FDA advisors will meet Tuesday and Wednesday to address high doses of opioids in outpatient settings, suggesting that the agency believes dosing strengths of approved products represent a lever it can use to discourage overprescribing.
On Tuesday and Wednesday, members of the FDA’s Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesia Drug Products Advisory Committee will meet to hear from experts and the public about the clinical utility and safety concerns associated with outpatients who use higher ranges of opioid doses, both higher dosage strength products and higher daily doses.
After more than a dozen presentations by clinicians, patients, and experts, the advisory committee will discuss:
- The role of higher daily doses and higher dosage strength products in pain management
- The risks of misuse, abuse, addiction, and overdose attributable to higher doses and higher dosage strength products versus lower doses and products
- Potential effects if the FDA were to take regulatory action to reduce prescribing and use of higher dosage strength opioids
- Whether there’s value in the FDA taking new regulatory actions to reduce prescribing and use of higher dosage strength opioids
The FDA increasingly is moving toward a systems-based approach to assessing potential regulatory actions that may help address the opioid crisis, noted Judy Staffa, PhD, RPh, associate director for the Public Health Initiatives Office of Surveillance and Epidemiology at the FDA’s Center for Drug Evaluation and Research (CDER), in an overview published before the meeting. “This means considering the decisions and behaviors of multiple stakeholders: healthcare providers, patients, communities, insurers and others,” she wrote. “It also means fully evaluating the interrelated set of factors that can affect opioid analgesic use, and impact opioid misuse, abuse, addiction, overdose and death.”
The agency frequently hears from patients and providers that higher-dose opioid analgesics are necessary to manage pain for some patients, but also is aware of increasing public concern about the risks these products pose to patients and others in the community, Staffa observed. “There is a strong need to bring together the community of stakeholders to consider the collective scientific understanding of the issues relating to higher daily doses and higher dosage strength opioid analgesic products and potential strategies to reduce risks to patient and public health,” she noted.
Opioid products present unique risks and benefits, but risks associated with inadequate pain management also must be addressed, Ning Hu, MD, medical officer of CDER’s Division of Anesthesia, Analgesia, and Addiction Products, pointed out in a memo included in the FDA briefing materials.
Nearly 12% of Veterans Health Administration patients whose clinicians discontinued long-term opioids for chronic pain had documented suicidal ideation and suicidal self-directed violence within a year, she observed. Rapid, forced opioid tapering can destabilize chronic pain patients, precipitating severe opioid withdrawal with worsening pain and profound loss of function, and some patients may seek relief from illicit drugs, she added.
“In support of the idea that there should be absolute limits on the total daily dose of opioid analgesics, many have inappropriately turned to the CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016,” Hu wrote. “However, the guidelines were misinterpreted and misapplied, contributing to substantial harms to patients, particularly patients with chronic pain who were forced to taper their previously stable opioid doses to lower doses, or who were forced to discontinue their opioids through forced tapers or patient abandonment.”
The FDA briefing materials also included a review from the agency’s Division of Epidemiology, which concluded that while claims-based studies suggest an association between higher prescribed daily opioid doses and increased risks of abuse and addiction, it “remains unclear whether the higher dose plays a causal role in the development of opioid addiction.” The reviewers also noted that epidemiologic evidence suggests a higher daily opioid dose likely contributes causally to increased overdose risk, but is only one of several factors.
The FDA has established a docket for public comment on this meeting, which will be open until June 30. To date, about 1,000 comments have been registered.
The agency will not issue a final determination until input from the advisory committee process has been considered and all reviews have been finalized. That determination may be affected by issues not discussed at the advisory committee meeting.