(203) Association of opioid and benzodiazepine co-prescribing with adverse events among older adults with cancer

Background: Opioids continue to be the mainstay of cancer-related pain management, and benzodiazepines are frequently prescribed to help patients manage other common symptoms of cancer and its treatment; however, little is known about the risks of coprescribing for this population.

Objectives: Among older adults with breast, lung, or colorectal cancer, we assessed the immediate impact of opioid and benzodiazepine co-prescribing on the risk of opioid overdose events, fall-related events, and all-cause hospitalization.

Methods: We conducted a retrospective cohort study of patients who received a first diagnosis of stage I-IV breast, colorectal, or lung cancer using the Surveillance Epidemiology and End Result (SEER) database linked with fee-for-service Medicare claims (i.e., SEER-Medicare). We required continuous medical insurance from 1 year before cancer diagnosis through at least 1 month after diagnosis. Prescription drug coverage was required from 3 months before diagnosis to at least 1 month after diagnosis. Patients were followed for up to 1 year after diagnosis. Our outcomes were binary measures of overdose events, fall/fracture events, and all-cause hospitalizations. The primary independent variable, measured at the day level, was having an opioid and/or benzodiazepine prescription supplied. We fit Cox proportional hazards models with time-dependent covariates, with patients censored at death or the end of available follow-up. We adjusted for socio-demographic characteristics, patient clinical characteristics, prior opioid or benzodiazepine use, and time-varying measures of opioid and benzodiazepine use.

Results: One quarter (25.2%) of patients had overlapping opioid and benzodiazepine prescriptions in the year following cancer diagnosis. Adjusted analysis showed that opioid exposure alone was associated with an increase in the immediate risk of experiencing an overdose (HR: 5.64, 95% CI: 4.86-6.53), fall or fracture (HR: 1.57, 95% CI: 1.42-1.74), and all-cause hospitalization (HR: 1.10, 95% CI: 1.07-1.13). Benzodiazepine exposure was similarly associated with an increase in the immediate risk of each outcome (HR, overdose: 1.31, 95% CI: 0.98, 1.75; HR, falls or fractures: 1.16, 95% CI: 1.01, 1.33; HR, all-cause hospitalization: 1.11, 95% CI: 1.07-1.15). The interaction of both opioid exposure and benzodiazepine exposure was not associated with an additional increase in risk of any of the three outcomes.

Conclusions: Patients were commonly prescribed opioids and benzodiazepines at the same time. However, there was no incremental increase in the risk of experiencing an overdose, fall or fracture, or all-cause hospitalization from being prescribed both drugs together compared to being prescribed one medication or the other.