Methylnaltrexone for opioid-induced constipation in advanced illness (MNTX 302)
In people with advanced illness whose strong painkillers had caused constipation that laxatives could not shift, a methylnaltrexone injection produced a bowel movement within four hours in about half, against about one in seven on placebo, without undoing pain relief.
Overview
Primary publication of MNTX 302 (NCT00402038). A total of 133 patients who had received opioids for two or more weeks, with stable doses of opioids and laxatives for three or more days without relief of opioid-induced constipation, were randomly assigned to subcutaneous methylnaltrexone 0.15 mg per kilogram or placebo every other day for two weeks. Coprimary outcomes were laxation within four hours after the first dose and laxation within four hours after two or more of the first four doses.
Laxation within four hours of the first dose occurred in 48 percent of the methylnaltrexone group and 15 percent of the placebo group; laxation without a rescue laxative after two or more of the first four doses occurred in 52 percent versus 8 percent (P less than 0.001 for both). The response rate held through a three-month open-label extension. Median time to laxation was significantly shorter with methylnaltrexone. No evidence of centrally mediated opioid withdrawal or change in pain scores was seen; abdominal pain and flatulence were the most common adverse events.
- Laxation within 4 hours of the first dose: 48 percent with methylnaltrexone vs 15 percent with placebo (P<0.001).
- Laxation without rescue laxative within 4 hours after two or more of the first four doses: 52 percent vs 8 percent (P<0.001).
- No evidence of central opioid withdrawal or change in pain scores; abdominal pain and flatulence were the commonest adverse events.
This trial, with its single-dose companion MNTX 301, is the evidence behind the 2008 US approval of Relistor for opioid-induced constipation in palliative care when laxatives fail. For a patient on strong opioids, it shows that the constipation can be reversed at the gut without touching the pain relief.
- Two-week double-blind phase; longer-term data come from the open-label extension.
- The abstract gives no per-arm patient numbers; the 62 and 71 split is from the Relistor label.
- Patients had advanced illness of mixed cause; most, per the label, had incurable cancer, but the trial did not select by cancer type.