Methylnaltrexone.
Author(s): Garnock-Jones KP, McKeage K.
Affiliation(s): Adis, Wolters Kluwer Business, Auckland, New Zealand. demail@adis.co.nz
Publication date & source: 2010, Drugs. , 70(7):919-28
Methylnaltrexone is a selective mu-opioid receptor antagonist that has restricted
ability to cross the blood-brain barrier, thus enabling reversal of
opioid-induced peripheral effects, such as constipation, without affecting the
central effects, such as pain relief. Treatment with subcutaneous
methylnaltrexone 0.15-0.30 mg/kg, relative to placebo, significantly increased
the rescue-free laxation response rate within 4 hours of the first dose (primary
endpoint) in adult patients with opioid-induced constipation and advanced illness
in two randomized, double-blind, placebo-controlled, multicentre, phase III
studies; one was a single-dose study (n = 154), the other a multiple-dose study
(n = 133). In the multiple-dose study, rescue-free laxation response rates within
4 hours after at least two of the first four doses (coprimary endpoint) were also
significantly higher in methylnaltrexone recipients than in placebo recipients.
Moreover, median time to laxation after the first dose was significantly shorter
in methylnaltrexone recipients than in placebo recipients in both studies.
Methylnaltrexone was not associated with any significant changes in pain scores
or central opioid withdrawal in these studies. Methylnaltrexone was generally
well tolerated in clinical trials; most adverse events were of mild to moderate
severity.
|