Acnes grades III and IV or unresponsive to previous treatments11 King K, Jones DH, Daltrey DC, Cunliffe WJ. A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population. Br J Dermatol. 1982;107:583-90.,22 Peck GL, Olsen TG, Butkus D, Pandya M, Gross EG, et al. Isotretinoin versus placebo in the treatment of cystic acne. A randomized double-blind study. J Am Acad Dermatol. 1982;6 Pt 2 Suppl:735-45.,44 Sampaio SAP, Bagatin E. A 65-year experience treating acne, including 26 years with oral isotretinoin. An Bras Dermatol. 2008;83:361-7.,55 Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1:162-9.,3636 Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-73.,4040 Costa CS, Bagatin E, Martimbianco AL, Silva EM, LúcioMM, Magin P, et al. Oral isotretinoin for acne. Cochrane Database Syst Rev. 2018;11:CD009435.
41 Brasil. Ministério da Saúde, Secretaria de Atenção à Saúde. Portaria N◦. 1159. Aprova o Protocolo de uso da isotretinoínano tratamento da acne grave; 2015. Avilable from: http://portalarquivos.saude.gov.br/images/pdf/2015/novembro/20/PT–SAS-PCDT-Acne-Grave-ATUALIZADO-10-11-2015.pdf[accessed 20.10.19]. http://portalarquivos.saude.gov.br/image...
42 Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskais E, Cabal MI, et al. Practical management of acne for clinicians: an international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2018;78 Suppl 1:S1-23.-4343 Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acne with 13-cis-retinoic acid. Evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol. 1980;3:602-11.,4646 Jones DH, Forster RA, Mitchell J, Cunliffe WJ. A comparison of 13-cis-retinoic acid and erythromycin treatment in severe acne. Br J Dermatol. 1983;109 Suppl 24:27-8.,5151 Lester RS, Schachter GD, Light MJ. Isotretinoin and tetracycline in the management of severe nodulocystic acne. Int J Dermatol. 1985;24:252-7.
52 Prendiville JS, Logan RA, Russell Jones R. A comparison of dapsone with 13-cis retinoic acid in the treatment of nodular cystic acne. Clin Exp Dermatol. 1988;13:67-71.
53 Gollnick HP, Graupe K, Zaumseil RP. Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne. Eur J Dermatol. 2001;11:538-44.-5454 Strauss JS, Leyden JJ, Lucky AW, Lookingbill DP, Drake LA, Hanifin JM, et al. A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne. J Am Acad Dermatol. 2001;45:187-95.,5656 Akman A, Durusoy C, Senturk M, Koc CK, Soyturk D, Alpsoy E. Treatment of acne with intermittent and conventional isotretinoin: a randomized, controlled multicenter study. Arch Dermatol Res. 2007;299:467-73.,5858 Dhir R, Gehi NP, Agarwal R, More Y. Oral isotretinoin is as effective as a combination of oral isotretinoin and topical anti-acne agents in nodulocystic acne. Indian J Dermatol Venereol Leprol. 2008;74:187.,5959 Wahab MA, Rahman MH, Monamie NS, Jamaluddin M, Khrondker L, Afroz W. Isotretinoin versus weekly pulse dose azithromycin in the treatment of acne—a comparative study. J Pak Assoc Dermatol. 2008;18:9-14.,6464 Faghihi G, Rakhsshanpour M, Abtahi-Naeini B, 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.,6565 Tan J, Humphrey S, Vender R, Gooderham M, Kerrouche N, Audibert F, et al. A treatment for severe nodular acne: a randomized investigator-blinded, controlled, noninferiority trial comparing fixed-dose adapalene/benzolyl peroxide plus doxycycline vs. oral isotretinoin. Br J Dermatol. 2014;171:1508-16.,6767 Ahmad HM. Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin. Dermatol Ther. 2015;28:151-157.,7171 Nast A, Dréno B, Bettoli V, Mokos ZB, Degitz K, Dressler C, et al. European evidence-based (S3) guideline for the treatment of acne – update 2016 – short version. J EurAcad Dermatol Venereol. 2016;30:1261-8.
72 American Academy of Dermatology. Position statement on isotretinoin (Approved by the Board of Directors December 9, 2000; amended by the Board of Directors March 25, 2003, March 11, 2004, November 13, 2010 and February 19, 2018). Available from: https://server.aad.org/Forms/Policies/Uploads/PS/PS-Isotretinoin.pdf [accessed 20.10.19]. https://server.aad.org/Forms/Policies/Up...
73 British Association of Dermatologists. Patient Information Leaflets (PILs). Isotretinoin. Available from: http://www.bad.org.uk/for-the-public/patient-information-leaflets/isotretinoin/?showmore=1&returnlink=http%3A%2F%2Fwww.bad.org.uk%2Ffor-the-public%2Fpatient-information-leaflets-.Xa4RuC3OqCQ [accessed 20.10.19]. http://www.bad.org.uk/for-the-public/pat...
-7474 The Australasian College of Dermatologists. The Australasian College of Dermatologists. Position Statement Isotretinoin for treatmentof acne. Available from: https://www.dermcoll.edu.au/wp-content/uploads/ACD-Position-Statement-isotretinoin-June-2018.pdf [accessed 20.10.19]. https://www.dermcoll.edu.au/wp-content/u...
,7979 Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379:361-72.,8080 Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesth Dermatol. 2014;7 Suppl:S3-21.,8383 Roche. Roacutan (isotretinoína) Produtos Roche Químicos e Farmacêuticos S.A. Available from: http://www.anvisa.gov.br/datavisa/fila_bula/frmVisualizarBula.asp?pNuTransacao=14365632016&pIdAnexo=3212245 [accessed 20.10.19]. http://www.anvisa.gov.br/datavisa/fila_b...
|
0.5-1 mg/kg/day |
Up to a dose of 120-150 mg/kg/day or until complete regression of the lesions |
Acne - "low daily dose"1010 Plewig G, Dressel H, Pfleger M, Michelsen S, Kligman AM. Low dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne. J Dtsch Dermatol Ges. 2004;2:31-45.,3838 Rademaker M, Wishart JM, Birchall NM. Isotretinoin 5mg daily for low-grade adult acne vulgaris – a placebo-controlled, randomized double-blind study. J Eur Acad Dermatol Venereol. 2014;28:747-54.,4848 Corlin R, Maas B, Mack-Hennes A. 13-cis-retinoic acid. Low dosage oral use in acne papulopustulosa. Results of a multicenter study. Hautarzt. 1984;35:623-9.,5555 Kapadia NF, Khalid G, Burhany T, Nakhoda T. Comparative efficacy and safety and efficacy of systemic 13-cis retinoic acid 20mg/day vs. 40mg/day in acne vulgaris. J Pak Assoc Dermatol. 2005;15:238-41.,6161 De D, Kanwar AJ. Standard-dose isotretinoin vs. a combination of low-dose isotretinoin and azithromycin pulse in management of severe acne: preliminary report of a randomized study. Br J Dermatol. 2011;165 Suppl 1:41.,6262 Lee JW, Yoo KH, Park KY, Han TY, Li K, Sei SJ, et al. Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. Br J Dermatol. 2011;164:1369-75.,6969 Shetti SA, Nagesh HN, Hanumantharaya N. A randomized, open-label, comparative study of efficacy of low-dose continuous versus low-dose intermittent oral isotretinoin therapy in moderate-to-severe acne vulgaris. Natl J Physiol Pharm Pharmacol. 2017;7:941-6.,7171 Nast A, Dréno B, Bettoli V, Mokos ZB, Degitz K, Dressler C, et al. European evidence-based (S3) guideline for the treatment of acne – update 2016 – short version. J EurAcad Dermatol Venereol. 2016;30:1261-8.,8080 Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesth Dermatol. 2014;7 Suppl:S3-21.
81 Borghi A, Mantovani L, Minghetti S, Giari S, Virgili A, Bettoli V, et al. Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in achieving stable remission. J EurAcad Dermatol Venereol. 2011;25:1094-8.-8282 Tan J, Boyal S, Desai K, Knezevic S. Oral Isotretinoin: new developments relevant to clinical practice. Dermatol Clin. 2016;34:175-84.
|
0.1-0.5 mg/kg/day |
Up to 18 months or up to 1 to 2 months after lesion resolution |
Acne flares100100 Borghi A, Mantovani L, Minghetti S, Virgili A, Bettoli V. Acute acne flare following isotretinoin administration: potential protective role of low starting dose. Dermatology. 2009;218:178-80.,101101 Greywal T, Zaenglein AL, Baldwin HE, Bhatia N, Chernoff KA, Del Rosso JQ, et al. Evidence-based recommendations for the management of acne fulminans and its variants. J Am Acad Dermatol. 2017;77:109-17.
|
Low dose (up to 8 weeks) associated with prednisone |
8 weeks low dose oral isotretinoin |
|
|
Prednisone: 0.5-1 mg/kg/day for 2 weeks or until resolution of the flare |
Severe and extensive acne associated with macrocomedones3636 Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-73.,4242 Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskais E, Cabal MI, et al. Practical management of acne for clinicians: an international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2018;78 Suppl 1:S1-23.,100100 Borghi A, Mantovani L, Minghetti S, Virgili A, Bettoli V. Acute acne flare following isotretinoin administration: potential protective role of low starting dose. Dermatology. 2009;218:178-80.,101101 Greywal T, Zaenglein AL, Baldwin HE, Bhatia N, Chernoff KA, Del Rosso JQ, et al. Evidence-based recommendations for the management of acne fulminans and its variants. J Am Acad Dermatol. 2017;77:109-17.
|
01-0.2 mg/kg, 8 weeks, may or may not be increased gradually with fractionated prednisone used in the first 2 to 4 weeks |
Low dose: 8 weeks |
|
|
Prednisone: 2-4 weeks |
Rosacea112112 Nikolowski J, Plewig G. Oral treatment of rosacea with 13-cis-retinoic acid. Hautarzt. 1981;32:575-84.,119119 Uslu M, Savk E, Karaman G, Sendur N. Rosacea treatment with intermediate-dose isotretinoin: follow-up with erythema and sebum measurements. Acta Derm Venereol. 2012;92:73-7.
|
0.25 to 0.3 mg/kg |
4 months |
|
Selected cases, "microdoses": mean 0.07 mg/kg/day, up to 33 months |
Microdose: up to 33 months |
Rosacea fulminans120120 Walsh RK, Endicott AA, Shinkai K. Diagnosis and treatment of rosacea fulminans: a comprehensive review. Am J Clin Dermatol. 2018;19:79-86.
|
0.2-0.5 mg/kg, increased up to 0.5-1 mg/kg, associated with prednisone 40-60 mg/day |
3-4 months |
Phymatous rosacea121121 Wee JS, Tan KB. Phymatous rosacea presenting with leonine facies and clinical response to isotretinoin. Australas J Dermatol. 2017;58:72-3.
|
20 mg/day active phase, maintenance at 10 mg/day |
6 months for active phase |
Ocular rosacea125125 Webster G, Schaller M. Ocular rosacea: a dermatologic perspective. J Am Acad Dermatol. 2013;69 Suppl 1:S42-3.,126126 Andrade FM, Picosse FR, da Cunha LP, Valente CM, Bezerra FM, Miot HA, et al. Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline. Arq Bras Oftalmol. 2020;83:109-12.
|
10 mg/day |
4 months |
Seborrheic dermatitis139139 Geissler SE, Michelsen S, Plewig G. Very low dose isotretinoin is effective in controlling seborrhea. J Dtsch Dermatol Ges. 2003;1:952-8.
140 Bartell H, Ransdell BL, Ali A. Tinea versicolor clearance with oral isotretinoin therapy. J Drugs Dermatol. 2006;5:74-5.
141 Gualtieri B, Panduri S, Chiricozzi A, Romanelli M. Improvement of severe facial seborrheic dermatitis following low-dose isotretinoin therapy. G Ital Dermatol Venereol. 2018 [Online ahead of print].
142 Rademaker M. Low-dose isotretinoin for seborrhoeic dermatitis. J Cutan Med Surg. 2017;21:170-1.
143 Kamamoto CSL, Sanudo A, Hassun KM, Bagatin E. Low-dose oral isotretinoin for moderate to severe seborrhea and seborrheic dermatitis: a randomized comparative trial. Int J Dermatol. 2017;56:80-5.-144144 Kamamoto CSL, Nishikaku AS, Gompertz OF, Melo AS, Hassun KM, Bagatin E. Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial. Dermatoendocrinol. 2017;9:e1361573.
|
0.05-0.51 mg/kg/day |
Mean of 33 weeks |
Pustular psoriasis148148 Al-Shobaili H, Al-Khenaizan S. Childhood generalized pustular psoriasis: successful treatment with isotretinoin. Pediatr Dermatol. 2007;24:563-4.
149 Wilken R, Sharma A, Patel F, Maverakis E. Successful treatment of palmoplantar pustulosis with isotretinoin. Dermatol Online J. 2015;21, 13030/qt4b4776gb.-150150 Obeid G, Kirby L, Hughes C, Sbidian E, Le Cleah L. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev. 2020;1:CD011628.
|
Children: 0.75 mg/kg/day |
4 months |
|
Adults: 1.5-2.0 mg/kg/day |
|
Photoaging159159 Hernandez-Perez E, Khawaja HA, Alvarez TY. Oral isotretinoin as part of the treatment of cutaneous aging. Dermatol Surg. 2000;26:649-52.
160 Kalil CL, Fachinello FZ, Lamb FM, Comunello LN. Use of oral isotretinoin inphotoaging therapy. Skinmed. 2008;7:10-4.
161 Rabello-Fonseca RM, Azulay DR, Luiz RR, Mandarim-de-Lacerda CA, Cuzzi T, Manela-Azulay M. Oral isotretinoin in photoaging: clinical and histopathological evidence of efficacy of an off-label indication. J Eur Acad Dermatol Venereol. 2009;23:115-23.
162 Bagatin E, Parada MO, Miot HA, Hassun KM, Michalany B, Talarico S. A randomized controlled trial about the use of oral isotretinoin for photoaging. Int J Dermatol. 2010;49:207-14.
163 Bagatin E, Guadanhim LR, Enokihara MM, Sanudo A, Talarico S, Miot HA, et al. Low-dose oral isotretinoin versus topical retinoic acid for photoaging: a randomized, comparative study. Int J Dermatol. 2014;53:114-22.-164164 Bravo BS, Azulay DR, Luiz RR, Mandarim-de-Lacerda, Cuzzi T, Azulay MM. Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability. An Bras Dermatol. 2015;90:479-86.
|
10-20 mg 3 × /week |
2-6 months |
Field cancerization190190 Levine N, Moon TE, Cartmel B, Bangert JL, Rodney S, Dong Q, et al. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997;6:957-61.
|
10 mg/day |
6 months |
Frontal fibrosing alopecia205205 Segurado-Miravalles G, Camacho-Martínez FM, Arias-Santiago S, Serrano-Falcón C, Serrano-Ortega S, et al. Epidemiology, clinical presentation and therapeutic approach in a multicentre series of dissecting cellulitis of the scalp. J Eur Acad Dermatol Venereol. 2017;31:e199-200.,206206 Taylor AE. Dissecting cellulitis of the scalp: response to isotretinoin. Lancet. 1987;2:225.
|
20 mg/day |
Mean: 13 months |
Facial papules of frontal fibrosing alopecia207207 Scerri L, Williams HC, Allen BR. Dissecting cellulitis of the scalp: response to isotretinoin. Br J Dermatol. 1996;134:1105-8.
208 Koudoukpo C, Abdennader S, Cavelier-Balloy B, Gasnier C, Yédomon H. Dissecting cellulitis of the scalp: a retrospective study of 7 cases confirming the efficacy of oral isotretinoin. Ann Dermatol Venereol. 2014;141:500-6.-209209 Badaoui A, Reygagne P, Cavelier-Balloy B, Pinquier L, Deschamps L, Crickx B, et al. Dissecting cellulitis of the scalp: a retrospective study of 51 patients and review of literature. Br J Dermatol. 2016;174:421-3.
|
10 mg every other day or 20 mg/day |
2-4 months |
Dissecting cellulitis212212 Miguel-Gómez L, Rodrigues-Barata AR, Molina-Ruiz A, Martorell-Calayud A, Fernández-Crehuet P, Grimat R, et al. Folliculitis decalvans: effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up. J Am Acad Dermatol. 2018;79:878-83.
213 Aksoy B, Hapa A, Mutlu E. Isotretinoin treatment for folliculitis decalvans: a retrospective case-series study. Int J Dermatol. 2018;57:250-3.
214 Rambhia PH, Conic RZ, Murad A, Atanaskova-Mesinkovska N, Piliang M, Berfeld W, et al. Updates in therapeutics for folliculitis decalvans: a systematic review with evidence-based analysis. J Am Acad Dermatol. 2019;80:794-801.
215 Thomas J, Aguh C. Approach to treatment of refractory dissecting cellulitis of the scalp: a systematic review. J Dermatolog Treat. 2019:1-6.
216 Goldsmith LA, Weinrich AE, Shupack J. Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J Am Acad Dermatol. 1982;6 Pt 2 Suppl:710-5.
217 Dicken CH. Isotretinoin treatment of pityriasis rubra pilaris. J Am Acad Dermatol. 1987;16 Pt 1:297-301.
218 Kromer C, Sabat R, Celis D, Mössner R. Systemic therapies of pityriasis rubra pilaris: a systematic review. J Dtsch Dermatol Ges. 2019;17:243-59.
219 D’Erme AM, Milanesi N, Difonzo EM, Lotti T, Gola M. Treatment of refractory subacute cutaneous lupus erythematosus with oral isotretinoin: a valid therapeutic option. Dermatol Ther. 2012;25:281-2.
220 Pasmatzi E, Georgiou S, Monastirli A, Tsambaos D. Temporary remission of disseminated granuloma annulare under oral isotretinoin therapy. Int J Dermatol. 2005;44:169-71.-221221 Georgala S, Katoulis AC, Georgala C, Bozi E, Mortakis A. Oral isotretinoin in the treatment of recalcitrant condylomata acuminata of the cervix: a randomised placebo-controlled trial. Sex Transm Infect. 2004;80:216-8.
|
0.5-1 mg/kg/day |
3-12 months |
|
Low dose - 10 mg/day |
|
Pityriasis rubra pilaris222222 Yang TH, Lee TH, Huang YC. Oral isotretinoin for treating mucocutaneous human papillomavirus infections: a systematic review and meta-analysis. Indian J Dermatol Venereol Leprol. 2019;85:569-77.
223 Bhat RM, Ullal KR, Pinto AC, Sukumar D. Darier-White disease in siblings responding to isotretinoin. Indian Dermatol Online J. 2010;1:18-20.-224224 Eimer L, Lagodin C, Bonavia P, Stringa M, Rébora I, Anaya J. Darier-White disease treated with oral isotretinoin. Arch Argent Pediatr. 2011;109:e63-6.
|
0.5-2 mg/kg/day |
16-24 weeks |
Cutaneous lupus erythematosus225222 Yang TH, Lee TH, Huang YC. Oral isotretinoin for treating mucocutaneous human papillomavirus infections: a systematic review and meta-analysis. Indian J Dermatol Venereol Leprol. 2019;85:569-77.
|
0.2-1 mg/kg/day |
5 months |
Generalized granuloma annulare226223 Bhat RM, Ullal KR, Pinto AC, Sukumar D. Darier-White disease in siblings responding to isotretinoin. Indian Dermatol Online J. 2010;1:18-20.
|
0.5 mg/kg/day |
2-6 months, maintenance at lower doses |
Condyloma acuminatum and recalcitrant warts227227 Vigarios E, Comont T, Piroth M, Cougoul P, Sibaud V. Severe aphthous stomatitis secondary to vitamin B12 deficiency with isotretinoin therapy. J Am Acad Dermatol. 2019;5:563-5.,228228 Rodriguez-Garijo N, Querol-Cisneros E, Tomas-Velazquez A, Estenaga A, Moreno-Artero E, Idoate MA, et al. Recalcitrant granulomatous periorificial dermatites with good response to low-dose oral isotretinoin. Pediatr Dermatol. 2019;36:980-1.
|
0.5 mg/kg/day (cervical condyloma)227224 Eimer L, Lagodin C, Bonavia P, Stringa M, Rébora I, Anaya J. Darier-White disease treated with oral isotretinoin. Arch Argent Pediatr. 2011;109:e63-6.
|
12 weeks |
|
0.5-1 mg/kg/day228225 Sehgal VN, Srivastava G, Sardana K. Isotretinoin – unapproved indications/uses and dosage: a physician's reference. Int J Dermatol. 2006;45:772-7.
|
Mean: 3 months |
Darier's disease229229 Tomasini D, Crivelli F. Additional findings supporting systemic isotretinoin as a useful treatment for Galli-Galli disease. Eur J Dermatol. 2019;29:428-9.,230230 Elosua-Gonzalez M, Lopez-Estebaranz JL, Garcia-Zamora E, Vela-Ganuza M, Rodrigez-Vasquez X. Severe acneiform eruption associated with vemurafenib with response to isotretinoin. Dermatol Online J. 2018;24, 13030/qt4p5887m2.
|
0.2 mg/kg at the beginning, increase to 0.5-1 mg/kg, according to the hue of the lesion |
Continuous use (genodermatosis) |