FDA approves ninth update to the iPLEDGE REMS for isotretinoin, introducing flexible pregnancy testing and workflow changes. Learn what this means for patients, prescribers, and pharmacies.
Written By: Pharmacally Medical News Desk
Isotretinoin is one of the most effective medicines for severe, treatment-resistant acne. Because it can cause serious birth defects if taken during pregnancy, the US Food and Drug Administration created a controlled safety system called the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS).
This program was first implemented in 2005, formally approved as a REMS in 2010, and this February 2026 update is among the latest major modifications to the iPLEDGE REMS since its launch, reflecting years of incremental changes to the program. iPLEDGE requires patients, prescribers, and pharmacies to follow specific enrolment, testing, and dispensing requirements to minimize embryo-fetal exposure risk.
On February 9, 2026, the FDA approved set of changes to the iPLEDGE REMS aimed at reducing administrative and logistical hurdles for physicians, pharmacies, and patients while maintaining the core safety intent. These updates are planned to take full effect about 180 days after approval (around August 2026).
Why These Changes Were Initiated
In November 2023, the FDA notified isotretinoin manufacturers that they needed to modify the iPLEDGE REMS to minimize burden on the health care delivery system while still complying with the REMS requirements.
To reach this determination, the agency reviewed the existing REMS and considered advice from the March 2023 joint meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, as well as public feedback. The modifications approved in 2026 also include additional changes proposed by the isotretinoin manufacturers.
Main Changes in the 2026 Update
The FDA outlined several specific updates intended to make the iPLEDGE system more practical in real-world clinical settings:
More Flexible Pregnancy Testing
- Patients who can become pregnant may now complete monthly pregnancy tests outside of a clinical setting (for example, at home), if the prescriber allows.
- However, the pre-treatment pregnancy test must still be done in a medical setting before starting isotretinoin.
Removal of the “Waiting Period” After Missed Pickup
- Under the previous rules, if someone who can become pregnant did not pick up their prescription within the required 7-day window, they faced a waiting period before retesting and another prescription could be issued.
- The updated REMS eliminates that waiting period, allowing an immediate repeat pregnancy test and continuation of treatment.
Streamlined Counseling Requirements
- Patients who cannot become pregnant still must receive counseling at enrollment, but monthly documentation of this counseling is no longer required. Prescribers are encouraged to reinforce safety messaging during treatment.
Pharmacy Workflow Adjustments
- The prior 30-day prescription pickup window for patients who cannot become pregnant has been removed.
- Pharmacies now need to promptly reverse unclaimed authorizations in the REMS system and return unpicked medication to stock.
- The updated REMS clarifies that annual staff training and recordkeeping are required for pharmacies certified to dispense isotretinoin.
Safety Risks Outside the iPLEDGE System
Alongside these REMS modifications, the FDA has long warned the public about the dangers of buying isotretinoin over the internet without a prescription, since purchasing the drug outside the certified iPLEDGE system bypasses critical safety measures and supervision. In its most recent advisory on this topic, the agency reminded patients that isotretinoin should only be obtained through a licensed healthcare professional and a certified pharmacy, and should never be bought online without proper oversight. This warning reinforces the importance of following the revised iPLEDGE REMS requirements as they are implemented later in 2026.
Clinical and Practical Implications
These revisions follow years of discussion and structured feedback from advisory committee meetings and public comments, along with formal FDA engagement with manufacturers beginning in late 2023. The updates are designed to reduce obstacles that contributed to treatment delays and workflow challenges, particularly around pregnancy testing and prescription access, while maintaining the program’s core safety safeguards.
FDA has considered the impact of the collective changes and determined that the modifications will minimize burden for patients, prescribers, and pharmacists while continuing to ensure that the benefits of isotretinoin therapy outweigh the risk of embryo-fetal toxicity, including life-threatening severe birth defects.
References
iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), 10 February 2026, https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/ipledge-risk-evaluation-and-mitigation-strategy-rems
Questions and Answers on the iPLEDGE REMS, 10 February 2026, https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-ipledge-rems
Risk evaluation and mitigation strategy (rems) requirement, November 2023, https://www.fda.gov/media/174325/download?attachment
Isotretinoin Capsule Information, 10 February 2026, https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/isotretinoin-capsule-information
