Current Strategies and Future Perspectives in the Management of Opioid‐Induced Constipation: A Review of International and Japanese Guidelines

BACKGROUND: Opioids are indicated for pain that occurs with cancer and other disorders that become more prevalent with aging. The most prevalent and persistent adverse effect of opioid therapy is opioid-induced constipation (OIC). OIC impairs patient quality of life (QoL) and leads to suboptimal pain management due to medication non-adherence. Unlike other adverse effects, OIC persists and is not associated with pharmacological tolerance, necessitating long-term management. OBJECTIVES: The objective of this study is to evaluate current clinical strategies for OIC by comparing recommendations from American, European, and Japanese clinical guidelines. We reviewed the clinical evidence for the peripherally acting μ-opioid receptor antagonist (PAMORA) naldemedine (the only PAMORA approved in Japan) and the rationale for early intervention in OIC. METHODS: The clinical guidelines and recent clinical trial data, including the COMPOSE program (phase III clinical trials of naldemedine for OIC in patients with chronic non-cancer pain), were reviewed to establish an evidence-based framework for the management of chronic cancer and non-cancer pain. RESULTS: Conventional laxatives frequently provide inadequate relief as they address secondary symptoms rather than the underlying receptor-mediated cause. PAMORAs (including naldemedine, methyl naltrexone, and naloxegol) antagonize gastrointestinal opioid receptors without compromising central analgesia. Early initiation of PAMORAs stabilizes bowel function and reduces the incidence of treatment-related diarrhea that occurs when using conventional laxatives to treat OIC. CONCLUSION: The 2023 Japanese guidelines advocate the proactive use of the PAMORA naldemedine as a primary treatment option. This mechanism-based early intervention model offers a promising framework for optimizing QoL and implementing effective analgesia in an aging global population.