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Editor's Memo: Long-Acting Opioids: More Than a Labeling Issue

Early in September, the US Food and Drug Administration (FDA) announced class-wide safety labeling changes for all extended-release and long-acting (ER/LA) opioids. Prior to their announcement, indications for most opioids had been “moderate to severe pain” when “around the clock pain relief is needed.” The new label removes the word “moderate” and states that “ER/LA opioids are indicated 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.”

The updated FDA indication further clarifies that, “because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risks of overdose and death, these drugs should be reserved for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. ER/LA opioid analgesics are not indicated for as-needed pain relief.”

This is an excellent development and I salute and compliment FDA’s efforts. I believe this will appropriately modify physician behavior and establish the common sense belief that opioids should be the last-line and not the first-line of therapy for patients in pain. I have long used a checklist to help determine whether a patient should be given an opioid (Table 1), which may be of practical for readers to review this checklist.

Anecdotally, many physicians have admitted that their use of long-acting opioids in pain management has been on the decline recently. The cause for the decrease is multiple and includes the availability and aggressive use of new (last decade) anti-inflammatory, antidepressant, and neuropathic agents as well as electromagnetic measures, and hormone replacement. This is not to say, however, that there are never indications for long-acting opioids—there certainly are. However, I think pain management has become more nuanced in its approach and many clinicians now treat patients with a variety of medications, rather than rely on one specific class.

Brief History

Let’s briefly review the history of LA opioids. Prior to the mid-1990, the only LA opioid available was methadone. Very few practitioners used methadone for pain, and when used, it was almost always reserved as a last resort for intractable pain management. In the mid 90’s, extended-release formulations of fentanyl, oxycodone (OxyContin), and oxymorphone (Opana) were introduced. In many cases, these medications were promoted as better options than immediate release versions because they lasted longer and wouldn’t be prone to abuse like short-acting opioids. This notion was misguided from the start and, in some quarters, has continued to this day.

In my opinion, the problem with LA opioids relative to overdose deaths relates to acutely increased blood levels in someone who’s not tolerant to the sedative effect of opioids. When an LA opioid is taken intact it is released in the blood system over several hours, during which time a steady state of medication can be achieved. When crushed or injected, the release of the LA opioid is instantaneous, creating an immediate rush. In someone who is opioid naïve, a lethal dose may be only a small percent of what a chronic pain patient on high-dose opioids may be doing well on.

Let’s be frank. Long-acting opioids will always have a place in relieving the suffering and misery of some unfortunate intractable pain patients. There are still many good arguments for using LA opioids, including improved sleep, more even blood levels leading to less breakthrough pain, less clock-watching during the day, less central nervous system effects, etc. etc. But just as the new, welcome FDA label says, try to avoid LA opioids by first trying a lot of alternatives first.

Practical Pain Management has invited the authors of the PROP and PROMPT petitions to comment on the new FDA ruling. We also have asked our Editorial Board to weigh in on the topic.

Forest Tennant, MD, DrPH
Editor in Chief
Last updated on: November 21, 2013
First published on: October 1, 2013