In a move that could lead to a national ban, two federal advisory panels voted Tuesday that the risks outweigh the benefits of a widely-abused opioid that was reformulated to deter addicts from snorting it.
The new extended-release version of Endo Pharmaceuticals' Opana may even be more dangerous than the version it replaced, according to critics including the advocacy group Public Citizen. Two Food and Drug Administration advisory panels seemed to agree, voting 18 to 8 that it presents more risks than benefits to society.
Next it's up to the FDA to decide whether to act on the panels' advice, which it generally does. Possible actions include changes to labels, restriction of prescriptions and an outright ban.
Instead of being snorted by abusers, Opana ER is now being injected, which has led to multiple deaths.
Injection of Opana ER by abusers was the primary cause of an HIV outbreak in Scott County, Ind. in 2015.
The drug is also identified as a possible factor in a recent East Tennessee outbreak of the life-threatening blood disease, Thrombotic Thrombocytopenic Purpura (TTP). Opana ER is a form of the opioid oxymorphone.
Emily Walden, whose 21 year old son T.J. died of an Opana overdose in 2012, has become the drug's most vocal opponent since his death. She testified at the FDA hearing and described herself later as "very pleased" by the vote.
"I believe the advisory committee made the right decision and I believe there will be more coming out of this discussion today, specifically to crush resistant opioids," she said.
She says the term "abuse deterrent" is a marketing ploy by drugmakers.
“I do not understand how a drug that does not cure anything can have this much death and destruction and still be available for use," said Walden, whose son was in the Kentucky National Guard. "He loved his country and his country failed him.”
There was an uptick in abuse of Opana ER after OxyContin was reformulated in 2010, making that drug harder to crush and snort. Two years later, Opana was reformulated into a crush-resistant or purportedly "abuse-deterrent” formula. That, however, led users to inject the drug.
When it's injected, oxymorphone becomes 10 times more potent than morphine, says Andrew Kolodny, a doctor who is executive director of Physicians for Responsible Opioid Prescribing,
"This characteristic makes the drug especially desirable and especially dangerous to opioid-addicted injection drug users," he says.
Calling the drug "abuse deterrent is misleading because making opioids hard to crush does not deter abuse," says Kolodny.
Baltimore health commissioner Leana Wen agrees.
"Abuse-deterrent forms of opioids still contain similar risks," says Wen, an emergency medicine doctor who says there is an "epidemic of overprescribing."
If the drug were instead called "crush resistant," it would "certainly give doctors a clearer picture," said Indiana health commissioner Jerome Adams, an anesthesiologist.
Safety and public health has to be a big concern "when you're putting these very potent medications out there in the midst of an opioid epidemic," Adams said after the meeting. He doesn't support a ban, however, instead favoring improved labeling and education of prescribers.
Endo insisted its drug is not contributing to overdoses any more than other opioids.
“All opioids, including oxymorphone, are abused,” said Harris Rotman, vice president of regulatory affairs for Endo.
The company argued that the changing environment brought by the reformulation of OxyContin led users to Opana and, according to Endo data, abuse had been appropriately deterred by the reformulation of Opana ER.
The company also provided data showing the number of Opana ER pills being dispensed has fallen gradually since the reformulation.
A Centers for Disease Control and Prevention study, however, found Opana's reformulation caused users to inject several times a day because of a short half-life that causes withdrawal symptoms to begin sooner. The study, conducted in Scott County, found users had found a way to heat the pills to melt the gel covering which creates the extended release effect when swallowed. After the gel was melted, it had to be mixed with an unusual amount of water, which diluted the amount of drug a user injected in each shot, leading the user to inject several times.
Because of the drug’s high street price, speakers at the FDA meeting said Opana ER abusers typically share as little as one quarter of a pill between two or three people who gather up the money to buy together. This likely leads to needle sharing, which was a major factor in the Scott County HIV outbreak.
There is no doubt that Opana changed and accelerated substance use disorder behaviors, Adams testified. He said it also increased pharmacy robberies and had what he called an "unpredictable" effect on overdoses. Unlike street drugs, which vary in potency, he says users “know what they’re getting when they’re getting Opana” so are less likely to overdose.
Endo representatives said as soon as they were notified they passed on notification to the FDA and met with sales reps in East Tennessee where the outbreak was concentrated. The company said it instituted drug take-back programs and got in touch with providers, as well as keeping tabs on providers deemed “suspicious” in that area.
According to Endo, there were 65 total reports of TTP cases, but the last was June 2016 and that likely occurred earlier than was reported.
Endo said TTP has also been reported with intravenous abuse of OxyContin’s abuse-deterrent formula tablets. This led the company to believe that the problem comes from an inactive ingredient, PEO, that, according to Endo, has not been well studied.
PEO is an ingredient used to create the gel coating on extended release tablets often used in many abuse-deterrent formulas, suggesting some of the issues made raise broader questions about these formulas.
Still, anything short of a ban won't satisfy Walden: “You can put a coating around it and pretend it is safer and people will still become addicted and people are still going to die."