While isotretinoin can be an effective medication for the treatment of severe acne, the drug is also known to disturb the development of an embryo or fetus. Despite the known risks, pregnancies among women taking isotretinoin have continued, according to a paper published in JAMA Dermatology (July 17, 2019).
In 2006, the U.S. Federal Drug Administration (FDA) created a special restricted distribution program, known as iPLEDGE. iPLEDGE requires that women of childbearing age have a negative pregnancy test and attest to using two forms of birth control or abstinence before they can begin taking isotretinoin. They then must repeat a pregnancy test and attestation every month they continue taking the drug.
Even with the introduction of iPLEDGE to patients and clinicians, the extent to which the program has reduced pregnancy and other adverse effects has been unknown.
Researchers at Brigham and Women’s Hospital in Boston evaluated the frequency of reported pregnancies and pregnancy-related adverse events among women taking isotretinoin. The study shows that while the number of pregnancies has decreased, pregnancies among women taking isotretinoin have continued even after the implementation of iPLEDGE.
“While the number of pregnancies among patients taking isotretinoin is low, even 200 pregnancies is too high,” said study author Dr. Arash Mostaghimi in a press release. Dr. Mostaghimi serves as the director of dermatology inpatient service and co-director of the complex medical dermatology fellowship program at the Brigham. “We need to think about regulations that can reduce that number without being overly burdensome for patients and physicians.”
In the study, researchers looked at FDA reports of pregnancy-related adverse events associated with isotretinoin from Jan. 1, 1997 to Dec. 31, 2017. Using the FDA Adverse Event Reporting System (FAERS), a database of medication adverse event reports filed by prescribers, consumers and manufacturers, researchers saw that the number of reported pregnancies peaked in 2006 (768 pregnancies) before settling into a range of 218 to 310 per year after 2011.
Pregnancies, abortions and fetal defects all decreased after iPLEDGE was implemented in 2006, but continue to persist. The study authors note several factors beyond iPLEDGE, which could be contributing to the downward trend, including a national decrease in teen pregnancy, increased usage of long-term birth control and emergency contraception.
Dr. Mostaghimi and his colleagues used the FAERS database to look at a different constellation of side effects: those related to mental health. In that study, they found that a large proportion of patients taking isotretinoin experienced mental health issues, including anxiety, depression and suicidality.
“With mandated, monthly visits for iPLEDGE, we have an opportunity to improve screening for other side effects, such as mental health, in addition to identifying more effective ways to lower pregnancy rates,” said Dr. Mostaghimi. “iPLEDGE springs from the desire to protect newborns and women, but we should think of it as a testing ground for identifying the best system to reduce isotretinoin-related complications while maintaining access to an important drug.”