medRxiv · Jan 16, 2026

Short-term risk of falls among initiators of controlled-release tapentadol versus oxycodone: A population-based cohort study

By Camacho X, Schäffer A, Brett J et al.

Abstract Objective Given the potential severity and economic burden of falls, we compared the short-term risk of falls following initiation of sustained-release (SR) tapentadol versus controlled-release (CR) oxycodone in real-world clinical practice. Design Active comparator, new user retrospective cohort study using routinely collected health data from 2014 to 2020. Setting New South Wales, Australia. Participants People aged ≥18 years initiating publicly subsidised tapentadol (SR) or oxycodone (CR). Interventions Initiation of tapentadol (SR) or oxycodone (CR). Main outcome measures Composite measure of fall-related emergency department presentations, hospitalisations or deaths. We used propensity score matching to adjust for baseline confounding and approximated relative risks (RR) of falls at 7, 14, and 28 days after initiation using conditional logistic regression models. We calculated absolute risk differences and estimated the number of people that would need to be treated with oxycodone (CR) vs tapentadol (SR) for one additional fall to occur (NNTH). We conducted subgroup analyses restricted to people aged ≥65 and ≥80 years and by recent opioid exposure (within 90 days prior to initiation). Results We identified 103,924 tapentadol (SR) and 419,732 oxycodone (CR) initiators; after matching each cohort comprised 103,758 initiators. Most people (74%) were aged between 45-84 years, and slightly more than half were female. Within 28 days of initiation, 652 (0.6%) oxycodone (CR) initiators and 457 (0.4%) tapentadol initiators suffered a fall. Across all time points, tapentadol (SR) initiation was associated with a lower risk of falls compared with oxycodone (CR) (7 days: RR 0.57 [95% CI 0.48 to 0.69]; 14 days: 0.62 [0.54 to 0.71]; 28 days: 0.70 [0.62 to 0.79]). Absolute differences were small at all time points (approximately 1-2 fewer falls per 1,000 patients treated), corresponding to NNTH for one additional fall ranging from 739 to 529. These patterns persisted regardless of recent opioid exposure. Relative risks were similar in the older age groups while absolute differences were slightly larger (≥65 years: 2-3 fewer falls/1,000; ≥80 years: 4-8 fewer falls/1,000). The greatest absolute differences were among opioid-naïve people aged ≥80 years (6-10 fewer falls/1,000, corresponding to NNTH ranging from 173 to 97). Fall risks were attenuated among people aged ≥80 years with recent opioid exposure. Conclusions Tapentadol (SR) was associated with a lower risk of falls than oxycodone (CR) up to four weeks after initiation, although absolute differences were small. The reduction in risk may be an important consideration in older patients where the consequences of falls are most severe. What is already known on this topic Clinical trials suggest that sustained-release (SR) tapentadol has a lower incidence of adverse central nervous system effects compared to controlled-release (CR) oxycodone pioids are associated with increased risks of falls, particularly immediately following initiation What this study adds Initiation of tapentadol (SR) was associated with a lower short-term risk of falls resulting in ED presentation, hospitalisation, or death compared to initiation of oxycodone (CR) Absolute risk differences were small but reached 1% among opioid-naïve people aged 80 years and older where consequences of falls are most severe

doi.org/10.64898/2026.01.14.26344133Open accessInterventions