Arash Mostaghimi

Arash Mostaghimi

For patients whose severe acne has not responded to other drugs, isotretinoin (also known by its former brand name Accutane or Roaccutane) can be an extremely effective option. But if a pregnant woman takes this medication, even for a short period of time, the risk of severe birth defects is high.

In 2006, the U.S. Federal Drug Administration (FDA) imposed a special restricted-distribution program known as iPLEDGE, which has stringent, recurring requirements for patients, prescribers and dispensing pharmacists. Despite this rigor, the extent to which the program has reduced pregnancy and other unwanted effects has been unknown

In a new study, Brigham investigators evaluated the frequency of reported pregnancies and pregnancy-related adverse events among women taking isotretinoin. In a paper published in JAMA Dermatology, the team reported that although the number of pregnancies has decreased, pregnancies among women taking isotretinoin have continued to persist even after the implementation of iPLEDGE.

Pregnancy-Related Adverse Events

“While the number of pregnancies among patients taking isotretinoin is low, even 200 pregnancies is too high,” said corresponding author Arash Mostaghimi, MD, MPA, MPH, director of Dermatology Inpatient Service and co-director of the Complex Medical Dermatology Fellowship Program. “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 then 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 iPLEDGE authorization.

In their study, investigators analyzed FDA reports of pregnancy-related adverse events associated with isotretinoin from Jan. 1, 1997, to Dec. 31, 2017. Reported pregnancies peaked in 2006 (768 pregnancies) before settling into a range of 218–310 annually after 2011.

Pregnancies, abortions and fetal defects all decreased after iPLEDGE was implemented in 2006 but continued to occur. Several factors beyond iPLEDGE may be contributing to the downward trend, including a national decrease in teen pregnancy and increased usage of long-term birth control and emergency contraception.

Paving a Testing Ground

Earlier this month, Mostaghimi and his team used the same FDA 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 those related to 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.”