A post hoc analysis of two clinical trials depicted that Methylnaltrexone when administered subcutaneously was well-tolerated, safe, and successfully caused rescue-free laxation (RFL) in people with active cancer and noncancer illnesses and suffering from opioid-induced constipation. Eric D. Shah et al. sought to assess the safety and effectiveness of Methylnaltrexone for opioid-triggered constipation in people with and without active malignancy.

Two Phase 3/4, placebo-controlled, randomized, double-blind studies were examined. Every other day for two weeks, subjects were given subcutaneous Methylnaltrexone (study 302, 0.15 mg/kg; study 4000, 8 mg or 12 mg depending on body weight) or a placebo. By cancer status, volunteers were stratified. Percentage of subjects achieving RFL was the major outcome, whereas, tolerability/safety, pain intensity scores, and time to RFL were the secondary outcomes ascertained. Results from each trial were assessed individually.

A total of 364 participants (study 302, n = 134; study 4000, n = 230) were incorporated in the safety population (subjects receiving ≥ 1 study drug dosage). 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).

A total of 78 volunteers had active malignancy (Methylnaltrexone, n=37; placebo, n = 41) and 56 individuals did not have active cancer (Methylnaltrexone, n = 26; placebo, n = 30) in study 302. Overall, 152 patients had active cancer (Methylnaltrexone, n = 79; placebo, n = 73) and 78 patients did not have cancer (Methylnaltrexone, n=37; placebo, n = 41) in study 4000.  When given as a weight-adjusted fixed dosage (cancer, 59.5% vs 6.8%; noncancer, 70.3% vs 14.6%), Methylnaltrexone considerably caused a laxation response within 4 hours after minimum two of the first four doses than placebo.

Average time to RFL after the first dose of fixed-dose Methylnaltrexone for subjects with and without cancer was less than one hour. With Methylnaltrexone dosed according to body weight, the first RFL took place in less than four and less than seven hours of intervention in people with and without active malignancy, respectively. Pain scores did not differ considerably from one another. In all patient groups, Methylnaltrexone had good tolerability at all dosages. Also, it exhibited a favorable safety profile for opioid-induced constipation in people having advanced cancer and noncancer illnesses.