Mu-opioid receptor antagonists were safe and effective for the treatment of opioid-induced constipation, while prescription-strength laxatives were slightly better than placebo in reducing the condition, a meta-analysis found.
Researchers searched the medical literature through March 2017 to identify randomized controlled trials of peripheral mu-opioid receptor antagonists (methylnaltrexone, naloxone, naloxegol, alvimopan, axelopran, or naldemedine) and the prescription-strength laxatives lubiprostone or prucalopride. Twenty-seven placebo-controlled trials were included in the meta-analysis. Of these, 23 evaluated mu-opioid receptor antagonists, three evaluated lubiprostone, and one evaluated prucalopride. Results were published by Clinical Gastroenterology and Hepatology on Feb. 5.
In the included trials, 5,390 patients received a drug and 3,491 received a placebo. Overall, mu-opioid receptor antagonists, lubiprostone, and prucalopride were superior to placebo for opioid-induced constipation, with a relative risk (RR) of failure to respond to therapy of 0.70 (95% CI, 0.64 to 0.75) and an overall number needed to treat of 5 (95% CI, 4 to 7). When analyses were restricted to only FDA-approved medications, the relative risk of failure to respond to therapy was 0.69 (95% CI, 0.62 to 0.77) with a number needed to treat of 5 (95% CI, 4 to 7). Individual numbers needed to treat were 15 (95% CI, 9 to 51) for lubiprostone , 7 (95% CI, 4 to 26) for naloxegol, 3.4 (95% CI, 3 to 6) for methylnaltrexone, 4 (95% CI, 4 to 6) for naloxone, and 5 (95% CI, 4 to 8) for naldemedine.
Treatment was more likely to be effective in study populations who were taking higher doses of opiates at baseline or who were refractory to laxatives, the authors found. Study duration and prespecified primary outcome did not affect the relative risk of failure. Participants who received mu-opioid receptor antagonists were significantly more likely to have diarrhea, abdominal pain, nausea, or vomiting than patients who received placebo, although the frequencies for these events were still relatively low in treatment groups (for example, 8.5% for diarrhea, 12.8% for abdominal pain, and 11.5% for nausea and vomiting).
The authors noted that no formal guidelines exist for use of mu-opioid antagonists in clinical practice, leading to underuse. “While some consensus is developing in regards to utilizing these agents in clinical practice for those patients with chronic pain on opiate treatment, this provides further evidence demonstrating the efficacy and safety of [mu]-opioid receptor antagonists and lubiprostone in the treatment of [opioid-induced constipation],” they concluded.