Physicians and their teams have been unable to access the iPLEDGE site during an update to incorporate an FDA-approved modification to the iPLEDGE REMS that took effect December 13, 2021.
A scheduled change to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) has led to a delay in isotretinoin prescriptions. The iPLEDGE Program was implemented in early 2005 and approved as the iPLEDGE REMS in 2010 with the goal of preventing fetal exposure to isotretinoin. It also aims to inform prescribers, pharmacists, and patients about isotretinoin’s serious risks and safe-use conditions.1
According to the FDA website, iPLEDGE is a “shared system”, REMS, meaning that it includes all FDA-approved isotretinoin products. It acts as a centralized system for prescribers, pharmacies, and patients to manage patient risk, regardless of which isotretinoin product is being used. This is not the first update to the iPLEDGE platform, as it was last updated in 2018.
The FDA had posted an update on its website on October 8, 2021, stating that it had approved a modification to the iPLEDGE REMS which would take effect December 13, 2021, with system changes for health care professionals and patients. “Please note that prior to this modification, the iPLEDGE website and iPLEDGE REMS Contact Center phone service will undergo maintenance starting Friday, December 10 at 11:59 p.m. EST until Sunday, December 12 at 11:59 p.m. EST. During this time, iPLEDGE will be completely unavailable,” the FDA stated on its website.1
Changes for health care providers included reducing patient risk categories from 3 options to 2: patients who can get pregnant and patients who cannot get pregnant, according to the FDA website. The old categories were females of child-bearing potential (FCBPs), females not of child-bearing potential (FnCBPs), or male. Physicians had to assign and confirm their currently enrolled patients’ risk category for each patient on their first login to the website on or after December 13, 2021.
The website stated, “Prescribers and their designees should ensure that any patient whose isotretinoin prescription risk management authorization (RMA) (iPLEDGE authorization) expires on December 11 to 12, 2021, is instructed to obtain their prescription before 11:59 p.m. (Eastern) on December 10, 2021.”
New for pharmacies was a change in the REMS administrator and removal of the current “switch” pharmacy management system as a method to verify authorization to dispense isotretinoin, according to the website.
This change to the pharmacy management system means pharmacists will no longer use the switch system to obtain a predispense authorization, known as an RMA. Starting on December 13, 2021, all pharmacists were required to obtain an RMA prior to dispensing isotretinoin by accessing the iPLEDGE REMS website or the iPLEDGE REMS Contact Center. This is an issue as both were unreachable at press time. “Isotretinoin manufacturers anticipate the phone and internet systems for the modified iPLEDGE REMS will be available on December 13, 2021,” the FDA website stated.
The changes for patients included not only the risk categories, but also the option of presenting a unique QR code at the pharmacy on their smartphone instead of providing their iPLEDGE identification number. Patients should be able access their unique QR code by logging into their account on the iPLEDGE REMS site.
If a patient’s isotretinoin prescription RMA expired during December 11 or December 12, 2021, they would have had to obtain a prescription before midnight on Friday, December 10, 2021. It is important to note that if the RMA expires before the prescription is picked up from the pharmacy, the patient is required to go back to the physician and start the authorization process over again.
Christopher Bunick, MD, PhD, associate professor of dermatology at Yale University and member of Dermatology Times®’ editorial advisory board confirmed that this is an issue he is dealing with. He emphasized that patients should not panic as isotretinoin remains in the blood for about 5 to 7 days. So, “missing one or even several weeks will not impact the overall therapeutic outcome,” Bunick said.
He also mentioned that patients should know dermatologists did not cause the problem and are affected by it along with the patients. “It is essential that doctors and patients continue to work together as a team to get through the ‘iPLEDGE crisis’. That begins with appropriate communication and patience with office staff,” Bunick said. “We all hope this unfortunate problem resolves quickly.”
The American Academy of Dermatology (AAD) is actively working to support dermatologists and patients who are on isotretinoin by communicating with administrators of the iPLEDGE program to encourage timely fixes to the system errors, Bunick continued.
The AAD has sent Syneos Health and the iPLEDGE sponsors correspondence about their concerns with the modifications of the program. The letter can be found here. The AADA also sent a letter to Patrizia Cavazzoni, the director of the Center for Drug Evaluation and Research at the FDA.
On December 14, 2021 the AAD issued this statement:
"iPLEDGE issues are an unacceptable disruption to patient care
The Academy is aware of the issues faced by dermatologists and patients attempting to use the new iPLEDGE platform beginning yesterday; and leadership agrees that this is not acceptable for our patients or our practices. We have contacted the FDA and Syneos to urgently communicate that the new platform rollout has been a nightmare for dermatology practices and patients; and it has created an unacceptable disruption in patient care. In addition, we are reaching out to congressional committees overseeing the FDA asking them to take action and have contacted health policy reporters to shine a light on the crisis.
Over the last several weeks we have repeatedly warned the FDA and Syneos that the proposed changes did not reflect clinical practice and would impede patient care; and we asked for a halt to the program until our concerns could be addressed. We were told “no,” with the explanation that suspending the iPLEDGE program would not, from FDA’s perspective, provide the safeguards that are necessary to prevent embryofetal exposure. They also assured us that the iPLEDGE administrator was taking steps to address many of our concerns before launch. Clearly, those steps have not been effective.
The Academy appreciates all members’ messages via our Member Resource Center. We will use those messages and shared experiences as we renew our calls for an immediate suspension to the program and continue efforts to urgently seek solutions to the current crisis as well as to longstanding issues with the program.
It’s also critical that the FDA hear the collective voice of dermatologists about the impact on your patients. Please look for an email link later today and share your experience via the Academy’s grassroots Take Action Center.
Kenneth J. Tomecki, MD, FAAD
President, American Academy of Dermatology Association"
Gary Gatyas, the executive director of external communications at Syneos Health, shared Syneos Health's statement: "We appreciate the concern about iPLEDGE. While Syneos Health doesn’t maintain the iPLEDGE system or contact center, we are doing what we can to help the responsible parties with a resolution. For updates please contact the call center or visit https://www.ipledgeprogram.com."
The FDA was invited to comment but did not provide input.
1. Ipledge risk evaluation and mitigation strategy (REMS). FDA. Published online December 14, 2021. Accessed December 14, 2021. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/ipledge-risk-evaluation-and-mitigation-strategy-rems