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FDA Tightens REMS Program on Transmucosal Immediate-Release Fentanyl

April 3, 2019
The breakthrough pain opioid medications known as TIRF fill a void in pain care but also come with high risks.

In a recent statement1 by outgoing Commissioner Scott Gottlieb, MD, FDA reviewed its Risk Evaluation and Mitigation Strategy (REMS) program on transmucosal immediate-release fentanyl (TIRF) medicines, which the agency put in place in 2011. He also announced new steps to strengthening the TIRF REMS program based on a 2018 public joint advisory meeting.

TIRF medicines are indicated for breakthrough pain in adults with cancer who are routinely taking other opioid pain medicines to treat around-the-clock pain. Breakthrough pain may come on suddenly for short periods of time and is not alleviated by a normal pain management plan. Thus, TIRF medicines fill an important need for a very specific, opioid-tolerant population.

However, these medications come with significant risks. The original 2011 REMS program for TIRF was intended to ensure that prescriptions were given only to appropriate patients, while other measures included limiting use to opioid-tolerant patients; avoiding inappropriate conversion between TIRF medicines; reducing accidental exposure; and educating prescribers, pharmacists, and patients on the potential for misuse, abuse, addiction, and overdose.

A statement from outgoing FDA Commissioner Scott Gottlieb, MD, on new steps to strengthen agency’s safety requirements aimed at mitigating risks associated with TIRF products. (Source: 123RF)

Outpatient utilization of TIRF products has substantially declined in recent years:1

  • In 2012, approximately 14,400 patients received TIRF prescriptions dispensed from US outpatient retail pharmacies.
  • In 2017, utilization declined to an estimated 4,700 patients who received TIRF dispensed prescriptions, and TIRF products accounted for only 0.02% of all opioid analgesic prescriptions dispensed from US outpatient retail pharmacies.

However, despite this drop, historical data on TIRF indicates that the prescribing behavior has not been consistent with its strict labeling. According to FDA, an estimated 35% to 55% of patients treated with a TIRF product were not opioid-tolerant, and many received a prescription for an unapproved use to treat other types of pain.

Now, FDA is taking further steps to help improve the safety of TIRF medicines by tightening the existing REMS program. The agency will be issuing letters to manufacturers notifying them of the following changes, which will require that:

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

The changes are intended to drive more judicious prescribing and better patient awareness of the serious risks of these medications, according to the statement. These new goals for TIRF products are the first steps taken by the agency this year to update all REMS programs over the course of 2019.

“We’ll continue to take steps to ensure the TIRF REMS program is achieving its goal of assuring safe use and mitigating the risks of misuse, abuse, addiction, overdose, and accidental exposure associated with these medicines. At the same time, we must also make sure that patients suffering from significant pain, in this case, adults with breakthrough cancer pain, have access to appropriate medications and aren’t unduly burdened in getting the treatment they need,” Dr. Gottlieb concluded.

In September 2018, FDA approved its final Risk Evaluation and Mitigation Strategy (REMS) on opioid analgesics, which expanded to include immediate-release (IR) formulations intended for use in an outpatient setting.

Last updated on: April 4, 2019
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