Slatkin, N., Thomas, J., Lipman, A.G., Wilson, G., Boatwright, M., Wellman, C., . . . Israel, R. (2009). Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients. Journal of Supportive Oncology, 7, 39-46.
To determine the safety and efficacy of subcutaneous (SC) methylnaltrexone in opioid-induced constipation (OIC).
Patients were randomized to a single dose of study drug or placebo administered SC. Groups were 0.15 mg/kg, 0.3 mg/kg, or placebo. Patients were randomly assigned in a 1:1:1 ratio to each study group. Baseline laxative regimens could be continued. Rescue laxatives (laxatives administered on an as needed [PRN] basis) were allowed, except within four hours before or after dose administration.
This phase was 28 days with 1 dose per 24 hours PRN. The initial dose of 0.15 mg/kg could be decreased to 0.075 mg/kg or increased to 0.3 mg/kg, based on response.
Patients completing the open-label phase could enter a three-month extension. The initial dose was the same as in the open-label phase, with dosing adjusted to 0.075 mg/kg, 0.15 mg/kg, or 0.3 mg/kg by investigator discretion.
This was a double-blind, randomized, placebo-controlled, single-dose study, followed by an open-label phase, and then an open-label extension phase.
SC methylnaltrexone is effective in the treatment of OIC and generally is well tolerated. No relationship exists between dose and laxation response, suggesting the optimal dose is 0.15 mg/kg.