Oliceridine for acute pain management: pharmacology, clinical efficacy, safety, and future perspectives: a narrative review

Opioids are a cornerstone in the management of moderate-to-severe acute pain; however, their clinical utility is limited by well-recognized challenges, including respiratory depression, gastrointestinal (GI) dysfunction, and the potential for misuse and abuse. Oliceridine is a novel μ-opioid receptor agonist with G-protein-biased signaling and reduced β-arrestin recruitment. It exhibits potent analgesic effects while potentially reducing opioid-related adverse events. In preclinical investigations, oliceridine was associated with lower rates of GI dysfunction and respiratory depression than morphine. In the phase III clinical trials APOLLO-1 and APOLLO-2, certain oliceridine regimens produced rapid and effective analgesia comparable to that of morphine, with lower incidences of nausea, vomiting, and respiratory events. However, current evidence has not demonstrated a clinically meaningful overall advantage compared to conventional opioids. In addition, a clinically meaningful reduction in abuse liability relative to conventional opioids has not been established, underscoring the complexity of opioid reward mechanisms. This narrative review examines the pharmacological properties, clinical efficacy, safety profile, and ongoing controversies surrounding oliceridine and evaluates its potential role in perioperative pain management.