LAS VEGAS—Fixed-dose methylnaltrexone, a peripherally restricted mu-opioid receptor antagonist, demonstrated robust and durable efficacy in patients with opioid-induced constipation and advanced illness, Janet Bull, MD, and colleagues reported at PAINWeek 2014.

Similar to weight-based dosing, fixed-dose methylnaltrexone was generally well tolerated for up to 12 weeks.

The Phase 4 trial randomly assigned adults with opioid-induced constipation receiving stable doses of opioids to methylnaltrexone 8 mg or 12 mg by body weight (38 kg to <62 kg or ≥62 kg, respectively; n=116) or placebo (n=114) every other day for 2 weeks.

The most common underlying advanced illness was cancer (66.1%). Median daily morphine equivalent dose was 176.8 mg/day and mean duration of opioid-induced constipation, 76.6 weeks.

Patients treated with fixed-dose methylnaltrexone were significantly more likely to have a rescue-free bowel movement, the primary end point, within 4 hours after 2 or more of the first 4 doses in the first week of treatment; this rate was 62.9% and 9.6% for methylnaltrexone and placebo groups, respectively (P<0.0001). The time to rescue-free bowel movement after the first methylnaltrexone dose was rapid, a median time of 0.8 hours versus 23.6 hours in the placebo group (P<0.0001).

The most common adverse events (methylnaltrexone versus placebo, respectively) were abdominal pain (33.6% vs 16.7%), nausea (11.2% vs 15.8%), and disease progression (8.6% vs 14.9%).