Isotretinoin (also known by its former brand names Accutane or Roaccutane) is an extremely effective acne medication that can help patients whose severe acne has not responded to other drugs.
But the drug is also a potent teratogen — if a woman takes isotretinoin while pregnant, even for a short time, her fetus runs a high risk of severe birth defects.
In 2006, the U.S. Federal Drug Administration imposed a special restricted distribution program, known as iPLEDGE, that has stringent, recurring requirements for patients, prescribing physicians, and dispensing pharmacists. Despite the substantial imposition of iPLEDGE on patients and clinicians, the extent to which it has reduced pregnancy and other adverse effects had been unknown.
In a new study, investigators at Brigham and Women’s Hospital evaluated the frequency of reported pregnancies and pregnancy-related adverse events among women taking isotretinoin. In a paper published in JAMA Dermatology, the team reports that although the number of pregnancies among women taking isotretinoin has decreased, incidences of pregnancy persisted even after iPLEDGE was implemented.
“While the number of pregnancies among patients taking isotretinoin is low, even 200 pregnancies is too high,” said corresponding author Arash Mostaghimi, 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.”
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 must repeat a pregnancy test and attestation every month they continue taking the drug. Each month, physicians prescribing the drug must enter the test results and the pharmacist must obtain authorization from the iPLEDGE program.
In the current study, investigators analyzed 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 adverse reactions to medications filed by prescribers, consumers, and manufacturers. Reported pregnancies peaked in 2006 (768) 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 they did not stop. The authors note that several factors beyond iPLEDGE may be contributing to the downward trend, including a national decrease in teen pregnancies and increased use of long-term birth control and emergency contraception.
Earlier this month, Mostaghimi and 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, eating disorders, and sometimes suicide.
“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 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.”