Systemic Isotretinoin Treatment and Pregnancy: A Longitudinal Cohort Study from Turkey

Abstract

Objective: Isotretinoin is known to be the most effective treatment of severe and persistent acne. However, one of the most important adverse effects of this drug is known to be teratogenicity. In this regard, tests are administered before initiating the treatment, to assure that an unknown pregnancy is not present and accordingly, patients are advised to take contraceptive precautions during their systemic isotretinoin treatments. On the contrary, many cases of unwanted pregnancies and relevant abortuses have been reported all over the world. In the Turkish literature, only a few reports have been identified about foetal exposure to isotretinoin. Materials and Methods:In this respect, a study was carried out on fifty-seven female patients, aiming to fulfil the gap of information mentioned above. Female patients, with ages ranging between 14 and 35 years, were recruited to the study and they were administered isotretinoin treatments (cumulative dose of 120 mg/kg) for an average period of 6 months. The patients were followed up during and after the treatment for a total period of 18 months. Results:As a result, it has been observed that none of the patients got pregnant during the treatment period and relevantly, no abortuses or foetal abnormalities were recorded. Moreover, none of the patients got pregnant 12 months after the termination of the treatment. Additionally, the socio-demographic analysis of the patients indicates that most of the patients were single and 81% of the patients were sexually inactive. Conclusion:Our findings suggest that the low reportage of teratogenicity due to isotretinoin usage in Turkey could be due to several reasons, such as the sociocultural profile of the female patients undertaking the isotretinoin treatment, and strict adherence to contraceptive methods, and/or underreporting of teratogenic incidents due to lack of studies held in cooperation with obstetricians.Keywords: Acne, isotretinoin, pregnancy, contraception, teratogenicity Özet Amaç: İzotretinoin şiddetli ve inatçı aknenin bilinen en etkili tedavisidir. Ancak bu ilacın en önemli yan etkilerinden biri teratojenik olmasıdır. Bu sebepten tedavi öncesinde bilinmeyen bir gebelik durumu olup olmadığını ortaya çıkarmak için testler yapılmakta ve beraberinde hastaların sistemik izotretinoin tedavileri boyunca kontraseptif önlemler almaları önerilmektedir. Buna rağmen dünyanın pek çok ülkesinden istenmeyen gebelikler ve bununla ilişkili düşükler bildirilmektedir. Ancak Türk literatüründe fetal izotretinoin maruziyeti ile ilgili yalnızca birkaç bildiri tespit edilmiştir. Gereç ve Yöntem:Yukarıda belirtilen bu veri eksikliğini gidermeye yönelik olarak 57 kadın hasta geriye dönük olarak değerlendirilmiştir. 14-35 yaş arası kadın hastalar ortalama 6 ay boyunca total kümülatif doz olarak 120 mg/kg izotretinoin tedavisi almıştı. Bu hastalar tedavi süresinde ve sonrasında toplam 18 ay boyunca izlenmişti. Bulgular: Sonuç olarak hiçbir hastanın tedavi sürecinde gebelik yaşamadığı ve dolayısıyla herhangi bir düşük ya da fetal ano...

Risk management of teratogenic medicines: A systematic review

“…Characteristics of the included studies are shown in Table 2 and summarized in Appendix B. (Chave et al, 2001;Mulryan et al, 2018) to 95.1% (Cheetham et al, 2006), pregnancy testing during treatment from 12.7% (Raguideau et al, 2015) to 100% (Hayward et al, 2016), contraception use before starting treatment from 15.7% (Uuskula et al, 2018) to 94% (Brandenburg et al, 2017), and contraception use during treatment from 1.7% (Tsur et al, 2008) to 100% (Ozyurt & Kaptanoglu, 2015).…”

“…B. Schwarz, Parisi, Williams, Shevchik, & Hess, 2012;E. B. Schwarz et al, 2007;Stancil et al, 2016;Steinkellner et al, 2010;Teichert et al, 2010;Uuskula et al, 2018;Wieck et al, 2007), while others used patients surveys (Algoblan et al, 2019;Banas et al, 2014;Bell et al, 2002;Boucher & Beaulac-Baillargeon, 2006;Brandenburg et al, 2017;Brinker et al, 2005;Castaneda et al, 2008;Chang et al, 2018;Ferguson et al, 2016;Goyal et al, 2015;Lelubre et al, 2018;Leverenz et al, 2019;Mitchell et al, 1995;Ozyurt & Kaptanoglu, 2015;Rao et al, 2000;E. B. Schwarz, Mattocks, et al, 2013;Shilalukey et al, 1997;Tsur et al, 2008;Valle et al, 1998;Werner et al, 2014;Yazdany et al, 2011), a combination of medical records and patient surveys (Bosak et al, 2019;Entezari-Maleki et al, 2012;Hogan et al, 1988;E.…”

“…B. Schwarz, Parisi, Williams, et al, 2012;E. B. Schwarz et al, 2007;Stancil et al, 2016;Steinkellner et al, 2010) Isotretinoin 16 (29.1%) (Algoblan et al, 2019;Boucher & Beaulac-Baillargeon, 2006;Brinker et al, 2005;Cheetham et al, 2006;Crijns et al, 2012;Entezari-Maleki et al, 2012;Hogan et al, 1988;Lelubre et al, 2018;Mitchell et al, 1995;Ozyurt & Kaptanoglu, 2015;Pinheiro et al, 2013;Rao et al, 2000;Teichert et al, 2010;Tsur et al, 2008;Uuskula et al, 2018;Werner et al, 2014) Antiepileptic or anticonvulsant medications 5 (9.1%) (Bell et al, 2002;Bhakta et al, 2015;Bosak et al, 2019;Langan et al, 2013;Wieck et al, 2007) Arthritis or lupus medications 4 (7.3%) (Banas et al, 2014;Ferguson et al, 2016;Leverenz et al, 2019;Yazdany et al, 2011) Valproate/valproic acid 4 (7.3%) (Atturu & Odelola, 2015;Gotlib et al, 2016;Mulryan et al, 2018;Paton et al, 2018) Thalidomide or lenalidomide 3 (5.5%) (Brandenburg et al, 2017;Castaneda et al, 2008;Chave et al, 2001) Acitretin 1 (1.8%) (Raguideau et al, 2015) Chemotherapy for breast cancer 1 (1.8%) (Valle et al, 1998) Deferoxamine a...…”

Acneiform Eruptions and Pregnancy

“…But on the contrary, many cases of unwanted pregnancies and relevant abortuses have been reported all over the world [18]. This indicates that there is still insufficient control of isotretinoin associated with pregnancy.…”

“…Penicillins, macrolides, and cephalosporins are thought to have the best safety profile in pregnancy with erythromycin the oral antibiotic most commonly used for acne in pregnancy [18]. But tetracyclines should not be used during pregnancy, as use in the second and third trimester can cause discoloration of teeth and bones [20].…”