engl J Med. 1985; 313:837-41.

29. Rosa FW, Wilk AL, Kelsey FO. Teratogen update: vitamin A congeners. Teratology. 1986; 33:355-64.

30. Cohen M, Rubenstein A, Li JK et al. Thymic hypoplasia associated with isotretinoin embryopathy. Am J Dis Child. 1987; 141:263-6.

31. Galderma. Differin (adapalene) solution 0.1% prescribing information. Fort Worth, TX; 1997 Jul.

32. Galderma Laboratories. Differin cream 0.1% (adapalene) prescribing information. Fort Worth, TX; 2000 May.

33. Galderma Laboratories, Fort Worth, TX: Personal Communication.

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