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FDA Fell Short in Preventing Fentanyl Abuse Crisis, Report Claims

TUESDAY, Feb. 19, 2019 -- Drug makers and federal regulators dropped the ball in tracking the use of a potentially deadly fast-acting form of the synthetic opioid fentanyl, putting thousands of patients at risk of a fatal overdose, a new study claims.

Transmucosal Immediate-Release Fentanyl (TIRF) drugs are approved for use in cancer patients who've developed tolerance against the around-the-clock opioids normally used to treat their pain.

As many as 55 percent of patients prescribed TIRFs did not meet this criteria and should never have been prescribed them, according to a new report.

"Despite what should have been a very restrictive distribution system, a large proportion of patients -- as many as half -- receiving these products were not already on around-the-clock opioids," said senior researcher Dr. Caleb Alexander. He is co-director of the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health, in Baltimore.

"For those patients, there's an unacceptably high risk of fatal overdose," Alexander said.

What's worse, both the drug makers and the U.S. Food and Drug Administration knew this was going on and failed to take prompt action, Alexander and his colleagues allege.

For example, doctors and pharmacists require special certification to hand out TIRFs, but there's no evidence that anyone had their certification revoked despite mounting evidence of inappropriate prescribing, the researchers said.

The findings were published Feb. 19 in the Journal of the American Medical Association.

In a statement responding to the study, the FDA said it "shares the concerns about how TIRF products are being used and whether the Risk Evaluation and Mitigation Strategy (REMS) program is working as intended."

At least one drug company now faces criminal charges related to TIRF marketing.

Executives and former sales directors of Insys Therapeutics are being tried in Boston on racketeering charges, according to the Boston Globe. The criminal case alleges that they paid bribes and kickbacks to health professionals in exchange for prescribing their TIRF, the oral spray Subsys, to patients who didn't need it.

TIRFs are designed to deliver the synthetic opioid fentanyl -- which is up to 100 times more powerful than morphine -- into the bloodstream within seconds to minutes, Alexander said. The FDA indicates they should be used to manage breakthrough pain in adults with cancer.

TIRFs come in tablets, lozenges and films intended to melt in the mouth, as well as nasal sprays and sprays applied under the tongue, the FDA says.

According to Dr. Robert Glatter, an emergency physician with Lenox Hill Hospital in New York City, "Taken on or under the tongue, or in the cheek, TIRFs are rapidly absorbed with a quick onset of action. This very property increases the risk of overdose and death in a patient who is opioid-naive and has not developed a tolerance to opioids."

Because of their potency, the FDA requires special certification by both pharmacists and doctors to prescribe TIRFs, and mandates that manufacturers track the drugs' use to make sure they don't end up in the wrong hands.

Unfortunately, Alexander said, "both the FDA and the fentanyl makers failed to design and implement an effective monitoring program."

As part of the FDA-mandated monitoring program, drug makers conducted annual surveys of prescribers, pharmacists and patients to track unsafe prescribing.

Data from these surveys reveal that the vast majority of pharmacists and doctors understood that TIRFs are only for patients who have developed a tolerance to opioids, the researchers reported.

Despite this, about 39 percent of TIRF prescribers reported having doled out the drugs "off label" for patients with chronic non-cancer pain, the investigators found.

Assessments of health insurance clams found that as many as 55 percent of patients receiving TIRFs had not developed tolerance to opioids.

This misuse revealed itself between 2012 and 2017, but the drug makers failed to report any errant prescribers to the FDA, and no prescribers had their special certification revoked, Alexander said.

"What's alarming is it's taken so long. Serious deficiencies in the program have been known for some time, and the pace of change has not been faster," Alexander said. "We're more than six years out from the program's inception, and there have been many opportunities that have been missed on the part of opioid manufacturers and [the] FDA."

The FDA held a public advisory committee meeting on the matter in August 2018, and "has been actively assessing the recommendations of our advisory committee on the effectiveness of the REMS and necessary changes," the FDA statement says.

"The FDA will soon be sharing planned next steps, including intended modifications to the current TIRF REMS, to make sure the program is working to mitigate the risks of these medicines and that they're prescribed only to opioid-tolerant patients, and that those patients understand the risks and how to use TIRF medicines safely," the statement adds.

TIRFs are still being prescribed, but only account for a small fraction of all opioid medications, Alexander said.

FDA Commissioner Dr. Scott Gottlieb said last August, there has been a "significant decline in prescribing of TIRF products, and currently they are only prescribed to approximately 5,000 patients nationwide."

Nevertheless, Alexander believes their improper prescription has contributed to the U.S. opioid epidemic, which in 2017 claimed the lives of nearly 50,000 people through fatal overdoses.

"There's no argument people have died from these products," Alexander said. "I think it's symptomatic of larger deficiencies on the part of pharmaceutical manufacturers and the FDA in how opioid products have been regulated."

More information

The U.S. Food and Drug Administration has more about TIRFs.

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Posted: February 2019

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