Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics
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The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics.
The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency.
Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME).
There were 19,480 cases of SAE during the 7-year study period. Hydrocodone and oxycodone contributed to 77% of SAE cases. Comparing rates of outcome by relative potency, a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold difference among individual opioid products. SAE rate and potency were related linearly—SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in MME (p = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency identified that MME comprised 96% of the variation observed. In contrast, potency did not explain variation seen using other study denominators (prescriptions dispensed, dosage units dispensed, and the number of individuals filling a prescription).
Conclusions and Relevance
Potency of a prescription opioid analgesic demonstrates a significant, highly positive linear relationship with exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers. Potency should be carefully considered from both individual provider and public health perspectives.
Conceived and designed the experiments: DM JL GS RD. Performed experiments: GS. Analyzed the data: DM JL GS HO ND RD. Drafted the manuscript: DM JL GS ND RD.
Compliance with Ethical Standards
The Poison Center Program study protocol received its most recent review and approval from the Colorado Multiple Institutional Review Board (COMIRB) on 21 December 2016. In addition, the study protocol was reviewed and approved by the IRB of each participating poison center.
There were no sources of financial assistance that were used to conduct this study or used to assist with the preparation of the manuscript.
Conflict of interest
David Murphy, Jacob Lebin, Stevan Severtson, Nabarun Dasgupta, Heather Olsen, and Richard Dart have no conflicts of interest that are directly relevant to the content of this study. It should be noted that most manufacturers of prescription opioid analgesics or stimulants have subscription contracts to receive data from RADARS System. RADARS System is the property of Denver Health and Hospital Authority, a political subdivision of the State of Colorado (public hospital for Denver, Colorado). The subscribers receive data, they do not participate in developing the System, participate in data collection or the analysis of the data, nor do they have access to the raw data. No employee of Denver Health has a financial relationship nor receives any payment from any pharmaceutical company.
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