Pregnancy-Related Adverse Events Linked to Isotretinoin Persist Despite REMS Implementation

According to the findings of a recent retrospective analysis, pregnancy and pregnancy-related adverse events related to isotretinoin administration have dropped since the initiation of the iPLEDGE program by the Food and Drug Administration (FDA) in 2006, however reports of fetal exposure persist. 

The iPLEDGE program is a Risk Evaluation and Mitigation Strategy (REMS) that aims to reduce fetal exposure to isotretinoin, a highly teratogenic disease-modifying agent used for the treatment of severe recalcitrant nodular acne unresponsive to conventional therapy (eg, systemic antibiotics). For this study, the authors utilized data obtained from the FDA Adverse Event Reporting System (FAERS) to assess pregnancy-related outcomes (ie, abortion, pregnancy while on contraception, fetal defects) in patients taking isotretinoin between 1997 and 2017. “Each individual reporting any pregnancy-related adverse event signified 1 pregnancy,” the authors explained. 

Between 1997 and 2017, 6740 pregnancies in women using isotretinoin were reported to the FDA. The number of pregnancies peaked in 2006 (n=768), but then decreased and stabilized to a range of 218 to 310 annual reports after 2011. “The rate of pregnancy for females of childbearing potential was between 0.33% (388 of 115,925) and 0.65% (768 of 117,784), with a peak in 2006,” the study authors reported. 

According to the findings, the rates of pregnancy, abortion, and fetal defects associated with isotretinoin use have decreased since the establishment of iPLEDGE in 2006. “Explanations for this trend include a broader national decrease in teenage pregnancies and abortion rates, improvements in access to effective long-term and emergency contraception, stringent iPLEDGE requirements, and reporting fatigue over time,” the authors explained. They noted, however, that despite this decreasing trend, a “substantial number” of pregnancy and pregnancy-related adverse events related to isotretinoin use are still reported. 

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In an editorial discussing the findings of this analysis, Arielle Nagler, MD, concluded that “Although this study is unable to directly link a decrease in fetal exposures with the implementation of the iPLEDGE program, the study shows that fetal exposure to isotretinoin continues to occur at levels that demand modification and improvement of this REMS program.”

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