Abstract
Background: There is little information on the status of the implementation of the isotretinoin Pregnancy Prevention Programme (PPP) in the EU, and on compliance with this programme by the regulatory agencies.
Objective: The aim of the study was to obtain information on implementation of the harmonized PPP of isotretinoin in the EU member states plus Norway and Iceland.
Materials and Methods: In January 2009, a questionnaire (request for nonurgent information [NUI]) was sent to all 25 EU member states, plus Norway and Iceland, to collect information on the implementation status of the PPP and its effectiveness.
Results: The response rate was 82% (22 of the 27 countries). In 21 of the 27 member states, isotretinoin is marketed and the PPP is in force, and in 18 of the 22 responding countries, the total required elements (seven) following a formal EU review are incorporated in the PPP. Seven member states had additional measures in place. In spite of implementation of the PPP and additional measures, a total of 143 isotretinoin-exposed pregnancies have been reported in 16 of the 22 responding member states since implementation of the harmonized PPP.
Conclusions: Despite implementation of the isotretinoin PPP in most member states, isotretinoin-exposed pregnancies were reported. This has led some member states to implement additional measures to the PPP, resulting in inconsistency with the approach agreed in 2003 following the European-wide review. It has been further suggested that common elements should be developed for PPPs for all medicines that are known to carry a high teratogenic risk.
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References
Commission decision background information on Article 29 referral isotretinoin (2003) [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Isotretinoin_29/WC500010881.pdf [Accessed 2011 Jun 21]
Lammer E, Chen D, Hoar R, et al. Retinoic acid embryopathy. N Engl J Med 1985 Oct; 313: 837–41
FDA. Labelling and prescription drug advertising: content and format for labelling for human prescription drugs. Fed Regist 1979; 44: 37434–67
Robertson J, Polifka JE, Avner M, et al. A survey of pregnant women using isotretinoin. Birth Defects Res A Clin Mol Teratol 2005 Nov; 73: 881–7
Dai W, LaBraico J, Stern R. Epidemiology of isotretinoin exposure during pregnancy. J Am Acad Dermatol 1992; 26: 599–606
Rosa F. Teratogenicity of isotretinoin [letter]. Lancet 1983 Aug; 322: 513
Abroms L, Maibach E, Lyon-Daniel K, et al. What is the best approach to reducing birth defects associated with isotretinoin? Plos Med 2006 Nov; 3: 1978–83
Roaccutane®. Summary of product characteristics. Roche, September 2001
Autret-Leca E, Kreft-Jais C, Elefant E, et al. Isotretinoin exposure during pregnancy: assessment of spontaneous reports in France. Drug Saf 2010; 33: 659–65
Schaefer C, Meister R, Weber-Schoendorfer C. Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy. Arch Gynecol Obstet 2010; 281: 221–7
Eudralex. Volume 9A of the rules governing medicinal products in the European Union: pharmacovigilance for medicinal products for human use (version September 2008) [online]. Available from URL: http://ec.europa.eu/health/files/eudralex/vol-9/pdf/vol9a_09-2008_en.pdf [Accessed 2011 Oct4]
Arriegas M, Pégo A, Lemos M, et al. Isotretinoin-PPP compliance [abstract]. Drug Saf 2009; 32(10): 984
Brewer T, Colditz G. Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 1999 Mar; 281: 824–9
Kanelleas A, Thornton S, Berth-Jones J. Suggestion for effective contraception in isotretinoin therapy. BJCP 2009; 67: 137–8
Cheetham T, Wagner M, Chiu G, et al. A risk management program aimed at preventing fetal exposure to isotretinoin: retrospective cohort study. J Am Acad Dermatol 2006 Sep; 55: 442–8
Centers for Disease Control (CDC). Update on overall prevalence of major birth defects: Atlanta, Georgia, 1978–2005. MMWR Morb Mortal Wkly Rep 2008; 57: 1–5
Källén B. Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden: a prospective population study. Congenit Anom 2007; 47: 119–24
Mansour D, Inki P, Gemzell-Danielsson K. Efficacy of contraceptive methods: a review of the literature. Eur J Contracept Reprod Health Care 2010 Feb; 15: 4–16
Finer L, Henshaw S. Disparities in rates of unintended pregnancy in the United States 1994–2001. Perspect Sex Reprod Health 2006 Jun; 38: 90–6
Mitchell A, van Bennekom C, Louik C. A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med 1995 Jul; 333: 101–6
Acknowledgements
No sources of funding were used to conduct this study or prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study.
The Authors would like to thank the EU member states’ regulatory agencies for providing information on implementation of the isotretinoin PPP in their country.
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Crijns, I., Straus, S., Luteijn, M. et al. Implementation of the Harmonized EU Isotretinoin Pregnancy Prevention Programme. Drug Saf 35, 27–32 (2012). https://doi.org/10.2165/11595570-000000000-00000
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DOI: https://doi.org/10.2165/11595570-000000000-00000