Breakthrough Pain and REMS

Several posters presented the American Pain Society Annual Meeting focused on risk evaluation and mitigation strategies.

The American Pain Society 29th Annual Meeting featured more than 250 poster presentations, with posters assigned an odd number displayed on Thursday, May 6, and posters assigned an even number displayed on Friday, May 7. Here are three abstracts of noteworthy posters: one focuses on the management of breakthrough pain in opioid-tolerant patients with chronic pain; the other two posters focus on one of the most talked about topics at this year’s conference — Risk Evaluation and Mitigation Strategies (REMS).

Fentanyl Buccal Tablet vs. Oxycodone Immediate-release for the Management of Breakthrough Pain in Opioid-tolerant Patients with Chronic Pain: Patient Disposition and Dose Titration (Poster # 294)

Ashburn and colleagues note that “Data show the effective dose of a rapid-onset, transmucosal opioid for breakthrough pain (BTP) is not related to the around-the-clock (ATC) dose of the drug. No data exist, however, on more traditional, short-acting oral opioids.” They designed a study to compare fentanyl buccal tablet (FBT) with oxycodone immediate-release (OxyIR) for “BTP, opioid-tolerant patients titrated FBT and OxyIR to a successful dose that provided adequate analgesia without unacceptable adverse events (AEs).” During the study, 320 patients received treatment; 203 were titrated to a successful dose of FBT and OxyIR, and 183 were “evaluable for efficacy.” Sixty patients discontinued treatment during the titration period while receiving FBT and 69 discontinued while receiving OxyIR. Reasons for discontinuation were “similar between treatments.” Just over half of participants reported AEs. The authors reported that “the titrated, successful dose of OxyIR for BTP was not predicted by the [around-the-clock] opioid dose. However the successful OxyIR dose was concordant with a dose of FBT estimated to be equivalent. The tolerability profiles were similar.”

A Risk Evaluation and Mitigation Strategy (REMS) to Manage the Risks of Overdose, Abuse, Addiction, and Diversion with Rapid-onset Opioids (Poster # 190)

As empowered by the FDA Amendments Act (FDAAA) of 2007, the FDA has asked Cephalon and other sponsors of opioid products to submit a REMS to manage the risks of abuse, misuse, and diversion associated with this class of medications. Kaper et al. presented a poster at APS 2010 that outlined the REMS proposed by Cephalon for its fentanyl rapid-onset opioid products. According to the poster, the proposed REMS “has been designed to provide safe and appropriate access to Cephalon’s rapid-onset opioids through a closed system that requires participants’ education/assessment and certification/enrollment to gain access” to the products. The program would require prescribers to register before gaining prescribing privileges for the products. Pharmacies would have to achieve certification before purchasing and dispensing the products, and patients would be required to enroll in the REMS program before receiving a prescription.

It is proposed that prescribers complete “an online educational module and knowledge assessment built around key safety information,” including the risks associated with chronic opioid therapy and rapid-onset opioids, the importance of establishing tolerance before prescribing these medications, and effective counseling of patients. A similar education and assessment program has also been developed for pharmacies.

As part of the patient counseling component of the REMS, prescribers would provide patients with the product-specific medication guide, discuss and complete a patient-prescriber agreement, write the prescription, and direct the patient to a certified pharmacy (this is key). Using an “integrated REMS data repository” (which allows pharmacies to process and dispense prescriptions only from registered prescribers to appropriate patients), the certified pharmacy would verify the validity of the prescription and then, prior to dispensing the medication, “review scripted safety information with the patient/caregiver” and provide him or her with another medication guide.

Kaper et al. outline several benefits to the proposed REMS: * It provides controlled access to appropriate patients * Enables coordinated patient counseling between prescriber and pharmacist to promote safe use * Preserves the prescriber-pharmacy relationship * Enhances patient access to pharmacists * Incorporates e-prescribing tools * Enables the detection of diversion

As part of the proposed REMS, a communication plan designed to “raise awareness of the need for education/assessment and certification/enrollment among wholesalers, distributors, prescribers, and pharmacists” will be distributed to all relevant stakeholders. Following FDA approval, the program includes a built-in transition period to provide adequate time for affected healthcare professionals to achieve the necessary enrollments and certifications.

User Acceptance and Performance Assessment of an Opioid REMS System: A Pilot Study (Poster #188)

Katz et al. undertook this study to “evaluate user acceptance and system performance of a REMS system comprising prescriber and patient education, stakeholder enrollment, and point-of-dispensing verification of safe-use conditions in patients receiving opioids.” To test user acceptance, the authors designed a multi-component REMS program that incorporated a Web-based prescriber training module, a brief (5-minute) patient-training script “suitable for implementation by any office medical staff,” and an enrollment verification system that was integrated with the standard pharmacy claim.

Participating prescribers (four total) completed “baseline assessments of risk knowledge, self-efficacy in managing opioid risks, and adherence to safe use guidelines.” They also completed a brief educational module on safe opioid prescribing and completed an online enrollment form that stated they followed safe use guidelines.

They each selected five patients who were receiving opioid medications for chronic pain; patients filled their prescriptions in-person at a participating pharmacy, which used the eRx switch network for processing claims. The physicians completed the training program and enrolled in a REMS database and provided patients with medication safety plans. Patients also enrolled in the database and their information was screened, as part of the pharmacy claims process, against the REMS database, as was the the patient, provider, and pharmacy enrollment status. Pharmacists had to verify (via code) in the system that patients had received a medication safety plan and counseling about important safety issues.

All participants were asked to complete surveys measuring their risk knowledge, self-efficacy in managing opioid risks, and adherence to safe opioid guidelines. The authors report a high degree of patient and provider baseline and post-training knowledge of risk knowledge. Patients and providers both also scored high on self-efficacy in risk management. Based on these and other results, the authors concluded that there is “high user acceptability by patients, prescribers, and pharmacists of a REMS system designed to meet all FDA requirements,” and that this study, “combined with previously reported technical tests, demonstrates that this system can support a class-wide REMS with up to hundreds of millions of prescriptions per year.”

Originally published online at, May 8, 2010.