Opioid-Induced Constipation: Unmet Needs & Future Directions

David Wang, MD: We talked a bit about the novelty of this new class of agents, peripherally acting mu-opioid receptor antagonists [PAMORAs], and how effective they are. Let’s talk a little about where things still need to go and the gaps in care. Theresa, you alluded to education. What would you identify just broadly as some of the unmet need in this area?

Theresa Mallick-Searle, MS, NP-BC, ANP-BC: Something that we’ve already talked about is the differentiation, not only being able to make the diagnosis about opioid-induced constipation [OIC]—whatever tools you’re going to use, being comfortable having that dialogue with your patient—but also differentiating between OIC and idiopathic constipation. And if they’re conjoined, if they’re presenting together, then being able to treat them conjoined.

Then be able to not only educate your patients but educate your peers—peer-to-peer education about making the diagnosis and appropriate treatment is really important. The guidelines that are out there, even if they’re not the best guidelines and not what new organizations, like American Association of Physicists in Medicine, recommend. Early recognition is important, so preemptive treatment and then early recognition in terms of failures in treatment.

Brett B. Snodgrass, FNP-C, CPE, FACPP, FAANP: I think education, too, is so important when giving a PAMORA, because what are they used to doing with their over-the-counters [OTCs]? If 1 didn’t work, 2 are better. If 2 didn’t work, double it up. Oftentimes they think, well, it’s the same situation here. If we don’t educate appropriately, then we very likely could have problems, and we know that there could be overexposure of 1 of these products, and it could cause it to cross blood-brain barrier and potentially lower the analgesic effect and offset those opioids there. Education is clearly needed when you are putting a patient on a new class of drugs such as this, because they’re used to handling these types of medications differently.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: Another issue, especially with a push to take people off opioids, thinking about a patient who has chronic pain, they haven’t made lifestyle changes, and now they’ve made a commitment to do that, and they come off the opioids. They’ve been on massive amounts of OTCs, and now they’re dependent on them without an opioid. That’s another issue that needs to be considered.

Richard Rauck, MD: Another deals with education. I think you’re right, Brett. Certainly you should never double these, and patients don’t always think that if 1 isn’t good, 2 have got to be better, but they get in trouble that way. The other thing is sometimes when they choose to take a pro re nata [as needed], because we know 1 of the things that happens with initiation of the drugs is they can get abdominal pain. I like to tell patients about that. I find that if you warn patients about adverse effects of a drug, they’re much more likely to be tolerant to it or they understand it. When you first start this, we think you’re waking the gut up, and you may get some abdominal pain. The risk is if they take it prn [as needed] every third or fourth day when they really think they need to have a bowel movement. They can really tend to expose themselves to a lot more adverse effects, particularly abdominal pain and cramping versus if they take it on a daily basis as these drugs are indicated for.

Theresa Mallick-Searle, MS, NP-BC, ANP-BC: That is an incredibly important point for pharmacists as well. They do a great job about looking at drug-to-drug interactions and some of these other factors that we had talked about. If you can normalize and let the patient know if they’re going to expect, they’re going to be a lot more compliant, yes.

David Wang, MD: Steve, what are your thoughts on where the field of opioid-induced constipation management is evolving?

Stephen Anderson, MD, FACEP: OK, I’m going to go all the way back to the start. We’re looking at alternatives to opioids. That whole sphere is expanding, so that may be part of that. That said, we are here really talking about people who have found a way to move on with their life by the use of opioids. Getting back to education, what we’re probably going to see the field evolve with is educating more providers to expand who might be patients who would benefit from this.

Most of us didn’t have this in our toolbox a decade ago. Now providers need to make sure that it’s in their toolbox, and it’s not just for palliative-pain patients. It may also be for patients with a chronic pain that is not just solved, as you said brilliantly, by taking fewer opiates. Let’s find a solution and wake them up to the fact that this is actually a drug that acts at the site of a problem to reverse that problem. If you put it to providers that way, it’s great. Not just expanding who’s going to benefit from these and who’s going to possibly prescribe them more often.

I actually have to say I’m going to spend 1 more minute going back to the opioid use disorder. A lot of those patients present to us with abdominal pain, and they don’t tell you that their prescription monitoring says, “I’m on an opioid,” but they’re using an opioid every day. Starting that conversation with them and get back to the fact that the first solution to them is to get off their addiction, find other options for them, etc. But if you don’t treat the problem they came for, a lot of them will dismiss the medical practice as being a solution. What we want to do is open the doors and say, “Yes, we’re here to help.” That’s part of where the field is evolving. Plus, I’m thrilled to hear what the next mu-receptor antagonist is going to be that’s out there, because this is clearly an area that needs to be expanded.

Theresa Mallick-Searle, MS, NP-BC, ANP-BC: I think 1 of the things, just speaking in the broader sense, is this idea that we can get so specific in our treatments, in our development of different pharmaceutical agents, and have as few systemic adverse effects as possible. It’s just amazing. I think that’s where we’re going in medicine and drug development in general.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: That’s makes pharmacists, industry, and medicinal chemists…

Theresa Mallick-Searle, MS, NP-BC, ANP-BC: Indispensable.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: Right, indispensable, no pun intended. Because, from a chemical standpoint, at least to me it doesn’t seem that difficult. You pegylate a chain, and you do something to prevent the passage through the blood-brain barrier. Of course, we do need to remember that there are people who may be prone to blood-brain barrier issues, people with Alzheimer’s, traumatic brain injury or something like that, seizure disorders. We have to be careful about that, but I agree, it’s pretty cool that they were able to manipulate the chemicals in the way that we are, which leads me to, where are we going with this, right?

David Wang, MD: Exactly.

Jeffrey Fudin, BS, PharmD, DAIPM, FCCP, FASHP, FFSMB: The next group of drugs coming out are the serotonin type 4 drugs. In Europe, there’s actually 1 called tegaserod, and I think it’s in phase III studies in this country now and again its activities on serotonin. There are other drugs, too, that look at peristalsis. Some of you guys may remember from years ago, there was a drug called cisapride. It increased peristalsis, and that was a great drug. But there are a lot of drug interactions, so it came off the market. Now of course we have metoclopramide. We’ve had that, but the problem with that is there are central nervous system dopamine problems. There are a bunch of drugs that are looking at increasing peristalsis that are coming down the pipeline as well.

Transcript edited for clarity.