William F. Peacock, MD

 I’ve enjoyed the opportunity to talk with you because I’ve learned a ton. Your experience and acknowledge is outstanding. To wrap this up, what would be your take-home messages for health care providers treating opioid-induced constipation?

 One would be to open the conversation if you see it on their list. I find that being a PCP [primary care physician] these days is the hardest job. The patients are living longer and in and out of the hospital. With the amount of record review, interaction with the charts, and certain care measures, this may be 10th on the list. They may be doing well from a pain relief perspective. We ask that question, but it’s hard when they have a million other medical problems. But it’s a simple question.

Patients oftentimes don’t want to bring it up or talk about it. It’s embarrassing. But it can affect their quality of life. We’re happy to help. I’m happy to see patients and have the longer discussion with them, especially if we can initiate the appropriate-line therapies to start. It’s important to open that conversation and ask them the simple question: “I see you’re on opiates. How are your bowel habits?” If there’s an issue, then start to get them on the right track to treatment, because it’s very efficacious and safe, as we talked about. They don’t have to bear this burden. We can help fix it for them.

 Yes, the conversation or even the prompt to have that conversation is important. We transitioned to electronic intake forms, and we have smart responses, where if somebody is taking opioids, it starts to ask about all the things related to opioids, including feeling sleepy, being able to function at work, and driving. Constipation came up there, and we were surprised by the number of people who were responding to this. We had never thought to have that discussion. With the time that you have to be able to discuss this, it might be very low on the list. But if you’re able to screen and have the conversation based on that response, it cuts out a lot of time, and thankfully we have some great options to choose from that will make the conversation go quickly and smoothly.

 Excellent. Thank you once again for participating in 

Expert Perspectives in the Management of Opioid-Induced Constipation

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A panel of experts discuss their key takeaways and the future of treating opioid-induced constipation. 

Future Directions in the Treatment of Opioid-Induced Constipation

 What other recommendations do you have for PCPs [primary care physicians] and emergency departments [EDs] for collaborating on care and treatment when selecting in OIC [opioid-induced constipation]?

 I tend to go back to what Neel was alluding to. Sometimes it’s harder for the ED, because the prescription process for us is very different in the outpatient setting. We get earlier flags from pharmacies or pharmacies can communicate with us within a short period of time, whereas the EDs are often mayhem, and if Walgreens is calling because something isn’t on the formulary, they aren’t going to get anyone.

For us, it’s a little different. The biggest issue that we run into when choosing one is drug-to-drug interactions. That’s why we use methylnaltrexone the most while transitioning inpatient to outpatient with subacute orals. The ability to not have that concern with the lack of being metabolized by a CYP3A4 is generally how I’d do it. But the best therapy is going to be the one that the patient gets and the one that’s going to be efficacious for them. Regardless of which one, as long as it’s efficacious and safe for them to take and they benefit from it, then we’re happy.

 I absolutely agree. No. 1 is speed of onset. Making a decision on how quickly this patient needs relief leads me down to this subcutaneous recommendation. With the transition to oral therapies, matching the one that you tried in the subcutaneous formulation and avoidance of any drug-to-drug interactions is key. If it can be avoided, why go through the risk of trying something else? In terms of working with our colleagues, hopefully they’re familiar, and access to getting the drug is so vital. Sometimes we have to argue with the insurance companies for we want, and hopefully we’re successful.

William F. Peacock, MD; Conar Fitton, MD; and Neel Mehta, MD, discuss a multidisciplinary approach to treating patients with opioid-induced constipation.

Collaboration Among Specialists in the Management of Opioid-Induced Constipation

 How would you address the issue that OIC [opioid-induced constipation] is both common and undertreated at the same time?

 We’re doing part of it now. We’re spreading the word and making people aware. Certainly, the guidelines that you guys helped author, getting it out into the literature to spread it among our prescribing physicians, nurse practitioners, and physician assistant colleagues. Campaigns in direct-to-consumer have been eye-opening. The Super Bowl ad from several years back still gets talked about by patients and providers alike. It’s a topic that isn’t discussed and isn’t thought to be a major burden, but we’ve done a great job trying to highlight that. Also having frank conversations with our patients and trying to understand the adverse effects, because we’re giving them medications and we aren’t trying to discontinue the opioids. We’re trying to give them the most benefit that they can have with the least amount of adverse effects. Developing that trust and open dialogue with your patients hopefully will allow them to disclose exactly what they’re feeling.

 There are also some interesting new avenues to explore. When we talk to a gastroenterologist about this issue, they usually don’t have trouble diagnosing it, per se. But one thing that we see a small percentage of the time is patients who come in for a screening colonoscopy who have an incomplete preparation. They did everything appropriately, but for a variety of reasons, a small percentage of patients will have an incomplete prep.

We’re working it into our preprocedural questionnaire. Because in order to save health care dollars, most patients won’t have a doctor’s visit first if they’re relatively healthy. It’s called open access screening. We ask them a number of questions about things like cardiac history, blood thinners, something that would trigger a doctor to need to review their chart. But oftentimes, it’s just an order placed by their PCP [primary care provider], so we worked it in where we ask about constipation. If they say, “I generally only have 2 or 3 bowel movements weekly,” then we’ll say, “We’ll look through your medication list.” If they’re on opiates, we’ll say, “Maybe you’d benefit from seeing our nurse practitioner or having a visit with one of our doctors.”

That’s for health care costs reasons, to avoid having someone do all that and then possibly go under anesthesia for a procedure and then not be able to complete it, and having to redo it all again. That’s been a way, and it has been surprising how many procedures we’ve been able to improve by initiating a different therapy, something that we wouldn’t have thought of.

I want to ask Neel a question too. Have you noticed that it seems the trend over the last number of years is to funnel the opioid prescriptions to a fewer number of providers who specialize in that more? Do you think that’s going to improve recognizing these issues, because you deal with it so often? It’s a question that maybe is going to be asked at a higher percentage.

 To be honest, I haven’t seen that trend up here in the Northeast. The challenge comes in that many pain management providers are doing a variety of treatments, so they get a bit inundated just managing opioids. That said, we try our best to optimize things. We may tweak dosing on opioids. We may change things to better-suited regimens and introduce other multimodal therapies. While we’re doing that, we take the opportunity to talk about OIC. That’s where we hope that we’re getting more people to understand these differences. Certainly, those who are prescribing opioids will inevitably see the challenges of OIC, and hopefully they’ll educate themselves on what they can do to make things better. If you prescribe enough of these opioids, it’s going to come back to haunt you at some point.

 Conar, I wanted to expand on your description of having flags for patients who are going to be difficult to do a colonoscopy on. When you figure out that someone’s on opioids and may have a problem, would you give them a 3-day precolonoscopy treatment with methylnaltrexone, or would you do it the day of? How do you see that happening?

 I’d generally see the patient in the clinic and start them for a longer period to see if I can improve their baseline before scheduling them at all. We want to make sure they’re going to respond to that medication. It’s an interesting thought to have someone treated preprocedurally. But a colonoscopy from a screening standpoint is rarely urgent. It’s oftentimes urgent or emergent from a diagnostic bleeding or following abnormal imaging. But I’d see that person in the clinic.

Like Neel was saying, I usually have the patient get in touch with me in a shorter period of time about the efficacy, and then I usually see them about a month later. This would be someone I’d tell, “I want to make sure that when we do your procedure, we have the best chance, but it seems like you may have been suffering from this and it hasn’t been brought up or diagnosed. We’d consider this abnormal. Let’s talk about it a little.” I’d open that dialogue to say that, as we were alluding to earlier, when 4% to 5% of the population possibly have chronic pain, that’s tens of millions of people. We certainly aren’t seeing that degree of people coming to their doctor. It’s underrecognized, and that’s why it’s good that we can get together and try to get some more education out there.

I wouldn’t only do it preprocedurally. I’d see them in the normal office outpatient setting and prescribe them medication. Or maybe they haven’t tried the first-line therapy, usually people have. Then if we were going to prescribe a PAMORA [peripherally acting μ-opioid receptor antagonists], I’d do it for weeks to generally a month. As we resolve their OIC, then I’d schedule them.

 Whenever given the opportunity to ask a company to do a study, as the research director for emergency medicine at Baylor College of Medicine, I always do it. I’d think that would be something that would benefit from a validated protocol because other people would follow your protocol. You could call it the Fitton protocol. Then they’d get out there and do it because you published your results. That would be extremely valuable. There’s nothing worse than going to a colonoscopy, getting put to sleep, and then leaving with nothing done.

William F. Peacock, MD; Conar Fitton, MD; and Neel Mehta, MD, share their thoughts on how to bring awareness to opioid-induced constipation.

Increasing Awareness Regarding Opioid-Induced Constipation

 What are the most common adverse effects you’ve seen with the PAMORAs [peripherally acting μ-opioid receptor antagonists]?

 It’s a conversation you’re going to want to have with people. I tie it in when I give the general overview of the pathophysiology in that it does a couple of things. No. 1, people should always be aware of the adverse effects of their medications, but you can also tell them a little about what to expect and why. Obviously, abdominal cramping or discomfort would be the most common one. It isn’t surprising. These patients essentially have had almost an intestinal stunning by the action of the opioid medications, and when you’re restarting peristalsis, it can cause some cramping, so I tell them about that. A small percentage of patients will have some nausea. Abdominal cramping is the most common. Flatulence isn’t uncommon. It shouldn’t be severe. It’s generally very short-acting.

A very small percentage of patients discontinue the medication due to adverse effects, but it shouldn’t be severe. In some of the studies, the percentages were in the 20s, 27% of patients. If it’s mild, it does a few things. No. 1, it’s important for them to know. No. 2, if you don’t tell people this, they’re going to call your office, and your medical assistant is going to quit. Patients should know, and I’m very honest with them about it. Low rates of diarrhea can happen, but we go through each one in detail with percentages because they should know and be aware. Also, if something significant happens, you want them to be aware of it and to call. But I let them know that those rates are very low.

 Conar hit on that very well. It’s also a good time to talk about when a patient should disclose something that we should be aware of in terms of contraindications. If they have outright obstruction, severe nausea, or vomiting, hopefully that would be apparent to us. But we want to make sure that if somebody has an obstruction, we want to avoid the risk of perforation by using one of these drugs. At the same time, if they’ve had prior risk of disruption to that blood-brain barrier, like if they’ve had brain surgery or significant traumas to the head, there’s a chance that it could trigger some withdrawal. Therefore, we need to be conscious about that as well.

 Those are excellent points. For an emergency doctor, it’s going to get you in trouble if they might be obstructed. Another thing that’s important here is that it isn’t an adverse event. It won’t take away their pain relief from their narcotic. When I talk to doctors, I hear this all the time. “It’s a narcotic reversal agent. That’s the last thing I want to do with my patient with cancer.”

In the meta-analysis we looked at, we lumped 3 of the randomized controlled trials together. We got a big population, and we looked at pain scores in patients regardless of frailty. We used the WHO [World Health Organization] classification on that. Even if they’re really frail, or if they’re pretty robust but they have severe cancer, having cancer and getting the drug, their pain scores didn’t change at all. They didn’t go up or down, which is exactly what you want. They maintained their pain relief despite the fact that they had relief of their OIC [opioid-induced constipation]. The lack of an adverse event is part of what makes these drugs more attractive.

William F. Peacock, MD; Conar Fitton, MD; and Neel Mehta, MD, discuss managing adverse events that stem from using peripheral μ-opioid receptor antagonists to treat opioid-induced constipation.

William F. Peacock, MD

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