By Pat Anson

Patients suffering from severe cancer pain are scrambling to find alternatives after a drug maker discontinued production of potent fentanyl analgesics.

Cephalon, which is owned by Teva Pharmaceuticals, notified the FDA in August that it was stopping production of Transmucosal Immediate-Release Fentanyl Medicines, known as TIRF medications. The FDA then told patients and prescribers that all TIRF meds would be discontinued on September 30.  

“The moment I heard TIRF medicine was being discontinued, I was nearly brought to tears because I fear going back to the way things were before.  I have until the supply runs out and that's it,” said Anthony, a 46-year-old Georgia man who has severe headaches from an inoperable brain tumor. He asked that we not use his last name. 

Anthony has been taking TIRF meds since 2016. He also had a pain pump surgically implanted to deliver opioids around-the-clock, but still needed TIRF for occasional breakthrough pain.

“To transition back to traditional opiates will be a major step back treating my breakthrough pain,” Anthony explained. “Before TIRF medications, I struggled, and my quality of life followed suit.  I spent more time laying horizontal in my bed. It's been a long battle. I'm lucky to still be here.”

TIRF meds are effective because they are absorbed quickly through the mouth and provide pain relief within minutes. The two meds discontinued by Teva are Actiq, a fentanyl lozenge, and Fentora, a fentanyl buccal tablet that dissolves in the mouth.

“Because both of these meds and possibly other forms of TIRF medications bypass the gastrointestinal tract, they are overwhelmingly beneficial in my breakthrough pain,” says Anthony, who is regularly drug tested to make sure he isn’t abusing TIRF.

“I do not get high or feel euphoria.  If I abused these meds that might be an issue, but I take as prescribed.  Plus, if I took more than intended, I would run out of meds before my next refill leaving me without.  Not to mention, I don't want to stop breathing.”   

‘I Think They’re Good Drugs’

Because TIRF medication is made with fentanyl, a synthetic opioid 100 times more potent than morphine, it is poorly understood by the public and often demonized by anti-opioid activists.

Illicit fentanyl is involved in about 70% of fatal overdoses, but prescription fentanyl is rarely diverted and has long played an essential role in treating severe pain. Less than one-tenth of one percent of prescription fentanyl – 0.088% -- is diverted, according to DEA estimates.

“I think breakthrough pain is a horrible thing, and I think these patients really benefit from these breakthrough pain medications,” said Tom Jenkins, PhD, Chief Scientific Officer and Co-Founder of Elysium Therapeutics, which is developing a new class of opioids with less risk of abuse.

“These transmucosal fentanyl drugs are really complementary to the profile of the breakthrough pain and really help patients manage it quite effectively. I think they're good drugs. I don't think they're widely prescribed, so I think the diversion of them is not as significant of a problem.”

Despite that, an op/ed being published in U.S. newspapers refers to TIRF meds as “candy” and “lollipops” – implying they are widely abused and marketed to children, not cancer patients.

“The withdrawal of these potent, short-acting fentanyl products is good news, but they never should have been approved in the first place,” wrote Dr. Adriane Fugh-Berman and Judy Butler, who are affiliated with PharmedOut and Physicians for Responsible Opioid Prescribing (PROP).

“Classified as transmucosal immediate-release fentanyl or TIRF products, these delivery methods are highly potent and highly addictive. The faster an addictive substance enters the bloodstream, the more abuse potential it has. TIRFs acted almost as fast as opioids used intravenously, and addicted many people.”

Fugh-Berman and several other PROP members have collectively been paid several million dollars by plaintiff law firms to be consultants or expert witnesses in opioid litigation, a detail not mentioned in the op/ed or by the news organizations that published it.

Adverse Events

It’s true that TIRF medications have been abused, but many of those cases involved Subsys, an oral fentanyl spray that was illegally marketed by Insys Therapeutics. Insys filed for bankruptcy in 2019, and the company’s founder and several top executives were later convicted of racketeering and bribing doctors.

According to the FDA, adverse events involving TIRF peaked in 2018, with nearly 22,000 reported cases. Since then, they’ve fallen by about 80%.

The decline in adverse events coincided with a steep drop in the number of cancer patients enrolled in the FDA’s Risk Evaluation and Mitigation Strategy (REMS) Program, which facilitated the safer prescribing of TIRF. Over 4,700 patients were enrolled in the TIRF program in 2017. Today there are fewer than 150.

Anthony is one of them.

“The small number of people on the meds are a result of the FDA strengthening the REMS requirements, making it a huge headache for doctors to not only prescribe TIRF meds, but also to keep patients on them, making so much extra work for the doctors,” Anthony told PNN. “Too much red tape involved, so doctors avoid like the plague.”

Another factor is cost. A supply of Actiq or Fentora that might last a few days or weeks for a cancer patient in severe pain will cost thousands of dollars. The drugs are often not covered by insurance.

‘It’s Opioid Phobia’

Why did Teva stop making TIRF medication? The company has not made any public statements about the discontinuation of Actiq and Fentora, and did not reply to PNN requests for comment.

The most likely explanation is that Teva’s bottom line was suffering, due in part to the costs of opioid litigation. In 2008, its Cephalon subsidiary paid a $425 million fine for the off-label marketing of Actiq and two other drugs. Then in 2022, Teva agreed to pay $4.25 billion to settle thousands of opioid liability lawsuits.

Last year, as part of a strategic restructuring, Teva discontinued production of generic oxycodone to focus on more profitable branded drugs.

“It's opioid phobia. I think these companies were spooked by the lawsuits. Maybe some of them did misbehave a little bit and deserved it,” said Elysium’s Jenkins. “I feel for the patients that were using these things appropriately, were getting relief, that are no longer able to access the drug.

“I can only imagine corporate lawyers were just saying, ‘Hey, this isn't worth it. Let's get out of this.’ And also the REMS program. I mean, the FDA is deliberately making it difficult for physicians to prescribe this drug, right?”

Caught in the middle of opioid litigation and a profit-driven healthcare system are cancer patients like Anthony.

“I do not feel the few remaining patients should be made to suffer by discontinuing TIRF medications.  I'm guessing they are doing this because it's no longer as profitable as it once was,” he said. “Why can't small batches be done to maintain the quality of life of the remaining TIRF patients?”

The FDA has shown no interest in keeping the REMS program alive by finding a new TIRF manufacturer. New applications from patients and prescribers are no longer being accepted. And calls to the program’s hotline go unanswered.

“FDA did not request this discontinuation. It is important to note that FDA does not manufacture medicine and cannot require a pharmaceutical company to make a medicine, make more of a medicine, or change the distribution of a medicine,” the agency said in a brief online statement.