Preventive Naldemedine Reduces Opioid-Induced Constipation and Nausea in Patients Starting Strong Opioids

Multicenter, double-blind randomized trial published in Journal of Clinical Oncology

Overview

Opioid-induced constipation (OIC) is a common and burdensome adverse effect when initiating strong opioids for cancer pain. This randomized, double-blind, placebo-controlled trial investigated whether starting naldemedine prophylactically at the time of opioid initiation prevents OIC and improves patient-reported outcomes compared with placebo.

Graphical Abstract – Proportion of patients without constipation (BFI < 28.8)

Key Findings

Primary endpoint achieved: Bowel Function Index (BFI) < 28.8 at Day 14 in 64.6% with naldemedine vs 17.0% with placebo (between-group difference 47.6%; p < 0.0001).
Higher proportions achieving ≥3 spontaneous bowel movements (SBM) and complete SBM per week on Days 7 and 14 with naldemedine vs placebo.
General and constipation-related quality of life improved with naldemedine (EORTC QLQ-C15-PAL, PAC-QOL, PAC-SYM).
Antiemetic drug use within 72 hours of opioid initiation was lower with naldemedine; fewer episodes of nausea/vomiting on Days 1–3.
No increase in serious adverse events; vomiting occurred less often with naldemedine during the protocol period.

Study Details

Design: Multicenter, double-blind, randomized, placebo-controlled trial at four academic hospitals in Japan.
Population: Adults with cancer initiating regularly dosed strong opioids for cancer pain (n = 99 randomized; efficacy n = 95).
Intervention: Naldemedine 0.2 mg once daily for 14 days starting with first opioid dose versus matching placebo; rescue sennosides permitted; pre-existing regular laxatives continued.
Registration: Japan Registry of Clinical Trials (jRCT) jRCTs031200397.
Funding: Grant for Research Advancement on Palliative Medicine, Japanese Society for Palliative Medicine (No. 192).

Clinical Implications

Prophylactic naldemedine may be considered to prevent opioid-induced constipation at opioid initiation in patients with cancer, while longer-term effects and cost-effectiveness warrant further study.
Potential dual benefit: prevention of constipation and reduction in early opioid-induced nausea/vomiting may improve adherence to analgesia and overall comfort.

Article information

Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial
Hamano J, Higashibata T, Kessoku T, Kajiura S, et al.
Journal of Clinical Oncology. 2024;42(35):4206–4217. Published September 10, 2024.

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