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Abuse-Deterrent Formulations

Part of the Prescription Drug Abuse Solution But Not a Cure

Prescription drug abuse is a significant public health issue, with opioid analgesics playing a major role. According to the Centers for Disease Control and Prevention, of the 22,767 deaths related to pharmaceutical overdoses that occurred in 2013, 16,235 (71.3%) involved opioid analgesics. Of the 1.4 million Emergency Department visits in 2011 involving the nonmedical use of pharmaceuticals, 420,040 (30%) were related to opioid analgesics.

In response to this problem, pharmaceutical companies have been developing abuse-deterrent formulations of extended-release/long-acting (ER/LA) opioid pain relievers, starting in 2010 with Purdue Pharma’s reformulation of OxyContin. To discuss the effect of abuse-deterrent formulations on prescription drug abuse, Practical Pain Management talked with Lynn Webster, MD, Vice President of Scientific Affairs at PRA Health Sciences and Past President of the American Academy of Pain Medicine (AAPM).

Q: How do abuse-deterrent formulations work to deter people from abusing them?

Dr. Webster: An ER/LA opioid is intended to be released over 8 to 24 hours, but when it is crushed, the entire dose is available to be injected or for immediate absorption from the gastrointestinal (GI) tract if ingested. This makes it more attractive to an addicted person, but it also makes it more lethal. Abuse-deterrent formulations make it harder to inject, snort, or crush the drug, but they do not prevent a person from swallowing more of the intact medication than is intended.

The abuse-deterrent formulations on the market are designed in one of several ways. One technology makes it difficult for people to crush or dissolve opioid pills (such as OxyContin, Hysingla) to snort or inject the drug. Another technology uses an opioid antagonist (naloxone in the ER/LA opioid Targiniq and naltrexone in Embeda) that is released if the product is crushed, making the opioid ineffective if it is ingested, snorted, or injected.

When taken properly, the drug releases only the opioid in the capsule. However, when the capsule is crushed, the opioid antagonist is released, blocking some of the euphoric effects of the opioid and possibly causing withdrawal in people who are dependent on opioids. Table 1 reviews the available abuse-deterrent formulations.

Q: How big a role do abuse-deterrent formulations play in the overall effort to reduce prescription drug abuse?

Dr. Webster: Abuse-deterrent technology has the potential to prevent some users from abusing the medications and overdosing. But most abuse we see is with short-acting opioids, which are taken orally, not snorted or injected.

For this reason, abuse-deterrent technology may not have a major impact on the overall number of people who overdose or become addicted to opioid analgesics. However, it likely will prevent some deaths. It also is forcing nonmedical users to seek alternatives without abuse-deterrent features to get high.

A study from Brigham and Women’s Hospital analyzed medical claims data after the introduction of 2 reformulated ER opioids with abuse-deterrent technology.1 The authors found that a total of 31% to 50% of patients avoided switching to reformulated ER opioids; rates of diagnosed opioid abuse were higher among these patients compared to patients who transitioned to the reformulated ER opioids.1

Additional measures will be needed to help address the increases in the abuse of those alternatives.

Q: Is there evidence that these formulations are having the desired effect?

Dr. Webster: Yes. After OxyContin was reformulated into an abuse-deterrent formulation, there was a significant drop in the number of reported cases of people abusing it. There was a recent report in the New England Journal of Medicine that found that although the abuse and diversion of prescription opioid medications increased between 2002 and 2010, both appear to have plateaued or decreased between 2011 and 2013.2 The rate of opioid-related deaths rose and fell in a similar fashion.

Q: Do you think it should be mandatory that all ER/LA opioids have abuse-deterrent technology?

Dr. Webster: I think the FDA should set a time by which all ER/LA opioid drugs have a minimum level of abuse-deterrent technology—perhaps 5 years. After that time, formulations that are not abuse-deterrent should be removed from the market. A recent retrospective study found patients who initiated therapy with LA opioids were more than twice as likely to overdose compared with those initiating therapy with short-acting opioids.3 I would suggest that many of the deaths were due to the ease of manipulating the LA formulation to immediately release the drug. Of course, this is only speculative. But when ER/LA formulations are converted into an immediate-release delivery, the drug load can be lethal. That alone indicates the potential value of abuse-
deterrent formulations.

Q: Is there a downside to these formulations?

Dr. Webster: Even with abuse-deterrent features, these drugs are still opioids, and they have many side effects, including sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. In addition, some people may derive no benefit from opioids. Prescribers still have to look at the risk/benefit ratio of prescribing any opioid, even abuse-deterrent formulations. They are not safe drugs, but they may be safer with abuse-deterrent properties than without.

Q: Is the increased cost of these medications worth it?

Dr. Webster: To answer that, we have to weigh the cost of the drugs against the cost of not having them. Without abuse-deterrent formulations, there are increases in ER visits due to opioid-related toxicities, admissions to substance-abuse treatment centers for addiction, and costs of law enforcement to counteract abuse and diversion. These are real societal costs that can offset the increased costs of abuse-deterrent technology. Abuse-deterrent formulations may reduce costs in all of those areas, but more research is needed before we can say that definitively.

Q: What still needs to be done to make opioids safer from abuse?

Dr. Webster: Unless they are reformulated to deter abuse, opioids will be abused. They have rewarding properties that some people seek. As long as they are available, some people will find these drugs and abuse them, become addicted to them, and possible die from them. Abuse-deterrent technology will not prevent that from happening. Ultimately, we need to develop pain medicine with no rewarding properties—at least not within the dose range that provides most pain relief.

—Reported by Celia Vimont

Last updated on: April 16, 2015
First published on: April 1, 2015
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Abuse-Deterrent Guidelines Issued by FDA