IBS-C Management: Laxatives and Lubiprostone

JULY 09, 2019


Switching their focus to irritable bowel syndrome with constipation (IBS-C), panelists evaluate the use of laxatives and lubiprostone, respectively.


Mark Pimentel, MD: Going to the other end of the pendulum, not the table pendulum, the spectrum of symptoms—IBS-C [irritable bowel syndrome with constipation]. We have a lot of products that are FDA approved for IBS with constipation. Why not just use over-the-counter laxatives? They’re there. Is that what people are doing anyway? Can you talk about what we’ve got on the market, regarding laxatives? And what is the approach when using Miralax or not to use a brand but something that makes the stool moist?

Ali Rezaie, MD: There’s no shortage of over-the-counter laxatives out there. But a lot of times, by the time patients come to your office, they’ve tried multiple options. On average, patients have tried 5 over-the-counter medications before they come to you. The most common ones include the herbal laxatives, such as Senokot. There are medications that are becoming very common, like Triphala. There are supplements, such as magnesium supplements, that can be used. There are Miralax type of drugs, whether the generic form or Miralax, which are very safe, and we use these very commonly for constipation and also for colonoscopy preparation at the largest doses. So there is a very large therapeutic window, and it’s quite safe and it’s nonabsorbable. There are stool softeners as well. But again, for somebody with mild symptoms, can we use these to help with their symptoms? Absolutely. If that helps their symptoms and controls what bothers them, that’s definitely the way to go. You don’t need necessarily to go to the big guns that are now being approved.

Anthony J. Lembo, MD: I think it’s also worth mentioning that there is 1 study with polyethylene glycol that was done in Europe—it had electrolytes but essentially the same product. It didn’t improve abdominal pain. So as Ali said, it’s quite effective at improving bowel function, but it doesn’t seem to help with pain. It’s still my first go-to treatment for someone with IBS with constipation, and I agree. The nice thing about polyethylene glycol is that you can titrate the dose. What I’ll tell my patients is that you’ve got to give this 4 to 6 or 8 weeks, where you’re playing with a dose—and not every day but every 4 or 5 days or every week, to make it easier for patients—to find a point where your stools are soft. Not loose but soft, and give it time. Don’t expect it to improve all your symptoms, but see if that’s enough for you. Because for those patients, [as] Ali said, they’re mild. That may be sufficient for them, and they may be quite happy.

I personally combine it with fiber. I will give them a variety of different types of fiber, and that’s what takes the 6 to 8 weeks—to find that right combination that they think is best for them. And we use different types of fiber. Personally, I use prunes, but I may also use psyllium-based products. There are a bunch of different types of fibers. I use the combinations. But your question was on the bigger guns?

Mark Pimentel, MD: Oh, no, I’m not there yet. I’m just surprised that I used the word moist on stool. So maybe we’re moving to the moisturizers, otherwise known as secretagogues. First out of the gate is lubiprostone. You were involved heavily in some of that work, Bill. Can you start us off in the moisturizers or secretagogues here? Lubiprostone.

William D. Chey, MD: Sure. Lubiprostone acts directly on the CLC-2 channel, which is an important chloride channel. It acts predominantly in the small intestines. It increases chloride secretion, and that negatively charged chloride leads to paracellular movement of sodium and water, which you can imagine helps with stool consistency, and increases the mass of stool, which can stimulate peristalsis. So lubiprostone has been shown to be a benefit to constipation, and there are 2 doses that are available in the United States. There’s a 24-microgram dose given twice a day for chronic idiopathic constipation and an 8-microgram dose given twice a day for IBS-C.

The big issue to be aware of—outside of the fact that it seems to improve, by the way, the constipation symptoms and the abdominal symptoms—is the fact that there’s dose-dependent nausea. So with the higher dose of lubiprostone, in the clinical trials, 29% of patients developed some degree of nausea, although most of it mild. But there’s the occasional patient who can get significant nausea. People should remember that you should give this drug with food to try to minimize the likelihood of developing nausea.

Anthony J. Lembo, MD: It’s transient, though.

Mark Pimentel, MD: Anybody else on the panel use lubiprostone often? Brennan, do you use that in your practice?

Brennan Spiegel, MD: Not very much anymore, because there have been so many other medicines that have come along since then that, in my experience, are equally or more effective with better tolerance. But I do want to make the point that more generally, as we discuss IBS-C management, it is important for the viewers to distinguish chronic constipation from IBS with constipation. I don’t think we’ve made that point explicit just yet. Constipation and IBS with constipation—obviously both have constipation, but what distinguishes them is the abdominal symptoms: pain, the discomfort, the sensory experience, the bloating. And it’s not as if these are 2 completely different conditions. There’s a bit of a spectrum as people get more or less abdominal pain. I think it’s important because some of the treatments we’re talking about, like laxatives, might do a really good job at the constipation but might not improve the symptoms of abdominal pain or discomfort. As we go through these different treatments, I think about some of them as just bowel treatments. Others are multisymptom—targeting the multiple symptoms of IBS-C. Lubiprostone is an example that does really hit multiple symptoms based upon the clinical trials. It’s the first of a few that we’ll talk about here that I think are able to do that.

 


Switching their focus to irritable bowel syndrome with constipation (IBS-C), panelists evaluate the use of laxatives and lubiprostone, respectively.


Mark Pimentel, MD: Going to the other end of the pendulum, not the table pendulum, the spectrum of symptoms—IBS-C [irritable bowel syndrome with constipation]. We have a lot of products that are FDA approved for IBS with constipation. Why not just use over-the-counter laxatives? They’re there. Is that what people are doing anyway? Can you talk about what we’ve got on the market, regarding laxatives? And what is the approach when using Miralax or not to use a brand but something that makes the stool moist?

Ali Rezaie, MD: There’s no shortage of over-the-counter laxatives out there. But a lot of times, by the time patients come to your office, they’ve tried multiple options. On average, patients have tried 5 over-the-counter medications before they come to you. The most common ones include the herbal laxatives, such as Senokot. There are medications that are becoming very common, like Triphala. There are supplements, such as magnesium supplements, that can be used. There are Miralax type of drugs, whether the generic form or Miralax, which are very safe, and we use these very commonly for constipation and also for colonoscopy preparation at the largest doses. So there is a very large therapeutic window, and it’s quite safe and it’s nonabsorbable. There are stool softeners as well. But again, for somebody with mild symptoms, can we use these to help with their symptoms? Absolutely. If that helps their symptoms and controls what bothers them, that’s definitely the way to go. You don’t need necessarily to go to the big guns that are now being approved.

Anthony J. Lembo, MD: I think it’s also worth mentioning that there is 1 study with polyethylene glycol that was done in Europe—it had electrolytes but essentially the same product. It didn’t improve abdominal pain. So as Ali said, it’s quite effective at improving bowel function, but it doesn’t seem to help with pain. It’s still my first go-to treatment for someone with IBS with constipation, and I agree. The nice thing about polyethylene glycol is that you can titrate the dose. What I’ll tell my patients is that you’ve got to give this 4 to 6 or 8 weeks, where you’re playing with a dose—and not every day but every 4 or 5 days or every week, to make it easier for patients—to find a point where your stools are soft. Not loose but soft, and give it time. Don’t expect it to improve all your symptoms, but see if that’s enough for you. Because for those patients, [as] Ali said, they’re mild. That may be sufficient for them, and they may be quite happy.

I personally combine it with fiber. I will give them a variety of different types of fiber, and that’s what takes the 6 to 8 weeks—to find that right combination that they think is best for them. And we use different types of fiber. Personally, I use prunes, but I may also use psyllium-based products. There are a bunch of different types of fibers. I use the combinations. But your question was on the bigger guns?

Mark Pimentel, MD: Oh, no, I’m not there yet. I’m just surprised that I used the word moist on stool. So maybe we’re moving to the moisturizers, otherwise known as secretagogues. First out of the gate is lubiprostone. You were involved heavily in some of that work, Bill. Can you start us off in the moisturizers or secretagogues here? Lubiprostone.

William D. Chey, MD: Sure. Lubiprostone acts directly on the CLC-2 channel, which is an important chloride channel. It acts predominantly in the small intestines. It increases chloride secretion, and that negatively charged chloride leads to paracellular movement of sodium and water, which you can imagine helps with stool consistency, and increases the mass of stool, which can stimulate peristalsis. So lubiprostone has been shown to be a benefit to constipation, and there are 2 doses that are available in the United States. There’s a 24-microgram dose given twice a day for chronic idiopathic constipation and an 8-microgram dose given twice a day for IBS-C.

The big issue to be aware of—outside of the fact that it seems to improve, by the way, the constipation symptoms and the abdominal symptoms—is the fact that there’s dose-dependent nausea. So with the higher dose of lubiprostone, in the clinical trials, 29% of patients developed some degree of nausea, although most of it mild. But there’s the occasional patient who can get significant nausea. People should remember that you should give this drug with food to try to minimize the likelihood of developing nausea.

Anthony J. Lembo, MD: It’s transient, though.

Mark Pimentel, MD: Anybody else on the panel use lubiprostone often? Brennan, do you use that in your practice?

Brennan Spiegel, MD: Not very much anymore, because there have been so many other medicines that have come along since then that, in my experience, are equally or more effective with better tolerance. But I do want to make the point that more generally, as we discuss IBS-C management, it is important for the viewers to distinguish chronic constipation from IBS with constipation. I don’t think we’ve made that point explicit just yet. Constipation and IBS with constipation—obviously both have constipation, but what distinguishes them is the abdominal symptoms: pain, the discomfort, the sensory experience, the bloating. And it’s not as if these are 2 completely different conditions. There’s a bit of a spectrum as people get more or less abdominal pain. I think it’s important because some of the treatments we’re talking about, like laxatives, might do a really good job at the constipation but might not improve the symptoms of abdominal pain or discomfort. As we go through these different treatments, I think about some of them as just bowel treatments. Others are multisymptom—targeting the multiple symptoms of IBS-C. Lubiprostone is an example that does really hit multiple symptoms based upon the clinical trials. It’s the first of a few that we’ll talk about here that I think are able to do that.

 
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