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Medline ® Abstract for Reference 28

of 'Prevention and management of side effects in patients receiving opioids for chronic pain'

Randomized, Double-Blind Trial of Oral Methylnaltrexone for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain.
Rauck R, Slatkin NE, Stambler N, Harper JR, Israel RJ
Pain Pract. 2017;17(6):820. Epub 2017 Feb 10.
BACKGROUND: Subcutaneous methylnaltrexone, a peripherally actingμ-opioid receptor antagonist, improves opioid-induced constipation (OIC) in patients with chronic noncancer pain. An oral methylnaltrexone formulation has been developed.
METHODS: In this phase 3, double-blind trial, adults with chronic noncancer pain receiving opioid doses of≥50 mg/day oral morphine equivalents with OIC were randomly assigned to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily (QD) for 4 weeks followed by as-needed dosing for 8 weeks. Patients who had≥3 rescue-free bowel movements (RFBMs)/week, with an increase of≥1 RFBM/week from baseline for≥3 of 4 weeks during the QD period, were responders.
RESULTS: Overall, 803 patients were included in the analyses. A significantly greater percentage of patients had an increase in mean percentage of dosing days resulting in an RFBM within 4 hours of dosing during weeks 1 through 4 (QD period; primary endpoint) with methylnaltrexone (300 mg/day [24.6%; P = 0.002]and 450 mg/day [27.4%; P<0.0001]) vs. placebo (18.2%). The percentage of responders (49.3% for 300 mg [P = 0.03]and 51.5% for 450 mg [P = 0.005]vs. 38.3% with placebo) and change from baseline in mean number of weekly RFBMs (difference vs. placebo, 0.5 for 300 mg [P = 0.03]and 0.5 for 450 mg [P = 0.02]) was significantly greater with methylnaltrexone 300 and 450 mg/day vs. placebo during the QD period. All dosages of oral methylnaltrexone were well tolerated.
CONCLUSIONS: Oral methylnaltrexone was efficacious and well tolerated for OIC in patients with chronic noncancer pain, particularly the 450-mg dose.
The Center for Clinical Research, Winston-Salem, North Carolina, U.S.A.