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. 2025 Jul 1;117(7):1465-1473.
doi: 10.1093/jnci/djaf072.

Association of opioid and benzodiazepine coprescribing with adverse events among older adults with cancer

Devon K Check  1   2 , Samir Soneji  1 , Harvey Jay Cohen  2   3 , Andrea Des Marais  1 , Katie F Jones  4   5 , Charles E Gaber  6 , Jessica S Merlin  7 , Amy O'Regan  1 , Nicole Fergestrom  8 , Lauren E Wilson  1 , Aaron N Winn  6
Affiliations

Association of opioid and benzodiazepine coprescribing with adverse events among older adults with cancer

Devon K Check et al. J Natl Cancer Inst. .

Abstract

Background: Many older adults with cancer are coprescribed opioids/benzodiazepines; evidence on harms is lacking.

Methods: Using SEER-Medicare (2012-2019), we identified patients with breast, colorectal, or lung cancer. Cox proportional hazards models estimated the adjusted hazard ratios (HRs) of coprescribing (measured from claims, at the day level) with the immediate risk of overdose, fall/fracture, and all-cause hospitalization. In a secondary analysis, models were stratified by ≥90 days of continuous medication supply.

Results: In our cohort of 107 288 patients, compared with those prescribed neither medication, those prescribed benzodiazepines had an increase in the immediate risk of falls/fractures (HR = 1.17, 95% CI = 1.02 to 1.34) and all-cause hospitalizations (HR = 1.08, 95% CI = 1.04 to 1.12). Patients prescribed opioids had an increase in the immediate risk of overdose (HR = 5.62, 95% CI = 4.86 to 5.62), falls/fractures (HR = 1.56, 95% CI = 1.41 to 1.73), and all-cause hospitalizations (HR = 1.26, 95% CI = 1.23 to 1.30). HRs were similar for patients coprescribed opioids/benzodiazepines. For patients without continuous exposure to 1 or both medications, effects were larger for coprescribed opioids/benzodiazepines vs opioids for overdose (HR = 15.22, 95% CI = 8.79 to 26.35 vs HR = 6.85, 95% CI = 6.85 to 26.35) and all-cause hospitalization (HR = 3.21, 95% CI = 2.60 to 3.96 vs HR = 1.98, 95% CI = 1.87 to 2.10).

Conclusions: Overall, compared with no prescribing, benzodiazepine prescribing and opioid prescribing were each associated with an increase in the immediate risk of adverse events. Effects were similar for those prescribed opioids and those coprescribed opioids/benzodiazepines. For patients with intermittent vs long-term medication exposure, coprescribing additionally increased the risk of overdose and all-cause hospitalization.

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Conflict of interest statement

D.K.C. reports grant funding from AstraZeneca. J.S.M. reports payment or honoraria from the Center to Advance Palliative Care. A.N.W. reports consulting fees from Novo Nordisk and CorMedix, payment for expert testimony from Takeda, and research funding from the NIH and AHRQ.

References

    1. Centers for Disease Control and Prevention. Multiple Cause of Death, 1999-2015. CDC WONDER Online Database; 2020.
    1. Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698. 10.1136/bmj.h2698 - DOI - PMC - PubMed
    1. Smink BE, Egberts AC, Lusthof KJ, Uges DR, de Gier JJ. The relationship between benzodiazepine use and traffic accidents: a systematic literature review. CNS Drugs. 2010;24:639-653. 10.2165/11533170-000000000-00000 - DOI - PubMed
    1. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169:1952-1960. 10.1001/archinternmed.2009.357 - DOI - PubMed
    1. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-c.... Accessed April 29, 2024.

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