It's Time to Harden All Extended-release and Long-acting Opioids

In previous editorials, I addressed Risk Evaluation and Mitigation Strategies (REMS) for the use of opioids, the decision by the US Food and Drug Administration (FDA) to bar generic OxyContin from the US market, and the Physicians for Responsible Opioid Prescribing (PROP) proposal for absolute time and dosage limits on opioids for chronic non-cancer pain.

Now, I think it is time to get tough and propose that all extended-release (ER)/long-acting (LA) formulations of opioids be required to be “hardened” to resist the usual forms of manipulation and tampering used for abuse. A first step in this direction came earlier this year when the FDA released “Guidance for Industry” recommendations that informed manufacturers of the studies that should be done to demonstrate abuse-deterrent properties in a given formulation, and the steps they had to take for their medications to be recognized as abuse-resistant/deterrent.

If physicians want to continue to have the option to prescribe ER/LA opioids for patients with chronic noncancer pain, we must have products that will resist the usual forms of abuse. There’s nothing currently available to stop someone from taking more tablets or wearing more patches than are lawfully prescribed. Nothing can be done to truly stop people bent on self-destruction, but we can make the subclass of ER/LA medications “harder” to abuse by employing several effective strategies.

The broader question will be the problem of what to do with short-acting opioid medications. What can be done to “harden” them and yet make them immediately available? The point of short-acting opioid medications is to be immediately biologically available for breakthrough pain. Sadly, many patients take more milligrams per day of their breakthrough medications than they take of their ER/LA medications. This represents a failure to stabilize on ER or LA medications, and leads to an unstable and unsafe situation in which patients have wildly varying blood levels of medication.

We definitely need more prescriber education. Many of the people who read articles on this website already know how to prescribe ER/LA opioids as the foundation for managing chronic noncancer pain, and then limit the use of breakthrough immediate-release medications to only one or two doses daily. They know to increase the basal ER/LA dosage to keep the use of immediate-release medication to a minimum. However, many pain specialists and most primary care physicians lock in an arbitrary ER/LA “base” and then allow patients to take an additional 6, 8, or even 10 tablets or capsules of immediate-release medication daily. From my experience, even if told their immediate-release medication is only for breakthrough pain, most patients take as much medication as they are permitted to take. That means that the prescriber must set hard limits, and not tolerate “wandering” doses of immediate-release medication.

Although Purdue Pharma Canada has developed OxyNEO, a tamper-resistant form of OxyContin for sale in Canada, Health Canada (the Canadian government department responsible for national public health) in November 2012 approved the sale of non-hardened generic forms of OxyContin.

In an April 27, 2013, editorial in The Toronto Sun, Mark Bonokoski declared that Health Canada is “playing with fire” and that allowing generic OxyContin on the market is “too dangerous a risk.” He wrote that “There is no upside for allowing it” and sarcastically questioned if Health Canada’s intent was to “enhance the bottom line of generic drug manufacturers who had been salivating for Purdue Pharma’s patent to expire, to give organized crime another branch of illicit business to pursue, or to cripple more of the public with addictions.” This move is puzzling, especially when one considers that original OxyContin was removed from the market in the US due to concerns about safety and efficacy.

Emotion aside, why do we need ER/LA medications that can be defeated by crushing, chewing, snorting, and injecting intravenously? Why don’t we demand a level playing field in which all ER/LA are “hardened?” So what if the new OxyContin becomes heroin again? People wanting to abuse opioids will always have heroin and many different immediate-release medications. Let’s work toward a reality in which only abuse-resistant/deterrent medications are used for our patients taking ER/LA medications. If hardening medication and prescriber REMS education don’t help to reduce the number of people dying from overdose, we can then consider the PROP proposal to place upper limits on daily doses and time limits on duration of opioid therapy for patients living with chronic non-cancer pain. Government action usually moves through incremental steps; before taking drastic action, we should try common-sense approaches to solve the problem of opioid abuse.

What do you think? Please let me know.

B. Eliot Cole, MD, MPA, is a member of the Pain Management editorial advisory board. He has served in executive positions for several prominent pain management organizations and societies, including the American Society of Pain Educators and the American Academy of Pain Management. He has been a pain management fellow, clinician, educator, and advocate for nearly 30 years and has practiced in a variety of settings serving a wide range of patients.