TIRF (transmucosal immediate-release fentanyl) medicines contain fentanyl, a prescription opioid pain reliever. TIRF medicines are used to manage breakthrough pain in adults with cancer who are routinely taking other opioid pain medicines around-the-clock for pain. TIRF medicines include Actiq (fentanyl citrate) oral transmucosal lozenge and its generic equivalent, Fentora (fentanyl citrate) buccal tablet and its generic equivalents, Lazanda (fentanyl) nasal spray, Onsolis (fentanyl) buccal soluble film, Subsys (fentanyl) sublingual spray and fentanyl citrate sublingual tablets. FDA has required a Risk Evaluation and Mitigation Strategy, or REMS for these products, since 2011. In part, the REMS was put in place to ensure that only patients who are opioid tolerant are prescribed and dispensed TIRF medicines.
To accomplish this, the TIRF REMS consisted of a restricted distribution program, including a requirement that healthcare providers who prescribe TIRF medicines for outpatient use and pharmacies that dispense TIRF medicines be certified in the program. Additionally, patients were required to sign a patient-provider agreement form to participate in the REMS program. Despite these steps, FDA became aware that many patients who were not opioid tolerant were receiving TIRF medicines. This issue was discussed with an Advisory Committee, which suggested that the REMS be strengthened to further prevent opioid non-tolerant patients from receiving a TIRF medicine.
Shortly after the Advisory Committee meeting, FDA notified the manufacturers of the TIRF medicines that a modification to the REMS would be required, and in December 2020, the modified TIRF REMS was approved. Under this modified REMS, healthcare providers who prescribe for outpatient use and pharmacies that dispense must still be certified in the program. Additionally, prescribers must now document opioid tolerance with every TIRF prescription for outpatient use, and outpatient pharmacies must assess for a change in patients’ opioid tolerance with every dispensing of a TIRF medicine. Inpatient pharmacies must develop policies and procedures to verify opioid tolerance. Patients treated with a TIRF medicine for outpatient use must be enrolled in a registry. The registry, along with other data sources, is used to monitor for accidental exposure, misuse, abuse, addiction, and overdose.
The Agency’s aim with this REMS is to prevent inappropriate prescribing to opioid non-tolerant patients, and help mitigate the risks of accidental exposure, misuse, addiction, and overdose. While FDA’s goals are to reduce these serious outcomes due to inappropriate prescribing, these goals must be met while maintaining patient access to necessary pain medications.
- Statement from FDA Commissioner Stephen M. Hahn, M.D., on new steps to confront opioid crisis through risk evaluation and mitigation strategy programs
- Statement from FDA Commissioner Scott Gottlieb, M.D., on new steps to strengthen agency’s safety requirements aimed at mitigating risks associated with transmucosal immediate-release fentanyl products
- Statement from FDA Commissioner Scott Gottlieb, M.D., on FDA’s continued, careful oversight of the REMS associated with transmucosal immediate-release fentanyl products
- TIRF REMS Modification Letter Template (PDF - 45 KB)
- August 3, 2018: Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee Meeting Announcement
- Questions and Answers: FDA approves a class Risk Evaluation and Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl (TIRF) medicines