New opioid labeling restricts the type of patient who should be prescribed long-acting/extended release formulations.
The Food and Drug Administration recently announced labeling changes for the extended release/long-acting (ER/LA) opioid analgesics with the announced goal of combating, in the words of the FDA commissioner, "the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs."1
The current labeling states that these drugs are for "the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time."
The new labeling, which will be required by the end of the year, will state that the drugs 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" and that "because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulation, reserve [drug tradename] for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain."2
What does the new labeling mean to the clinicians who currently prescribe or are considering prescribing these drugs? Probably not very much if you are already prescribing them according to the current clinical guidelines that address their use. As both the old and new labels state, these drugs are for those who require around-the-clock opioids because of pain that is expected to be present for an extended period of time and that is relatively constant throughout the day.
The major change is that the new labeling says they are only meant for severe and not moderate pain. The problem with this is, of course, that we are left with how to differentiate between these two. Even the FDA commissioner acknowledged in her accompanying statement that "We know that the way a patient characterizes pain is always going to be subjective: 'moderate' pain for one patient may be "severe' pain to another."3
As far as determining that other treatment options are "inadequate," the new labeling doesn't appear to provide any guidance for how this is to be decided. It doesn't specify whether these other options have to be tried or for how long before ER/LA opioids are prescribed.
The FDA states that "the new labeling language emphasizes that patients in pain should be assessed not only by their rating on a pain intensity scale, but also based on a more thoughtful determination that their pain-however it may be defined-is severe enough to require daily around-the-clock, long-term opioid treatment” and that "it allows prescribers to make an assessment of pain relative to a patient's ability to perform daily activities or enjoy a reasonable quality of life."2
I certainly agree that when prescribing opioid analgesics or, for that matter, any other medication or non-pharmacologic treatment for chronic pain, that the focus should be on the impact on the patient's ability to function and not on pain level. However, this is something that any clinician treating chronic pain should already know.
It is interesting that the new labeling is only for the ER/LA opioids. Studies have shown that it is the immediate release/short-acting (IR/SA) opioids that are the most abused and are associated with more deaths from overdose than are the ER/LA opioids. In fact, now that several of the ER/LA opioids, most notably this form of oxycodone (OxyContin), are only available in tamper-resistant formulations that make it difficult to subvert the systems that delay the release of these drugs in the body, the risk of overdose is probably not very different from that associated with the IR/SA forms. Nor is there anything to indicate that the ER/LA opioids are more addictive than the IR/SA ones.
Along with the labeling change, the FDA also announced that it is going to require drug companies to conduct longer-term studies of these drugs. There is a dearth of studies on the long-term benefits and adverse events associated with their use. The same is true, however, for virtually every other medication we use for the management of chronic pain.
We have very few studies on any drugs that have lasted for more than a few months. Many patients take these medications for much longer periods of time, so it would obviously be helpful, to say the least, to know whether or not they are benefitting from these drugs and when they are doing so.
I have no problem with the new labeling, although I must admit that I doubt it will have the impact on the problems associated with the use of LA/ER opioids that the FDA intends. Yes, prescription opioid abuse and addiction are major problems that need to be addressed. But, to my mind, the change in labeling is a bit like rearranging the deck chairs on the Titanic; it gives the appearance of trying to do something about the problem while not really having much of an effect on it. I hope I am wrong and that the label change will result in all physicians who prescribe ER/LA opioids adhering to the published guidelines on their use, but I doubt it.
There are clinicians who are aware that they are prescribing these agents to patients who falsify complaints to receive them or to exchange the prescriptions for money or other compensation. For this group of clinicians, the problem is a law enforcement one and it is doubtful that they would care about revised labeling. For the rest of the prescribers it is reasonable to assume that they are doing so because they believe these drugs are indicated and that they are prescribing them correctly.
Obviously, the FDA doesn't wish to deny these drugs to those patients who could benefit from them. Unfortunately, however, some clinicians and patients may interpret the action this way. One of the major groups that pushed for the labeling change, Physicians for Responsible Opioid Prescribing, focused on the misuse of these drugs with limited attention to their efficacy and essentially no attention to how they fit into the hierarchy of medication management of pain. Similarly, in its statements on the new labeling, the FDA focused primarily on the risks associated with the use of these drugs.
Patients who request ER/LA opioids thinking that they are more effective than other drugs for all pain conditions and are denied them by clinicians may interpret this as punishment for the misuse of these drugs by others. Unfortunately, many physicians may not take the time and effort to explain the relative efficacies of the various treatment options, especially to patients who believe that they need opioids, leaving these patients with the impression that abuse potential is the paramount issue at hand.
I firmly believe that the only thing that will really make a change for the better in the way pain is treated in this country is to improve physician education on pain management. This will require far more than the Risk Evaluation and Mitigation Strategy, or REMS, programs that all the manufacturers of the ER/LA opioids are now required to offer-participation in which, by the way, is voluntary on the part of physicians.
Changing labeling doesn't address the more systemic problem that many physicians have received limited education not only on the use of the ER/LA opioids but also on IR/SA opioids and non-opioid analgesics, including the anti-epileptics and serotonin-norepinephrine reuptake inhibitor antidepressants, which are the most effective agents for many forms of pain, as well as on non-pharmacologic treatments.
1. US Food and Drug Administration. “FDA announces safety labeling changes and postmarket study requirements for extended-release and long-acting opioid analgesics: New boxed warning to include neonatal opioid withdrawal syndrome.” US Food and Drug Administration press release, Sept 10, 2013. FDA Web site. Accessed 9/11/13.
2. US Food and Drug Administration. Goal of labeling changes: better prescribing, safer use of opioids. For Consumers; FDA Web site. Accessed September 11, 2013.
3. Hamburg MA. Crafting better drug labeling to ensure safer use of opioids. FDA Voice. Sept 10, 2013. Accessed 9/11/13