Adverse Event Risk With Oxycodone Compared With Other Opioids

Low-dose oxycodone was found to be associated with increased risk for opioid-related adverse events compared with low-dose tramadol or hydrocodone, according to results of a study published in The Clinical Journal of Pain.

Investigators from the University of Arkansas for Medical Sciences used a 10% random sample from the IQVIA PharMetrics^® Plus database for this study. Administrative health insurance claims between 2006 and 2020 were evaluated for opioid-related adverse events among adults who received tramadol, hydrocodone, and/or oxycodone for noncancer-related chronic back or joint pain. Outcomes of interest included overdoses, accidents, self-inflicted injuries, violence-related injuries, and opioid and nonopioid substance use disorders (SUDs).

A total of 1,062,167 individuals were included in the opioid-related adverse event analysis, among whom 61.1% initiated treatment with short-acting hydrocodone, 22.4% initiated treatment with short-acting oxycodone, and 16.5% initiated treatment with tramadol. A subgroup of 986,809 individuals were included in the substance use analysis, among whom 61.3% initiated treatment with short-acting hydrocodone, 22.2% initiated treatment with short-acting oxycodone, and 16.5% initiated treatment with tramadol.

The mean age of patients among all groups ranged from 47.4 to 49.7 years, approximately three-quarters had chronic osteoarthritis, and the average Charlson comorbidity index score ranged from 0.4 to 0.5.

The overall opioid overdose rate was 50.0 per 100,000 person-years (py). Stratified by opioid, the highest rates were observed among recipients of high-dose nontramadol combination medication (1385.4 per 100,000 py), followed by other opioids at high doses (928.2 per 100,000 py) and high-dose tramadol combination treatment (899.8 per 100,000 py) recipients. Among the low-dose groups, the highest overdose rate was observed for short-acting oxycodone (405.2 per 100,000 py), followed by hydrocodone (203.7 per 100,000 py) and tramadol (155.4 per 100,000 py).

Accidents occurred at a rate of 4086.4 per 100,000 py, self-inflicted injuries and poisoning occurred at a rate of 102.7 per 100,000 py, and violence-related injuries occurred at a rate of 74.1 per 100,000 py. The highest rates of accidents were associated with high-dose short-acting hydrocodone or high-dose tramadol combination treatment, the highest rates of self-inflicted injuries were associated with high-dose tramadol or nontramadol combination regimens, and the highest rates of violence-related injuries were associated with low-dose tramadol or nontramadol combination treatments.

The overall rate of opioid use disorder was 337.8 per 100,000 py, and the overall rate of nonopioid SUD was 3549.9 per 100,000. The highest risk for opioid use disorder was associated with high-dose nontramadol combination regimens among high-dose treatments (7564.2 per 100,000 py) and for low-dose nontramadol combination regimens among low-dose treatments (4191.9 per 100,000 py).

In general, high-dose opioids were associated with increased risk for adverse outcomes. In the fully adjusted analysis, low-dose short-acting oxycodone was associated with higher risk for opioid overdose (adjusted hazard ratio [aHR], 1.79), self-inflicted injury (aHR, 1.47), opioid use disorder (aHR, 1.47), and nonopioid SUD (aHR, 1.13); low-dose tramadol was associated with lower risk for accidents (aHR, 0.73), self-inflicted injuries (aHR, 0.75), and violence-related injuries (aHR, 0.55) compared with hydrocodone.

These findings may be limited by not adjusting for patient characteristics, which may affect opioid use outcomes.

Study authors indicate that exclusive use of low-dose oxycodone was found to increase the risk for adverse outcomes compared with other low-dose opioids among individuals with noncancer-related chronic pain. The study authors comment, “These findings confirm the well-established risks of prescribing higher opioid doses and suggest that tramadol at low doses have lower risk of opioid-related adverse outcomes than low dose oxycodone.”

Disclosure: One study author declared an affiliation with a biotech, pharmaceutical, or device company.