Methylnaltrexone Effective in Advanced Illness With Opioid-Induced Constipation

Repeated methylnaltrexone (MNTX) use was a safe and effective therapy for opioid-induced constipation (OIC) among patients with advanced illness who were refractory to laxative regimens. These findings, from a post hoc analysis, were published in Current Therapeutic Research.

The investigators from Loma Linda University Medical Center in Murrieta, California pooled data for this study from clinical study 302 (NCT00402038) and clinical study 4000 (NCT00672477) which were both randomized, placebo-controlled trials. In the analysis, the subset of patients (N=364) with OIC, were refractory to laxatives, and had a diagnosis of an advanced illness with a life expectancy of 1 month or longer and received a placebo (n=185) or 0.15 mg/kg or weight-based 8 mg or 12 mg MNTX (n=179) every other day were included. The outcomes of interest were rescue-free laxation (RFL) rates at 4- and 24-hours postdose for the first 3 doses. Opioid-induced constipation was defined as fewer than 3 bowel movements in the previous week and no clinically significant laxation event during the 24 hours prior to the first treatment dose.

The patients were aged median 66.0 (range, 27-101) years, 51.5% were women, 93.9% were White, 41.6% had a performance status score of 3, and they were taking a morphine equivalent daily dose of 145.7 (range, 0-10,160) mg/d. The most common advanced illness diagnoses were cancer (63.4%), cardiovascular disease (11.3%), other diseases (7.4%), and chronic obstructive pulmonary disease (3.9%).

Patients who received MNTX had more RFL events within 4 hours of the first, first and second, and first 3 doses compared with placebo (all P <.0001), in which cumulative RFL events increased from 62.4% within the first 4 hours of dose 1 to 80.9% within the first 4 hours of dose 3 among MNTX recipients.

The median time to RFL was 1.11 hours among the MTNX recipients compared with 23.58 hours among placebo recipients (P <.0001). Similar trends were observed when patients were stratified into performance status of 2 or less (median, 0.87 vs 17.79 h; P <.0001) and more than 3 (median, 1.46 vs >24 h; P <.0001) subgroups of MTNX and placebo recipients, respectively.

The proportion of patients with 1 or more treatment-emergent adverse events was 26.3% on treatment day 1 and 22.5% on treatment day 2 for the MTNX group and 14.6% and 14.1% for the placebo group, respectively. The most common events were abdominal pain, flatulence, nausea, vomiting, and back pain.

The limitations of this post hoc analysis were the different MTNX dosing strategies and study designs of the 2 underlying studies.

These data indicated that MTNX was safe and effective for the treatment of laxative-refractory OIC among patients with advanced illness. The study authors concluded, “MNTX represents a safe and effective OIC-specific therapy that should be considered for any patient with advanced illness receiving opioid analgesic therapy who fails to respond adequately to conventional laxatives.”

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.