Subcutaneous methylnaltrexone for treatment of acute opioid-induced constipation:
phase 2 study in rehabilitation after orthopedic surgery.
Author(s): Anissian L, Schwartz HW, Vincent K, Vincent HK, Carpenito J, Stambler N,
Ramakrishna T.
Affiliation(s): Department of Orthopaedic Surgery, Louisiana State University Health Sciences
Center-Shreveport, Shreveport, LA 71130-3932, USA. Laniss@lsuhsc.edu
Publication date & source: 2012, J Hosp Med. , 7(2):67-72
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.
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