PALM SPRINGS, Calif. – Abuse-deterrent formulations of hydrocodone appear to work as promised, studies presented here indicated, although whether they can thwart real-life abusers remains to be seen.
In one, recreational opioid users allowed to try both a conventional immediate-release product and an abuse-deterrent form -- made so that it can't be crushed into a snortable powder -- in a cross-over format told the investigators that they preferred the immediate-release formulation.
And in the other, a different hydrocodone product that also resists crushing as well as mixing in alcohol or water (to discourage injecting it) passed benchtop tests that confirmed the intended qualities.
The two studies were presented here at the American Academy for Pain Medicine (AAPM) annual meeting.
Among conventional opioids, both immediate and extended-release formulations are prone to abuse, said , of PRA Health Sciences in Salt Lake City and a former president of the AAPM.
Extended release formulations have a lower proportion of people abusing them because abusers want a quick effect from a drug, and don't get that with extended release, he said. But some people tamper with the extended release versions, such as by crushing them so they can be snorted, or find other ways to tamper with them.
But there is increased danger because extended-release opioids have a higher load of drug in them. "People get a large dose of the drug. Many people have died as a result of that," Webster told ڴŮ.
Webster presented results of the cross-over clinical study. It focused on a hydrocodone extended-release bitartrate tablet formulated with an abuse-deterrence technology in otherwise healthy recreational (i.e., nondependent) opioid users. This population was selected for the study because they were familiar with the effects of opioids.
The abuse-deterrence technology "is a new technology that prevents the drug from being manipulated," he said. The tablets can't be crushed into fine enough particles for snorting.
A total of 195 adults were enrolled into the randomized, triple dummy, placebo-controlled cross-over study. Participants were 18 to 50 years old, were medically healthy, and had a history of recreational opioid use to achieve a "high" at least 10 times in the last year. They were also assessed for their responsiveness to hydrocodone. People who were physically dependent on opioids were excluded.
Four different conditions were tested, in which participants were given (in random order):
- Placebo tablet plus a flavored carbonated beverage with crushed extended-release hydrocodone mixed in
- Placebo tablet plus the beverage with 45 mg of immediate-release hydrocodone mixed in
- A 45-mg extended-release hydrocodone table plus the beverage with a crushed placebo tablet
- Placebo tablet plus the beverage with a crushed placebo mixed into it
Questionnaires were administered throughout to help assess the abuse potential for the new extended-release hydrocodone. Subjects were asked if they liked the drugs given to them, what effects they felt, and whether they would take the drug again. A total of 49 people completed the entire study.
Overall, participants preferred the immediate release hydrocodone over the extended-release version, Webster said. The difference was statistically significant. Both intact and crushed extended release hydrocodone were less desirable by study participants, an indicator they may not be a drug of choice for abusers.
Because abuse of opioids is so common, these sorts of technologies are an exciting and needed advance, said , an addiction medicine specialist in private practice in Aurora, Colo. He was not involved in the study.
In another poster presented here, researchers described work on a similar abuse-deterrent formulation of hydrocodone. The new formulation, ZX007, uses proprietary technology to prevent physical manipulation of the tablet, drug extraction using typical solvents such as alcohol, and maintains the extended-release feature even when a tablet is crushed.
To test this, researchers crushed tablets with various materials, and attempted to dissolve crushed tablets in hot water, high and low pH solutions, alcohol, varnish, and nail polish remover. When crushed, the remaining particles were too large for snorting. When mixed into water, a gel formed. In other liquids, the hydrocodone maintained its extended-release features such that a "high" would be difficult to obtain.
The gel "won't go through a syringe, which would deter people wanting to inject it," Errol Gould, PhD, director of medical affairs at manufacturer Pernix Therapeutics, told ڴŮ.
Disclosures
Webster's study was sponsored by Cephalon (now a unit of Teva); some co-authors were Cephalon/Teva employees.
The ZX007 study was funded by Pernix.