What Dose of Naldemedine Is Appropriate for Opioid-Induced Constipation?

Once-daily 0.2 mg naldemedine is likely safe and effective for the treatment of opioid-induced constipation, according to a recent study.

For their study, the researchers assessed 244 patients with opioid-induced constipation due to long-term opioid therapy for chronic noncancer pain. Patients were randomly assigned to receive either 0.1 mg, 0.2 mg, or 0.4 mg of oral naldemedine or a placebo.
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The primary efficacy endpoint was defined as change in weekly spontaneous bowel movement (SBM) frequency from baseline to the last 2 weeks of treatment. Secondary efficacy endpoints were the proportion of SBM responders, defined as patients with at least 2 SBMs per week and an increase of at least 1 SBM per week from baseline during the last 2 weeks of treatment. Adverse events, effects on analgesia, and opioid withdrawal symptoms were also examined.

Results indicated that weekly SBM frequency was significantly higher among patients taking 0.2 mg naldemedine and 0.4 mg naldemedine vs placebo, but not with 0.1 mg naldemedine.

Furthermore, 0.2 mg and 0.4 mg naldemedine yielded a significantly higher proportion of SBM responders (71.2% and 66.7%, respectively) compared with placebo (39.3%), but not with 0.1 mg naldemedine (52.5%).

The researchers noted that most treatment-emergent adverse events had been mild to moderate in severity, with incidence increasing with higher doses of naldemedine.

“Naldemedine 0.2 mg once daily is the optimal dose for future confirmatory trials in [opioid-induced constipation],” the researchers concluded.

—Christina Vogt

Reference:

Webster LR, Yamada T, Ferreira JCA. A phase 2b, randomized, double-blind placebo-controlled study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation in patients with chronic noncancer pain. Pain Med. 2017;18(12):2350-2360. https://doi.org/10.1093/pm/pnw325.