A Tamper-Resistant Opioid Yields Mixed Results

A new formulation of oxycodone curbs tampering among high-risk individuals but doesn’t change overall opioid use or related harm at a population level, according to a new Australian study. Image credit: anatchant/123RF Stock Photo.

Editor’s Note: This article originally appeared on the IASP Pain Research Forum, and has been lightly adapted for RELIEF.

Like the United States, Australia is in the midst of an opioid crisis. In response, companies in both countries have introduced versions of oxycodone that are difficult to tamper with, in order to deter opioid abuse.

Now, new research led by Briony Larance at the University of New South Wales in Sydney, Australia, suggests that one such formulation successfully curbed tampering in those at high risk of doing so across several cities in Australia. The study also found no evidence that these individuals switched to illicit drugs, such as heroin or amphetamine.

But, when looking at a broader population of opioid users (rather than assessing just high-risk individuals), there was no effect on overall opioid use, overdose rates, or treatment seeking, though the researchers did detect a dip in the use of two higher-strength tablets.

Still, the study “adds an important perspective showing that the reformulated OxyContin product reduced the extractability of the active pharmaceutical ingredient [oxycodone] and produced measureable decreases in drug usage by the target drug-abusing population,” says William Schmidt of NorthStar Consulting in Davis, California, an expert on drug development who was not involved in the study.

While not the first of its kind, it’s “likely to be the most complete and compelling evaluation so far of the replacement of a traditional controlled-release opioid analgesic [pain reliever] with a tamper-resistant formulation,” writes Nabarun Dasgupta, University of North Carolina, Chapel Hill, US, in a commentary published alongside the results January 11 in the journal Lancet Psychiatry.

Less tampering among a high-risk group, but few population-level effects
In April 2014, the company Mundipharma Australia began distributing tablets of oxycodone with two crucial tweaks. These tablets would be plastic-like, hindering attempts to crush and then snort the pills, and if placed in water, they would transform into a thick gel, discouraging efforts to dissolve and inject them.

The move followed decades of growing opioid use, and abuse, in Australia. Indeed, pharmaceutical opioids now are responsible for the majority of fatal drug overdoses in the country.

“There was always the broader hope that by targeting risky practices like snorting and injecting, the formulation might also reduce opioid-related harm more generally. Until this study, it wasn’t clear whether or not it would do this. There were a range of opinions on the issue, and individual studies had examined aspects of these questions, but not in a coordinated fashion,” Larance says.

So began the National Opioid Medication Abuse Deterrence (NOMAD) study, an effort spanning the cities of Sydney, New South Wales; Hobart and Launceston, Tasmania; and Adelaide, South Australia. To assess tampering in these areas, Larance and her colleagues conducted in-person interviews with 606 people, aged 18 or older, who regularly used and injected pharmaceutical opioids. These interviews took place both before and after the new version entered the market. The team also looked at data from needle and syringe programs (NSPs), as well as from a medically supervised injection center.

The research was funded in part by an unrestricted educational grant from Mundipharma Australia, but otherwise the company did not contribute to the study in any way.

Together, the three data sets painted a cohesive picture: People reported that they injected oxycodone less often than they had just months earlier. And, they did not seem to compensate by injecting more of either heroin or amphetamine, according to records from the NSP. Nonetheless, 18 percent of the NOMAD group said they had made an attempt at tampering within a month after the reformulated tablets were released, with 6 percent ultimately succeeding.

Using sales reports, the researchers also examined rates of oxycodone and overall opioid use at a population level, and neither of those changed. The number of opioid and other drug overdoses also did not change, nor did the degree to which opioid users sought out or received medical help. Still, there was a decline in the use of two higher-strength tablets. That stands out, says Schmidt, “because those would be the formulations that someone who would be interested in abusing the product would be most interested in.”

“As a strategy for reducing the attractiveness of oxycodone for tampering among high-risk populations, this formulation achieved what it was intended to do,” said Larance. “However, the vast majority of people exposed to opioids in Australia who are prescribed them don’t inject drugs, so we definitely need a range of other strategies in responding to the broader opioid problem.”

International implications?
To Schmidt, it’s unclear whether these outcomes will generalize beyond Australia. “Is this representative of what’s going to happen in the United States? Maybe not. Even within the United States, we have seen there are substantial differences in the abuse of opioids across selected population areas. For instance, compare Appalachia to California, or certain regions of the Midwest to New England.”

Larance agrees. “Australia has not experienced the same rapid escalation in opioid harms as observed in the US.” Moreover, “in Australia, it appears that among those tampering with oxycodone, most were doing so via injection. This is different from the situation in the US, where non-injecting routes of oxycodone tampering were more diverse.”

In support of such thinking, a 2017 report from the Institute for Clinical and Economic Review (ICER), a US nonprofit, independent research organization, reached a different set of conclusions upon evaluating tamper-resistant oxycodone in the US (see here). While the report found that the reformulated opioid lowered the risk of abuse for the individual patient, it also cited several studies showing that the drug’s introduction may have caused some people to turn to heroin or other pharmaceutical opioids.

Ultimately, any solution to the opioid crisis will involve more than hindering tampering, said Larance. For those taking pharmaceutical opioids as intended, the new formulations may do little in addressing issues such as overprescription and overuse, as well as heroin addiction. As a result, Larance advocates for strategies that will minimize unnecessary exposure to opioids, such as prescriber/patient education and prescription drug monitoring programs, as well as for more attractive and accessible treatments for opioid use disorders.

“We also need enhanced approaches to the management of pain and co-occurring mental health problems, especially in areas outside major cities,” she says.

Matthew Soleiman is a science writer residing in Nashville, Tennessee. Follow him on Twitter @MatthewSoleiman.