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Can the U.S. Win the War On Opioids?

Remember the “War on Drugs”? This may conjure images of Mexican drug lords, packages of smuggled cocaine, or clandestine DEA agents. But now we all know that the real bandit is found right in our own home — in our bathroom medicine cabinets.

According to the Centers for Disease Control (CDC), 44 people in the United States die from an overdose of prescription opioid painkillers each day. Grandmothers, small children, someone’s son. Lost not because they went outside of the boundaries to use illicit drugs, but because they were caught inside a web of prescription drug addiction, accidental overdose, or suicide with a pain medication that was dispensed to someone with a valid, legal prescription.

Yes, we are all to blame: healthcare providers, policy makers, and patients.

Here are some sobering U.S. statistics:

• More people now die from prescription painkillers than from car accidents.
• In 2014, opioid addiction resulted in 18,893 overdose deaths.
• In 2011, hydrocodone combination painkillers were involved in almost 100,000 abuse-related emergency department visits, more than double the number in 2004.
• In 2010, 20 percent of patients received an opioid for complaints of pain at the doctor’s office.
• Since 1999, the amount of prescription painkillers prescribed and sold in the U.S. has nearly quadrupled.

Abuse-Deterrent Formulations

The answers aren’t easy, but there are many measures being put in place to address prescription opioid overprescribing, diversion, and addiction while still ensuring adequate pain coverage for those who really need it.

Novel ‘abuse-deterrent’ formulations of hydrocodone, morphine and oxycodone, are increasingly becoming available on the U.S. market. These formulations were developed as one method to fight back at the opioid abuse epidemic in the U.S.

Examples include:
Oxycontin (oxycodone [reformulated])
Embeda (morphine/naltrexone)
Hysingla ER (hydrocodone)
Targiniq ER (oxycodone/naltrexone)
Zohydro ER (hydrocodone)

But what exactly constitutes an ‘abuse-deterrent’ drug? ‘Abuse-deterrent’ means that the medication has been developed in line with FDA guidelines to exhibit properties that can lower, but not totally eliminate, the ability to abuse of the formulation. Chewing, crushing, snorting, or injecting are some of the more common ways these opioids are abused. Mechanisms that are being built into abuse-deterrent formulations to prevent these actions include:

• Prodrug: Lacks opioid activity until transformed in the gastrointestinal tract
• Built-in opioid antagonist reversal agents (such as naloxone) that release upon crushing
• Tablets less amenable to crushing or dissolving
• Sustained-release depot injectable
• Gelling upon dissolution that makes hypodermic needle injection difficult
• Burning or irritation when crushed and snorted

By incorporating abuse-deterrent technology into dosage forms of commonly abused opioids, the immediate and intense high that can be achieved by unintended routes can be prevented.

Initial studies outlined in the package labeling have shown that these drugs can decrease ‘drug-liking’ and the desire to take the drug again; however, the FDA has mandated postmarketing studies, as well. The most common way that drugs are abused — simply by swallowing a handful of them — can’t be stopped.

Just how well are abuse-deterrent dosage forms working? Studies with Oxycontin show a 32 percent reduction in the rate of reported abuse at poison control centers, a 50 percent reduction in Oxycontin diversion, and a 66 percent decline in non-oral abuse. Some research suggests a link between elevated heroin abuse and overdoses occurring as users seek out alternatives due to lower availability of prescription opioids. However, a January 2016 review article in JAMA Internal Medicine suggests otherwise. Postmarketing studies of other products are forthcoming. But abuse-deterrent forms can’t work by themselves.

Hydrocodone Reschedule

In October 2014, the DEA changed hydrocodone from a schedule III to a schedule II controlled substance in an effort to combat overprescribing. In doing so, refills are now restricted unless the patient has a newly written prescription. Although hydrocodone prescriptions had already dropped by 8.4 percent in the three years prior the the reschedule, in the year after rescheduling, the number of prescription dropped dramatically by 22 percent, equal to 26 million fewer prescriptions and 1.1 billion fewer dispensed tablets.

What Else Can Be Done?

Winning the war on prescription opioid abuse and fatalities requires a multi-pronged approach:

• Health insurance plans should aim to cover at least one abuse-deterrent pain formulation for members who require chronic pain management, such as severe cancer pain, preferably without prior authorization or stepped treatment and on lower tiers to ensure access and affordability. Legislation on this topic is ongoing in many states.
• New abuse-deterrent formulations are single-source with no generic equivalents. By ensuring formulary coverage and an affordable tier, physicians will not have to default to immediate-release (and abusable) opioids for chronic pain where a longer-acting, abuse-deterrent opioid is appropriate.
• Healthcare providers – including physicians, pharmacists, and nurses – need to work together to develop and adopt evidence-based pain guidelines that include abuse-deterrent forms. Use of acetaminophen, NSAIDs, physical therapy and exercise, antidepressants and anticonvulsants for neuropathic (nerve) pain. Safe and effective non-opioid pain alternatives in the elderly should be addressed. Pain treatment guidelines should be incorporated within clinical decision support systems.
• Patients should be questioned at the point-of-care about the potential for drug diversion within their own households. Patients should be encouraged to safeguard prescription opioids at home to prevent diversion and abuse by teens, their friends, or other household members. Education should be provided on safe disposal of unused pain medications (for example, at the next DEA National Prescription Take Back Day or with safe disposal at their home, as outlined in FDA guidelines.)
• Increased availability and education on easy-to-use forms of naloxone, such as the auto-injector (Evzio) or nasally administered forms (Narcan Nasal), for all emergency personnel as well as consumers who have known overdose issues within their families and homes.
• New or enhanced development of specific and targeted drug abuse prevention campaigns in US middle schools, high schools, and colleges.
• Facilitate treatment instead of incarceration for nonviolent, individual drug abusers.

Guidelines and Patient Engagement

In February 2016, the FDA called for a “far-reaching” action plan to reassess their approach to opioid medications. The goal is to focus on ways to reverse the epidemic while maintaining access to adequate pain relief for patients who require it.

The CDC has released a new guideline: Guideline for Prescribing Opioids for Chronic Pain, 2016. CDC developed the opioid guideline to provide recommendations about prescribing for primary care providers who are treating adult patients with chronic pain in outpatient settings, outside of active cancer treatment. The guideline also identifies important gaps in the literature where further research is needed.

The CDC has also launched a consumer campaign to listen to those whose lives have been affected by painkiller addiction or death of a loved one. Via social media, the CDC aims to engage those in need of treatment, those working to change their lives, or those taking charge to inspire their communities to have a deeper impact on the way we — that is, healthcare providers, policy makers, and patients — think about and treat pain.

Leigh Anderson, PharmD

Sources:

Jones CM, Lurie PG, Throckmorton DC. Effect of US Drug Enforcement Administration’s Rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing. JAMA Intern Med. Published online January 25, 2016. Accessed February 2, 2016 at http://archinte.jamanetwork.com/article.aspx?articleid=2484293.

Compton W, Jones C, Baldwin G. Relationship Between Nonmedical Prescription-Opioid Use and Heroin Use. N Engl J Med 2016;374:154-163. DOI: 10.1056/NEJMra1508490. Accessed February 2, 2016 at http://www.nejm.org/doi/full/10.1056/NEJMra1508490.

The Medical Letter on Drugs and Therapeutics. Abuse-Deterrent Opioid Formulations. Issue 1476, August 31, 2015.

Centers for Disease Control and Prevention. Social Media. When the Prescription Becomes the Problem: Resources. Updated August 18, 2015. Accessed February 1, 2016 at http://www.cdc.gov/drugoverdose/media/index.html

Duffy S. One Year Later: The Impact of Hydrocodone Combination Product Rescheduling. EMPR Online. January 28, 2016. Accessed February 1, 2016 at http://www.empr.com/news/one-year-later-the-impact-of-hydrocodone-combination-product-rescheduling/article/469189/

Regulations.gov. Federal Register Notice: Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain. Posted December 14, 2015. (docket # CDC-2015-0112)

FDA. Abuse-deterrent Opioids: Evaluation and Labeling. Guidance for Industry. April 2015. Accessed February 2, 2016 at http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm334743.pdf

Posted February 2016