Abuse of Endo's second-generation Opana ER formulation implicated in Indiana HIV epidemic

The Centers for Disease Control and Prevention says that a formulation of Endo's ($ENDP) pain med, Opana ER--that's supposed to be difficult to crush--is responsible for an outbreak of HIV in southern Indiana, because the changes made it easier to prepare the drug for more dangerous intravenous or subcutaneous injection.

Time reports that drug addicts prefer the formulation to heroin even though it is more expensive and doesn't last as long. HIV spread through the sharing of needles, resulting in at least 135 HIV infections in a rural Indiana county of 4,200 people.

The new formulation was introduced in 2012. The FDA became aware of the risks of abuse by intravenous or subcutaneous injection in postmarket testing that was performed to determine if the prior version of Opana was withdrawn by Endo because of a lack of safety or effectiveness. The company wanted the FDA to conclude that those were the reasons for the withdrawal, for such a ruling would prevent generic versions of the old formulation from being approved and marketed.

But the agency rejected Endo's claim in 2013 and said the old formulation remained on-limits to generics manufacturers. Although the FDA acknowledged that the new version was harder to crush that its predecessor, it also wrote that one of the tests "suggests the troubling possibility that a higher percentage of reformulated Opana ER abuse is via injection than was the case with the original formulation."

In addition, the "reformulated version's extended-release features can be compromised when subjected to other forms of manipulation, such as cutting, grinding, or chewing, followed by swallowing" and "can be prepared for snorting using commonly available tools and methods," the agency said on its website.

Furthermore, the agency wrote in a formal notice that the abuse potential and warning section of the new formulation's labeling is "virtually identical" to the previous version, and did not grant it abuse-deterrent labeling.

Time reports that Endo is denying that Opana is responsible and thinks generic medications might be responsible. But county sheriff Dan McClain told the publication: "I've got an evidence room full of Opana over there right now, and I don't have any generic forms of that pill that are being purchased off the street."

If Opana ER injections are indeed the culprit, as is widely believed, the HIV outbreak demonstrates the importance of paying attention to all routes of illicit administration when designing abuse-deterrent formulations; that's a point the FDA stressed in its guidance on abuse-deterrent opioid formulations.

Sen. Joe Donnelly (D-IN) recently toured the area hard hit by the HIV and prescription drug abuse epidemic. He's pushing Congress to pass the Heroin and Prescription Opioid Abuse Prevention, Education, and Enforcement Act, which failed to make it out of committee in 2014.

It would pay for a program to give first responders demonstrations on the use of naloxone, which is given to fight emergency overdoses (and the subject of drug delivery efforts from Reckitt Benckiser, BioDelivery Sciences and others). The bill also calls for enhanced drug management and drug monitoring, as well as a federal task force on responsible prescribing practices of opioids.

"What we've seen time after time is somebody who may have suffered an injury where they need five days of pain pills," Donnelly told Indiana news outlet Newsandtribune.com. "The default prescription is 30 days, so you have a massive amount of additional pills on the market that are on the illicit market. We need to eliminate that."

Events like the Indiana HIV outbreak have put opioid overdose is in the public spotlight, leading to a mad dash to develop abuse-deterrent formulations. KemPharm recently touted the results of a human abuse liability clinical trial of its abuse deterrent candidate. It's a prodrug, meaning the main ingredient remains inactive until it is metabolized, such as when broken down by naturally occurring bacteria within the body.

- read the article in Time
- get more about KemPharm's candidate