By Pat Anson, PNN Editor

Illicit fentanyl may be a deadly scourge on the black market, but for thousands of Americans in severe cancer pain, prescription fentanyl is an essential medicine. And for some, the potent synthetic opioid may soon be harder to obtain.

The U.S. Food and Drug Administration recently announced plans to tighten its Risk Evaluation and Mitigation (REMS) program for transmucosal immediate-release fentanyl (TIRF) products. TIRF medicines such as Actiq and Subsys are approved for breakthrough pain in cancer patients, who regularly take other opioids around-the-clock and are considered “opioid tolerant.”

TIRF lozenges, sprays and tablets are so effective that they’re often prescribed off-label for other types of breakthrough pain. The problem with that, according to the FDA, is that up to 55% of patients prescribed a TIRF medicine are not opioid tolerant and received a TIRF prescription for an unapproved use.

“Data have suggested that prescribing of TIRF medicines still occurs in patients who are not opioid tolerant,” FDA Commissioner Stephen Hahn, MD, said in a statement. “With this in mind, the FDA finalized modifications to the REMS program to address the persistence of these concerning prescribing practices. These changes will also improve our ability to monitor for adverse events and ensure safe use of these medicines.”

Under the strengthened REMS program, prescribers and pharmacies will be required to document a patient’s opioid tolerance for every TIRF prescription that is written or dispensed, including refills. A new patient registry is also being established for everyone who receives a TIRF medicine, so the prescriptions can be monitored for signs of misuse, addiction and overdose.

“All patients prescribed for outpatient use must be enrolled in the registry prior to receiving the first TIRF prescription. The Patient Enrollment Form is used to ensure that patients are aware of the registry requirement and that patients have been counseled appropriately about the safe use of the TIRF medicines, including the risk of respiratory depression, the need to be opioid tolerant as defined in labeling and proper storage of the TIRF medicines,” an FDA spokesperson explained in an email to PNN.

The email said the patient registry would not be available to law enforcement. Prescribing information will only be collected by TIRF manufacturers and will not publicly identify individual patients or prescribers.

“Collection of patient registry information is intended to help assure the safe use of these products, not for law enforcement purposes,” the email said. “FDA’s disclosure laws and regulations relating to information in FDA’s possession protect from public disclosure any information where the release would constitute a clearly unwarranted invasion of personal privacy.”

That pledge is noteworthy, because prescription drug monitoring programs (PDMPs) and other databases are being weaponized by law enforcement agencies to target physicians, pharmacies and patients who are deemed to be lawbreakers based on the dose and quantity of opioid prescriptions.

Fewer TIRF Prescriptions

Why the FDA is acting now is a bit unclear, because the number of people prescribed TIRF products has been declining for years, from about 14,400 patients in 2012 to just 4,700 patients in 2017. TIRF medications in 2017 accounted for just 0.02% of all opioid prescriptions dispensed at retail pharmacies.  

Reports of deaths and other adverse events from using the drugs have also fallen sharply. The FDA’s Adverse Events Reporting System received over 20,500 reports of adverse events involving Actiq in 2018, but there were only a few dozen cases in 2019.

“I would like to know what data the FDA has that prompted this action,” says Lynn Webster, MD, a pain management expert and past president of the American Academy of Pain Medicine. “TIRF opioids are rarely abused or associated with overdoses.”

Webster is also concerned that the additional paperwork and scrutiny by the REMS program may discourage doctors and pharmacists from writing or filling TIRF prescriptions. 

“Since TIRF opioids are only indicated for cancer related pain, more barriers to prescribing these medications may mean they will not be prescribed.  That would be unfortunate because the TIRFs are the most effective treatment for severe breakthrough pain,” Webster said. “I hope this policy is more than just checking a box for the FDA, and that they plan to measure the impact on patients' access to the medication and on their pain relief.”

The tougher REMS regulations for TIRF products go into effect in March 2021.