Dangerous fentanyl ‘candy’ is finally off the market. It fueled the opioid crisis | Opinion

On Sept. 30, prescription fentanyl lollipops, lozenges and mouth sprays finally came off the market in the United States. The withdrawal of these potent, short-acting fentanyl products is good news, but they never should have been approved in the first place. 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.

The first TIRF, a lollipop placed between cheek and gum, was approved by the Food and Drug Administration in 1993 only for hospital use. Oralet was never very useful for medical purposes: It lasted only 45 minutes or so, just enough time for cleaning an open wound or other quick but painful procedures. That was never a large market and the Oralet lollipop was not a commercial success. So fentanyl manufacturers invented a new market, getting their products approved for “breakthrough pain” associated with cancer. The concept was that someone on round-the-clock opioids for end-of-life care sometime had pain before the next dose was scheduled, a situation best treated by decreasing the time between doses. Instead, the makers of TIRFs persuaded doctors to prescribe these drugs in between doses of morphine or other opioids. Combining opioids sometimes resulted in dangerously high levels.

Actiq, the first TIRF lollipop for breakthrough pain in cancer patients, was approved by the FDA in 1998 for outpatient use in opioid-tolerant patients. The drug quickly began to be promoted — illegally — for pain associated with chronic noncancer conditions including arthritis, back pain, migraines and injuries. The company’s mantra was “Pain is pain,” and sales representatives focused promotion on general practitioners and other physicians who were not oncologists. The manufacturers of the TIRF lollipop paid a $425 million fine in 2008 to resolve claims that it marketed Actiq and two other drugs for unapproved uses between 2001 and 2006.

The commercial success of Actiq spurred development of more TIRFs. In 2006, Fentora, a TIRF lozenge — essentially the lollipop without the stick — was approved and again used widely off-label, for conditions the FDA had not approved it for. Two years later, the manufacturer sought approval of the lozenge for treatment of noncancer pain. At the time, FDA officials noted that 95% of Fentora use already was for the treatment of noncancer pain. What’s more, Fentora was linked to greater safety risks than other opioids and those risks were greatest for noncancer patients. Although the FDA refused to approve Fentora for noncancer pain, the company continued to promote the drug illegally for that use.

In 2012, fentanyl spray was approved, expanding the TIRF market, and the brand name Subsys quickly became a market leader. Although approved only for breakthrough cancer pain, the fentanyl spray, like its predecessors, was inappropriately prescribed for other types of pain. The company that made the spray paid $225 million in fines and other penalties after being charged with paying bribes and kickbacks to prescribers in exchange for increased prescriptions.

Pain advocacy groups were important in demanding unrestricted access to opioids. In 2018, Missouri Sen. Claire McCaskill published a report showing that opioid manufacturers paid millions of dollars to pain advocacy groups, who fought against any restrictions on opioids.

Our group’s research revealed how industry-funded educational activities directed at physicians reassured them that opioids were safe and effective. Physician-prescribed opioids fueled the opioid crisis in the U.S., and TIRFs played a significant role. Manufacturers’ recent voluntary withdrawal of the drug is good news, but these drugs should never have been approved. Their presence on the market for more than 20 years is a testament to inadequate regulation of drugs. Good riddance to bad medicine.

Adriane Fugh-Berman is a physician and professor at Georgetown University Medical Center, where she directs PharmedOut, a research and education project that analyzes unethical pharmaceutical marketing practices. Judy Butler is a senior research fellow at PharmedOut.