Subcutaneous methylnaltrexone for treatment of acute opioid-induced constipation: phase 2 study in rehabilitation after orthopedic surgery.

BACKGROUND

Methylnaltrexone has been shown to be effective for treating opioid-induced constipation (OIC) in chronic settings, but its effects on acute OIC have not been studied.

OBJECTIVE

To assess safety and efficacy of subcutaneous methylnaltrexone in patients with acute OIC after orthopedic procedures.

DESIGN

Double-blind, randomized, parallel-group, placebo-controlled, hypothesis-generating phase 2 study.

SETTING

Sixteen US hospitals and rehabilitation facilities.

PATIENTS

Adult patients with acute OIC after orthopedic surgical procedure, expected to require opioids for at least 7 days postrandomization.

INTERVENTIONS

Patients received once-daily subcutaneous methylnaltrexone 12 mg or placebo for up to 4 or 7 days.

MEASUREMENTS

All endpoints were exploratory and included the percentage of patients achieving laxation within 2 and 4 hours of first dose and time to laxation.

RESULTS

Thirty-three patients received at least 1 dose of study drug (methylnaltrexone, n = 18; placebo, n = 15). Within 2 and 4 hours, significantly more patients receiving methylnaltrexone achieved laxation (2 hours: 33.3% vs 0%, P = 0.021; 4 hours: 38.9% vs 6.7%, P = 0.046) compared with placebo. Time to laxation was significantly shorter with methylnaltrexone (median = 15.8 hours) versus placebo (median = 50.9 hours), P = 0.0197. The most common adverse events related to the gastrointestinal tract. Pain scores remained stable and were similar to those of placebo, and signs and symptoms of opioid withdrawal did not emerge in patients receiving methylnaltrexone.

CONCLUSIONS

Methylnaltrexone was generally well tolerated and was active in inducing laxation in this study of patients experiencing acute OIC following orthopedic surgery.