Methylnaltrexone Treatment of Opioid-Induced Constipation in Patients with Advanced Illness

Abstract

Methylnaltrexone, a peripherally acting mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, reverses opioid-induced constipation (OIC) without affecting analgesia. A double-blind study in patients with advanced illness and OIC demonstrated that methylnaltrexone significantly induced laxation within four hours after the first dose compared with placebo. In this study, patients with advanced illness and OIC on stable doses of opioids and laxatives were randomized to methylnaltrexone 0.15mg/kg (n=62) or placebo (n=71) subcutaneously every other day for two weeks. Laxation was assessed daily. Constipation distress, bowel status change, pain, laxative use, and opioid withdrawal symptoms were assessed weekly using standardized scales. Additional analyses to further characterize response to methylnaltrexone revealed that among patients with a bowel movement within four hours following the first dose, the median time to response was 0.5 hours for methylnaltrexone. Response rates among methylnaltrexone-treated patients who had responded to all previous doses were 57%-100% for doses two to seven. Among methylnaltrexone-treated patients who did not respond to the first or to the first two consecutive doses, 35% and 26% responded to the second and third dose, respectively. Higher percentages of patients and clinicians rated bowel status as improved in the methylnaltrexone than the placebo group. Fewer methylnaltrexone than placebo patients reported use of common laxative types, particularly enemas, during the study. Subcutaneous methylnaltrexone promptly and predictably induced laxation, improved constipation distress, and was associated with less laxative use in patients with advanced illness and OIC.

Subcutaneous methylnaltrexone for treatment of acute opioid‐induced constipation: Phase 2 study in rehabilitation after orthopedic surgery

“…Similar to findings demonstrated in a clinical study evaluating methylnaltrexone for OIC in a different patient population, those with advanced illness, 22 this study supports the premise that future laxation response with prolonged use is most likely to occur when a laxation response was achieved after the first or second initial administrations of methylnaltrexone. In contradistinction, if laxation does not occur with these early doses, continued methylnaltrexone dosing is less likely to produce a response later.…”

Methylnaltrexone in Treatment of Opioid-induced Constipation in a Pediatric Patient

“…Among these patients, opioid and laxative usage remained stable. 6 Similar results have been achieved by other investigators. 7,8 …”

Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms

“…Previous studies of methylnaltrexone therapy of patients with advanced illness and OIC showed a favorable impact on patient-reported constipation distress and Global Clinical Improvement of Change (GCIC) in bowel status scores [22,31]. Our study measured constipation symptoms from a broader perspective using the PAC-SYM, a validated multi-item instrument to assess constipation symptoms with a change of approximately half a point corresponding to minimal clinical improvement and changes of about 1 point corresponding to moderate clinical improvement [17].…”