REMS Program for Transmucosal Immediate-release Fentanyl Products is Operational, But Success Remains Uncertain

The FDA announced late in 2011 the approval of a single shared Risk Evaluation and Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl (TIRF) products. Covering rapid-onset opioid products indicated for the management of breakthrough pain (Abstral, Actiq, Fentora, Lazanda, Onsolis, and Subsys), the TIRF REMS Access program was designed to “ensure patient access to important medications” and mitigate the risk of misuse and medication-related errors by requiring that patients, prescribers, and pharmacies register in order to prescribe, dispense, or utilize any prescription fentanyl citrate product or its generic equivalent. The TIRF REMS Access program went live in March 2012.

In order to prescribe TIRF mediations in the outpatient setting, prescribers must first review the TIRF REMS Access Education Program (including the full prescribing information for each TIRF product), successfully complete the 11-question Knowledge Assessment (with a perfect score), and sign a prescriber enrollment form. Prescribers who write prescriptions for inpatient use only do not need to enroll in the TIRF REMS Access program.

To help ensure they make informed risk-benefit decisions before initiating treatment, providers are also required to “counsel the patient about the benefits and risks of TIRF medicines and together review the appropriate product-specific Medication Guide.” For each new patient, providers must also submit a completed TIRF REMS Access Program Patient-Prescriber Agreement Form, signed by them and the patient, within 10 days of the prescription being filled.

Because only authorized pharmacies can purchase or dispense TIRF medicines, all pharmacy staff involved in the processing and dispensing of TIRF medicines must be trained to only dispense TIRF medicines in accordance with the TIRF REMS Access program requirements. They must review the TIRF REMS Access Education Program and successfully complete the Knowledge Assessment and enrollment form.

Before dispensing each TIRF prescription, the pharmacist must verify that the prescriber and patient are enrolled in the TIRF REMS Access program. Pharmacists are also required to advise patients on how to properly take, store, and dispose of TIRF medicine, and should give each patient a copy of the product-specific Medication Guide for each TIRF prescription filled.

At the American Pain Society’s 32nd Annual Scientific Meeting, held May 8-13, 2013, in New Orleans, LA, Pergolizzi and colleagues presented a poster that outlined the development of the TIRF REMS program, and reviewed the requirements for prescribers, patients, and pharmacists who wish to participate in the program.

The poster authors noted several positive developments and encouraging signs from the program, including that it streamlines and makes safer the prescribing process for TIRF products, and facilitates prescribers choosing appropriate products based on a patient’s individual pain needs. It will also potentially deter the prescribing and dispensing of products that are not indicated for a particular type of pain.

The poster also identified several potential limitations of the TIRF REMS program, chief of which is that the program may be impeding patients from gaining appropriate access to TIRF products. “Prescriptions for TIRF products in the United States have decreased since the beginning of TIRF REMS development in 2009,” while “prescriptions of TIRF products have increased steadily in Europe, where a TIRF REMS program does not currently exist,” the authors wrote. Despite the program’s stated goals, “it is currently unknown whether the implementation of the shared TIRF REMS program will simplify prescribing and result in a rebound of TIRF prescriptions in the United States.”

The authors concluded that the TIRF REMS program “will require adjustment over time as we learn more about the benefits and drawbacks of the current program.”