Assessment of the FDA Risk Evaluation and Mitigation Strategy for Transmucosal Immediate-Release Fentanyl Products

Area of Science:

• Pharmacology
• Drug Safety
• Regulatory Science

Background:

• Transmucosal immediate-release fentanyls (TIRFs) are indicated solely for breakthrough cancer pain in opioid-tolerant patients.
• A US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) was implemented to prevent inappropriate TIRF prescribing.

Purpose of the Study:

• To evaluate knowledge assessments of pharmacists, prescribers, and patients regarding appropriate TIRF use.
• To assess whether the REMS program met its goals using claims data.
• To characterize FDA's response to REMS assessments.

Main Methods:

• Qualitative analysis of 4877 pages of FDA documents (2012-2017).
• Included REMS assessment reports, FDA evaluations, and FDA-sponsor correspondence.
• Utilized Freedom of Information Act (FOIA) requests.

Main Results:

• Substantial rates of inappropriate TIRF use were identified through claims data and surveys.
• Prescribers and patients frequently misunderstood or misreported appropriate TIRF indications.
• Few substantive changes were made to the REMS program despite identified issues.

Conclusions:

• Surveys indicated generally high knowledge of proper TIRF prescribing.
• Claims-based analyses revealed substantial rates of inappropriate TIRF use.
• The FDA did not require significant modifications to the TIRF REMS program.