Post Hoc Analysis of Single-Dose Methylnaltrexone Efficacy in OIC

William F. Peacock, MD: We did an analysis of 3 of the previously published OIC [opioid-induced constipation] treatment studies and took their populations and lumped them together so we could look at the effect of a single dose of methylnaltrexone. There ended up about 250 people in each group: those who got it, and those who got placebo. We were able to find out that methylnaltrexone works very quickly. Most patients had relief within an hour or 2. The reason we did this specifically in this population was to find what the applicability could be in the emergency department because I don’t have 6 or 8 hours; I have 1 or 2. That’s the advantage, and that’s what we found out.

This works very quickly in the majority of patients: 60% of patients will go to the bathroom within an hour or 2. From an ER [emergency room] point of view, that’s a plus because the other options I have are enemas or giving you something. We call it working from above or working from below. Either give you something that you take orally and we wait a long time for you to defecate, or we do an enema. Nobody wants to have an enema in the ER. It’s unpleasant for everybody involved. The nurses don’t like it, the patient hates it, and it doesn’t work that well. An option that wasn’t unpleasant and that actually worked was the goal.

The advantage of something that works within an hour or 2 is that if you come to the ER with a problem and it’s gone in an hour or 2, I can send you home. Nobody wants to be admitted to the hospital. It’s very unusual for people to say, “I want to be hospitalized.” Most want to have their problem fixed and go home. Here’s an opportunity to fix their problem and send them home. One challenges we have with OIC is that we have difficulty fixing it. Those patients will frequently get hospitalized or at least put into observation where they stay for a day or 2 and get enemas and are just miserable the whole time. Here’s a subcutaneous shot that you give them, they defecate, and then you have a conversation: “Do you feel good enough to go home?” Most of them say yes.

In that population, 40% of them did not have a reflex. They call it reflex relaxation. Those patients didn’t defecate and got no relief. They’re going to get hospitalized or at least put in observation to be worked upon more, but the majority have a benefit and are able to leave. The 40% who are left are going to have to go to what I call plan B, the historical methods of fixing their problem. You can repeat the dose of methylnaltrexone, but you’re supposed to wait 24 hours. If it didn’t work the first time in the emergency department, it’s plan B time.

The limitation in the study is that it’s a lump of all the other previously published data. The advantage is that it’s examined from an emergency medicine point of view. The disadvantage to it is that it’s a retrospective analysis of a different study with a different primary end point. The primary end point was not what happens in an hour or 2 but what happens more chronically than that. From an emergency department perspective, this is an important end point.

Transcript Edited for Clarity