Select Facts You Need to Know

Many news stories about opioids conflate oxycodone and OxyContin. Oxycodone is the active ingredient contained in different opioid analgesic formulations, while OxyContin is a brand name for an extended-release form of oxycodone, representing a small percentage of the total oxycodone market and only 1.3% of the total prescriptions for opioid pain medications.¹⁸ When reading about oxycodone, it is important to understand whether the author is referring to OxyContin, which makes up a small fraction of the market, or oxycodone, the active ingredient present in a number of formulations.

The FDA’s New Drug Application (NDA) for OxyContin was approved based on 24 total studies – six well-controlled clinical studies, four additional clinical studies, and 14 pharmacokinetic studies, involving more than 700 patients.¹⁹ The FDA-approved OxyContin labeling has always explicitly warned about the risks of abuse and misuse.

OxyContin Label Warnings Over Time

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The contents shown have been excerpted from full FDA prescribing information at that time. Highlighting has been added for emphasis.

Scientific evidence amassed over more than 20 years as well as extensive clinical trials supports the FDA’s approval of 12-hour dosing for OxyContin. The OxyContin label has been updated more than 30 times and at no point did the FDA request a change to the dosing frequency. In fact, the FDA-approved label clearly states, “There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours.” Nearly a decade ago, the FDA cited a lack of clinical evidence when it formally rejected the premise that patients receiving OxyContin at intervals more frequent than twice-daily are at increased risk of “side effects and serious adverse reactions.”²⁰ In doing so, the agency reinforced the twice-daily labeling for OxyContin.

To address overprescribing of prescription opioids, many healthcare entities and state governments have imposed restrictions on opioid prescribing. Some of these restrictions, however, risk creating unintended consequences for pain patients that require attention. Several studies suggest that forced tapering of opioid pain medication leaves many legitimate patients in perpetual pain; this severe withdrawal can even lead to suicide and increased risk for heart attacks and strokes.^21,22 Almost 18 million patients rely on prescription opioids to treat long-term, severe pain,²³ and they should not be forgotten as we work together to prevent abuse and addiction.

The FDA has approved extended-release, long-acting opioids for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. ²⁴

Some people have claimed that opioid manufacturers have “misled” prescribers into underestimating the risks of prescription opioids. Oxycodone, the active ingredient in OxyContin, has always been a Schedule II controlled substance. Only healthcare providers licensed to practice medicine, and who are registered with the Drug Enforcement Administration (DEA), are authorized to prescribe controlled substances including opioid analgesics. In addition to obtaining a DEA registration, physicians must also adhere to their state’s prescribing requirements.

The FDA continues to support the use of prescription opioids for the management of pain severe enough to require long-term opioid treatment and for which alternative treatment options are inadequate. The CDC also supports the use of opioid therapy if a healthcare provider determines that expected benefits for both pain and function are anticipated to outweigh risks.^25,26 The American Medical Association approved a resolution recognizing that for some patients opioid medications are medically necessary and appropriate.^27,28 The Pain Management Best Practices Inter-Agency Task Force, created by Congress in 2016, has issued a draft report that also recognizes that opioids are the appropriate option for some patients.²⁹

_{Centers for Disease Control. Drug Overdose Deaths in the United States, 1999-2017. Accessed April 30, 2019 (link)}

While every overdose death is a tragedy, as of 2018, most overdose deaths in the US involve illegal opioids ³⁰ primarily sourced from China and Mexico. ³¹ According to the Centers for Disease Control and Prevention (CDC),³² the top five drugs involved in US overdose deaths in 2016 were fentanyl and heroin, followed by cocaine, methamphetamine, and alprazolam. While the percentage of overdose deaths involving oxycodone decreased from 13.5% in 2011 to 9.7% in 2016, the percentage of deaths involving fentanyl and heroin increased during that time from 4% to 28.8% and 11.1% to 25%, respectively. Together, fentanyl and heroin are now involved in over 53% of drug overdose deaths.³³

Between 2012 and 2017, the overall national opioid prescribing rate declined by 25% to the lowest rate in more than 10 years.³⁴ The available data also indicate that opioid prescribing rates have decreased in every state. Unfortunately, opioid-related deaths have increased during this same period, driven by illegal opioids such as heroin and illicit fentanyl.³⁵ These data points underscore that prescription opioid manufacturers alone cannot end the opioid crisis, and that any meaningful solution must involve input and expertise from a variety of stakeholders, including manufacturers, insurers, distributers, academia, regulators, legislators, healthcare providers, and law enforcement agencies.

Although a single case of addiction is one too many, those who imply that these medicines are not safe and effective for patients when used as prescribed are mistaken. However, even when used as prescribed, there is a risk of addiction, which may lead to overdose and death.

Research from leading medical practitioners suggests that addiction is not a predictable result of opioid prescribing. A research article published in the New England Journal of Medicine suggests that many different factors – such as genetic vulnerabilities and demographics – contribute to the likelihood of addiction. In addition, existing literature has not reached a consensus on the highly complex issue of determining how biological predisposition to addiction – as well as non-medical use and abuse of prescription opioids – affects substance abuse. Although prescription opioids indisputably carry risk for physical dependence, abuse, and addiction, oversimplifying this topic is detrimental to both understanding and addressing this multifaceted medical and societal issue.

In 2010, Purdue received FDA approval for reformulated OxyContin after spending nearly a decade and hundreds of millions of dollars on its development. In 2013, based on laboratory and clinical data, the FDA granted OxyContin the first-ever label stating that the medication has abuse-deterrent properties that are expected to make it more difficult to abuse via injection and snorting. However, abuse by injection, intranasal and oral route is still possible, and all opioids, including those with FDA-recognized abuse-deterrent properties, carry risks of addiction, abuse, and misuse, which can lead to overdose and death. Today, the FDA continues to encourage the development of opioid pain medications that are harder to manipulate and abuse.³⁶

One recent study published in Science suggests that the “epidemic of drug overdoses in the United States has been inexorably tracking along an exponential growth curve since at least 1979, well before the surge in opioid prescribing in the mid-1990s.”³⁷ Opioid abuse is a subset of drug abuse in the United States,³⁸ and the opioid addiction crisis is a complex societal problem that involves a number of different stakeholders, including manufacturers, prescribers, distributors, pharmacies, insurance companies, and governments at all levels. Because this crisis touches so many different stakeholders, any efforts to meaningfully advance solutions must involve the input and expertise of everyone involved, including academia, regulators, legislators, healthcare providers and law enforcement agencies.