The Risk of Opioid Intoxications or Related Events and the Effect of Alcohol-Related Disorders: A Retrospective Cohort Study in German Patients Treated with High-Potency Opioid Analgesics
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Intoxications involving prescription opioids are a major public health problem in many countries. When taken with opioids, alcohol can enhance the effects of opioids, particularly in the central nervous system. However, data quantifying the impact of alcohol involvement in opioid-related intoxications are limited.
Using claims data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a retrospective cohort study based on users of high-potency opioid (HPO) analgesics during the years 2005–2009. HPO use was classified as extended-release, immediate-release or both. We calculated incidence rates (IRs) for opioid intoxications or related events as well as adjusted IR ratios (aIRR) comparing HPO-treated patients with alcohol-related disorders (ARDs) to those without ARDs overall and within each HPO category.
During the study period, 308,268 HPO users were identified with an overall IR of 340.4 per 100,000 person-years [95 % confidence interval (CI) 325.5–355.7]. The risk was highest when patients received concomitant treatment with extended- and immediate-release HPOs (IR 1093.8; 95 % CI 904.6–1310.9). ARDs increased the risk during HPO use by a factor of 1.7 and the highest aIRR was seen when comparing patients simultaneously exposed to extended- and immediate-release HPOs with ARDs to those without ARD also after excluding patients with potential improper/non-medical HPO use.
Physicians should be aware of these elevated risks in HPO patients with ARDs. Active patient education by healthcare providers regarding the risk of opioid intoxications or related events due to alcohol in conjunction with HPOs is warranted.
KeywordsBuprenorphine Oxycodone Acamprosate Cohort Entry Prescription Drug Monitoring Program
The authors thank Inga Schaffer and Stefanie Heidbreder for contributing to the statistical analyses and Heike Gerds for editing the manuscript. The authors are grateful to all statutory health insurances that provided data for this study, namely the AOK Bremen/Bremerhaven, the DAK-Gesundheit, the Techniker Krankenkasse (TK) and the hkk.
Compliances with ethical standard
This study was funded by Mundipharma Research GmbH & Co. KG. The authors had complete autonomy for the process of establishing the protocol, carrying out the analyses and interpreting the results. This also includes the full right to publish the results without limitation. Mundipharma Research GmbH & Co. KG was provided the opportunity to review a preliminary version of this manuscript for factual accuracy but the authors are solely responsible for final content and interpretation.
Conflict of interest
Edeltraut Garbe is running and Kathrin Jobski, Bianca Kollhorst and Tania Schink are working for a department that occasionally performs studies for pharmaceutical industries. These companies include Bayer, Celgene, GlaxoSmithKline, Mundipharma, Novartis, Purdue, Sanofi-Aventis, Sanofi Pasteur MSD and STADA. Edeltraut Garbe served in an advisory or consultancy role for Bayer-Pharma, Nycomed, GlaxoSmithKline, Schwabe, Teva and Novartis. These advisory functions were unrelated to the topic of this study.
- 8.Paulozzi LJ, Jones CM, Mack KA, Rudd RA. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR Morb Mortal Wkly Rep. 2011;60(43):1487–92.Google Scholar
- 10.United Nations Office on Drugs and Crime. The non-medical use of prescription drugs—policy direction issues. 2011. http://www.unodc.org/docs/youthnet/Final_Prescription_Drugs_Paper.pdf. Accessed 28 Apr 2015.
- 11.Rehm J. Prescription opioids and public health in the European Union (Policy Paper 4) Addictions and lifestyles in contemporary Europe—reframing addictions policy. 2013. http://www.alicerap.eu/. Accessed 12 Nov 2014.
- 18.EMA. Assessment report for authorised modified-release oral medicinal products of the WHO level III scale for the management of pain. 2011. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Modified-released_oral_opioids_31/WC500107316.pdf. Accessed 12 Nov 2014.
- 21.Fassmer A, Schink T. Representativity of outpatient drug prescriptions in the German Pharmacoepidemiological Research Database (GePaRD). In: Annual Conference of the German Society for Epidemiology (DGEpi); 17–20 Sept 2014; Ulm. http://www.dgepi2014.de/images/docs/Abstractband.pdf.
- 23.Schink T, Garbe E. Assessment of the representativity of in-patient hospital diagnoses in the German Pharmacoepidemiological Research Database (Abstracts of the 26th International Conference on Pharmacoepidemiology & Therapeutic Risk Management, 19–22 August 2010, Brighton, UK). Pharmacoepidemiol Drug Saf. 2010;19:S178–9.Google Scholar
- 25.WHO. Cancer pain relief and palliative care. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1990;804:1–75.Google Scholar
- 26.Greevy RA Jr, Huizinga MM, Roumie CL, Grijalva CG, Murff H, Liu X, et al. Comparisons of persistence and durability among three oral antidiabetic therapies using electronic prescription-fill data: the impact of adherence requirements and stockpiling. Clin Pharmacol Ther. 2011;90(6):813–9. doi: 10.1038/clpt.2011.228.CrossRefPubMedGoogle Scholar
- 28.AKDAE. Tumorschmerzen [Empfehlungen zur Therapie von Tumorschmerzen]. 3. Aufl. ed. Arzneiverordnung in der Praxis, vol 34, 2007 Sonderh 1. Köln: Arzneimittelkomm. der Dt. Ärzteschaft; 2007.Google Scholar
- 31.Kim HM, Smith EG, Stano CM, Ganoczy D, Zivin K, Walters H, et al. Validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use. BMC Health Serv Res. 2012;12:18. doi: 10.1186/1472-6963-12-18.CrossRefPubMedCentralPubMedGoogle Scholar
- 33.Katz N, Panas L, Kim M, Audet AD, Bilansky A, Eadie J, et al. Usefulness of prescription monitoring programs for surveillance–analysis of Schedule II opioid prescription data in Massachusetts, 1996–2006. Pharmacoepidemiol Drug Saf. 2010;19(2):115–23. doi: 10.1002/pds.1878.CrossRefPubMedGoogle Scholar
- 36.Coplan P, DeVeaugh-Geiss A, Kadakia A. Comparison of the risk of opioid overdose among patients prescribed immediate-release and extended-release opioid analgesics (abstracts presented at the 33rd Annual Scientific Meeting of the American Pain Society). J Pain. 2014;15(4 Suppl):S9.Google Scholar
- 38.FDA. FDA issues second safety warning on fentanyl skin patch. 2007. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109046.htm. Accessed 12 Nov 2014.
- 39.FDA. Extended-release (ER) and long-acting (LA) opioid analgesics Risk Evaluation and Mitigation Strategy (REMS). 2013. http://www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm311290.pdf. Accessed 23 Jan 2015.
- 40.AKDAE. UAW-News International: Die unkritische Anwendung von Fentanylpflastern erhöht das Risiko für schwerwiegende Nebenwirkungen. Dtsch Arztebl International. 2012;109(14):724–5.Google Scholar
- 42.FDA. FDA approves new extended-release oxycodone with abuse-deterrent properties. 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406407.htm. Accessed 28 Apr 2015.
- 43.Sessler NE, Downing JM, Kale H, Chilcoat HD, Baumgartner TF, Coplan PM. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation. Pharmacoepidemiol Drug Saf. 2014;23(12):1238–46. doi: 10.1002/pds.3658.CrossRefPubMedCentralPubMedGoogle Scholar
- 44.FDA. New safety measures announced for extended-release and long-acting opioids. 2014. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm363722.htm. Accessed 12 Nov 2014.
- 45.King S, Forbes K, Hanks GW, Ferro CJ, Chambers EJ. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project. Palliat Med. 2011;25(5):525–52. doi: 10.1177/0269216311406313.CrossRefPubMedGoogle Scholar
- 46.Office of National Drug Control Policy. Prescription Drug Monitoring Programs. 2011. http://www.whitehouse.gov/sites/default/files/ondcp/Fact_Sheets/pdmp_fact_sheet_4-8-11.pdf. Accessed 12 Nov 2014.
- 48.Narcotic Drugs Prescription Ordinance (BtMVV). Bundesgesundheitsblatt 1998;1(4):74–80.Google Scholar
- 51.GBA. Appendix III: overview of limitations and exclusions on prescriptions [in German]. 2013. https://www.g-ba.de/downloads/83-691-351/AM-RL-III-Verordnungeinschraenkungen_2014-05-13.pdf. Accessed 23 Jan 2015.
- 55.Coplan P, Wentworth C, Sessler N, Downing J, Alexander L, Chilcoat.H. Opioid analgesic dosage strength as a predictor of overdose risk in the UK (Abstracts of the 29th International Conference on Pharmacoepidemiology & Therapeutic Risk Management, August 25–28, 2013, Montréal, Canada). Pharmacoepidemiol Drug Saf. 2013;22(Suppl. 1):120. doi: 10.1002/pds.3512.
- 56.Pain Treatment Topics. Opioid dose alone may not influence overdose risk. 2013. http://updates.pain-topics.org/2013/04/opioid-dose-alone-may-not-influence.html. Accessed 12 Nov 2014.