Real-world Implications and Unmet Needs of OIC Management

William F. Peacock, MD: Trying to grade severity of OIC [opioid-induced constipation] is very difficult because this is a patient perception parameter. They can tell you, “I feel miserable on a scale of 1 to 10.” If they’re 10, that’s terrible; if they’re a 1, that’s great. But people never go to the ER [emergency department] with a 1. Everybody is more than a 5, and this is a made-up scale. I don’t think there’s an OIC scale, at least not for emergency doctors. It’s what the patient is telling you.

The population that we selected for our study was pretty diverse. It did predominantly contain patients with cancer—about 70%—but the important part is that another third of them were not. There were people with chronic back pain, chronic arthritis pain, and other reasons that people take narcotics. It’s a fairly representative population suffering from OIC that you’d see in an emergency department.

The point of picking the population and the diverse nature of this is that it can be used for real-world application. It’s not just a cancer drug. It’s not just for rheumatoid arthritis and broken bones. It’s for the full spectrum of people who will show up with the complications from an opioid.

The challenge of OIC is that our normal therapies don’t work very well. Our normal therapies include getting an enema—that’s not enjoyable, and it doesn’t work that well. You can get manually disimpacted—nobody likes that; it’s painful. Doctors and nurses have to do it but don’t like it, and it doesn’t work very well. Then you can give them something orally and wait around for 3 or 4 hours. You end up in this cycle of a bunch of stuff that doesn’t work well and is uncomfortable for everybody. A medication that could have a beneficial effect and be done in an hour or 2 is an option that we haven’t had.

Emergency doctors will be familiar with naltrexone. Naltrexone is the narcotic antagonist. You give it to them, and narcotics go away. The patient immediately goes into withdrawal if they were addicted. That’s a problem, but it’s the function. We call it Narcan-naltrexone. Methylnaltrexone is just as it sounds: they added a methyl group to it. The beauty of that is it doesn’t get into your brain, it goes to your colon. The way I think about this is your colon goes into withdrawal immediately, and you have to go to the bathroom, which normally happens with somebody who gets Narcan [naloxone], but Narcan [naloxone] goes in the brain and allows you to override the other effects of opioids. Methylnaltrexone can’t do that. It only acts peripherally. It’s 1 of the huge strengths of what we discovered in our analysis. When you give methylnaltrexone to a patient with cancer, they still have their pain relief. They don’t lose it, but their colon goes into withdrawal and they have to go to the bathroom, which is exactly the target. This is 1 of the nicest examples of designed medications I’ve ever seen. We have a medication that works really well and creates withdrawal, and we can prevent it from reversing all the effects. They maintain their pain medication effect but not their colon effect.

Transcript Edited for Clarity