Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients

Abstract

Objective: To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals. Materials and Methods: A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated. Results: A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone. Discussion: Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.