P202: Characteristics of Opioid-Induced Hyperalgesia Occurring with Short and Long-Term Opioid Use
Poster Presenter
Sarah E Kang
Safety Evaluator
FDA United States
Objectives
We sought to provide a detailed characterization of cases of opioid-induced hyperalgesia (OIH) to inform regulatory decisions surrounding labeling of this adverse event.
Method
We identified cases of OIH submitted to FDA or published in the literature through 2021 and characterized preceding opioid use, demographics, opioid analgesic product, route of administration, reasons for use, risk factors, as well as approaches to clinical management.
Results
We identified 46 cases of OIH that met our case definition. Of these cases, 38 described OIH with long-term (>12 weeks) and 8 with short-term (=12 weeks) opioid use. Affected individuals ranged from 6 weeks in age to 92 years with an equal proportion of males and females. OIH cases involved a range of opioids, though the most commonly reported products (note: some cases reported more than one product) were morphine (n=21), fentanyl/fentanyl analogs (n=15), oxycodone (n=10) and hydromorphone (n=8); some cases involved more than one route of administration. OIH occurred in the context of various routes of opioid exposure such as oral, transdermal, intravenous (IV) and the intrathecal route. OIH occurred with various doses of opioids. Among OIH cases reporting long-term opioid use: frequently reported reasons for use included pain management for cancer (n=21), neuropathy (n=5) and chronic back pain (n=5); 14 of these cases reported cumulative duration of opioid use at the time of suspected OIH ranging from 4 months to greater than 30 years; 14 cases also reported concomitant use of a serotonergic agent, and 10 cases reported clonus/myoclonus, regardless of concomitant use of serotonergic agent, as a clinical finding. Among OIH cases reporting short-term opioid use: reasons for use included post-operative pain, abdominal pain, appendicitis, and juvenile arthritis; duration of opioid use at the time of suspected OIH ranged from 40 hours to 7 weeks; a subset of cases also reported concomitant use of serotonergic agents. Reported management of OIH included opioid dose reduction or discontinuation, opioid dose reduction followed by opioid switch, immediate switch to another opioid, or addition of other therapies such as ketamine, clonidine or dexmedetomidine.
Conclusion
Case-level data from FAERS and the literature supports an association between short and long-term opioid use and hyperalgesia, and offers insight into characteristics of OIH such as durations of use, doses and specific opioid types potentially associated with OIH.
On April 13, 2023, FDA issued a drug safety communication, announcing updates to opioid labels, including a new warning regarding OIH. OIH should be considered in the context of unexplained pain associated with both short and long-term opioid use, and strategies such as dose reduction or opioid switching should be considered.
