Friday, March 29, 2019

REMS Program for Fentanyl Formulation Found to Be Inadequate But Slated for Change

Prescriptions for transmucosal immediate-release fentanyl (TIRF) medications decreased in the first year after the Food and Drug Administration (FDA) implemented a Risk Evaluation and Mitigation Strategy (REMS) program to restrict distribution of the potent opioids, but then prescriptions rose to near pre-REMS levels, a study published today in JAMA Network Open has found.

The results suggest that the REMS program, begun in 2011, did not have as strong and lasting an impact as intended. Furthermore, although TIRF medications are approved for treating breakthrough pain in cancer patients who are tolerant to other, around-the-clock opioid analgesics, 72% of the prescriptions in the study period were for patients who did not have cancer. However, overall, prescriptions for TIRF products represented only 0.03% of all opioid prescriptions.

William Fleischman, M.D., M.H.S., an employee of the Centers for Medicare & Medicaid Services at the time of the study, and colleagues assessed TIRF prescribing by analyzing prescription claims data submitted to Medicare Part D for 2010 through 2014. The main outcome measures were TIRF prescription fills per 100,000 Medicare Part D beneficiaries. They also assessed prescribing for patients with no known opioid tolerance.

From the beginning of the study in 2010 through 2012, the first full year of the REMS implementation, TIRF prescribing had decreased by 1% per month. In the year after the REMS program took effect, TIRF prescribing dropped by 26.7%, then rose 2% each month through the study’s end.

“One explanation for the observed attenuation of the decrease in prescribing associated with the program could be that it may have taken a year for patients, prescribers, and pharmacists to familiarize themselves with REMS requirements and to register and complete the educational program,” the researchers wrote. “However, the subsequent return to baseline prescribing levels occurred despite a persistent decrease in the number of prescribers. This points to other possible contributing factors to the subsequent return of increased TIRF prescribing.”

From the beginning of the study in 2010 through 2012, a mean of 30% of initial TIRF prescriptions were for patients without known opioid tolerance. After the REMS was implemented, the number of prescriptions filled by patients without known opioid tolerance dropped 22.5%, followed by 1.98% monthly decreases for the remainder of the study. This outcome suggests that for this population, at least, the REMS program had a lasting impact.

Earlier this week, the FDA announced steps to strengthen the TIRF REMS. “Despite the decline in the use of these medicines, the historical data on the prescribing of TIRF products indicates that prescribing behavior is not consistent with the strict labeling. To the extent that some of these prescribing practices still persist, even as prescriptions declined sharply, that causes the FDA concern,” said FDA Commissioner Scott Gottlieb, M.D., in a statement.

Changes to the TIRF REMS include the following:

  • Requiring that prescribers document a patient’s opioid tolerance concurrently with each prescription of a TIRF medication for outpatient use.
  • Requiring inpatient pharmacies to develop internal policies and procedures to verify opioid tolerance in patients who require TIRF medications while hospitalized.
  • Requiring that a TIRF medication be dispensed for outpatient use with evidence or other documentation of safe use conditions, including concurrent documentation of opioid tolerance.
  • Requiring the development of a new patient registry to monitor for serious adverse events including overdose (both fatal and nonfatal).

For related information, see the Psychiatric News article “Tackling Opioid Overdose Epidemic Demands Multiple Approaches.”


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