Methylnaltrexone Induces Rescue-Free Laxation in Opioid-Induced Constipation

Subcutaneous methylnaltrexone was safe and effective in the relief of opioid-induced constipation (OIC) in patients with cancer-related or noncancer pain, according to findings from a post-hoc analysis published in Journal of Pain Research.

Researchers collected data from 2 randomized, double-blind, placebo-controlled phase 3/4 trials (study 302 [ClinicalTrials.gov Identifier: NCT00402038] and study 4000 [ClinicalTrials.gov Identifier: NCT00672477]. Patients with OIC were randomly assigned to receive placebo or 0.15 mg/kg or body weight-based dosing (8 or 12 mg) subcutaneous methylnaltrexone every other day for 2 weeks.

Study 302 had 78 patients with active cancer (methylnaltrexone, n=37; placebo, n=41) and 56 without cancer (methylnaltrexone, n=26; placebo, n=30). Study 4000 had 152 patients with active cancer (methylnaltrexone, n=79; placebo, n=73) and 78 without cancer
(methylnaltrexone, n=37; placebo, n=41).

The primary outcome of the study was the percentage of patients who achieved rescue-free laxation (RFL).

Stratified by study, treatment allocation, and cancer status, the patient cohorts had a mean age of 62.8 to 77.2 years; 42.5% to 61.0% were women; 90.2% to 100% were White; a current pain score of 3.0 to 4.7 points; and a median daily dose of opioid morphine from 72.0 to 204.5 mg.

In study 302, more methylnaltrexone vs placebo recipients achieved RFL in patients with (51.4% vs 14.6%; P <.005) and without (44.0% vs 16.7%; P <.05) cancer. Similar results were observed in patients with (69.6% vs 15.1%; P <.001) and without (70.3% vs 22.0%; P <.0001) cancer in study 4000.

Significant differences in RFL were maintained through 24 hours and significant improvements in laxation responses within 4 hours of methylnaltrexone were observed in the first 4 doses.

The median time to first RFL was significantly lower among methylnaltrexone vs placebo recipients with (median, 3.47 vs >24 h; P <.005) and without (median, 6.52 vs >24 h; P <.05) cancer in study 302 and patients with (median, 0.75 vs 18 h; P <.001) and without (median, 0.92 vs 23.8 h; P <.0001) cancer in study 4000.

No significant group differences in pain scores were observed during the study.

The most common treatment-emergent adverse events in both trials included abdominal pain, diarrhea, nausea, and vomiting. Serious adverse events were reported by 16.2% and 11.4% of methylnaltrexone recipients with cancer and 29.3% and 17.8% of placebo recipients with cancer in studies 302 and 4000, respectively.

Limitations of the study included the short follow-up duration in both source trials and the lack of data on the frequency of chronic idiopathic constipation prior to opioid treatment.

The study authors concluded, “Methylnaltrexone effectively and rapidly induced rescue-free laxation in patients with OIC occurring in active cancer and noncancer diagnoses and generally was well tolerated in all patient groups.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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