Statement from FDA Commissioner Scott Gottlieb, M.D., on FDA’s continued, careful oversight of the REMS associated with transmucosal immediate-release fentanyl products

FDA Statement

• For Immediate Release: August 01, 2018

On Aug. 3, the U.S. Food and Drug Administration will be hosting a public advisory committee meeting to review data from the most recent assessment of the Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU) for transmucosal immediate-release fentanyl (TIRF) products. The FDA will be asking the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee to discuss the findings from the assessments conducted by manufacturers of these products, as well as additional data about their use patterns and adverse events. Asking the FDA’s advisory committees to take a closer look at this opioid-related REMS reflects our commitment to further evaluating this critical program and making sure we’re providing transparency around its effectiveness and whether any modifications may be necessary. These TIRF products are medically important but also pose serious risks. We’re seeking the advice of outside experts on the effectiveness of the REMS and whether changes to the REMS might be necessary.

Combatting the crisis of opioid addiction facing our nation is a priority for me and the entire agency. As we work to mitigate the risks of misuse, abuse, addiction, overdose, and complications due to medication errors associated with these opioid analgesic drugs; we’re also committed to ensuring that patients suffering from significant pain have access to appropriate medication and are not unduly burdened in getting the treatment they need. We are committed to striking a careful balance between access and safety, based on reliable evidence. Our REMS are an important tool for helping to ensure safe use and reduce the risk of abuse and misuse. Making sure they’re achieving their purpose is critical.

In 2010, the FDA determined that a REMS would be necessary to ensure the benefits of TIRF products outweigh their risks. The TIRF REMS was approved in December 2011 to include all members of the TIRF class. The REMS is intended to make sure that TIRF products are prescribed only to appropriate patients. The REMS also includes measures that are designed to limit use only in opioid-tolerant patients; to avoid inappropriate conversion between TIRF medicines; to reduce accidental exposure; and to educate prescribers, pharmacists, and patients on the potential for misuse, abuse, addiction, and overdose.

TIRF medicines are indicated 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.

Since the REMS was implemented, there has been a significant decline in prescribing of TIRF products and currently they are only prescribed to approximately 5,000 patients nationwide. Because surveillance data are limited and look at a relatively small number of patients compared to overall opioid analgesic prescriptions, this affects our ability to evaluate the effectiveness of the REMS. Therefore, one topic we’ll discuss is how to best evaluate the REMS program, including our methods for data collection and assessment tools.

Another critical issue we’ll ask our outside advisory committee experts to address is how the TIRF REMS has affected the prescribing patterns for TIRF products, and how the TIRF REMS can better promote safe prescribing. The assessments show that approximately 42 percent of TIRF products may have been prescribed to non-opioid-tolerant patients. Understanding the reasons for this, whether these patients are truly opioid-non-tolerant, and the range of outcomes for these patients will be a central focus of our public meeting. We know that there may be limitations in the current data, and that we may have an incomplete picture of the kinds of patients being prescribed these products. We’ll ask the advisory committee to evaluate the reliability of our current trend information, and how we can collect even more accurate data. We’re seeking expert input into whether the TIRF products are helping patients who most need these products, as well as whether there are adverse outcomes associated with the current prescribing patterns.

We know that from an operations perspective, the TIRF REMS program appears to be functioning as intended to ensure that prescribers and pharmacists receive training on the risks and the safe use of TIRF medicines prior to prescribing or dispensing, and to ensure that patients are informed of the risks and safe use of TIRF medicines before taking them. But we also know that there may be more to be done. With any REMS, our goal is to achieve a public health purpose. It’s possible that a REMS can achieve functional compliance with all its discrete requirements, but not fully achieve its intended public health purpose. For these reasons, its critical we review REMS to make sure their achieving their goals.

Going forward, to understand the impact of the REMS better we want the manufacturers to obtain additional information about the use of these products. Ultimately, we need the advisory committee experts to advise the FDA on whether the new approaches we are considering will put us on the right path to helping patients in pain by making it possible for them to get these medicines while also reducing their known serious risks. These products can fill an important medical need for a small and carefully selected group of patients. But these products have significant risks associated with their use and should not be used in non-opioid-tolerant patients.

As part of our ongoing commitment to the safe use of these products, the FDA will seek the committee’s feedback on any possible modifications to the TIRF REMS goals and requirements, as well as input on the adequacy of the evaluations conducted in the REMS assessments to determine whether the TIRF REMS goals are being met. I welcome the advice of the advisory committee. I am committed to working with our professional staff to take appropriate steps to ensure the TIRF REMS is meeting its goals and that patients are adequately informed of and protected from the risks associated with these medicines.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.