Abuse-deterrent Opioids

From 2000 to 2015, more than half a million people in the U.S died from drug overdoses.[1] Most of these deaths were due to prescription opioid overdoses, which have more than quadrupled in the U.S. since 1999. This staggering increase prompted former President Barack Obama’s administration to declare an opioid abuse “epidemic.”[2]

Some of these prescription opioid overdose deaths were due to patients crushing, cutting, grinding or grating opioid pills and then inhaling, injecting, smoking or chewing the medications instead of swallowing them whole as prescribed.[3] Taking the pills in these non-prescribed ways increases the pleasurable sensation (the “high”) but simultaneously increases the risk of severe and often fatal side effects, including inhibiting or even stopping a person’s breathing.

Abuse-deterrent opioid products approved in the U.S.[16] (All are Limited Use)*

* For each active ingredient, different brand names may have different abuse-deterrent mechanisms.

Such routes of abuse prompted many drugmakers to attempt to formulate opioid pills that were supposedly resistant to such manipulation and, therefore, resistant to abuse by these methods. The first such opioid was approved by the Food and Drug Administration (FDA) in 2009,[4] and there are now 10 so-called abusedeterrent opioid products on the U.S. market (see table above).[5]

However, there are several problems with these new formulations. First, they do not prevent abuse by the common method of swallowing whole pills in excess of the prescribed dose. Second, they do not have to undergo adequate studies prior to approval to determine whether they actually prevent abuse. Third, there is evidence that some physicians incorrectly perceive abuse-deterrent opioids as less addictive, and therefore safer, than the evidence demonstrates them to be.

Abuse deterrence largely untested in practice

The idea behind abuse-deterrent opioids is laudable, as a substantial number of patients who misuse or abuse opioids do so by tampering with and snorting, injecting or chewing the drugs.[6] However, the FDA does not currently require drugmakers to investigate, prior to the drugs’ approval, whether abuse-deterrent opioids actually lead to lower rates of abuse and misuse.[7] Drugmakers just have to show that the drugs have certain chemical or physical properties that could potentially make it less likely that patients or others will tamper with, and abuse, the drugs.

Although the drugs are undoubtedly harder to abuse through tampering, a 2014 study of internet forums found users discussing 32 “feasible” ways of overcoming the abuse-deterrent properties of extended-release oxycodone (OXYCONTIN).[8] In 2016, Public Citizen testified against the approval of the abuse-deterrent opioid extended-release oxycodone and naltrexone (TROXYCA ER) because pre-approval studies showed that the pills could be easily manipulated for abuse.[9] Abuse-deterrent opioids also are just as addictive as their non-abuse-deterrent counterparts through the most common route of abuse: swallowing the pills whole, often at higher doses or more frequently than prescribed.

In the absence of rigorous studies looking at the effect of abusedeterrent formulations on rates of abuse, independent researchers have depended on poison control databases and surveys to determine abuse rates with new formulations. A 2017 study that reviewed these analyses of abuse-deterrent opioids found that abuse and overdose rates fell following the introduction of abuse-deterrent OXYCONTIN in 2010 but that this fall may have been accompanied by higher rates of abuse of heroin and non-abuse-deterrent opioids as well as abusers increasingly switching from non-oral to oral routes of abuse.[10]

A further concern is that the “abusedeterrent” label for the new formulations may make some physicians more likely to prescribe them. A survey of primary care physicians, published in 2016, revealed that nearly one-half of the physicians thought, incorrectly, that abuse-deterrent opioids were less addictive than other opioids.[11] In the same survey, just one-third knew that swallowing opioid pills intact was the most common method of abuse. It is likely that the pharmaceutical companies making abuse-deterrent opioids are aware of the false sense of reassurance that the drugs provide some physicians and are exploiting this to push previously reluctant doctors to prescribe the drugs to patients known to be at risk of abuse or misuse.

Safety issues with opioids

Opioid overdoses can cause people to stop breathing, leading to death. All opioids taken with certain antidepressants or migraine medications can cause a condition known as serotonin syndrome, with symptoms including hallucinations, rapid heart rate, fever and diarrhea.[12] In addition, opioids can lead to a rare but serious, potentially life-threatening condition in which the body does not produce enough cortisol, a hormone that helps the body respond to stress. The long-term use of opioids also can lead to reduced sex hormone levels, which can result in decreased sex drive, impotence or infertility. The simultaneous use of opioids and either alcohol[13] or another class of drugs known as benzodiazepines, such as diazepam (VALIUM), can significantly increase the risk of serious side effects, including trouble breathing and death.[14]

What You Can Do

If you need to take an opioid for severe pain, you can use an abusedeterrent formulation, but remember that these drugs are just as addictive and dangerous as non-abusedeterrent opioids if taken orally, even at the prescribed doses. Always take opioids at the lowest dose for the shortest time needed to achieve adequate relief. Also ask your doctor to prescribe a short-acting opioid whenever feasible.

Opioids have not been proven to be a safe and effective treatment for chronic non-cancer pain.[15] In fact, there is substantial evidence that the risks of opioids for chronic noncancer pain outweigh the benefits. Therefore, you should limit use of opioids to no more than 90 days. If you need pain management beyond 90 days and have non-cancer pain, discuss non-opioid options with your doctor and consider consulting a pain management specialist for nonpharmacologic options as well.

When you or a loved one starts taking an opioid, be alert for early signs of an overdose or other severe adverse events, especially during the first few weeks. If a loved one experiences signs of an overdose, seek emergency medical care immediately.

References

[1] Centers for Disease Control and Prevention. Opioid basics: Understanding the epidemic. https://www.cdc.gov/drugoverdose/epidemic/. Accessed July 7, 2017.

[2] The White House. FACT SHEET: President Obama proposes $1.1 billion in new funding to address the prescription opioid abuse and heroin use epidemic. February 2, 2016. https://www.whitehouse.gov/the-press-office/2016/02/02/president-obama-proposes-11-billion-new-funding-address-prescription. Accessed July 7, 2017.

[3] Food and Drug Administration. Abuse-deterrent opioids — evaluation and labeling: Guidance for industry. April 2015. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Accessed July 7, 2017.

[4] Food and Drug Administration. Approval letter for EMBEDA. August 13, 2009. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/022321s000ltr.pdf. Accessed July 7, 2017.

[5] Food and Drug Administration. FDA facts: Abuse-deterrent opioid medications. Last updated April 21, 2017. https://www.fda.gov/newsevents/newsroom/factsheets/ucm514939.htm. Accessed July 7, 2017.

[6] Vietri J, Joshi AV, Barsdorf AI, Mardekian J. Prescription opioid abuse and tampering in the United States: results of a self-report survey. Pain Med. 2014;15(12):2064-2074.

[7] Food and Drug Administration. Abuse-deterrent opioids — evaluation and labeling: Guidance for industry. April 2015. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Accessed July 7, 2017.

[8] McNaughton EC, Coplan PM, Black RA, et al. Monitoring of internet forums to evaluate reactions to the introduction of reformulated OxyContin to deter abuse. J Med Internet Res. 2014;16(5):e119.

[9] Public Citizen. Testimony before the FDA’s Drug Safety and Risk Management Committee and Anesthetic and Analgesic Drug Products Advisory Committee regarding ALO-02 (Oxycodone/Naltrexone). June 8, 2016. http://www.citizen.org/hrg2326. Accessed July 7, 2017.

[10] Institute for Clinical and Economic Review. Abuse deterrent formulations of opioids: Effectiveness and value. Evidence report. June 28, 2017. https://icer-review.org/wp-content/uploads/2016/08/NECEPAC_ADF_Evidence_Report_062817.pdf. Accessed July 7, 2017.

[11] Hwang CS, Turner LW, Kruszewski SP, et al. Primary care physicians' knowledge and attitudes regarding prescription opioid abuse and diversion. Clin J Pain. 2016;32(4):279-284.

[12] Food and Drug Administration. Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. March 22, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm489676.htmhttp://www.fda.gov/Drugs/DrugSafety/ucm489676.htm. Accessed July 7, 2017.

[13] Purdue Pharma L.P. Label: OXYCONTIN (oxycodone). December 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bfdfe235-d717-4855-a3c8-a13d26dadede. Accessed July 7, 2017.

[14] Food and Drug Administration. Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. August 31, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm. Accessed July 7, 2017.

[15] Physicians for Responsible Opioid Prescribing. Petition to the Food and Drug Administration requesting changes to opioid drug product labeling. July 25, 2012. http://www.citizen.org/documents/2048.pdf. Accessed July 7, 2017.

[16] Food and Drug Administration. FDA facts: Abuse-deterrent opioid medications. April 21, 2017. https://www.fda.gov/newsevents/newsroom/factsheets/ucm514939.htm. Accessed July 7, 2017.