LAS VEGAS, NV — The cardiac safety of subcutaneous (SC) methylnaltrexone bromide is similar to placebo in patients with opioid-induced constipation and noncancer pain, reported Richard Rauck, MD, FIPP, of Carolinas Pain Institute, Winston-Salem, NC, at PAINWeek 2012.
Patients with chronic, noncancer pain taking long-term opioids are at increased risk of cardiac events compared with matched controls not taking opioids, likely confounding interpretation of non-controlled studies. Dr. Rauck and colleagues performed an analysis to evaluate the cardiac safety-related adverse event rates and changes in ECG findings of SC methylnaltrexone bromide using two approaches: 1) analysis of the pooled safety data from two randomized, double-blind, placebo-controlled studies (a Phase 3, 4-week double-blind phase of a 12-week with SC methylnaltrexone bromide 12mg daily or placebo; and a Phase 2, 4- or 7-day double-blind study with SC) in subjects with noncancer pain taking opioids, and 2) a case-control analysis from long-term open-label administration of SC methylnaltrexone.
In the pooled double-blind, placebo-controlled studies, mean daily opioid use, expressed as oral morphine equivalents, was 193.9mg and 194.3mg in the placebo and SC methylnaltrexone groups, respectively; no deaths occurred in the placebo or SC methylnaltrexone bromide groups. Specifically, there were no reported serious adverse events of myocardial infarction, cardiac failure congestive, or cerebrovascular accident in either of the treatment groups. Mean changes from baseline were small for all ECG parameter results for both groups, and no clinically significant changes in QTc interval were observed. These study results were consistent with findings from two thorough QT studies in healthy subjects.
Likewise, findings from the case-control analysis of patients maintained on long-term, open-label therapy indicated that the occurrence of potential cardiac-related events was not associated with days on study therapy. Events of a cardiac origin, therefore, appeared to be occurring at random and were not associated with duration of exposure.
The team was able to conclude that the lack of clinically significant changes in QTc interval with methylnaltrexone bromide is consistent with two thorough QT studies in healthy volunteers that found no clinically meaningful effect on QTc intervals with methylnaltrexone bromide administration. Overall, Dr. Rauck noted, “the data demonstrate no increased cardiac safety risk with SC methylnaltrexone bromide treatment in this noncancer pain patient population.”