How common is inappropriate use of transmucosal immediate-release fentanyl?

An analysis of FDA documents, including 6 years of Risk Evaluation and Mitigation Strategy (REMS) assessment reports, indicated that many prescribers are using transmucosal immediate-release fentanyl (TIRF) inappropriately in opioid-nontolerant patients and in those with chronic, noncancer pain.

In a recent issue of JAMA, Rollman and colleagues evaluated almost 5,000 pages of FDA documents obtained via a Freedom of Information Act to assess whether the REMS program for TIRF products was meeting its goals. Specifically, the researchers reviewed 6 years of REMS data from 2012 to 2017 for the TIRF products, which included REMS-mandated knowledge surveys of pharmacists and patients.

The researchers reviewed survey data from 786 participants at 12 months after the REMS program was initiated. The data revealed that the majority of prescribers (87.4%), pharmacists (86.1%), and patients (90.6%) correctly identified that TIRF products are contraindicated in opioid-nontolerant patients. However, claims data reviewed 60 months after the REMS program inception revealed that 34.6% to 55.4% of patients prescribed TIRFs were opioid nontolerant.

In addition, in a 48-month survey after program inception, 34.2% of prescribers reported using these products for patients with chronic, noncancer pain. In the 60-month survey, 18.4% of prescribers continued to report use in those with chronic, noncancer pain. The researchers noted that despite these risks, FDA failed to make any “substantive” changes to the TIRF REMS program.   

In March 2019, FDA announced changes to the REMS program for TIRF products, citing a further need to mitigate the risks associated with use of these medications. In a statement by former FDA Commissioner Scott Gottlieb, MD, the agency wrote, “The prescribing of these medicines for non-FDA-approved uses to [opioid-nontolerant] patients tells us that there may be a disconnect between prescriber knowledge and prescribing behavior.” The agency noted that the new changes to the TIRF REMS program are designed “to drive more judicious prescribing and better patient awareness of the serious risks of these medications.”  

FDA acknowledged that the data by Rollman and colleagues show that more needs to be done to ensure the safe use of TIRF products. The prevalent use of TIRP products in opioid-nontolerant patients puts these patients at a substantially increased risk for respiratory depression, overdose, and even death. In the previous REMS program, prescribers only had to attest to their understanding that patients had to be opioid-tolerant before using TIRF. No formal documentation of opioid tolerance was required.

Under the newly revised REMS program, the agency made the following revisions:

  • A requirement that prescribers document a patient’s opioid tolerance for each TIRF prescription used in the outpatient setting
  • A requirement of documentation for safe use conditions when TIRFs are used in the outpatient setting, including documentation of opioid tolerance as described above
  • A requirement that inpatient pharmacies verify opioid tolerance in patients who require TIRF products during their hospitalization
  • The development of a new patient registry to monitor for serious adverse events, including overdoses.

The agency acknowledged that this is the first step in revising the TIRF REMS program, and more changes may be implemented in the coming year.

For the full article, please visit for the June 2019 issue of Pharmacy Today.