June 04, 2014
ASA Presents at FDA Workshop on Postmarketing Requirements for ER LA Opioids
On May 19, ASA offered oral comments at a Food and Drug Administration (FDA) public hearing on the postmarketing requirements for extended-release and long-acting (ER/LA) opioid drug products. This meeting was convened to discuss the design and conduct of postmarketing studies that will assess the serious risks of misuse, abuse, hyperalgesia, addiction, overdose and death associated with the long-term use of ER/LA opioids. In September 2013, the FDA announced that drug sponsors would be required to conduct these studies in conjunction with the Agency’s decision to revise ER/LA drug product labels.
At the public hearing, Daniel Carr, M.D., Professor of Anesthesiology, Medicine and Public Health at Tufts University School of Medicine and member of ASA’s Committee on Pain Medicine, commended “the FDA for thoughtful, comprehensive progress in developing evidence to better balance the need for pain relief with adverse effects on both individuals and society.” Dr. Carr further noted that:
- The FDA is charting new ground, and it is challenging to frame the questions presented at the workshop and develop methods to answer them with confidence. For example, what is meant by "high dose"? Are outcome measures developed and validated in patients not receiving opioids generalizable to the population prescribed ER/LA opioids? Which mechanisms of, and methods to assess, tolerance and hyperalgesia should be selected for investigation?
- Hyperalgesia may result either from untreated or undertreated pain, or may follow chronic exposure to opioids. Patients who are candidates for ER/LA opioid therapy might have hyperalgesia as a result of chronic pain, and possibly, repeated doses of immediate-release opioids by the time ER/LA opioid therapy commences.
- The design of the studies is complex due to the multiple genetic, epigenetic, contextual and environmental mechanisms acting at every level of the pathophysiology of pain as well as the pharmacokinetics and pharmacodynamics of opioid therapy.
ASA will continue to monitor the postmarketing requirements for ER/LA opioids and work with the FDA and stakeholders to ensure the safe use of opioids.