FDA Updates iPLEDGE REMS with New Modifications for Pregnancy Testing and Prescription Windows

Today, the US Food and Drug Administration (FDA) has announced the approval of modifications to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, aiming to reduce administrative burden on patients, prescribers, and pharmacies while continuing to mitigate the risk of embryo-fetal toxicity.¹ The changes will take effect 180 days following approval. Until that time, the agency will continue to exercise enforcement discretion regarding pregnancy testing requirements, as outlined in its October 2023 update.

The iPLEDGE program was originally implemented in 2005 and formally approved as a REMS in 2010. As a shared system REMS, it encompasses all FDA-approved isotretinoin products and provides a centralized framework for prescribers, pharmacies, and patients to manage pregnancy-related risk regardless of the specific isotretinoin formulation prescribed.

While the program has been effective in mitigating isotretinoin-exposed pregnancies, it has also been widely criticized for contributing to treatment delays, workflow inefficiencies, and patient frustration. The newly approved modifications, previously communicated to isotretinoin manufacturers in November 2023, reflect FDA efforts to balance safety with real-world clinical practicality.

Key Changes for Patients

Under the updated REMS, prescribers may permit patients who can become pregnant to complete pregnancy testing outside of a medical setting—such as using at-home pregnancy tests—during and after isotretinoin treatment. However, pre-treatment pregnancy tests must still be completed in a medical setting prior to initiating therapy.

For dermatologists, this change may significantly reduce logistical barriers associated with monthly laboratory testing, particularly for patients in rural areas, those with limited transportation, or those facing insurance or scheduling constraints. Practices may see fewer missed treatment windows and less staff time spent coordinating laboratory visits.

In addition, if a patient who can become pregnant does not pick up their isotretinoin prescription within the required 7-day window, a repeat pregnancy test may now be performed immediately without an additional waiting period. This change eliminates the previously required “19-day lockout” period, which had been a significant source of treatment delays.

Key Changes for Clinicians

Although prescribers may now allow pregnancy testing outside of a medical setting during and after treatment, they must continue to ensure that pre-treatment pregnancy testing is performed in a medical setting. The FDA emphasized that prescribers will be responsible for establishing processes and procedures to minimize misinterpretation or falsification of pregnancy test results when tests are completed outside of a clinical environment.

If a patient who can become pregnant misses the prescription pickup window and has not yet received their first dose of isotretinoin, the repeat pregnancy test must still be conducted in a medical setting.

Counseling requirements have also been streamlined. Patients who cannot become pregnant must continue to receive counseling at enrollment. While prescribers are encouraged to reinforce counseling throughout treatment, monthly documentation of counseling in the REMS is no longer required for patients who cannot become pregnant.

Key Changes for Pharmacies

For patients who cannot become pregnant, the 30-day prescription window has been removed. Pharmacies will need to adjust workflow processes to ensure that if a prescription is not picked up, the authorization is reversed in the REMS and the medication is returned to stock.

The updated REMS also includes clarifying language regarding pharmacy staff training. Annual training remains mandatory, and certified pharmacies must maintain records of training completion through their authorized representative.

Looking Ahead

The FDA stated it will continue to post updates related to isotretinoin and the iPLEDGE REMS to ensure timely communication with prescribers, pharmacies, patients, and distributors. While the REMS remains complex, the approved changes may reduce treatment interruptions, improve patient adherence, and lessen administrative strain on dermatology practices—without compromising patient safety. Clinicians are encouraged to review the full requirements on the iPLEDGE REMS website or contact the iPLEDGE REMS Contact Center for additional guidance.

Reference

1. iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). FDA. Updated February 10, 2026. Accessed February 10, 2026. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/ipledge-risk-evaluation-and-mitigation-strategy-rems#10132023