The Food and Drug Administration is overhauling the safety labeling requirements for opioid analgesics, citing new evidence that problematic use and overdose are associated with taking the medications as a maintenance regimen. The FDA announced the mandate July 31, and manufacturers are expected to update their labeling and submit the new versions for review by August 30.
“Tragically, the new drug application for OxyContin was initially approved without study data supporting its long term use to treat pain in many patient populations for which it has been prescribed,” the FDA stated in a press release. “The updated labeling change reflects … new data on how long-term opioid use can lead to serious side effects.”
The new requirements have been on the horizon since May, when the FDA held a public advisory meeting to discuss the results of two postmarket review studies that catalyzed the decision. The studies defined long-term use as anything over 70 days out of a 90-day period.
Among a number of other updates, the new safety labeling for extended-release/long-acting opioids will bear the following:
“The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use.”
In the nearly two decades since the United States began its crackdown on opioid prescribing, the prevailing narrative around the overdose crisis become one where the blame lies entirely with pharmaceutical companies. Pain patients with opioid prescriptions are not a high-risk population for overdose, and limiting their access to their medications increases harm without making any dent in the overdose crisis or reducing rates of opioid use disorder. Villainizing OxyContin has come at a much higher cost to pain patients than it has to Purdue Pharma or the Sacklers.
Opioids are extremely effective medications for managing pain, and are a lifeline to many chronic pain patients who need them for day-to-day functioning. But the health care industry has long favored the myth that opioid analgesics are only advisable for short-term treatment, not ongoing maintenance. Long-term maintenance on medications for opioid use disorder is viewed the same way, as methadone and buprenorphine are FDA-approved for both OUD and pain.
What the labeling will not bear going forward is any reference to an “extended treatment period,” which the FDA has instructed pharmaceutical companies to remove in order “to avoid misinterpretation that there are data to support safety and efficacy of opioid analgesics over an indefinitely long duration.”
It’s true that there’s very little clinical evidence supporting prescription opioid use for chronic pain management. However, very little research has been conducted. The idea that opioid analgesics aren’t suitable for long-term maintenance comes from a body of evidence that mostly shows that short-term use is effective, rather than that long-term use is harmful.
In its longer guidance document accompanying the announcement, the FDA instructs providers to “[r]egularly re-evaluate” opioid prescriptions for any patient who’s been taking them for “more than a few days,” as well as “frequently assess for development of addiction, abuse or misuse.” The agency has also commissioned a new clinical trial to assess the merits of long-term use.
The labeling changes have also provided a slightly ironic opportunity for Big Pharma to further a separate agenda.
Providers are often unwilling to work with patients who need opioids analgesics to manage chronic conditions rather than short-term pain relief after a surgery or accident. In addition to any pre-existing bias, they’re conscious that they might be accused of inappropriate prescribing if they have too many pain patients who have—in the Drug Enforcement Administration’s view at least—been taking opioid analgesics for too long.
Prescriptions for various controlled substances, but mainly opioids, are tracked through state-level databases called prescription drug monitoring programs (PDMP). In many cases, before prescribing an opioid providers are required to screen the patient’s history for any activity that the DEA deems suspicious. Pharmacists are responsible for vetting incoming prescriptions the same way. In some states, local law enforcement can access PDMP data without a warrant.
PDMP algorithms are proprietary and the specific “red flags” that can trigger a DEA investigation are withheld from the public, but it’s widely understood that they include activity such as writing higher-dose prescriptions.
The labeling changes have also provided a slightly ironic opportunity for Big Pharma to further a separate agenda, in which references to “naloxone” are quietly replaced with references to “opioid overdose reversal agents like naloxone and nalmefene.”
Nalmefene, a longer-acting opioid antagonist compared to the better-known naloxone—which continues to reverse overdose from fentanyl and other opioids just fine, regardless of law enforcement misinformation—can put people at increased risk of overdose if they have a physical tolerance to opioids. The nalmefene-inclusive language has been increasingly appearing in every kind of overdose-response document from state legislation to school board policies since Indivior got FDA approval for the first nalmefene-based opioid overdose antidote product in late 2023.
The other pharma company that’s gotten a nalmefene antidote approved since then is Purdue.
Image (cropped) via Georgia Department of Public Health