March 05, 2018
2 min read

Opioid receptor antagonists safe, effective for OIC, review finds

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A meta-analysis published in Clinical Gastroenterology and Hepatology showed that mu-opioid receptor antagonists were safe and effective for treating opioid-induced constipation.

Judy Nee, MD, of Beth Israel Deaconess Medical Center, and colleagues analyzed data on several agents tested in the treatment of opioid-induced constipation (OIC) to provide updated guidance about their efficacy.

“The opioid epidemic highlights the rapid and widespread use of opioids in the United States in the last two decades,” Nee told Healio Gastroenterology and Liver Disease. “One of the most common side effects, but seldom discussed, is opioid induced constipation.”

Mu-opioid receptor antagonists approved by the FDA for the treatment of OIC include Relistor (methylnaltrexone, Salix), naloxone, Movantik (naloxegol, AstraZeneca), Entereg (alvimopan, Merck), and Symproic (naldemedine, Shionogi), and Amitiza (lubiprostone, Takeda) is an FDA-approved prescription laxative. Other agents not yet approved for OIC include mu-opioid receptor antagonist axelopran (Theravance), and the prescription laxative Resolor (prucalopride, Johnson & Johnson).

Nee and colleagues reviewed 27 placebo-controlled trials that evaluated mu-opioid receptor antagonists (n = 23), as well as prescription laxatives lubiprostone (n = 3) and prucalopride (n = 1) and reported their efficacy as relative risk (RR) for failure to respond to the therapy. The trials included 8,881 patients that either received some kind of OIC therapy (n = 5,390) or a placebo (n = 3,491).

Patients who received any drug were more likely to experience a favorable response (n = 2,784, 51.3%) than the patients who received a placebo (n = 1,157, 33.1%).

The overall RR for failure to respond to therapy was significantly lower for patients who were treated with a drug than those who received a placebo (RR = 0.7; 95% CI, 0.64–0.75). The researchers also noted that when their analysis was limited to just the drugs and dosage levels approved by the FDA the RR for failure to respond to therapy was 0.69 (95% CI, 0.62–0.77).

In a safety analysis, the investigators found that patients who took an OIC drug were more likely to experience adverse effects like diarrhea, abdominal pain and nausea when compared with the placebo group. However, the frequency of these effects was still low within the drug-treated groups — 8.5% experienced diarrhea, 12.8% experienced abdominal pain and 11.5% experienced nausea or vomiting.

Nee and colleagues also found the mu-opioid receptor antagonists were more effective for patients who took higher dosages of opioids, as well as those who were refractory to laxatives.

When the researchers analyzed the studies that included prescription laxatives lubiprostone and prucalopride — often used as first-line therapy for OIC — they found that, despite their efficacy versus placebo, they were not quite as effective when compared with the mu-opioid receptor antagonists.

“Despite [FDA] approval for the [mu-opioid] antagonists naloxegol, methylnatrexone, fixed-dosage oxycodone/naloxone, and naldemedine, no formal guidelines exist for their usage in clinical practice; thus, making them underutilized,” the writers noted in the study. “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 OIC.” – by Alex Young

Disclosures: The authors reported no relevant financial disclosures.