Oral methylnaltrexone is efficacious and well tolerated for the treatment of opioid-induced constipation in patients with chronic noncancer pain receiving concomitant methadone.

purposeTo evaluate the safety and efficacy of oral methylnaltrexone for opioid-induced constipation (OIC). PATIENTS AND

methodsThis was a post hoc analysis of patients receiving methadone in a randomized, double-blind, placebo-controlled, Phase 3 trial. The trial included adults with chronic noncancer pain for ≥2 months receiving opioid doses ≥50 mg/day of oral morphine equivalents for ≥14 days and with a history of OIC. Patients were assigned to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily (QD) for 4 weeks followed by 8 weeks as needed. Percentage of dosing days that resulted in a rescue-free bowel movement (RFBM) within 4 hours of dosing was assessed during QD dosing (primary efficacy endpoint). Other endpoints included percentage of responders (ie, ≥3 RFBMs/week, with an increase of ≥1 RFBM/week from baseline for ≥3 of the 4 weeks) during QD dosing and change in weekly number of RFBMs. Adverse events were assessed.

resultsConcomitant methadone was reported in 120 patients (oral methylnaltrexone: 150 mg [n=33], 300 mg [n=30], and 450 mg [n=31]; placebo [n=26]). Oral methylnaltrexone-treated patients had significant increases in mean percentage of dosing days with RFBMs within 4 hours of dosing during weeks 1-4 with 300 mg (33.6%;

conclusionOral methylnaltrexone, particularly 450 mg, was efficacious and safe for treating OIC in these patients.