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However, due to its high risks of teratogenicity, isotretinoin must be used with care in females of childbearing potential. Since isotretinoin's introduction, numerous risk management programs have been implemented across the world in an attempt to prevent isotretinoin use in pregnancy. This paper aims to provide an evidence\u2010based review of the risk management programs for isotretinoin in Australia, Europe, Singapore, New Zealand, and the United States of America. The effectiveness of these programs and the factors leading to isotretinoin exposure in pregnancy are critically analyzed in an effort to inform the future direction with respect to designing the ideal regulatory program. Stringent risk management programs, such as the <jats:styled-content style=\"fixed-case\">iPLEDGE<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content> and Pregnancy Prevention Program (<jats:styled-content style=\"fixed-case\">PPP<\/jats:styled-content>) in Europe, may not be effective in reducing the risks of fetal exposure to isotretinoin when used alone. There is evidence that such strenuous regulation results in increased fear of teratogenic risks but does not translate into a reduced rate of pregnancies exposed to isotretinoin. A successful program must prioritize education about effective contraception, while minimizing any extraneous requirements, to ensure that women are not inadvertently undertreated for acne.<\/jats:p>","DOI":"10.1111\/ijd.13950","type":"journal-article","created":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T11:46:40Z","timestamp":1520336800000},"page":"1035-1046","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A comparative review of the isotretinoin pregnancy risk management programs across four continents"],"prefix":"10.1111","volume":"57","author":[{"given":"Tom","family":"Kovitwanichkanont","sequence":"first","affiliation":[{"name":"The University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Driscoll","sequence":"additional","affiliation":[{"name":"The University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197902153000701"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700289"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33869"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.111"},{"key":"e_1_2_7_6_1","first-page":"127","article-title":"Expression of toll\u2010like receptor 2 on peripheral blood monocytes of patients with inflammatory and noninflammatory acne vulgaris","volume":"16","author":"Fathy A","year":"2009","journal-title":"Egypt J Immunol"},{"key":"e_1_2_7_7_1","first-page":"171","article-title":"Isotretinoin \u2013 a newly recognized human teratogen","volume":"33","author":"Centers for Disease Control","year":"1984","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-0960.1991.tb00674.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198510033131401"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198607243150416"},{"key":"e_1_2_7_11_1","unstructured":"Medicines and Healthcare Products Regulatory Agency.Review of Isotretinoin and Psychiatric Adverse Reactions 2014. 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