Researchers have found that methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may offer an effective solution to relieving patients' opioid-induced constipation with minimal side effects.

"Opioid-induced constipation (OIC) occurs in as many as 80% of patients treated with opioids, frequently leading to patients reducing their dose or stopping pain treatment altogether, which impacts their quality of life and keeps them experiencing pain," said researcher Neel Mehta, MD, in an email to Pharmacy Times®.

The research, presented in a poster at the 2019 PAINWeek conference, suggests that methylnaltrexone can effectively relieve constipation quickly and effectively without negatively impacting the effect of opioid pain relief. The major adverse effects of the drug were found to be more related to the fact that the patients were having their first bowel movement in a significant amount of time, rather than an effect of the drug itself.

The study utilized pooled data from 2 randomized, double-blind, placebo-controlled clinical trials that evaluated the safety and efficacy of subcutaneous or oral methylnaltrexone. One of the unique aspects of methylnaltrexone is that it's currently the only treatment available in both pill and injection form, Mehta said.

Patients in the subcutaneous study were randomized 1:1:1 to receive either 12 mg once daily, 12 mg every other day, or a placebo for 4 weeks, then as needed for an additional 8 weeks. Patients in the oral methylnaltrexone study were randomized 1:1:1:1 to receive 150 mg, 300 mg, 450 mg, or placebo once daily for 4 weeks, then as needed for an additional 8 weeks.

Both forms of the drug were effective, but the subcutaneous form was quicker to relieve patients' symptoms.

"However," Mehta added, "in the real world, patients generally prefer the oral formulation and the subcutaneous use is more popular in hospital usage when relief needs to be quicker."

Abdominal pain was the most commonly reported adverse event on treatment day 1 among patients who received methylnaltrexone or the placebo. On day 2, the frequency of abdominal pain had decreased among patients receiving methylnaltrexone, but remained the same among patients receiving the placebo.

The 5 most common adverse effects after abdominal pain included nausea, diarrhea, vomiting, urinary tract infection, and upper respiratory tract infection.

Mehta added that another unique aspect of methylnaltrexone is its lack of drug-drug interactions due to its chemical structure. This is especially important for the elderly patient population, Mehta said, because they are frequently on multiple medications.

The researchers were able to conclude that early-onset adverse effects experienced with methylnaltrexone treatment, and especially gastrointestinal adverse effects, were largely attributable to the patients' laxation after a long period of constipation. Treatment with the drug was also shown to relieve opioid-induced constipation without inducing withdrawal symptoms or compromising pain relief.

Constipation is a common and impactful side effect of opioid use, but Mehta said they're hopeful that pharmacists and physicians can begin to implement use of methylnaltrexone now that it has been found to be well-tolerated and effective.

  1. Mehta J, Slatkin NE, Stambler N, Israel RJ. Attrition of methylnaltrexone treatment-emergent adverse events in patients with chronic noncancer pain and opioid-induced constipation. Poster presented at: 2019 PAINWeek (Abstr 142-143). Sept. 3-7, 2019. Las Vegas, Nevada.