Reviewing Different PAMORAs for Opioid-Induced Constipation


A multidisciplinary panel shares individual experience with using oral peripherally acting μ-opioid receptor antagonists in managing opioid-induced constipation.

William F. Peacock, MD: There are other treatment options. A couple of them are oral. There’s another that’s subcutaneous as well. My concern with oral is that time is the consequence of that. Can you guys talk about your experience with these other PAMORAs [peripherally acting μ-opioid receptor antagonists]?

Conar Fitton, MD: We use the subcutaneous in the hospital. I’m not sure if it’s a bioavailability issue, where if you look at the data, it’s a little faster. A lot of times, especially in the patients I’m dealing with, whether it’s in the intensive care unit [ICU] or our patients who have gastrostomy tubes, the subcutaneous is a good option. About 15% of my patients will choose to continue that as an outpatient as their choice of PAMORA. Some of them are diabetic and comfortable with subcutaneous. It doesn’t matter to them. Or they have a family member who’s a health care provider and they like the speed at which it works.

Of the other options, the oral therapies as an outpatient are good options. Once the patients see how they’re going to respond to it, if they can get their schedule around taking it at a certain time and see how reliably it’s going to work for them, I’ve had good experiences with them. The key is that certain ones are metabolized by the same CYP3A4 enzymes, so you have to look out for medication interactions, especially as a lot of our patients are older and on lots of drugs. I blame the cardiologists for most of them, but they keep me in business, so I love them. The choice of therapy is going to be individualized on a patient-by-patient basis, but I haven’t had too much issue with people taking them as an outpatient. But subcutaneous in the hospital, for sure. I was surprised by how many people want to do subcutaneous as an outpatient. They’re like, “This works and I don’t want to change it.” I have no problem with that.

Neel Mehta, MD: Yes, I agree with Conar that subcutaneous is fabulous in the ED [emergency department] and inpatient setting, and many have sworn by it in the outpatient setting. When we transition patients from our hospital, when something has been effective, like the subcutaneous, we like to stick with the methylnaltrexone similar mechanism in the oral form. The other products are effective, too. The challenge that we face is wondering when we’re going to run into some of the drug-to-drug interactions that Conar talked about that we need to highlight. The other part is that some of it is channeled by what’s on the formulary for that particular insurance. Sometimes there’s no rhyme or reason as to which one is available and which one isn’t.

William F. Peacock, MD: We did a cost analysis. It was directed at CEOs, the C-suite, and insurance companies. We looked at 30,000 patients who ostensibly had OIC [opioid-induced constipation]. The challenge is that there’s no OIC code where you can just pull them out of a retrospective database. We had to create that. We said, “You were on narcotics for at least 3 days over the last week, you came to the hospital with abdominal pain, and you were hospitalized for less than 7 days,” because you shouldn’t be hospitalized for more than a week with OIC. We looked at that population and the cost implications of the availability of methylnaltrexone. We said that any PAMORA would work, but the dominant pharmacologic agent—at least in the United States—is methylnaltrexone, so it was 93% of the patients.

We looked at that as a function of what would happen next. If you got that in the ED, your probability of being hospitalized dropped tremendously. The odds ratio was about 2.4. It was enormous. If you were hospitalized, you stayed a day shorter than if you hadn’t had the treatment. All this turns into huge health care economic consequences. When we finished the analysis, we saw that every dose saved $732. For places that argue to not have this, I say, “You must not see OIC.” Because a consequence of not having it means a lot of those people get hospitalized and stay an extra day, and someone has to pay for that.

Conar Fitton, MD: It’s a lack of understanding. Because for someone who doesn’t suffer from this, it’s an issue that doesn’t seem that big a deal. We’ve all had issues. Everyone through their life will get sick and have constipation or diarrhea. After a few days, maybe you’re uncomfortable, but it isn’t that big a deal. You have to break things down in a way that you’re going to get the effect you want. With a cost analysis like that, when you said 30,000 patients, I was going to say, “Isn’t that a normal Sunday in the ED?”

William F. Peacock, MD: That’s how long the line is.

Conar Fitton, MD: That’s right. But you have to break things down in numbers where people will understand the degree of it. Although this is common for us, unless people are dealing with it, it doesn’t seem like that big a deal. I tell patients when I’m talking about risks, adverse effects, and procedural risks that when you say something like 1 in 5000, all people hear is “someone else.” They think, “That stinks for that person.” But for that 1 person, it’s 100%. Talking about or producing data where 1 injection or 1 subcutaneous treatment is saving $732 per dose, if you think about how many doses we’re using, the cost savings of that 1 day in the hospital or ICU is massive.

Neel Mehta, MD: Absolutely.

William F. Peacock, MD: A friend of mine is the director of the emergency department at the University of Texas MD Anderson Cancer Center, which is a big cancer hospital. I mentioned this to him, and he said, “I have to have that,” because he understood it. It took him about 10 seconds. He said, “I see 5 of these people every single day.” Then I talked to other friends of mine who are in smaller rural hospitals, and they said, “I see somebody like that maybe once a month.” There’s a huge spectrum bias based on your exposure. That has to fit in somehow. But having it on the formulary as an option saves $732, so it seems like a no-brainer.

Transcript Edited for Clarity

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