Occurrence of Pregnancy and Pregnancy Outcomes During Isotretinoin Therapy

Overview

Journal CMAJ

Date 2016 Apr 27

PMID 27114489

Citations 25

Authors

David Henry

Colin Dormuth

Brandace Winquist

Greg Carney

Shawn Bugden

Gary Teare

Linda E Levesque

Anick Berard

J Michael Paterson

Robert W Platt

Affiliations

Soon will be listed here.

Abstract

Background: Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario.

Methods: Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations.

Results: A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011.

Interpretation: Adherence to the isotretinoin pregnancy prevention program in Canada was poor during the 15-year period of this study.

Citing Articles

Fetal exposure to isotretinoin in Saudi Arabia: a multicenter real-world data analysis from 2015 to 2020.

Albogami Y, Almadani O, Almohareb S, Alshehri S, Alkhaibari A, Anzan M Ther Adv Drug Saf. 2024; 15:20420986241272822.

PMID: 39290803 PMC: 11406652. DOI: 10.1177/20420986241272822.

Advancing fetal diagnosis and prognostication using comprehensive prenatal phenotyping and genetic testing.

Fortin O, Mulkey S, Fraser J Pediatr Res. 2024; .

PMID: 38937640 DOI: 10.1038/s41390-024-03343-9.

Contraceptive counseling for iPLEDGE and its burden on dermatologists.

Owens K, Jiang S, Nicholas M Arch Dermatol Res. 2024; 316(6):287.

PMID: 38805059 DOI: 10.1007/s00403-024-03070-5.

Use of isotretinoin among girls and women of childbearing age and occurrence of isotretinoin-exposed pregnancies in Germany: A population-based study.

Reinold J, Kollhorst B, Wentzell N, Platzbecker K, Haug U PLoS Med. 2024; 21(1):e1004339.

PMID: 38271295 PMC: 10810459. DOI: 10.1371/journal.pmed.1004339.

Trends in harmful drug exposure during pregnancy in France between 2013 and 2019: A nationwide cohort study.

Louchet M, Collier M, Beeker N, Mandelbrot L, Sibiude J, Chouchana L PLoS One. 2024; 19(1):e0295897.

PMID: 38198446 PMC: 10781191. DOI: 10.1371/journal.pone.0295897.

References

Garcia-Bournissen F, Tsur L, Goldstein L, Staroselsky A, Avner M, Asrar F . Fetal exposure to isotretinoin-an international problem. Reprod Toxicol. 2007; 25(1):124-8. DOI: 10.1016/j.reprotox.2007.10.005. View

Pinheiro S, Kang E, Kim C, Governale L, Zhou E, Hammad T . Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States. Pharmacoepidemiol Drug Saf. 2013; 22(12):1251-7. DOI: 10.1002/pds.3481. View

Mitchell A, Van Bennekom C, Louik C . A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med. 1995; 333(2):101-6. DOI: 10.1056/NEJM199507133330206. View

Crijns H, Straus S, Gispen-de Wied C, de Jong-van den Berg L . Compliance with pregnancy prevention programmes of isotretinoin in Europe: a systematic review. Br J Dermatol. 2010; 164(2):238-44. DOI: 10.1111/j.1365-2133.2010.09976.x. View

Choi J, Koren G, Nulman I . Pregnancy and isotretinoin therapy. CMAJ. 2013; 185(5):411-3. PMC: 3602257. DOI: 10.1503/cmaj.120729. View

Raebel M, Ellis J, Andrade S . Evaluation of gestational age and admission date assumptions used to determine prenatal drug exposure from administrative data. Pharmacoepidemiol Drug Saf. 2005; 14(12):829-36. DOI: 10.1002/pds.1100. View

Rosa F . Teratogenicity of isotretinoin. Lancet. 1983; 2(8348):513. DOI: 10.1016/s0140-6736(83)90538-x. View

Berard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D . Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol. 2007; 63(2):196-205. PMC: 1859978. DOI: 10.1111/j.1365-2125.2006.02837.x. View

Lammer E, Chen D, Hoar R, Agnish N, Benke P, Braun J . Retinoic acid embryopathy. N Engl J Med. 1985; 313(14):837-41. DOI: 10.1056/NEJM198510033131401. View

10.

Atanackovic G, Koren G . Fetal exposure to oral isotretinoin: failure to comply with the Pregnancy Prevention Program. CMAJ. 1999; 160(12):1719-20. PMC: 1230407. View

11.

Wysowski D, Swann J, Vega A . Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000. J Am Acad Dermatol. 2002; 46(4):505-9. DOI: 10.1067/mjd.2002.120529. View

12.

Shin J, Cheetham T, Wong L, Niu F, Kass E, Yoshinaga M . The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system. J Am Acad Dermatol. 2011; 65(6):1117-25. DOI: 10.1016/j.jaad.2010.09.017. View

13.

Margulis A, Setoguchi S, Mittleman M, Glynn R, Dormuth C, Hernandez-Diaz S . Algorithms to estimate the beginning of pregnancy in administrative databases. Pharmacoepidemiol Drug Saf. 2012; 22(1):16-24. PMC: 3437228. DOI: 10.1002/pds.3284. View

14.

Pastuszak A, Koren G, Rieder M . Use of the Retinoid Pregnancy Prevention Program in Canada: patterns of contraception use in women treated with isotretinoin and etretinate. Reprod Toxicol. 1994; 8(1):63-8. DOI: 10.1016/0890-6238(94)90068-x. View

15.

Honein M, Paulozzi L, Erickson J . Continued occurrence of Accutane-exposed pregnancies. Teratology. 2001; 64(3):142-7. DOI: 10.1002/tera.1057. View

16.

Lott J, Kovarik C . Availability of oral isotretinoin and terbinafine on the Internet. J Am Acad Dermatol. 2010; 62(1):153-154. DOI: 10.1016/j.jaad.2009.04.038. View

17.

Azoulay L, Oraichi D, Berard A . Patterns and utilization of isotretinoin for acne from 1984 to 2003: is there need for concern?. Eur J Clin Pharmacol. 2006; 62(8):667-74. DOI: 10.1007/s00228-006-0151-x. View

18.

Boucher N, Beaulac-Baillargeon L . Pregnancy prevention among women taking isotretinoin: failure to comply with the recommendations. Can Fam Physician. 2006; 52:338-9. PMC: 1479707. View

19.

Honein M, Moore C, Erickson J . Can we ensure the safe use of known human teratogens? Introduction of generic isotretinoin in the US as an example. Drug Saf. 2004; 27(14):1069-80. DOI: 10.2165/00002018-200427140-00001. View

20.

Irvine B, Luo W, Leon J . Congenital anomalies in Canada 2013: a perinatal health surveillance report by the Public Health Agency of Canada's Canadian Perinatal Surveillance System. Health Promot Chronic Dis Prev Can. 2015; 35(1):21-2. PMC: 4939458. DOI: 10.24095/hpcdp.35.1.04. View