FDA: Transmucosal Immediate-release Fentanyl (TIRF) REMS

The Food and Drug Administration (FDA) recently approved a single shared Risk Evaluation and Mitigation Strategy (REMS) for the transmucosal immediate-release fentanyl (TIRF) products.  This new shared system will replace the individual REMS and allow prescribers and pharmacies to enroll into just one system, easing the burden on the health care system. 

TIRF medicines, which include the brand-name drugs Abstral (fentanyl) sublingual tablet, Actiq (fentanyl citrate) oral transmucosal lozenge and its generic equivalents, Fentora (fentanyl citrate) buccal tablet, Lazanda (fentanyl) nasal spray, and Onsolis (fentanyl) buccal soluble film, are narcotic pain medicines called opiods used to manage pain in adults with cancer who routinely take other opioid pain medicines around-the-clock.  TIRF medicines contain fentanyl, a prescription opioid (narcotic) 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. 

Breakthrough pain is pain that comes on suddenly for short periods of time and is not alleviated by a patient’s normal pain management plan. To use the TIRF medicines safely, these patients must be opioid tolerant based on concurrent regular use of another opioid medication. 

The shared system strategy, called the TIRF REMS Access Program, will be used by all sponsors of TIRF products and is expected to ease the burden on the health care system. The program will begin in March, 2012.Until that time, prescribers, patients, and pharmacies should continue to enroll in the individual REMS programs. 

“This TIRF REMS will ensure safe use and access to these drugs for patients who need them,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “We have worked with the sponsors of both the innovator and generic drugs to develop this single, shared system that will streamline the process and decrease the burden of the REMS on the health care system.” 

The goals of the TIRF REMS Access Program are to ensure patient access to important medications and mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by: 

• prescribing and dispensing TIRF medicines only to appropriate patients, including use only in opioid-tolerant patients
• preventing inappropriate conversion between fentanyl products
• preventing accidental exposure to children and others for whom TIRF medicines were not prescribed
• educating prescribers, pharmacists, and patients on the potential for misuse, abuse, addiction, and overdose. 

Several TIRF products already have an individual REMS in place. Prescribers and pharmacies already enrolled in an individual REMS program for at least one TIRF medicine will automatically be transitioned to the shared TIRF REMS Access program.

Health care professionals who prescribe TIRF medicines that will only be used in an inpatient setting (hospitals, hospices, or long-term care facilities) will not be required to enroll in the TIRF REMS Access program. Similarly, patients who receive TIRF medicines in an inpatient setting are not required to enroll in the program. Long term care and hospice patients who obtain their medications from outpatient pharmacies must still be enrolled. 

Questions and Answers 

Q1. What are transmucosal immediate-release fentanyl (TIRF) medicines?  

A. TIRF medicines contain fentanyl, a prescription opioid (narcotic) 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. Breakthrough pain is pain that comes on suddenly for short periods of time and is not alleviated by a patient’s normal pain management plan. To use the TIRF medicines safely, these patients must be opioid tolerant based on concurrent regular use of another opioid medication. 

The current list of TIRF medicines include Abstral (fentanyl) sublingual tablet, Actiq (fentanyl citrate) oral transmucosal lozenge and its generic equivalents, Fentora (fentanyl citrate) buccal tablet, Lazanda (fentanyl) nasal spray, and Onsolis (fentanyl) buccal. 

Q2.  What is a Risk Evaluation and Mitigation Strategy (REMS)? 

A.  A REMS is a risk management plan that uses risk minimization strategies beyond approved labeling to manage serious risks associated with a drug. Under the Food and Drug Administration Amendments Act of 2007, FDA has the authority to require a manufacturer to develop a REMS when FDA finds a REMS is necessary to ensure that the benefits of a drug outweigh its risks.  

A REMS can include a Medication Guide or patient package insert, communication plan, one or more elements to assure safe use, an implementation system, and a timetable for submission of the REMS assessments. 

Q3.  Why did FDA approve a shared, single-system Risk Evaluation and Mitigation Strategy (REMS) for the entire class of transmucosal immediate-release fentanyl (TIRF) medicines, when the TIRF medicines already had individual REMS in place?  

A.  FDA approved a shared, single-system REMS for TIRF medicines to reduce the burden on the healthcare system of having separate REMS programs in place for individual TIRF medicines. Under the new class REMS, prescribers, pharmacies, distributors, and outpatients will only need to enroll in one REMS program – the TIRF REMS Access program – to prescribe, dispense, or receive all drugs in the TIRF medicines class. 

Q4.  Does this new Risk Evaluation and Mitigation Strategy (REMS) apply to all opioids?  

A.  No. This REMS is approved specifically for transmucosal immediate-release fentanyl (TIRF) medicines. This REMS will not affect the prescribing and use of other opioids.  We are continuing work on another class REMS for the class of long-acting and extended-release opioids. 

Q5.  Will this action make it harder for patients to receive their transmucosal immediate-release fentanyl (TIRF) medicines?  

A.  No. FDA does not expect that this new class Risk Evaluation and Mitigation Strategy (REMS) will affect patient access to TIRF medicines compared to the individual REMS. Having a single shared REMS for all of the TIRF medicines will make it easier for prescribers and pharmacies to participate in the TIRF REMS Access program, which we expect to improve patient access. Sponsors will also be required to evaluate the impact of the REMS on patient access to their TIRF medicines as part of required periodic assessments of the REMS, and FDA will review these assessments. 

Q6.  What should prescribers know about the new shared TIRF REMS Access program?  

A.  Healthcare providers who prescribe transmucosal immediate-release fentanyl (TIRF) medicines for outpatient use are required to enroll in the TIRF REMS Access program. Healthcare providers who are already enrolled in an individual Risk Evaluation and Mitigation Strategy (REMS) program for at least one TIRF medicine will not need to re-enroll because they will be automatically transitioned to the shared TIRF REMS Access program. Prescribers will be required to re-enroll in the TIRF REMS program every two years from the date of enrollment into the TIRF class REMS or from the date of enrollment into the individual REMS, whichever was earlier.   

To enroll, prescribers must review the Education Program, successfully complete the Knowledge Assessment, and complete an enrollment form. Additional information about the enrollment process can be found on the TIRF REMS Access program website: www.TIRFREMSaccess.com. This website will be available in March 2012 when the TIRF REMS Access program “goes live”.  

In outpatient settings, all healthcare providers must complete and sign a TIRF REMS Access Patient-Prescriber Agreement Form with each new patient before writing the patient’s first TIRF prescription. Healthcare providers must also provide patients with a copy of the Medication Guide during counseling about the proper use of their TIRF medicine.  Healthcare providers who prescribe TIRF medicines for inpatient use only (e.g. hospitals, hospices, or long-term care facilities) are not required to enroll in the TIRF REMS Access program.  

Q7. What should pharmacies/pharmacists know about the new shared TIRF REMS Access program?  

A. Both outpatient and inpatient pharmacies that dispense transmucosal immediate-release fentanyl (TIRF) medicines are required to enroll in the TIRF REMS Access program. Pharmacies that were previously enrolled in an individual TIRF Risk Evaluation and Mitigation Strategy (REMS) will not need to re-enroll because they will be automatically transitioned to the shared TIRF REMS Access program. Pharmacies will be required to re-enroll in the TIRF REMS program every two years from the date of enrollment into the TIRF class REMS or from the date of enrollment into the individual REMS, whichever was earlier. 

For pharmacies to enroll, a designated authorized pharmacist must review the Education Program, successfully complete the Knowledge Assessment, and complete an enrollment form. Only then can the authorized pharmacist complete enrollment on behalf of the pharmacy. The authorized pharmacist will then train other pharmacy staff in the appropriate dispensing of TIRF medicines according to the TIRF REMS Access program. Additional information about the enrollment process can be found on the TIRF REMS Access program website: www.TIRFREMSaccess.com.  

Q8. What should patients know about the new shared TIRF REMS Access program? 

A. Patients who are prescribed TIRF medicines on an outpatient basis must sign a Patient-Prescriber Agreement with their healthcare provider and will be asked to read the Medication Guide provided to them by their prescriber. Patients can then take their prescription to an enrolled pharmacy. Patients can locate a participating pharmacy by consulting their prescriber or calling the TIRF REMS Access program at 1-866-822-1483. This phone number will be available in March 2012 when the TIRF REMS Access program “goes live”. Patients will be enrolled in the TIRF REMS Access program by the pharmacy at the time their first prescription is filled. 

Patients who receive TIRF medicines in an inpatient setting (e.g. hospitals, hospices, or long-term care facilities) are not required to participate in the TIRF REMS Access program. 

Q9. When does the TIRF REMS Access Program “go live” or become fully operational? What do patients on transmucosal immediate-release fentanyl (TIRF) medicines do in the interim? 

A. The TIRF REMS Access Program will “go live” in March 2012. Until this time, patients prescribed TIRF medicines will continue to get them through the individual Risk Evaluation and Mitigation Strategies (REMS) or risk management plan programs.