Skip to main content
SpringerLink
Log in

Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics

  • Original Research Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Introduction

The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics.

Objective

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.

Methods

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).

Results

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Philippines)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Nora D. Prescription Opioid and Heroin Abuse. Presentation included IMS Health, Vector One source data of National Prescription Audit, years 1997-2013, delivered at 2014 Testimony to U.S. Congress, House Committee on Energy and Commerce Subcommittee on Oversight and Investigations. Available at https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/prescription-opioid-heroin-abuse.

  2. Volkow N. Characteristics of Opioid Prescriptions in 2009. JAMA. 2011;305(13):1299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. U.S. Department of Health and Human Services. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. Rockville: Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality; 2014. Available at https://www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.pdf.

  4. Center for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System, Mortality File. Number and Age-Adjusted Rates of Drug-poisoning Deaths Involving Opioid Analgesics and Heroin: United States, 2000–2014. Atlanta: Center for Disease Control and Prevention; 2015. Available at https://www.cdc.gov/nchs/data/health_policy/AADR_drug_poisoning_involving_OA_Heroin_US_2000-2014.pdf.

  5. Florence C, Zhou C, Luo F, Xu L. The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013. Med Care. 2016;54(10):901–6.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wightman R, Perrone J, Portelli I, Nelson L. Likeability and Abuse Liability of Commonly Prescribed Opioids. J Med Toxicol. 2012;8(4):335–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Paulozzi L, Kilbourne E, Desai H. Prescription drug monitoring programs and death rates from drug overdose. Pain Med. 2011;12(5):747–54.

    Article  PubMed  Google Scholar 

  8. Rudd R, Aleshire N, Zibbell J, Gladden R. Increases in drug and opioid overdose deaths—United States, 2000–2014. MMWR Morb Mortal Wkly Rep. 2016;64(50–51):1378–82.

    Article  PubMed  Google Scholar 

  9. Frenk S, Porter K, Paulozzi L. Prescription opioid analgesic use among adults: United States, 1999–2012. NCHS Data Brief. 2015;189:1–8.

    Google Scholar 

  10. Dasgupta N, Kramer E, Zalman M, Carino S Jr, Smith M, Haddox J, et al. Association between non-medical and prescriptive usage of opioids. Drug Alcohol Depend. 2006;82(2):135–42.

    Article  PubMed  CAS  Google Scholar 

  11. Smith M, Dart R, Hughes A, Geller A, Senay E, Woody G, et al. Clinician validation of poison control center (PCC) intentional exposure cases involving prescription opioids. Am J Drug Alcohol Abuse. 2006;32(3):465–78.

    Article  PubMed  Google Scholar 

  12. Compton W, Volkow N. Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug Alcohol Depend. 2006;81(2):103–7.

    Article  PubMed  Google Scholar 

  13. Jones C, Lurie P, Throckmorton D. Effect of US drug enforcement administration’s rescheduling of hydrocodone combination analgesic products on opioid analgesic prescribing. JAMA Intern Med. 2016;176(3):399.

    Article  PubMed  Google Scholar 

  14. Budnitz D, Lovegrove M, Sapiano M, Mathew J, Kegler S, Geller A, et al. Notes from the field: pediatric emergency department visits for buprenorphine/naloxone ingestion—United States, 2008–2015. MMWR Morb Mortal Wkly Rep. 2016;65(41):1148–9.

    Article  PubMed  Google Scholar 

  15. Ritchey M, Tsipas S, Loustalot F, Wozniak G. Use of pharmacy sales data to assess changes in prescription- and payment-related factors that promote adherence to medications commonly used to treat hypertension, 2009 and 2014. PLoS One. 2016;11(7):e0159366.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Gummin D, Mowry J, Spyker D, Brooks D, Fraser M, Banner W. 2016 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th Annual Report. Clin Toxicol. 2017;55(10):1072–254.

    Article  Google Scholar 

  17. Iwanicki J, Severtson S, McDaniel H, Rosenblum A, Fong C, Cicero T, et al. Abuse and diversion of immediate release opioid analgesics as compared to extended release formulations in the United States. PLoS One. 2016;11(12):e0167499.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Green J, Bucher Bartelson B, Le Lait M, Roland C, Masters E, Mardekian J et al. Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration. Drug Alcohol Depend. 2017;175:140–5.

  19. Von Korff M, Saunders K, Thomas Ray G, Boudreau D, Campbell C, Merrill J, et al. De facto long-term opioid therapy for noncancer pain. Clin J Pain. 2008;24(6):521–7.

    Article  PubMed  Google Scholar 

  20. Hoppe-Roberts J, Lloyd L, Chyka P. Poisoning mortality in the United States: comparison of national mortality statistics and poison control center reports. Ann Emerg Med. 2000;35(5):440–8.

    Article  PubMed  CAS  Google Scholar 

  21. Dart R, Surratt H, Cicero T, Parrino M, Severtson S, Bucher-Bartelson B, et al. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med. 2015;372(3):241–8.

    Article  PubMed  CAS  Google Scholar 

  22. Dasgupta N, Davis J, Jonsson Funk M, Dart R. Using poison center exposure calls to predict methadone poisoning deaths. PLoS One. 2012;7(7):e41181.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Katz N, Dart R, Bailey E, Trudeau J, Osgood E, Paillard F. Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions. Am J Drug Alcohol Abuse. 2011;37(4):205–17.

    Article  PubMed  Google Scholar 

  24. Hall A. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA. 2008;300(22):2613.

    Article  PubMed  CAS  Google Scholar 

  25. Hirsch A, Proescholdbell S, Bronson W, Dasgupta N. Prescription histories and dose strengths associated with overdose deaths. Pain Med. 2014;15(7):1187–95.

    Article  PubMed  Google Scholar 

  26. Ryan N, Isbister G. Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely. Clin Toxicol. 2015;53(6):545–50.

    Article  CAS  Google Scholar 

  27. Moulis F, Rousseau V, Abadie D, Masmoudi K, Micallef J, Vigier C, et al. Serious adverse drug reactions with tramadol reported to the French pharmacovigilance database between 2011 and 2015. Thérapie. 2017;72(6):615–24.

    Article  PubMed  Google Scholar 

  28. Secora A, Trinidad J, Zhang R, Gill R, Dal Pan G. Drug availability adjustments in population-based studies of prescription opioid abuse. Pharmacoepidemiol Drug Saf. 2016;26(2):180–91.

    Article  PubMed  CAS  Google Scholar 

  29. Dunn K. Opioid prescriptions for chronic pain and overdose. Ann Intern Med. 2010;152(2):85.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gomes T, Mamdani M, Dhalla I, Paterson J, Juurlink D. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686–91.

    Article  PubMed  CAS  Google Scholar 

  31. Dowell D, Haegerich T, Chou R. CDC guideline for prescribing opioids for chronic Pain—United States, 2016. MMWR Recomm Rep. 2016;65(1):1–49.

    Article  PubMed  Google Scholar 

  32. Mowry J, Spyker D, Cantilena L, Bailey J, Ford M. 2012 Annual report of the american association of poison control centers’ national poison data system (NPDS): 30th annual report. Clin Toxicol. 2013;51(10):949–1229.

    Article  CAS  Google Scholar 

  33. Fischer B, Jones W, Urbanoski K, Skinner R, Rehm J. Correlations between prescription opioid analgesic dispensing levels and related mortality and morbidity in Ontario, Canada, 2005–2011. Drug Alcohol Rev. 2013;33(1):19–26.

    Article  PubMed  Google Scholar 

  34. Paulozzi L, Ryan G. Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med. 2006;31(6):506–11.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Colorado School of Medicine, Aurora, CO, USA

    David L. Murphy & Jacob A. Lebin

  2. Department of Emergency Medicine, University of Washington, Seattle, WA, USA

    David L. Murphy & Jacob A. Lebin

  3. Denver Health and Hospital Authority, Rocky Mountain Poison and Drug Center, Denver, CO, USA

    Stevan G. Severtson, Heather A. Olsen, Nabarun Dasgupta & Richard C. Dart

  4. Department of Emergency Medicine, University of Colorado, Denver, CO, USA

    Richard C. Dart

Authors
  1. David L. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacob A. Lebin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stevan G. Severtson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heather A. Olsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nabarun Dasgupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Richard C. Dart
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to David L. Murphy.

Ethics declarations

Ethics approval

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.

Funding

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 96 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murphy, D.L., Lebin, J.A., Severtson, S.G. et al. Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics. Drug Saf 41, 787–795 (2018). https://doi.org/10.1007/s40264-018-0660-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40264-018-0660-4

Search

Navigation