Status Report on the Safety of Topical Dapsone Therapy for Dermatologic Disease
Main Article Content
Keywords
topical dapsone, aczone, acne treatment
Abstract
Systemic dapsone therapy has historically been used to treat leprosy, inflammatory dermatoses, and severe cases of acne vulgaris. This article reviews the pharmacokinetics, short and long-term safety, drug-drug interactions, gender, and age effects of topical dapsone 5% and 7.5% gel formulations. In 20 human studies and 7 case reports, 39 of 6,384 total patients (<1%) experienced adverse effects that were considered more than mild or resulted in discontinuation of topical dapsone. The literature supports topical dapsone 5% and 7.5% gels as safe and effective medications for the treatment of dermatologic disease.
References
1. Webster GF. Is topical dapsone safe in glucose-6-phosphate dehydrogenase-deficient and sulfonamide-allergic patients? J. Drugs Dermatology. 2010;9:532–6.
2. Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch. Dermatol. Res. 2014;306:103–24.
3. Pickert A, Raimer S. An evaluation of dapsone gel 5% in the treatment of acne vulgaris. Expert Opin. Pharmacother. [Internet]. 2009;10:1515–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19505219.
4. Barranco VP. Dapsone — other indications. Int. J. Dermatol. 1982;21:513–5.
5. Del Rosso JQ. Newer topical therapies for the treatment of acne vulgaris. Cutis. 2007;80:400–10.
6. Guglielmetti A, Conlledo R, Bedoya J, Ianiszewski F, Correa J. Inverse psoriasis involving genital skin folds: Successful therapy with dapsone. Dermatol. Ther. (Heidelb). 2012;2:1–9.
7. Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: Overview and update. J. Am. Acad. Dermatol. 2001;45:420–34.
8. Allergan I. Aczone gel 5 % [Internet]. RX Prod. News. 2008 [cited 2016 Apr 17]. Available from: www.allergan.com
9. Kazmierowski JA, Ross JE, Peizner DS, Wuepper KD. Dermatitis herpetiformis : effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity. J. Clin. Immunol. 1984;4:55–64.
10. Bozeman PM, Learn DB, Thomas EL. Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. Biochem. Pharmacol. 1992;44:553–63.
11. Coleman MD. Dapsone: Modes of action, toxicity and possible strategies for increasing patient tolerance. Br. J. Dermatol. 1993;129:507–13.
12. Kircik LH. Harnessing the anti-inflammatory effects of topical dapsone for management of acne. J. Drugs Dermatology. 2010;9:667–71.
13. Scheinfeld N. Aczone, a topical gel formulation of the antibacterial, anti-inflammatory dapsone for the treatment of acne. Curr. Opin. Investig. Drugs. 2009;10:474–81.
14. Drucker CR. Update on topical antibiotics in dermatology. Dermatol. Ther. 2012;25:6–11.
15. Swartzenruber GS, Yanta JH, Pizon AF. Methemoglobinemia as a complication of topical dapsone. N. Engl. J. Med. [Internet]. 2015;372:491–2. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMc1414788
16. Thiboutot DM, Willmer J, Sharata H, Halder R, Garrett S. Pharmacokinetics of dapsone gel, 5% for the treatment of acne vulgaris. Clin. Pharmacokinet. 2007;46:697–712.
17. Draelos ZD, Carter E, Maloney JM, Elewski B, Poulin Y, Lynde C, et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J. Am. Acad. Dermatol. 2007;56:1–10.
18. Raimer S, Maloney JM, Bourcier M, Wilson D, Papp K, Siegfried E, et al. Efficacy and safety of dapsone gel 5% for the treatment of acne vulgaris in adolescents. Cutis. 2008;81:171–8.
19. Tanghetti E, Harper JC, Oefelein MG. The efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: Gender as a clinically relevant outcome variable. J. Drugs Dermatology. 2012;11:1417–21.
20. Del Rosso JQ, Kircik L, Gallagher CJ. Comparative efficacy and tolerability of dapsone 5% gel in adult versus adolescent females with acne vulgaris. J. Clin. Aesthet. Dermatol. 2015;8:31–7.
21. Lucky AW, Maloney M, Roberts J, Taylor S, Jones T, Ling M, et al. Dapsone 5% gel for the treatment of acne vulgaris: Safety and efficacy of long-term (1 Year) treatment. J. Drugs Dermatology. 2007;6:981–7.
22. Faghihi G, Rakhshanpour M, Nilforoushzadeh MA. The efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: A randomized double-blind study. Adv. Biomed. Res. 2014;3:177.
23. Faghihi G, Khosravani P, Nilforoushzadeh MA, Hosseini SM, Assaf F, Zeinali N, et al. Dapsone gel in the treatment of papulopustular rosacea: A double-blind randomized clinical trial. J. Drugs Dermatology. 2015;14:602–6.
24. Tanghetti E, Dhawan S, Green L, Ling M, Downie J, Germain MA, et al. Clinical evidence for the role of a topical anti-inflammatory agent in comedonal acne: Findings from a randomized study of dapsone gel 5% in combination with tazarotene cream 0.1% in patients with acne vulgaris. J. Drugs Dermatology. 2011;10:783–92.
25. Fleischer AB, Shalita A, Eichenfield LF, Abramovitz W, Lucky A, Garrett S. Dapsone 5% gel in combination with adapalene gel 0.1%, benzoyl peroxide gel 4%, or moisturizer for the treatment of acne vulgaris: A 12-week randomized, double-blind study. J. Drugs Dermatology. 2010;33–40.
26. Grove G, Zerweck C, Gwazdauskas J. Tolerability and irritation potential of four topical acne regimens in healthy subjects. J. Drugs Dermatology. 2013;12:644–9.
27. Piette WW, Taylor S, Pariser D, Jarratt M, Sheth P, Wilson D. Hematologic safety of dapsone gel, 5%, for topical treatment of acne vulgaris. Arch. Dermatol. [Internet]. 2008;144:1564–70. Available from: http://archderm.ama-assn.org/cgi/content/abstract/144/12/1564.
28. Lynde CW, Andriessen A. Cohort study on the treatment with dapsone 5% gel of mild to moderate inflammatory acne of the face in women. Skinmed. 2014;12:15–21.
29. Graff DM, Bosse GM, Sullivan J. Case report of methemoglobinemia in a toddler secondary to topical dapsone exposure. Pediatrics. 2016;138:e1–2.
30. Handler MZ, Chacon AH, Shiman MI, Schachner LA. Application of dapsone 5% gel in a patient with dermatitis herpetiformis. J. Dermatol. Case Rep. 2012;6:132–3.
31. Durham KC, Hebert A. Impact of 5% dapsone gel on the healing time of an ankle ulcer formed after achilles tendon rupture. J. Am. Acad. Dermatol. [Internet]. 2013;68:AB227. Available from: http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L70997991%5Cnhttp://dx.doi.org/10.1016/j.jaad.2012.12.940%5Cnhttp://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=01909622&id=doi:10.1016/j.jaad.2012.12.940&atitle=Impact+of+5%25+dapsone+gel+o.
32. Broussard KC, Berger TG, Rosenblum M, Murase JE. Erosive pustular dermatosis of the scalp: A review with a focus on dapsone therapy. J. Am. Acad. Dermatol. 2012;66:680=686.
33. Frieling GW, Williams NL, LIm SJ, Rosenthal SI. Novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective. J. Drugs Dermatology. 2013;12:481–4.
34. Babalola O, Zhang J, Kristjansson A, Whitaker-Worth D, McCusker M. Granuloma faciale treated with topical dapsone: a case report. Dermatol. Online J. 2014;20.
35. Jarratt M, Jones T, Chang-Lin J, Tong W, Berk D, Lin V, et al. Safety and pharmacokinetics of once-daily dapsone gel, 7.5% in patients with moderate acne vulgaris. J. Drugs Dermatology. 2016;15:1250–9.
36. Stein Gold L, Jarratt M, Bucko A, Grekin S, Berlin J, Bukhalo M, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: First of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J. Drugs Dermatology. 2016;15:553–61.
37. Eichenfield L, Lain T, Frankel E, Jones T, Chang-Lin J, Berk D, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J. Drugs Dermatology. 2016;15:962–9.
38. Draelos Z, Rodriguez D, Kempers S, Bruce S, Peredo M, Downie J, et al. Treatment response with once-daily topical dapsone gel, 7.5% for acne vulgaris: subgroup analysis of pooled data from two randomized, double-blind studies. J. Drugs Dermatology. 2017;16:591–7.
39. Thiboutot D, Kircik L, McMichael A, Cook-Bolden F, Tyring S, Berk D, et al. Efficacy, safety, and dermal tolerability of dapsone gel, 7.5% in patients with moderate acne vulgaris: A pooled analysis of two phase 3 trials. J. Clin. Aesthet. Dermatol. 2016;9:18–27.
40. Allergan. Phototoxicity test of dapsone gel in healthy volunteers [Internet]. Clinicaltrials.gov. 2014 [cited 2017 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT02108483.
41. Brown P. Clinical review: Dapsone gel 7.5% [Internet]. 2016. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/UCM554649.pdf.
2. Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch. Dermatol. Res. 2014;306:103–24.
3. Pickert A, Raimer S. An evaluation of dapsone gel 5% in the treatment of acne vulgaris. Expert Opin. Pharmacother. [Internet]. 2009;10:1515–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19505219.
4. Barranco VP. Dapsone — other indications. Int. J. Dermatol. 1982;21:513–5.
5. Del Rosso JQ. Newer topical therapies for the treatment of acne vulgaris. Cutis. 2007;80:400–10.
6. Guglielmetti A, Conlledo R, Bedoya J, Ianiszewski F, Correa J. Inverse psoriasis involving genital skin folds: Successful therapy with dapsone. Dermatol. Ther. (Heidelb). 2012;2:1–9.
7. Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: Overview and update. J. Am. Acad. Dermatol. 2001;45:420–34.
8. Allergan I. Aczone gel 5 % [Internet]. RX Prod. News. 2008 [cited 2016 Apr 17]. Available from: www.allergan.com
9. Kazmierowski JA, Ross JE, Peizner DS, Wuepper KD. Dermatitis herpetiformis : effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity. J. Clin. Immunol. 1984;4:55–64.
10. Bozeman PM, Learn DB, Thomas EL. Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. Biochem. Pharmacol. 1992;44:553–63.
11. Coleman MD. Dapsone: Modes of action, toxicity and possible strategies for increasing patient tolerance. Br. J. Dermatol. 1993;129:507–13.
12. Kircik LH. Harnessing the anti-inflammatory effects of topical dapsone for management of acne. J. Drugs Dermatology. 2010;9:667–71.
13. Scheinfeld N. Aczone, a topical gel formulation of the antibacterial, anti-inflammatory dapsone for the treatment of acne. Curr. Opin. Investig. Drugs. 2009;10:474–81.
14. Drucker CR. Update on topical antibiotics in dermatology. Dermatol. Ther. 2012;25:6–11.
15. Swartzenruber GS, Yanta JH, Pizon AF. Methemoglobinemia as a complication of topical dapsone. N. Engl. J. Med. [Internet]. 2015;372:491–2. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMc1414788
16. Thiboutot DM, Willmer J, Sharata H, Halder R, Garrett S. Pharmacokinetics of dapsone gel, 5% for the treatment of acne vulgaris. Clin. Pharmacokinet. 2007;46:697–712.
17. Draelos ZD, Carter E, Maloney JM, Elewski B, Poulin Y, Lynde C, et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J. Am. Acad. Dermatol. 2007;56:1–10.
18. Raimer S, Maloney JM, Bourcier M, Wilson D, Papp K, Siegfried E, et al. Efficacy and safety of dapsone gel 5% for the treatment of acne vulgaris in adolescents. Cutis. 2008;81:171–8.
19. Tanghetti E, Harper JC, Oefelein MG. The efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: Gender as a clinically relevant outcome variable. J. Drugs Dermatology. 2012;11:1417–21.
20. Del Rosso JQ, Kircik L, Gallagher CJ. Comparative efficacy and tolerability of dapsone 5% gel in adult versus adolescent females with acne vulgaris. J. Clin. Aesthet. Dermatol. 2015;8:31–7.
21. Lucky AW, Maloney M, Roberts J, Taylor S, Jones T, Ling M, et al. Dapsone 5% gel for the treatment of acne vulgaris: Safety and efficacy of long-term (1 Year) treatment. J. Drugs Dermatology. 2007;6:981–7.
22. Faghihi G, Rakhshanpour M, Nilforoushzadeh MA. The efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: A randomized double-blind study. Adv. Biomed. Res. 2014;3:177.
23. Faghihi G, Khosravani P, Nilforoushzadeh MA, Hosseini SM, Assaf F, Zeinali N, et al. Dapsone gel in the treatment of papulopustular rosacea: A double-blind randomized clinical trial. J. Drugs Dermatology. 2015;14:602–6.
24. Tanghetti E, Dhawan S, Green L, Ling M, Downie J, Germain MA, et al. Clinical evidence for the role of a topical anti-inflammatory agent in comedonal acne: Findings from a randomized study of dapsone gel 5% in combination with tazarotene cream 0.1% in patients with acne vulgaris. J. Drugs Dermatology. 2011;10:783–92.
25. Fleischer AB, Shalita A, Eichenfield LF, Abramovitz W, Lucky A, Garrett S. Dapsone 5% gel in combination with adapalene gel 0.1%, benzoyl peroxide gel 4%, or moisturizer for the treatment of acne vulgaris: A 12-week randomized, double-blind study. J. Drugs Dermatology. 2010;33–40.
26. Grove G, Zerweck C, Gwazdauskas J. Tolerability and irritation potential of four topical acne regimens in healthy subjects. J. Drugs Dermatology. 2013;12:644–9.
27. Piette WW, Taylor S, Pariser D, Jarratt M, Sheth P, Wilson D. Hematologic safety of dapsone gel, 5%, for topical treatment of acne vulgaris. Arch. Dermatol. [Internet]. 2008;144:1564–70. Available from: http://archderm.ama-assn.org/cgi/content/abstract/144/12/1564.
28. Lynde CW, Andriessen A. Cohort study on the treatment with dapsone 5% gel of mild to moderate inflammatory acne of the face in women. Skinmed. 2014;12:15–21.
29. Graff DM, Bosse GM, Sullivan J. Case report of methemoglobinemia in a toddler secondary to topical dapsone exposure. Pediatrics. 2016;138:e1–2.
30. Handler MZ, Chacon AH, Shiman MI, Schachner LA. Application of dapsone 5% gel in a patient with dermatitis herpetiformis. J. Dermatol. Case Rep. 2012;6:132–3.
31. Durham KC, Hebert A. Impact of 5% dapsone gel on the healing time of an ankle ulcer formed after achilles tendon rupture. J. Am. Acad. Dermatol. [Internet]. 2013;68:AB227. Available from: http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L70997991%5Cnhttp://dx.doi.org/10.1016/j.jaad.2012.12.940%5Cnhttp://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=01909622&id=doi:10.1016/j.jaad.2012.12.940&atitle=Impact+of+5%25+dapsone+gel+o.
32. Broussard KC, Berger TG, Rosenblum M, Murase JE. Erosive pustular dermatosis of the scalp: A review with a focus on dapsone therapy. J. Am. Acad. Dermatol. 2012;66:680=686.
33. Frieling GW, Williams NL, LIm SJ, Rosenthal SI. Novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective. J. Drugs Dermatology. 2013;12:481–4.
34. Babalola O, Zhang J, Kristjansson A, Whitaker-Worth D, McCusker M. Granuloma faciale treated with topical dapsone: a case report. Dermatol. Online J. 2014;20.
35. Jarratt M, Jones T, Chang-Lin J, Tong W, Berk D, Lin V, et al. Safety and pharmacokinetics of once-daily dapsone gel, 7.5% in patients with moderate acne vulgaris. J. Drugs Dermatology. 2016;15:1250–9.
36. Stein Gold L, Jarratt M, Bucko A, Grekin S, Berlin J, Bukhalo M, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: First of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J. Drugs Dermatology. 2016;15:553–61.
37. Eichenfield L, Lain T, Frankel E, Jones T, Chang-Lin J, Berk D, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J. Drugs Dermatology. 2016;15:962–9.
38. Draelos Z, Rodriguez D, Kempers S, Bruce S, Peredo M, Downie J, et al. Treatment response with once-daily topical dapsone gel, 7.5% for acne vulgaris: subgroup analysis of pooled data from two randomized, double-blind studies. J. Drugs Dermatology. 2017;16:591–7.
39. Thiboutot D, Kircik L, McMichael A, Cook-Bolden F, Tyring S, Berk D, et al. Efficacy, safety, and dermal tolerability of dapsone gel, 7.5% in patients with moderate acne vulgaris: A pooled analysis of two phase 3 trials. J. Clin. Aesthet. Dermatol. 2016;9:18–27.
40. Allergan. Phototoxicity test of dapsone gel in healthy volunteers [Internet]. Clinicaltrials.gov. 2014 [cited 2017 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT02108483.
41. Brown P. Clinical review: Dapsone gel 7.5% [Internet]. 2016. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/UCM554649.pdf.
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Published
Jan 2, 2018
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How to Cite
Jones, M. A., Winkelmann, R. R., & Del Rosso, J. Q. (2018). Status Report on the Safety of Topical Dapsone Therapy for Dermatologic Disease. SKIN The Journal of Cutaneous Medicine, 2(1), 30–43. https://doi.org/10.25251/skin.2.1.3
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In-Depth Reviews
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Author Biographies
Megan A Jones, Dermatology Resident Lehigh Valley Health Network Allentown, PA
Dermatology Resident
Lehigh Valley Health Network?
Allentown, PA?
Richard R Winkelmann, Dermatology Resident OhioHealth Columbus, OH
Dermatology ResidentOhioHealth
Columbus, OH