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Topical Acne Drugs

Review of Clinical Properties, Systemic Exposure, and Safety

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Abstract

This review examines the commonly available topical acne agents and factors that determine their percutaneous absorption. Reported and theoretical adverse effects from systemic exposure are detailed.

The topical retinoid class, which includes tretinoin, adapalene and tazarotene, and the topical antibacterials, clindamycin and erythromycin, are regulated by prescription in most countries. Used appropriately, the above-mentioned drugs deliver, at most, miniscule amounts of active ingredient into the circulation. Clear-cut links to systemic toxicity in humans are practically nonexistent, except in the case of topical clindamycin, which has been associated with diarrhea rarely, and there have been 2 cases of pseudomembranous colitis reported. Birth defects have occurred in two patients treated with tretinoin and one patient treated with adapalene, but causation was not proven. Another prescription drug, 20% azelaic acid, is associated with relatively high systemic exposure, which is presumed innocuous because it is a normal dietary constituent whose endogenous levels are not altered by topical use.

Benzoyl peroxide, salicylic acid, sulfur, and sodium sulfacetamide are available in concentrations of 2% or more in over-the-counter acne treatments and some prescription products. All of these agents are known to exhibit some degree of percutaneous absorption. They remain largely unregulated because, other than skin irritation, only local allergic contact dermatitis from benzoyl peroxide in about 2.5% of patients and rare local and systemic hypersensitivity reactions from sodium sulfacetamide have been reported. Salicylism has occurred using methyl salicylate ointments and high concentrations of salicylic acid on widespread areas of hyperkeratotic skin, but there are no known cases resulting from salicylic acid acne products.

Caution is advised in special circumstances, such as during childhood, pregnancy, lactation and concomitant therapy with other drugs, because relevant studies are lacking. Animal data support avoidance of many topical agents, particularly known teratogens such as retinoids and salicylic acid, in pregnant women. Salicylate avoidance is advised during lactation, because aspirin use carries the risk of bleeding disorders in nursing infants.

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Notes

  1. Use of tradenames is for product identification only and does not imply endorsement.

References

  1. Roberts J. Skin conditions of youths 12–17 years, United States. vital and health statistics: Series 11. Data from the National Health Survey, Data from the health examination survey; no. 157. DHEW publication no. (HRA) 76–1639, 1976

  2. Krowchuk DP, Stancin T, Keskinen R, et al. The psychosocial effects of acne on adolescents. Pediatr Dermatol 1991 Dec; 8 (4): 332–8

    Article  PubMed  CAS  Google Scholar 

  3. Lucky AW, Biro FM, Huster GA, et al. Acne vulgaris in premenarchal girls: an early sign of puberty associated with rising levels of dehydroepiandrosterone. Arch Dermatol 1994; 130: 308–14

    Article  PubMed  CAS  Google Scholar 

  4. Goulden V, Clark SM, Cunliffe WJ. Post-adolescent acne: a review of clinical features. Br J Dermatol 1997 Jan; 136 (1): 66–70

    Article  PubMed  CAS  Google Scholar 

  5. Lasek RJ, Chren MM. Acne vulgaris and the quality of life of adult dermatology patients. Arch Dermatol 1998 Apr; 134 (4): 454–8

    Article  PubMed  CAS  Google Scholar 

  6. Walton S, Wyatt EH, Cunliffe WJ. Genetic control of sebum excretion and acne: a twin study. Br J Dermatol 1988 Mar; 118 (3): 393–6

    Article  PubMed  CAS  Google Scholar 

  7. Imperato-McGinley J, Gautier T, Cai LQ, et al. The androgen control of sebum production: studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab 1993 Feb; 76 (2): 524–8

    Article  PubMed  CAS  Google Scholar 

  8. Marynick SP, Chakmakjian ZH, McCaffree DL, et al. Androgen excess in cystic acne. N Engl J Med 1983 Apr 28; 308 (17): 981–6

    Article  PubMed  CAS  Google Scholar 

  9. Lucky AW, McGuire J, Rosenfield RL, et al. Plasma androgens in women with acne vulgaris. J Invest Dermatol 1983 Jul; 81 (1): 70–4

    Article  PubMed  CAS  Google Scholar 

  10. Rasmussen JE. Diet and acne. Int J Dermatol 1977 Jul-Aug; 16 (6): 488–92

    Google Scholar 

  11. Fulton Jr JE, Plewig G, Kligman AM. Effect of chocolate on acne vulgaris. JAMA 1969 Dec 15; 210 (11): 2071–4

    Article  PubMed  Google Scholar 

  12. Leyden JJ. Therapy for acne vulgaris. N Engl J Med 1997 Apr 17; 336 (16): 1156–62

    Article  PubMed  CAS  Google Scholar 

  13. Webster GF. Inflammatory acne. Int J Dermatol 1990 Jun; 29 (5): 313–7

    Article  PubMed  CAS  Google Scholar 

  14. Kersey P, Sussman M, Dahl M. Delayed skin test reactivity to Propionibacterium acnes correlates with severity of inflammation in acne vulgaris. Br J Dermatol 1980 Dec; 103 (6): 651–5

    Article  PubMed  CAS  Google Scholar 

  15. Mills Jr OH, Kligman AM. Assay of comedolytic activity in acne patients. Acta Derm Venereol 1983; 63 (1): 68–71

    PubMed  Google Scholar 

  16. Goldstein JA, Comite H, Mescon H, et al. Isotretinoin in the treatment of acne: histologic changes, sebum production, and clinical observations. Arch Dermatol 1982; 118 (8): 555–8

    Article  PubMed  CAS  Google Scholar 

  17. Bershad SV. The modern age of acne therapy: a review of current treatment options. Mt Sinai J Med 2001; 68 (4–5): 279–86

    PubMed  CAS  Google Scholar 

  18. Sykes Jr NL, Webster GF. Acne: a review of optimum treatment. Drugs 1994; 48 (1): 59–70

    Article  PubMed  Google Scholar 

  19. Kawada A, Aragane Y, Kameyama H, et al. Acne phototherapy with a high-intensity, enhanced, narrow-band, blue light source: an open study and in vitro investigation. J Dermatol Sci 2002; 30 (2): 129–35

    Article  PubMed  Google Scholar 

  20. Paithankar DY, Ross EV, Saleh BA, et al. Acne treatment with a 1,450 nm wavelength laser and cryogen spray cooling. Lasers Surg Med 2002; 31 (2): 106–14

    Article  PubMed  Google Scholar 

  21. Schaefer H. Penetration and percutaneous absorption of topical retinoids: a review. Skin Pharmacol 1993; 6 Suppl. 1: 17–23

    Article  Google Scholar 

  22. Physicians’ desk reference. 56th ed. Montvale (NJ): Medical Economics Company Inc, 2002

    Google Scholar 

  23. Jensen BK, McGann LA, Kachevsky V, et al. The negligible systemic availability of retinoids with multiple and excessive topical application of isotretinoin 0.05% gel (Isotrex) in patients with acne vulgaris. J Am Acad Dermatol 1991; 24 (3): 425–8

    Article  PubMed  CAS  Google Scholar 

  24. Rougier A, Dupuis D, Lotte C, et al. The measurement of the stratum corneum reservoir: a predictive method for in vivo percutaneous absorption studies: influence of application time. J Invest Dermatol 1985; 84 (1): 66–8

    Article  PubMed  CAS  Google Scholar 

  25. Bershad S, Poulin YP, Berson DS, et al. Topical retinoids in the treatment of acne vulgaris. Cutis 1999 Aug; 64 (2 Suppl.): 8–20

    PubMed  CAS  Google Scholar 

  26. Bershad S, Kranjac Singer G, Parente JE, et al. Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel. Arch Dermatol 2002; 138 (4): 481–9

    Article  PubMed  CAS  Google Scholar 

  27. Rougier A, Lotte C, Maibach HI. In vivo percutaneous penetration of some organic compounds related to anatomic site in humans: predictive assessment by the stripping method. J Pharm Sci 1987; 76 (6): 451–4

    Article  PubMed  CAS  Google Scholar 

  28. Lotte C, Wester RC, Rougier A, et al. Racial differences in the in vivo percutaneous absorption of some organic compounds: a comparison between black, Caucasian and Asian subjects. Arch Dermatol Res 1993; 284 (8): 456–9

    Article  PubMed  CAS  Google Scholar 

  29. Dupuis D, Rougier A, Roguet R, et al. The measurement of the stratum corneum reservoir: a simple method to predict the influence of vehicles on in vivo percutaneous absorption. Br J Dermatol 1986; 115 (2): 233–8

    Article  PubMed  CAS  Google Scholar 

  30. Piacquadio D, Kligman A. The critical role of the vehicle to therapeutic efficacy and patient compliance. J Am Acad Dermatol 1998 Aug; 39 (2 Pt 3): S67–73

    Article  Google Scholar 

  31. Kligman AM, Fulton Jr JE, Plewig G. Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969; 99 (4): 469–76

    Article  PubMed  CAS  Google Scholar 

  32. Sporn MB, Dunlop NM, Newton DL, et al. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 1976; 35 (6): 1332–8

    PubMed  CAS  Google Scholar 

  33. Petkovich M, Brand NJ, Krust A, et al. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 1987; 330 (6147): 444–50

    Article  PubMed  CAS  Google Scholar 

  34. Mangelsdorf DJ, Ong ES, Dyck JA, et al. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 1990; 345 (6272): 224–9

    Article  PubMed  CAS  Google Scholar 

  35. Bershad S. Developments in topical retinoid therapy for acne. Semin Cutan Med Surg 2001; 20 (3): 154–61

    Article  PubMed  CAS  Google Scholar 

  36. Weiss JS, Ellis CN, Headington JT, et al. Topical tretinoin improves photoaged skin: a double-blind vehicle-controlled study. JAMA 1988; 259 (4): 527–32

    Article  PubMed  CAS  Google Scholar 

  37. Kang S, Leyden JJ, Lowe NJ, et al. Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Arch Dermatol 2001 Dec; 137 (12): 1597–604

    PubMed  CAS  Google Scholar 

  38. Duvic M, Nagpal S, Asano AT, et al. Molecular mechanisms of tazarotene action in psoriasis. J Am Acad Dermatol 1997; 37 (2 Pt 3): S18–24

    Article  Google Scholar 

  39. Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol 1997; 37 (1): 85–92

    Article  PubMed  CAS  Google Scholar 

  40. Walmsley S, Northfelt DW, Melosky B, et al. Treatment of AIDS-related cutaneous Kaposi’s sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group. J Acquir Immune Defic Syndr 1999; 22 (3): 235–46

    PubMed  CAS  Google Scholar 

  41. Duvic M, Hymes K, Heald P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 2001; 19 (9): 2456–71

    PubMed  CAS  Google Scholar 

  42. Marcelo CL, Madison KC. Regulation of the expression of epidermal keratinocyte proliferation and differentiation by vitamin A analogs. Arch Dermatol Res 1984; 276 (6): 381–9

    Article  PubMed  CAS  Google Scholar 

  43. Stadler R, Muller R, Detmar M, et al. Retinoids and keratinocyte differentiation in vitro. Dermatologica 1987; 175 Suppl. 1: 45–55

    Article  PubMed  CAS  Google Scholar 

  44. Lavker RM, Leyden JJ, Thorne EG. An ultrastructural study of the effects of topical tretinoin on microcomedones. Clin Ther 1992; 14 (6): 773–80

    PubMed  CAS  Google Scholar 

  45. Roos TC, Jugert FK, Merk HF, et al. Retinoid metabolism in the skin. Pharmacol Rev 1998; 50 (2): 315–33

    PubMed  CAS  Google Scholar 

  46. Mills Jr OH, Kligman AM. Treatment of acne vulgaris with topically applied erythromycin and tretinoin. Acta Derm Venereol 1978; 58 (6): 555–7

    PubMed  Google Scholar 

  47. Amblard P, Bazex A, Beylot C, et al. The association tretinoin-erythromycin base: a new topical treatment for acne: results of a multicentric trial on 347 cases (authors transl). Sem Hop 1980; 56 (17–18): 911–5

    PubMed  CAS  Google Scholar 

  48. Gould DJ, Ead R, Cunliffe WJ. Oral tetracycline and retinoic acid gel in acne. Practitioner 1978; 221 (1322): 268–71

    PubMed  CAS  Google Scholar 

  49. Bucknall JH, Murdoch PN. Comparison of tretinoin solution and benzoyl peroxide lotion in the treatment of acne vulgaris. Curr Med Res Opin 1977; 5 (3): 266–8

    Article  PubMed  CAS  Google Scholar 

  50. Swinyer LJ, Swinyer TA, Britt MR. Topical agents alone in acne: a blind assessment study. JAMA 1980; 243 (16): 1640–3

    Article  PubMed  CAS  Google Scholar 

  51. Krishnan G. Comparison of two concentrations of tretinoin solution in the topical treatment of acne vulgaris. Practitioner 1976; 216 (1291): 106–9

    PubMed  CAS  Google Scholar 

  52. Webster GF, Berson D, Stein LF, et al. Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Cutis 2001; 67 (6 Suppl.): 4–9

    PubMed  CAS  Google Scholar 

  53. Ellis CN, Millikan LE, Smith EB, et al. Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris. Br J Dermatol 1998; 139 Suppl. 52: 41–7

    Article  CAS  Google Scholar 

  54. Grosshans E, Marks R, Mascaro JM, et al. Evaluation of clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life. Br J Dermatol 1998; 139 Suppl. 52: 26–33

    Article  Google Scholar 

  55. Lucky AW, Cullen SI, Funicella T, et al. Double-blind, vehicle-controlled, multicenter comparison of two 0.025% tretinoin creams in patients with acne vulgaris. J Am Acad Dermatol 1998; 38 (4): S24–30

    Article  Google Scholar 

  56. Lucky AW, Cullen SI, Jarratt MT, et al. Comparative efficacy and safety of two 0.025% tretinoin gels: results from a multicenter double-blind, parallel study. J Am Acad Dermatol 1998; 38 (4): S17–23

    Article  Google Scholar 

  57. Cortes JE, Kantarjian H, O’Brien S, et al. All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia. Cancer 1994; 73 (12): 2946–52

    Article  PubMed  CAS  Google Scholar 

  58. Fritsch PO, Honigsmann H, Jaschke E, et al. Augmentation of oral methoxsalen-photochemotherapy with an oral retinoic acid derivative. J Invest Dermatol 1978; 70 (4): 178–82

    Article  PubMed  CAS  Google Scholar 

  59. Stuttgen G, Ippen H, Mahrle G. Oral vitamin A acid in treatment of dermatoses with pathologic keratinization. Int J Dermatol 1977; 16 (6): 500–2

    Article  PubMed  CAS  Google Scholar 

  60. Lucek RW, Colburn WA. Clinical pharmacokinetics of the retinoids. Clin Pharmacokinet 1985; 10 (1): 38–62

    Article  PubMed  CAS  Google Scholar 

  61. Latriano L, Tzimas G, Wong F, et al. The percutaneous absorption of topically applied tretinoin and its effect on endogenous concentrations of tretinoin and its metabolites after single doses or long-term use. J Am Acad Dermatol 1997; 36 (3 Pt 2): S37–46

    Article  Google Scholar 

  62. Van Hoogdalem EJ. Transdermal absorption of topical anti-acne agents in man; review of clinical pharmacokinetic data. J Eur Acad Dermatol Venereol 1998; 11 Suppl. 1: S13–9

    Article  Google Scholar 

  63. Buchan P, Eckhoff C, Caron D, et al. Repeated topical administration of all-trans-retinoic acid and plasma levels of retinoic acids in humans. J Am Acad Dermatol 1994; 30 (3): 428–34

    Article  PubMed  CAS  Google Scholar 

  64. 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 (6 Pt 2): S116–8

    Article  Google Scholar 

  65. Shibata K, Shimamoto Y, Ishibashi S, et al. Life-threatening hepatic toxicity caused by all-trans-retinoic acid in a patient with acute promyelocytic leukaemia. Clin Lab Haematol 1994; 16 (2): 191–5

    Article  PubMed  CAS  Google Scholar 

  66. Windhorst DB, Nigra T. General clinical toxicology of oral retinoids. J Am Acad Dermatol 1982; 6 (4 Pt 2 Suppl.): 675–82

    Article  PubMed  CAS  Google Scholar 

  67. Navarre-Belhassen C, Blanchet P, Hillaire-Buys D, et al. Multiple congenital malformations associated with topical tretinoin. Ann Pharmacother 1998; 32 (4): 505–6

    Article  PubMed  CAS  Google Scholar 

  68. Camera G, Pregliasco P. Ear malformation in baby born to mother using tretinoin cream [letter]. Lancet 1992; 339 (8794): 687

    Article  PubMed  CAS  Google Scholar 

  69. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med 1985; 313 (14): 837–41

    Article  PubMed  CAS  Google Scholar 

  70. Caron GA. Tretinoin and pregnancy [letter]. Lancet 1993; 341 (8861): 1664

    Article  PubMed  CAS  Google Scholar 

  71. Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and congenital disorders. Lancet 1993; 341 (8854): 1181–2

    Article  PubMed  CAS  Google Scholar 

  72. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med 1979; 300 (7): 329–33

    Article  PubMed  CAS  Google Scholar 

  73. Tang GW, Russell RM. 13-cis-retinoic acid is an endogenous compound in human serum. J Lipid Res 1990; 31 (2): 175–82

    PubMed  CAS  Google Scholar 

  74. Peck GL. Retinoids in dermatology: an interim report. Arch Dermatol 1980; 116 (3): 283–4

    Article  PubMed  CAS  Google Scholar 

  75. Chalker DK, Lesher Jr JL, Smith Jr JG, et al. Efficacy of topical isotretinoin 0.05% gel in acne vulgaris: results of a multicenter, double-blind investigation. J Am Acad Dermatol 1987; 17 (2 Pt 1): 251–4

    Article  PubMed  CAS  Google Scholar 

  76. Langner A, Stapor W, Donald AE, et al. Double-blind, placebo-controlled study of the efficacy and safety of isotretinoin cream (0.05% w/w and 0.10% w/w) with sunscreens in the treatment of mild to moderate acne vulgaris. J Dermatolog Treat 2000; 11: 7–14

    Article  CAS  Google Scholar 

  77. Cunliffe WJ, Glass D, Goode K, et al. A double-blind investigation of the potential systemic absorption of isotretinoin, when combined with chemical sunscreens, following topical application to patients with widespread acne of the face and trunk. Acta Derm Venereol 2001; 81 (1): 14–7

    Article  PubMed  CAS  Google Scholar 

  78. Chen C, Jensen BK, Mistry G, et al. Negligible systemic absorption of topical isotretinoin cream: implications for teratogenicity. J Clin Pharmacol 1997; 37 (4): 279–84

    PubMed  CAS  Google Scholar 

  79. Brazzell RK, Colburn WA. Pharmacokinetics of the retinoids isotretinoin and etretinate: a comparative review. J Am Acad Dermatol 1982; 6 (4 Pt 2 Suppl.): 643–51

    Article  PubMed  CAS  Google Scholar 

  80. Reniers DE, Howard JM. Isotretinoin-induced inflammatory bowel disease in an adolescent. Ann Pharmacother 2001; 35 (10): 1214–6

    Article  PubMed  CAS  Google Scholar 

  81. Rappaport EB, Knapp M. Isotretinoin embryopathy: a continuing problem. J Clin Pharmacol 1989; 29 (5): 463–5

    PubMed  CAS  Google Scholar 

  82. Benke PJ. The isotretinoin teratogen syndrome. JAMA 1984; 251 (24): 3267–9

    Article  PubMed  CAS  Google Scholar 

  83. Braun JT, Franciosi RA, Mastri AR, et al. Isotretinoin dysmorphic syndrome. Lancet 1984; I (8375): 506–7

    Article  Google Scholar 

  84. Hersh JH, Danhauer DE, Hand ME, et al. Retinoic acid embryopathy: timing of exposure and effects on fetal development. JAMA 1985; 254 (7): 909–10

    Article  PubMed  CAS  Google Scholar 

  85. Roche Laboratories Inc. SMART guide to best practices: system to manage accutane related teratogenicity. Nutley (NJ): Roche Laboratories Inc, 2001

    Google Scholar 

  86. Bershad S, Rubinstein A, Paterniti JR, et al. Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne. N Engl J Med 1985; 313 (16): 981–5

    Article  PubMed  CAS  Google Scholar 

  87. Roytman M, Frumkin A, Bohn TG. Pseudotumor cerebri caused by isotretinoin. Cutis 1988; 42 (5): 399–400

    PubMed  CAS  Google Scholar 

  88. Tangrea JA, Kilcoyne RF, Taylor PR, et al. Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin. Arch Dermatol 1992; 128 (7): 921–5

    Article  PubMed  CAS  Google Scholar 

  89. Archer CB, Elias PM, Lowe NJ, et al. Extensive spinal hyperostosis in a patient receiving isotretinoin: progression after 4 years of etretinate therapy. Clin Exp Dermatol 1989; 14 (4): 319–21

    Article  PubMed  CAS  Google Scholar 

  90. McElwee NE, Schumacher MC, Johnson SC, et al. An observational study of isotretinoin recipients treated for acne in a health maintenance organization. Arch Dermatol 1991; 127 (3): 341–6

    Article  PubMed  CAS  Google Scholar 

  91. Marini JC, Hill S, Zasloff MA. Dense metaphyseal bands and growth arrest associated with isotretinoin therapy. Am J Dis Child 1988; 142 (3): 316–8

    PubMed  CAS  Google Scholar 

  92. Martin P, Manley PN, Depew WT, et al. Isotretinoin-associated proctosigmoiditis. Gastroenterology 1987; 93 (3): 606–9

    PubMed  CAS  Google Scholar 

  93. Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 2001; 45 (4): 515–9

    Article  PubMed  CAS  Google Scholar 

  94. Marsden JR. Effect of isotretinoin on carbamazepine pharmacokinetics. Br J Dermatol 1988; 119 (3): 403–4

    Article  PubMed  CAS  Google Scholar 

  95. Gottfried NS. Pseudo-tumor cerebri and acne [letter]. Mil Med 1991; 156 (8): A5

    Google Scholar 

  96. Cunliffe WJ, Caputo R, Dreno B, et al. Efficacy and safety comparison of adapalene (CD271) gel and tretinoin gel in the topical treatment of acne vulgaris: a European multicentre trial. J Dermatol Treatment 1997; 8: 173–8

    Article  Google Scholar 

  97. 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 (3): 482–5

    Article  PubMed  CAS  Google Scholar 

  98. Shroot B. Pharmacodynamics and pharmacokinetics of topical adapalene. J Am Acad Dermatol 1998 Aug; 39 (2 Pt 3): S17–24

    Article  Google Scholar 

  99. Allec J, Chatelus A, Wagner N. Skin distribution and pharmaceutical aspects of adapalene gel. J Am Acad Dermatol 1997; 36 (6 Pt 2): S119–25

    Article  Google Scholar 

  100. Rolland A, Wagner N, Chatelus A, et al. Site-specific drug delivery to pilosebaceous structures using polymeric microspheres. Pharm Res 1993; 10 (12): 1738–44

    Article  PubMed  CAS  Google Scholar 

  101. 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 (5): 731–2

    Article  PubMed  CAS  Google Scholar 

  102. Autret E, Berjot M, Jonville-Bera AP, et al. Anophthalmia and agenesis of optic chiasma associated with adapalene gel in early pregnancy [letter]. Lancet 1997; 350 (9074): 339

    Article  PubMed  CAS  Google Scholar 

  103. Chandraratna RA. Tazarotene: first of a new generation of receptor-selective retinoids. Br J Dermatol 1996; 135 Suppl. 49: 18–25

    Article  Google Scholar 

  104. Leyden J, Lowe N, Kakita L, et al. Comparison of treatment of acne vulgaris with alternate-day applications of tazarotene 0.1% gel and once-daily applications of adapalene 0.1% gel: a randomized trial. Cutis 2001; 67 (6 Suppl.): 10–6

    PubMed  CAS  Google Scholar 

  105. Shalita AR, Chalker DK, Griffith RF, et al. Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double-blind, vehicle-controlled study. Cutis 1999; 63 (6): 349–54

    PubMed  CAS  Google Scholar 

  106. Chandraratna RA. Tazarotene: the first receptor-selective topical retinoid for the treatment of psoriasis. J Am Acad Dermatol 1997; 37 (2 Pt 3): S12–7

    Article  Google Scholar 

  107. Duvic M. Pharmacologic profile of tazarotene. Cutis 1998; 61 (2 Suppl.): 22–6

    PubMed  CAS  Google Scholar 

  108. Marks R. Early clinical development of tazarotene. Br J Dermatol 1996; 135 Suppl. 49: 26–31

    Article  Google Scholar 

  109. Tang-Liu DD, Matsumoto RM, Usansky JI. Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet 1999; 37 (4): 273–87

    Article  PubMed  CAS  Google Scholar 

  110. Marks R. Pharmacokinetics and safety review of tazarotene. J Am Acad Dermatol 1998; 39 (4 Pt 2): S134–8

    Article  Google Scholar 

  111. Menter A. Pharmacokinetics and safety of tazarotene. J Am Acad Dermatol 2000; 43 (2 Pt 3): S31–5

    Article  Google Scholar 

  112. Kligman AM, Leyden JJ, Stewart R. New uses for benzoyl peroxide: a broad-spectrum antimicrobial agent. Int J Dermatol 1977; 16 (5): 413–7

    Article  PubMed  CAS  Google Scholar 

  113. Cunliffe WJ, Stainton C, Forster RA. Topical benzoyl peroxide increases the sebum excretion rate in patients with acne. Br J Dermatol 1983; 109 (5): 577–9

    Article  PubMed  CAS  Google Scholar 

  114. Nacht S, Gans EH, McGinley KJ, et al. Comparative activity of benzoyl peroxide and hexachlorophene: in vivo studies against propionibacterium acnes in humans. Arch Dermatol 1983; 119 (7): 577–9

    Article  PubMed  CAS  Google Scholar 

  115. 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 (4): 487–92

    Article  PubMed  CAS  Google Scholar 

  116. Swinyer LJ, Baker MD, Swinyer TA, et al. A comparative study of benzoyl peroxide and clindamycin phosphate for treating acne vulgaris. Br J Dermatol 1988; 119 (5): 615–22

    Article  PubMed  CAS  Google Scholar 

  117. Burke B, Eady EA, Cunliffe WJ. Benzoyl peroxide versus topical erythromycin in the treatment of acne vulgaris. Br J Dermatol 1983; 108 (2): 199–204

    Article  PubMed  CAS  Google Scholar 

  118. Chalker DK, Shalita A, Smith Jr JG, et al. A double-blind study of the effectiveness of a 3% erythromycin and 5% benzoyl peroxide combination in the treatment of acne vulgaris. J Am Acad Dermatol 1983; 9 (6): 933–6

    Article  PubMed  CAS  Google Scholar 

  119. 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 (4): 590–5

    Article  PubMed  CAS  Google Scholar 

  120. Eady EA, Bojar RA, Jones CE, et al. The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin-resistant propionibacteria. Br J Dermatol 1996; 134 (1): 107–13

    Article  PubMed  CAS  Google Scholar 

  121. Leyden JJ, McGinley KJ, Cavalieri S, et al. Propionibacterium acnes resistance to antibiotics in acne patients. J Am Acad Dermatol 1983; 8 (1): 41–5

    Article  PubMed  CAS  Google Scholar 

  122. Morelli R, Lanzarini M, Vincenzi C, et al. Contact dermatitis due to benzoyl peroxide. Contact Dermatitis 1989; 20 (3): 238–9

    Article  PubMed  CAS  Google Scholar 

  123. Zbinden G. Scientific opinion on the carcinogenic risk due to topical administration of benzoylperoxide for the treatment of acne vulgaris. Pharmacol Toxicol 1988; 63 (5): 307–9

    Article  PubMed  CAS  Google Scholar 

  124. Mandell GL, Bennet JE, Dolin R, eds. Principles and practice of infectious diseases. 5th ed. Philadelphia (PA): Churchill Livingstone, 2000: 394–7

    Google Scholar 

  125. Cambazard F. Clinical efficacy of Velac, a new tretinoin and clindamycin phosphate gel in acne vulgaris. J Eur Acad Dermatol Venereol 1998; 11 Suppl. 1: S20–7

    Article  Google Scholar 

  126. Becker LE, Bergstresser PR, Whiting DA, et al. Topical clindamycin therapy for acne vulgaris: a cooperative clinical study. Arch Dermatol 1981; 117 (8): 482–5

    Article  PubMed  CAS  Google Scholar 

  127. Parker F. A comparison of clindamycin 1% solution versus clindamycin 1% gel in the treatment of acne vulgaris. Int J Dermatol 1987; 26 (2): 121–2

    Article  PubMed  CAS  Google Scholar 

  128. Goltz RW, Coryell GM, Schnieders JR, et al. A comparison of Cleocin T 1 percent solution and Cleocin T 1 percent lotion in the treatment of acne vulgaris. Cutis 1985; 36 (3): 265–8

    PubMed  CAS  Google Scholar 

  129. Ellis CN, Leyden J, Katz HI, et al. Therapeutic studies with a new combination benzoyl peroxide/clindamycin topical gel in acne vulgaris. Cutis 2001; 67 (2 Suppl.): 13–20

    PubMed  CAS  Google Scholar 

  130. Barza M, Goldstein JA, Kane A, et al. Systemic absorption of clindamycin hydrochloride after topical application. J Am Acad Dermatol 1982; 7 (2): 208–14

    Article  PubMed  CAS  Google Scholar 

  131. Stoughton RB, Cornell RC, Gange RW, et al. Double-blind comparison of topical 1 percent clindamycin phosphate (Cleocin T) and oral tetracycline 500 mg/day in the treatment of acne vulgaris. Cutis 1980; 26 (4): 424–5, 429

    CAS  Google Scholar 

  132. Thomsen RJ, Stranieri A, Knutson D, et al. Topical clindamycin treatment of acne: clinical, surface lipid composition, and quantitative surface microbiology response. Arch Dermatol 1980; 116 (9): 1031–4

    Article  PubMed  CAS  Google Scholar 

  133. Gordon RC, Regamey C, Kirby WM. Serum protein binding of erythromycin, lincomycin, and clindamycin. J Pharm Sci 1973; 62 (7): 1074–7

    Article  PubMed  CAS  Google Scholar 

  134. Bennett WM, Aronoff GR, Golper TA, et al. Drug prescribing in renal failure. 3rd ed. Philadelphia (PA): American College of Physicians, 1994

    Google Scholar 

  135. Fass RJ, Saslaw S. Clindamycin: clinical and laboratory evaluation of parenteral therapy. Am J Med Sci 1972; 263 (5): 368–82

    Article  PubMed  CAS  Google Scholar 

  136. DeHaan RM, Metzler CM, Schellenberg D, et al. Pharmacokinetic studies of clindamycin phosphate. J Clin Pharmacol 1973; 13 (5): 190–209

    PubMed  CAS  Google Scholar 

  137. Fleming GF, Crowe GR. Granulocytopenia due to clindamycin [letter]. Med J Aust 1976; 1 (3): 70

    PubMed  CAS  Google Scholar 

  138. Swenson RM, Michaelson TC, Daly MJ, et al. Clindamycin in infections of the female genital tract. Obstet Gynecol 1974; 44 (5): 699–702

    PubMed  CAS  Google Scholar 

  139. Vikenes K, Lund-Tonnesen S, Schreiner A. Clostridium difficile-associated diarrhea after short term vaginal administration of clindamycin. Am J Gastroenterol 1999; 94 (7): 1969–70

    Article  PubMed  CAS  Google Scholar 

  140. Elmore M, Rissing JP, Rink L, et al. Clindamycin-associated hepatotoxicity. Am J Med 1974; 57 (4): 627–30

    Article  PubMed  CAS  Google Scholar 

  141. Poxton IR, McCoubrey J, Blair G. The pathogenicity of Clostridium difficile. Clin Microbiol Infect 2001; 7 (8): 421–7

    Article  PubMed  CAS  Google Scholar 

  142. Feingold DS, Chen WC, Chou DL, et al. Induction of colitis in hamsters by topical application of antibiotics. Arch Dermatol 1979; 115 (5): 580–1

    Article  PubMed  CAS  Google Scholar 

  143. Parry MF, Rha CK. Pseudomembranous colitis caused by topical clindamycin phosphate. Arch Dermatol 1986; 122 (5): 583–4

    Article  PubMed  CAS  Google Scholar 

  144. Milstone EB, McDonald AJ, Scholhamer Jr CF. Pseudomembranous colitis after topical application of clindamycin. Arch Dermatol 1981; 117 (3): 154–5

    Article  PubMed  CAS  Google Scholar 

  145. [No authors listed]. The transfer of drugs and other chemicals into human breast milk. Pediatrics 1983; 72 (3): 375–83

    Google Scholar 

  146. Al Ahdal O, Bevan DR. Clindamycin-induced neuromuscular blockade. Can J Anaesth 1995; 42 (7): 614–7

    Article  PubMed  CAS  Google Scholar 

  147. Igarashi K, Ishitsuka H, Kaji A. Comparative studies on the mechanism of action of lincomycin, streptomycin, and erythromycin. Biochem Biophys Res Commun 1969; 37 (3): 499–504

    Article  PubMed  CAS  Google Scholar 

  148. Pochi PE, Bagatell FK, Ellis CN, et al. Erythromycin 2 percent gel in the treatment of acne vulgaris. Cutis 1988; 41 (2): 132–6

    PubMed  CAS  Google Scholar 

  149. Jones EL, Crumley AF. Topical erythromycin vs blank vehicle in a multiclinic acne study. Arch Dermatol 1981; 117 (9): 551–3

    Article  PubMed  CAS  Google Scholar 

  150. Puschmann M, Meyer-Rohn J. The efficacy of a topical preparation containing erythromycin in the treatment of acne. Dermatologica 1982; 164 (5): 343–9

    Article  PubMed  CAS  Google Scholar 

  151. Leyden JJ, Hickman JG, Jarratt MT, et al. The efficacy and safety of a combination benzoyl peroxide/clindamycin topical gel compared with benzoyl peroxide alone and a benzoyl peroxide/erythromycin combination product. J Cutan Med Surg 2001; 5 (1): 37–42

    PubMed  CAS  Google Scholar 

  152. Schmidt JB, Knobler R, Neumann R, et al. [External erythromycin therapy of acne]. Z Hautkr 1983; 58 (24): 1754–60

    PubMed  CAS  Google Scholar 

  153. Schmidt JB, Thurner J, Poitscheck C, et al. [Local acne therapy with erythromycin]. Z Hautkr 1982; 57 (2): 69–77

    PubMed  CAS  Google Scholar 

  154. Zafrani ES, Ishak KG, Rudzki C. Cholestatic and hepatocellular injury associated with erythromycin esters: report of nine cases. Dig Dis Sci 1979; 24 (5): 385–96

    Article  PubMed  CAS  Google Scholar 

  155. Avila P, Capella D, Laporte JR, et al. Which salt of erythromycin is most hepatotoxic [letter]? Lancet 1988; I (8594): 1104

    Article  Google Scholar 

  156. Haydon RC, Thelin JW, Davis WE. Erythromycin ototoxicity: analysis and conclusions based on 22 case reports. Otolaryngol Head Neck Surg 1984; 92 (6): 678–84

    PubMed  CAS  Google Scholar 

  157. Jorro G, Morales C, Braso JV, et al. Anaphylaxis to erythromycin. Ann Allergy Asthma Immunol 1996; 77 (6): 456–8

    Article  PubMed  CAS  Google Scholar 

  158. Cooper WO, Griffin MR, Arbogast P, et al. Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Arch Pediatr Adolesc Med 2002; 156 (7): 647–50

    PubMed  Google Scholar 

  159. Gilman AG, Rall TW, Nies AS, et al., eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York (NY): Pergamon Press, 1990

    Google Scholar 

  160. Olsen TG. Therapy of acne. Med Clin North Am 1982; 66 (4): 851–71

    PubMed  CAS  Google Scholar 

  161. Hjorth N. Traditional topical treatment of acne. Acta Derm Venereol Suppl (Stockh) 1980; Suppl. 89: 53–6

    Google Scholar 

  162. Olin B, editor. Facts and comparisons. St Louis (MO): JB Lippincott Co, 1990

    Google Scholar 

  163. Schwarb FP, Gabard B, Rufli T, et al. Percutaneous absorption of salicylic acid in man after topical administration of three different formulations. Dermatology 1999; 198 (1): 44–51

    Article  PubMed  CAS  Google Scholar 

  164. Morra P, Bartle WR, Walker SE, et al. Serum concentrations of salicylic acid following topically applied salicylate derivatives. Ann Pharmacother 1996; 30 (9): 935–40

    PubMed  CAS  Google Scholar 

  165. Pertoldi F, D’Orlando L, Mercante WP. [Acute salicylate intoxication after trancutaneous absorption]. Minerva Anestesiol 1999; 65 (7–8): 571–3

    PubMed  CAS  Google Scholar 

  166. Candy JM, Morrison C, Paton RD, et al. Salicylate toxicity masquerading as malignant hyperthermia. Paediatr Anaesth 1998; 8 (5): 421–3

    Article  PubMed  CAS  Google Scholar 

  167. Germann R, Schindera I, Kuch M, et al. [Life threatening salicylate poisoning caused by percutaneous absorption in severe ichthyosis vulgaris]. Hautarzt 1996; 47 (8): 624–7

    Article  PubMed  CAS  Google Scholar 

  168. Chiaretti A, Schembri Wismayer D, Tortorolo L, et al. Salicylate intoxication using a skin ointment. Acta Paediatr 1997; 86 (3): 330–1

    Article  PubMed  CAS  Google Scholar 

  169. Poe TE, Scott RB, Keith Jr JF. Drug interactions with furosemide [letter]. J Fam Pract 1984; 18 (2): 204

    PubMed  CAS  Google Scholar 

  170. Pec J, Strmenova M, Palencarova E, et al. Salicylate intoxication after use of topical salicylic acid ointment by a patient with psoriasis. Cutis 1992; 50 (4): 307–9

    PubMed  CAS  Google Scholar 

  171. Davies MG, Briffa DV, Greaves MW. Systemic toxicity from topically applied salicylic acid. BMJ 1979; 1 (6164): 661

    Article  PubMed  CAS  Google Scholar 

  172. Cross SE, Anderson C, Thompson MJ, et al. Is there tissue penetration after application of topical salicylate formulations [letter]? Lancet 1997; 350 (9078): 636

    Article  PubMed  CAS  Google Scholar 

  173. Raschke R, Arnold-Capell PA, Richeson R, et al. Refractory hypoglycemia secondary to topical salicylate intoxication. Arch Intern Med 1991; 151 (3): 591–3

    Article  PubMed  CAS  Google Scholar 

  174. Yokoyama A, Takakubo F, Eto K, et al. Teratogenicity of aspirin and its metabolite, salicylic acid, in cultured rat embryos. Res Commun Chem Pathol Pharmacol 1984; 46 (1): 77–91

    PubMed  CAS  Google Scholar 

  175. Lin AN, Reimer RJ, Carter DM. Sulfur revisited. J Am Acad Dermatol 1988; 18 (3): 553–8

    Article  PubMed  CAS  Google Scholar 

  176. Danto JL, Maddin WS, Stewart WD, et al. A controlled trial of benzoyl peroxide and precipitated sulfur cream in acne vulgaris. Appl Ther 1966; 8 (7): 624–5

    PubMed  CAS  Google Scholar 

  177. Wilkinson RD, Adam JE, Murray JJ, et al. Benzoyl peroxide and sulfur: foundation for acne management. CMAJ 1966; 95 (1): 28–9

    CAS  Google Scholar 

  178. Breneman DL, Ariano MC. Successful treatment of acne vulgaris in women with a new topical sodium sulfacetamide/sulfur lotion. Int J Dermatol 1993; 32 (5): 365–7

    Article  PubMed  CAS  Google Scholar 

  179. Pandey J, Chellani H, Garg M, et al. Congenital sulfhemoglobin and transient methemoglobinemia secondary to diarrhoea. Indian J Pathol Microbiol 1996; 39 (3): 217–20

    PubMed  CAS  Google Scholar 

  180. Blum JE, Coe FL. Metabolic acidosis after sulfur ingestion. N Engl J Med 1977; 297 (16): 869–70

    Article  PubMed  CAS  Google Scholar 

  181. Olansky S. Old drug – in a new system – revisited. Cutis 1977; 19 (6): 852–4

    PubMed  CAS  Google Scholar 

  182. Genvert GI, Cohen EJ, Donnenfeld ED, et al. Erythema multiforme after use of topical sulfacetamide. Am J Ophthalmol 1985; 99 (4): 465–8

    PubMed  CAS  Google Scholar 

  183. Rubin Z. Ophthalmic sulfonamide-induced Stevens-Johnson syndrome. Arch Dermatol 1977; 113 (2): 235–6

    Article  PubMed  CAS  Google Scholar 

  184. Gottschalk HR, Stone OJ. Stevens-Johnson syndrome from ophthalmic sulfonamide. Arch Dermatol 1976; 112 (4): 513–4

    Article  PubMed  CAS  Google Scholar 

  185. Spes CH, Angermann CE, Stempfle HU, et al. Sulfadiazine therapy for toxoplasmosis in heart transplant recipients decreases cyclosporine concentration. Clin Investig 1992; 70 (9): 752–4

    Article  PubMed  CAS  Google Scholar 

  186. Hansen JM, Kampmann JP, Siersbaek-Nielsen K, et al. The effect of different sulfonamides on phenytoin metabolism in man. Acta Med Scand Suppl 1979; 624: 106–10

    PubMed  CAS  Google Scholar 

  187. Fitton A, Goa KL. Azelaic acid: a review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs 1991; 41 (5): 780–98

    Article  PubMed  CAS  Google Scholar 

  188. Mackrides PS, Shaughnessy AF. Azelaic acid therapy for acne. Am Fam Physician 1996; 54 (8): 2457–9

    PubMed  CAS  Google Scholar 

  189. Cunliffe WJ, Holland KT. Clinical and laboratory studies on treatment with 20% azelaic acid cream for acne. Acta Derm Venereol Suppl (Stockh) 1989; 143: 31–4

    CAS  Google Scholar 

  190. Hjorth N, Graupe K. Azelaic acid for the treatment of acne: a clinical comparison with oral tetracycline. Acta Derm Venereol Suppl (Stockh) 1989; 143: 45–8

    CAS  Google Scholar 

  191. Verallo-Rowell VM, Verallo V, Graupe K, et al. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta Derm Venereol Suppl (Stockh) 1989; 143: 58–61

    CAS  Google Scholar 

  192. Katsambas A, Graupe K, Stratigos J. Clinical studies of 20% azelaic acid cream in the treatment of acne vulgaris: comparison with vehicle and topical tretinoin. Acta Derm Venereol Suppl (Stockh) 1989; 143: 35–9

    CAS  Google Scholar 

  193. Passi S, Nazzaro-Porro M, Picardo M, et al. Metabolism of straight saturated medium chain length (C9 to C12) dicarboxylic acids. J Lipid Res 1983; 24 (9): 1140–7

    PubMed  CAS  Google Scholar 

  194. Willshaw HE, Rubinstein K. Azelaic acid in the treatment of ocular and adnexal malignant melanoma. Br J Ophthalmol 1983; 67 (1): 54–7

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The manuscript received no commercial support. Dr Bershad has participated in clinical research studies funded by Roche Laboratories Inc. and Allergan Inc.; she has served as a consultant and lecturer for Roche Laboratories Inc. and Allergan Inc. and as a consultant to Warner Chilcott, division of Galen Holdings. Dr Bershad holds US patents and reserves all rights to international patents for the short-contact method of topical retinoid therapy to treat acne, photoaging and psoriasis.

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  1. Department of Dermatology, The Mount Sinai School of Medicine, New York, USA

    Arash Akhavan &  Susan Bershad

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  1. Arash Akhavan
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Correspondence to Susan Bershad.

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Akhavan, A., Bershad, S. Topical Acne Drugs. Am J Clin Dermatol 4, 473–492 (2003). https://doi.org/10.2165/00128071-200304070-00004

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