The FDA has approved long-awaited changes to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) to minimize the burden on patients, prescribers, and pharmacies while protecting safe use of the teratogenic acne drug isotretinoin, according to an announcement issued today by the agency.

The modifications include changes outlined in the November 2023 FDA notification to isotretinoin manufacturers. These modifications become effective 180 days after the February 9 approval. Until then, FDA continues to exercise enforcement discretion regarding pregnancy testing requirements as described in the agency’s October 2023 update.

The iPLEDGE Program was introduced in early 2005 and approved as the iPLEDGE REMS in 2010. The goal is to mitigate the risk of embryo-fetal toxicity. It is a “shared system” REMS, meaning it includes all FDA-approved isotretinoin products and centralizes the system for prescribers, pharmacies, and patients to manage patient risk with all the products.

The FDA’s announcement highlighted that prescribers must continue to complete pretreatment pregnancy tests in a medical setting prior to starting isotretinoin treatment. However, it describes the following major changes:

Changes for patients:

• If permitted by a prescriber, patients may complete pretreatment pregnancy tests outside the medical setting (eg, at-home tests) during and after treatment. But they will need to continue to complete their pre-treatment pregnancy tests in a medical setting.
• If a person who can get pregnant does not pick up a prescription within the 7-day window, another pregnancy test may be done immediately without an additional waiting period, which has been referred to as the “19-day lockout.”

Changes for prescribers:

• Prescribers may allow patients to complete pregnancy tests outside of a medical setting (eg, at-home tests) during and after treatment. However, patients must continue to complete their pretreatment pregnancy tests in a medical setting. Prescribers will need to establish processes and procedures to minimize misinterpretation and falsification of pregnancy tests completed by patients outside of a medical setting.
• If a person who can get pregnant does not pick up the prescription within the 7-day window, a repeat test may be done immediately without an additional waiting period. If the patient has not received a first dose of isotretinoin, the repeat pregnancy test must be done in a medical setting.
• Patients who cannot get pregnant must be counseled at enrollment and prescribers should reinforce counseling throughout treatment. But monthly documentation of counseling in the REMS for patients who cannot get pregnant is no longer required.

Changes for pharmacies:

• There is no longer a 30-day prescription window for patients who cannot get pregnant. Pharmacies may need to adapt their workflow to ensure that if a patient does not pick up the prescription, the authorization is reversed in the REMS and the prescription is returned to stock.
• Clarifying language was added to the REMS to communicate that pharmacy staff training is required annually, and records of the training completion should be maintained by the certified pharmacy’s authorized representative.

John Barbieri, MD, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, who has long championed these changes, posted a thank you on X today “to the hard work of (the American Academy of Dermatology) and the iPLEDGE workgroup on championing these reforms!” Barbieri chairs the workgroup, which works with both the FDA and the Isotretinoin Products Manufacturing Group.

In a 2024 Medscape story, Barbieri explained some of the biggest burdens related to the iPLEDGE REMS. Of the requested changes, he said at the time, “really the most important is eliminating the request for monthly counseling for patients who cannot become pregnant.” Because of that requirement, he noted, all patients need to have monthly visits with a dermatologist to get the medication refills, “and that creates a logistical barrier” and also reduces the time available for dermatologists to care for their patients with other issues. As for missing the 7-day window, Barbieri said that, in his experience, “it’s almost never the patient’s fault; it’s almost always an insurance problem.” 

Currently, isotretinoin, originally marketed as Accutane, is marketed under the brand names Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

Marcia Frellick is a Chicago-based, independent healthcare journalist and a regular contributor to Medscape.