Low Incidence of Opioid-Induced Respiratory Depression Observed with Oliceridine Regardless of Age or Body Mass Index: Exploratory Analysis from a Phase 3 Open-Label Trial in Postsurgical Pain.

INTRODUCTION: Advanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65 years) and/or obese (BMI ≥ 30 kg/m2) patients and analyzed risk factors of OIRD. METHODS: Patients aged ≥ 18 years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48 h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate < 10 breaths per minute and/or oxygen saturation < 90%. RESULTS: A total of 724 surgical patients with a mean age of 54.5 ± 15.9 years and a mean NRS score of 6.2 ± 2.1 were included in this analysis; 33.3% (241/724) were ≥ 65 years of age and 46.3% (335/724) had BMI (body mass index) ≥ 30 kg/m2. The overall OIRD incidence was 13.7% with no patients requiring naloxone. The OIRD incidence was similar in the elderly and younger adults' cohorts [10.8 vs. 15.1%, OR 0.68 (0.42, 1.1), p = 0.11], and in obese and non-obese groups [14.0 vs. 13.4%, OR 1.06 (0.69, 1.62), p = 0.80]. In patients that were both elderly and obese (n = 120), the incidence was 10.8%. The multivariate analysis identified baseline NRS ≥ 6 [OR 1.6 (1.0, 2.4), p = 0.0499], PCA administration [OR 1.9 (1.2, 3.1), p = 0.005], and concomitant use of benzodiazepines and/or gabapentinoids [OR 1.6 (1.0, 2.6), p = 0.045], as being associated with OIRD. CONCLUSIONS: Postoperative oliceridine use in patients with advanced age and/or increased BMI was not associated with increased risk of OIRD.