Background/Purpose:   The use of opioid analgesics for non-cancer, primarily musculoskeletal pain, in the U.S. has increased markedly and has been accompanied by an increase in deaths and hospitalizations due to opioid toxicity. Opioids likely vary with regard to these risks. There are particular concerns about transdermal fentanyl and long-acting oxycodone. Transdermal fentanyl has variable absorption and prolonged effects. There was an increase in opioid-related mortality after the addition of long-acting oxycodone to formularies and reports that oxycodone was involved in approximately one in three cases of opioid-related deaths. Thus, it is important to define the comparative safety of long-acting opioids, particularly transdermal fentanyl and oxycodone. We aimed to compare the risk of death in patients with chronic non-cancer pain receiving transdermal fentanyl, oxycodone slow release (SR), and morphine SR.

Methods:   We conducted a retrospective cohort study in 50,658 patients enrolled in Tennessee Medicaid who filled prescriptions for: transdermal fentanyl (n=8,717), oxycodone SR (n=14,118), or morphine SR (n=27,823) between 1/1/1999 through 12/31/2011. Individuals with cancer or other serious diagnoses were excluded. The primary outcome was out-of-hospital mortality. Relative risk was estimated with the use of Cox proportional hazard models; propensity scores were used to adjust for multiple potential confounders, using a time-dependent analysis.

Results:   Long-acting opioids were used primarily for musculoskeletal pain, which accounted for more than 90% of the prescriptions. There were 689 deaths during 44,385 person-years of follow-up; the all-cause mortality rate was 155/10,000 patient-years. All-cause mortality was not significantly different in patients using transdermal fentanyl compared to morphine SR (adjusted HR=0.96, 95% C.I.: 0.77-1.21). However, patients taking oxycodone SR had 21% lower mortality risk (adjusted HR=0.79, 95% C.I. 0.66-0.95) than those receiving morphine SR. Sensitivity analyses, including propensity score–matched cohorts and follow-up restricted to the first year of evaluation yielded similar results.

Conclusion:  Patients taking long-acting opioids for non-cancer pain, primarily musculoskeletal pain, have a high mortality risk. Our findings suggest that there is a significant decreased risk of death in patients taking oxycodone SR compared to those taking morphine SR.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-safety-of-long-acting-opioids-for-non-cancer-pain/