Narrator - Dr. Abel  00:00
Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions.

Narrator - ?  00:11
This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy.

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And now on to the show.

Dr. Sean Kane  00:31
Welcome to HelixTalk episode, 129 I'm your co host, Dr. Kane,

Dr. Khyati Patel  00:36
and I'm Dr. Patel. And in today's episode, let's take it down a notch. De prescribing PPIs. We're going to get into discussing how we have some strategies and what kind of evidence we have behind decrease the use of proton pump inhibitors when it's not necessary. You remember in our episode 57 we kind of had this entire discussion on safety issues and what are the general use and recommendations for the PPI therapy setting that ground in this episode, we're focusing more on how exactly to de prescribe these agents. Perfect.

Dr. Sean Kane  01:14
Well, Dr. Patel, why don't we get into a patient case to kind of set the tone? And I think that inpatient pharmacists and other other healthcare providers, those on the outpatient side. I think really, everyone can identify with a patient who's on a ppi. And maybe it's time to start thinking about whether it's appropriate to get rid of that PPI or not. We'll go through kind of the thought process there. So why don't you give us, like, a sample patient that I think many people could identify with?

Dr. Khyati Patel  01:40
Dr. Kane, you said it. So, right? I feel like it's my subtle mission in the clinic whenever I spot unwarranted use of PPIs to make sure the patients are, you know, taken off of them. And this is what we're going to talk about, how to take him off of them. So kind of patient case that I've encountered in the clinic when I to kind of provide that in this fictional patient case, it's a 56 year old male Mr. MT has past medical history of hypertension, pre diabetes, obstructive sleep apnea, obesity, kind of goes everything together, knee osteoarthritis and anemia. He's he's having some iron and B 12 deficiency issues and GERD. His last episode of GERD, however, was three years ago, and since then, he's been on pantoprazole 40 milligrams daily. You know, he doesn't really remember when the last time he had a sort of a flare from the first episode, but all of his other conditions, you know, there's just so many medications, and he comes to you and says, Are there any medications that I can stop using? I'm just tired of taking all this meds. As a student reviewer or pharmacist reviewer, you kind of look at and see pantoprazole 40 milligram. It's been three years. He's not really had another episode. Do we necessarily need to continue it? So you kind of spot that as a questionable medicine. But how do we actually approach this, you know, with Mr. MT, so let's, let's kind of talk with the background first.

Dr. Sean Kane  03:08
Yeah, so I mean, in terms of ppi, is kind of how they're working. You know, these obviously decrease gastric acid production, and the way that they do that is by blocking a protein called the hydrogen potassium ATPase exchanger or pump. And this is actually a protein present on the parietal mucosal cells of the stomach. And it's like the final pathway to get hydrogen ions, or, you know, acid, into your stomach. So it's blocking the final piece of the puzzle to get acid into your stomach, and it actually does a really good job of doing that. So this will increase the gastric pH, therefore you have less acid in your stomach. And hopefully that will help with heartburn, Gerd and things like that,

Dr. Khyati Patel  03:50
yeah, most common use, you know, even in the patient example we gave, was GERD. But there are some FDA approved indications in addition to treating GERD for these agents, and those are erosive esophagitis, gastritis or duodenitis. This kind of gives similar symptoms to GERD. But in addition to those, peptic duodenal ulcers, gastric ulcers certain hyper secretory conditions such as Zollinger-Ellison syndrome, we use them in combination regimens for H. pylori treatment. And then kind of your alley Dr. Kane, you've seen this in ICU patients or stress ulcer prophylaxis too,

Dr. Sean Kane  04:33
for sure, and we'll talk about later how the use of PPIs and really any acid suppression therapy for stress ulcer prophylaxis This is actually a really common reason why patients will end up on these acid suppression therapies and kind of not even realize why they're taking it. It's very common that these are continued beyond their indicated use, which is only in the ICU in terms of agents. You know, there's a lot of PPIs out there on the market. We'll go through kind of brand and generic. Just, if anything, for pronunciation reasons, but just to highlight how many there are out there. So protonix or pantoprazole, that's prescription only. We also have Prilosec or omeprazole, that's prescription and also over the counter. Dr. Patel, what are some that come to your mind?

Dr. Khyati Patel  05:14
Nexium is the brother, and it's the s omeprazole that's also available over the counter. Basically it's an acid and an tumor of the omeprazole. And then going along the lines of omeprazole, you add a little bit of sodium bicarb to it, maybe not a little, a lot, and you have a product called zegrid that's also available over the counter. And this one is not sort of a delayed release, like most other PPIs are, but adding that sodium bicarb helps improve that bioavailability. Otherwise, the stomach acid just kind of, you know, does not let the medication get absorbed properly, so that, but we have to kind of worry about all that sodium load that comes in with the additional sodium bicarb that's in there.

Dr. Sean Kane  05:59
Then, of course, we have Prevacid, which is available as prescription and OTC, the generic of that is lansoprazole. And then the brother to that one is Dexilant, which is dexlansoprazole, that's prescription only, and that's the dextrorotatory enantiomer of lansoprazole. That's why it's called dexlansoprazole. So again, we have kind of these similar formulations with many of these PPIs, some of which are kind of patent extenders. For the most part, these PPIs are fairly similar in terms of efficacy and safety with each other. Yeah.

Dr. Khyati Patel  06:30
and I think the one that's kind of not the mainstream one we see them in the you know, pharmacy only is prescription only is Aciphex or rabeprazole, and so that basically summarizes all different PPIs that we have available in the market so far.

Dr. Sean Kane  06:46
Yeah, in terms of dosing, you know, for the most part, these are dosed once a day, but they can be dosed twice a day depending on indication. Ideally you want to take these on an empty stomach, and the reason is that the actual half life of the drug is fairly short, and you want to maximize serum concentrations at the time that those acid pumps are being turned on. So if you take it 30 to 60 minutes before breakfast, your C max, your maximum concentration, is going to be at the time that you start having your acid pumps turn on because you're starting to eat your breakfast. So for optimal efficacy, you really want to take these early in the morning, right before breakfast, 30 to 60 minutes. And of course, if you take it twice a day, you're going to take it 30 to 60 minutes before your evening meal, like dinner again, to maximize efficacy of the medication

Dr. Khyati Patel  07:30
and Dr. Kane, that leads right into some of the important pkpd to discuss. So you're absolutely right, like the peak of C max of these agents can occur and even anywhere between 30 minutes to five hours, depending on the agent we're using. But going back to how you explain the mechanism, you know, it's it's a little bit interesting. The kinetics kind of sometimes match the dynamic. And it has to do with the fact that these agents bind to the hydrogen potassium ATPase pump covalently. And covalent binding is a forever binding. And so once taken a dose, the effect of a dose lasts for a little bit longer, because, you know, the the pumps that are bound by the ATPase are not working until the body makes new pumps. And it takes a little bit more so the maximum secretory inhibition, which is kind of like the full pharmacologic effect takes a little bit longer, three to five days, but once you stop taking the drug, it also stays there for longer, like I said, because the pumps have to be remade.

Dr. Sean Kane  08:31
And another interesting thing about these is that we do see drug interactions with these medications. Some of those drug interactions deal with the fact that altering gastric pH can also alter the absorption of certain medications, but we also see CYP2C19 and CYP3A4 interactions as well. So there can be implications with you know, some of the drugs that come to mind are things like warfarin, phenytoin, carbamazepine, diazepam, digoxin, levothyroxine, and some of these, you can draw drug levels or titrate to effect. Some you don't. So it does kind of depend on the patient and how big of a deal that interaction is. The one big one that I want to highlight is with omeprazole and the potential that it might decrease the efficacy of clopidogrel or Plavix. This is actually in the Warnings and Precautions section of the package insert for omeprazole. It's somewhat controversial, but the recommendation typically is to avoid concurrent use of omeprazole with clopidogrel, because it may make that Plavix or clopidogrel not work as well. But again, controversial. We don't think it's a class effect. We think it's more specific to omeprazole, whereas other PPIs probably don't have this problem.

Dr. Khyati Patel  09:41
So in addition to drug interactions, you know, there are some safety concerns. And as we recorded in Episode 57 you know, when these drugs came out in the market, they they were thought to be one of the safest medications out there, of course, with the short term studies that we had, and that's how the indications were. Work. They are not meant to be used for long term period. But fast forward, here we are, and we're using PPIs for years and years and so in quote, unquote, phase four data, we have a long list of things that can occur with uninhibited PPI use. So absorption related issues can occur, causing hypomagnesemia, reduced calcium absorption, leading to osteoporosis or increased risk for fractures, reduced B 12 iron levels, causing anemia. And then there are some other ones too. Dr. Kane,

Dr. Sean Kane  10:39
yeah, so especially on the inpatient side, there have been mostly retrospective reviews looking at when PPIs are given on the inpatient side, either for stressors or prophylaxis or just because it's continuation of a home medication. The use of PPIs has been associated with Clostridium difficile, diarrhea, colonization of multi drug resistant organisms, mostly enterobacteria, even vre which is vancomycin resistant, Enterococcus, even kind of more of an acute gastroenteritis. So a lot of things, potential increased risk of certain kinds of infections, even pneumonia. The problem with that data in particular, is that these are all retrospective studies, meaning that on the inpatient side, they compare people who got PPIs versus not, and people who get PPIs may be sicker at baseline and more predisposed to some of these problems in the first place. So cause and effect has not really been established, but it is certainly a consideration and a concern that absolutely comes up when discussing these agents.

Dr. Khyati Patel  11:39
That's good to hear. We definitely need more data to confirm this, but yeah, confounding variables needs to be addressed here. And when it comes to renal issues, acute interstitial nephritis as well as new onset ckds have been reported, and then those who have CKD like faster progression to ESRD have been reported again. The evidence is not as strong, but there is some pre indications that this could happen. And then let's talk about what happens actually with the long term use of PPIs, and that's a condition called hypergastrinemia. So as we discussed with the mechanism, PPIs are going to increase the pH of the gastric area, and this, this whole reaction is kind of negative. There is a negative feedback loop that's mediated by the somatostatin on the G cell, also located on the mucosal surface, and this whole process leads to increased gastrin release. Now, gastrin has more of a growth type, like tropic effect on these mucosal cells, and in some cases, there's been reports of hyperplasia occurring as well. We don't really know if that leads to polyp development or even cancer development. We just simply don't have that correlation. But with this hyperplasia, what really happens is when, when patients stop taking a ppi, there is this higher levels of gastrin produced, and that causes rebound hyper secretion. So rebound acid secretion. So you have somebody taking PPI for very long period of time, and now that we're going to stop it right away, and that gastr is just waiting, you know, to cause more heartburn. And so the patient will come back to you and hate you and say, I can't. I need to, you know, be back on it again. And it kind of forces patients and providers to be in this vicious cycle, you know, I stop it. I get this. But hey, the reason you got the this point is because we caused this negative feedback, and we we cause those gastrin levels to be high, and therefore, again, we need to make sure that patients are taking it just for the prescribed duration of time and not for long term.

Dr. Sean Kane  13:52
And Dr. Patel, I love this understanding of the kind of mechanism behind why it's hard to stop a ppi. And I just want to highlight that this is something that we see for many medications out there, where, when you take a medication and you block a certain pathway. So beta blockers are a great example. You block that pathway the body it knows that that pathway is blocked and it's going to increase either sympathetic tone or it's going to increase, in this case, gastrin, in an attempt to override that blockade that we've given pharmacologically. So we do see rebound effects of many medications if we abruptly stop them. And PPIs are no different. And as you said, these are really, really common medications, and the rebound can be severe enough that a patient just goes back on it and kind of gives up and says, Well, I guess I need to take this because my heartburn is so bad, when, in reality, it's really because of a withdrawal effect, as opposed to they truly need that PPI indefinitely. Some people do, but many people don't, but it's the withdrawal that is giving them that sense that they need to be on that ppi.

Dr. Khyati Patel  14:57
This also enforces some sort of. Um, lifestyle modification, right? Yes, PPI is going to help your, you know, heartburn, but you also have to follow certain things that triggers the heartburn. And there is this notion that, you know, I can pop these and eat whatever foods I want to eat, but that's not really the case. Those triggers are always going to cause, you know, heartburn in you, even if you've stopped taking the PPIs and gastrin. You know, hyper secretion is not an issue. So, yes, this explanation is really helpful. But then we also need to enforce the idea of avoiding triggers and kind of like that long term maintenance.

Dr. Sean Kane  15:36
And I think Dr. Patel, it might be reasonable to highlight kind of the nature of the problem in terms of, you know, I think generally people understand PPIs are really common. But perhaps there's some data that highlights the fact that of people who take PPIs, some of them don't have an actual indication for continuing it lifelong. And I think that might be worth highlighting. So, what data do you have that might emphasize the issue in the United States, at least of ppi, over prescribing or not, de prescribing when it's appropriate.

Dr. Khyati Patel  16:09
Yeah, and, you know, I've been looking into this Dr. Kane, I found data spanning from Canada to United States to, you know, Australia. So this problem of over prescribing and overuse. It's more of a worldwide problem, but looking at just United States, one of the studies said that 65% of the patients receiving PPI therapy have no documented ongoing indication for it. So you can imagine only 35% of the patients are appropriately being placed on PPI therapy.

Dr. Sean Kane  16:42
From my perspective, Dr. Patel, I see this very commonly, because I work in the ICU, and we use stress ulcer prophylaxis very commonly in the ICU. It is well supported by the data, roughly about 50% of the time when stress ulcer prophylaxis is initiated in the ICU, it is continued on the floor and then continued on hospital discharge. And for patients that have no indication for ppi and you continue on hospital discharge, you've now given them a new medication with drug interactions, co pays, costs, things like that, that in the future, people kind of don't know why they were started on it, and because they view it as kind of a benign therapy, they just continue it. And that literally feeds the problem of what we're talking about here, where, over a period of time, when you try to withdraw that ppi, now they're going to have a rebound effect, and now they will think that they have heartburn, even though they never had it in the first place. So getting rid of that stress, loss and prophylaxis after ICU is really important, for sure, not continuing it on hospital discharge if they don't have an indication for it.

Dr. Khyati Patel  17:43
And this, this this issue, and this is just one medication. This issue exactly highlights the importance of medication reconciliation upon, you know, discharge or upon changing the units in the hospital to continually evaluate whether the ongoing therapy, not just ppi, but any medication is necessary. And so transitions of care, pharmacists and students who are on rotations can play a huge role here, but kind of moving forward and discussing, you know, evidence one should know that there is actually no data to say long term PPIs can provide additional benefit for conditions such as GERD, and I'm just gonna spill the beans over here, but PPI use in GERD has been indicated for four weeks, and if must be, then eight weeks. So you can imagine, it's just eight weeks of therapy two months, and people are on it for years and years and years.

Dr. Sean Kane  18:38
And you know, there are data looking at patients that go from multiple doses of a PPI to a single dose of a ppi, so like bid to daily therapy, and at six months of follow up, once they do that transition from bid to daily about 80% of those patients report no recurrent GERD symptoms, meaning that if someone's on B ID therapy, the vast majority of patients will do fine if you transition them from bid to daily. And that is, as we'll talk about, one of the first steps in these patients that are on higher doses and more aggressive therapies is to start stepping them down and reevaluating their symptoms.

Dr. Khyati Patel  19:15
Yeah, you know, and then kind of looking at different indications. And we're here talking about indications such as GERD, because we know there is no long term use indicated for it. There are certain secretory conditions that we shouldn't really be talking about de escalating, because they're going to be on PPIs for lifelong but in some studies, they found that patients with GERD were more prone to continue PPIs than non GERD patients. And you know, only 21% of the patient GERD patients were off PPIs versus 48% of patients without GERD. So again, it's likely that these patients had higher gastrin levels at baseline and then they were on PPIs for. Is, you know, the patients who did not resume the pppi therapy. Yeah.

Dr. Sean Kane  20:05
And you know, another common thing to think about, again, more of an ICU topic, are those patients with GI bleeds, or if they've had recurrent gi bleeds, they probably will be on a PPI for a very long period of time. That's really not who we're talking about in this episode. I think, just to emphasize it, we're thinking about the patient with more routine heartburn, some patients with GERD, but those that are well controlled, that have been on it for some period of time. We're talking months to years, and the thought at some point in the future is, do they still need to take this therapy anymore? Again, we're not talking about those with like syndromes that are hyper secretory, that we're not talking about, or the patients with GI bleeds, things like that. We're talking more about the GERD type patient and the routine heartburn type patient, absolutely.

Dr. Khyati Patel  20:53
And, you know, similar to your point, Dr. Kane about, you know, standard dose versus low dose. So there's this other approach where, hey, standard dose pentaprasal might be 40 milligram, but 20 milligram may do just as well. And so the relapse rate, meaning patients having to return to the PPI therapy, again, was about similar in patients who were using low dose PPI versus the standard dose ppi. And again, this was statistically significant.

Dr. Sean Kane  21:22
And then there was another study that looked at kind of on demand PPI use which and then stepping it down to an h2 blocker like famotidine. And in that study, what they found was that doing that stepping down therapy versus continuing the PPI did result in an increased risk of symptom relapse. So as we'll talk about, if we can, we would love to step patients down from daily use to more of a PRN use. But as we'll talk about, there needs to be a reevaluation, because as you start withdrawing therapy, even when you're tapering down, some of these patients will have recurrence of their symptoms, and then you have to address it. And we'll talk about what those

Dr. Khyati Patel  22:00
steps would be. You know, one ideal or attractive thing about the on demand therapy is that it decreases the pill burden. So some some people may advocate for it, but we also, like you said, Dr. Kane, have to have a long term vision and figure out the patient doesn't relapse, and then be on it forever. So when we talk about deep prescribing PPIs, you know, what's the right approach? The answer is, there is no right approach. There has been all these little studies done on what's the right way to do it. Do we cut it from bid to ones daily? Do we go from standard dose to low dose? We kind of talked about some of the evidence amounted for it. But here is, in a nutshell, kind of the approach that we should take, and this boil down from different strategies, is always focus on what's the patient's indications for pppi use, what's the appropriate duration for the therapy and the effectiveness that would follow it. So meaning, is patient not complaining of the GERD anymore or heartburn anymore? Are they treated? So not assume that patients not okay and continue the medication, but re evaluate, right? Reevaluate the efficacy, and if you know that's the time to de escalate the therapy, then that's where we need to do it. So again, that approach is start with the lowest dose possible, with the shortest duration possible.

Dr. Sean Kane  23:23
And Dr. Patel, at least for me, one easy question I think that you could ask a patient is, do you know why you take this medication? And if they say heartburn, or they say they don't know, and you think it's appropriate to start de escalating therapy, then I think it's very reasonable to do so. If you have a patient who says that they had a GI bleed, or that they see a gastroenterologist and they've had, you know, an EGD done at some point where they had an upper GI scope done, then that might prompt a deeper discussion. But the vast majority of patients who are on PPIs either did it on their own because they had heartburn or they were given it at some point, and they kind of don't remember why anymore. At least for me, I see a lot of patients that had frequent hospitalizations or frequent transitions of care between different nursing homes and things like that. And it's easy for providers to add stuff like PPIs, but then it's really hard for someone to de prescribe. And I think that thinking, like you said about indication, that's really the first step to consideration of de prescribing some of these therapies like PPIs,

Dr. Khyati Patel  24:25
yeah, and Dr. Kane. That leads me to talk about some dosing too. Now you mentioned some hyper secretory conditions, and that's when the bid dosing is really indicated for conditions like GERD or even ulcer. Once daily regimen is usually the go to to start with. So sometimes I notice patients getting prescribed bid for such a such non hypersecretory conditions, and that should raise all the flags as well, and secondarily, if less, the patient says, you know, I. Take it once daily, and my heart burns not better. We need to talk and say, Okay, what time of the day does your heart burn occur? Mainly, sometimes they'll say, it's the evening that's probably when they're eating that larger meal. Maybe it's a little spicy or oily meal, and then, you know, maybe they're going to bed right after, you know, a short duration of time. All of these things can be addressed via lifestyle modification, or simply moving that morning dose to before they eat their dinner, because that's when their heartburn symptoms are happening, rather than adding another dose in the evening. So this means this strategy can also be helpful.

Dr. Sean Kane  25:35
I mean, you mentioned already kind of dietary considerations as a non pharmacologic therapy, so avoiding foods that give you heartburn, but also things like don't lay down if you're just to eat a meal, especially if your symptoms are worse when you're sleeping. Eat smaller meals. Eat more frequent meals. Weight loss for patients that are obese actually has really good data for improving heartburn symptoms. And I know that's harder and it's a longer term play, but again, it's probably more appropriate in an obese patient to recommend and target diet and lifestyle modifications to help with BMI and obesity and turn heartburn, as opposed to just saying, Okay, we'll just give you a pill to fix that problem, given all the other considerations of why obesity should be a target for intervention as well. And then, of course, in patients that have heartburn at night, there are kind of heartburn pillows out there that's like a slanted pillow that can help with nighttime symptoms as well. So there's a variety of non pharmacologic therapies that should be considered, especially as they're starting to taper down a regimen. And you want to kind of support the patient if they do have some rebound symptoms to prevent them from just going right back to their original PPI dose and therapy,

Dr. Khyati Patel  26:47
yeah, and this decision, you know, of de escalating again, it needs to be done in concert with the providers and the patients and there, that's where we need that benefit versus harm assessment, You know, is, is it giving you any additional benefit, or is it really causing harm in you? And sometimes that is an easier driver of the decision. And so definitely that needs to happen. And then really the options of how we deescalate or deprescribe PPIs, which we will talk a little bit more in detail, but we have multiple options, such as just completely discontinue it, meaning abrupt disruption. We can reduce the dose. We can do on demand dosing. And these strategies that I'm mentioning, all of these, are kind of tried in the literature when people have approached de escalation of PPI therapy. And the other one is, you know, kind of discontinuation by slowly tapering. And so that's when we are going to do that, those deep prescribing strategies. And in some cases, maybe heartburn is not completely gone, but we do have long term side effects of the PPI, but they still need some acid reducing therapy, perhaps switching to the, you know, the h2 receptor blockers might be something that could be discussed. And then all of this comes with monitoring and reassessment. You know, just because we have decided to de escalate or switch them or reduce the dose doesn't mean that we're not going to check up with them and be like, Hey, how are you doing? You know, how are your symptoms, et cetera, et cetera. So that also needs to be part of the plan.

Dr. Sean Kane  28:25
Dr. Patel, one interesting thing about this topic in particular is that there actually are guidelines specifically related to de prescribing. PPIs. There are other guidelines out there specifically for de prescribing, and these actually come out of Canada. So if you go to deprescribing.org there's a handful of guidelines about de prescribing certain medications in terms of what is an evidence based approach to doing. So, how do you monitor these patients? Things like that, other considerations. So either for the listeners going to deprescribing.org or if you go to HelixTalk.com and go to Episode 129 we'll have a link in our show notes as well. But these are great guidelines, because this is something that comes up very frequently, and these are evidence based guidelines in terms of what things to do when deep prescribing certain medications. And in this case, PPIs,

Dr. Khyati Patel  29:15
Dr. Kane, I absolutely love these deep prescribing guidelines, and I think that they're kind of flow diagram, or decision diagram on how to do it for the PPI is really inspiring. And like you said, it's it's not just bunch of expert coming together and throwing this together. It's evidence based. So let's kind of walk through what that algorithm looks like from this Canadian work group, as far as the PPI, the prescribing guidelines. So first of all, we need to decide what conditions qualify for this such such a deep prescribing and I think it's easier to kind of go with which do not so certain hypersecretory conditions such as Zollinger-Ellison syndrome, those who have Barrett's esophagus, those who have severe grade C or D esophagitis, those who have history of bleeding gi ulcers, or somebody who's on NSAID therapy on top of other anti platelets or anticoagulant therapy, and we are giving them PPIs for prevention of GI bleed. Those those patients are going to be on it for for a long term therapy.

Dr. Sean Kane  30:25
And you know, there is no perfect approach here. You know this needs to be somewhat patient specific, but generally speaking, our three main options in terms of decreasing the dose is going to be, if a patient is on bid dosing, you go to once a day dosing, if they're on a higher dose of a ppi and a lower dose formulation is available. Then do that. And then for someone who's on a lower dose on a daily basis, you can switch them from once daily dosing to every other day dosing. And that's effectively like the process of tapering down the dose over a period of time to help with that rebound that we would expect to see in many of these patients that have been on PPIs for a long period of time.

Dr. Khyati Patel  31:02
And as I said earlier, we definitely need to reassess where patient stands as we are views one of these strategies, right? So the reassessment is recommended anywhere between four to 12 weeks from deep prescribing. And what are we reassessing for? That's the first assessment. We're evaluating whether patients have heartburn, the regurgitation issues, any epigastric pain, dyspepsia, pain upon swallowing, etc, etc. And let's say that regimen worked and patients are okay, then we need to either do the next step and be prescribing, or if you want to continue on that smaller or lower dose or every other day regimen, then we can reassess that in six to 12 months. So in addition to kind of breaking this algorithm down from you know how to do it, what conditions don't meet, when to monitor, the next page of the guidelines, kind of talk about, what are the available PPIs out there, what are the standard doses and what are the low doses? So you can go from higher dose to or standard dose to lower dose therapy if you needed to. So all those kind of resources are on this intact guidelines. And it's, it's pretty neat, and they even talk about, you know, other issues, such as how to taper the dose, or what are the some of the on demand API dosing definitions,

Dr. Sean Kane  32:27
and not a big deal. But just to highlight, you know, these are Canadian guidelines, so you will see brand names that don't match what we have in the US, depending on the guideline, you may see dosage formulations, like standard tablet sizes that we may or may not have in the US, so just be aware of that. But the the overall approach is going to be identical in terms of high dose to low dose, and the kind of flow chart is going to be the same, just different brand names and potentially different formulations and what we have here in the US. Yeah, that's, that's

Dr. Khyati Patel  32:55
a good point to mention. Dr. Kane, thank you. We kind of, let's run it back to our patient, Mr. Empty, who presented with a concern that he's on too many medication, and he wants to, you know, kind of get rid of some of the medications, if possible. So kind of following this logic of deciding whether how we want to approach it, evaluating harm versus, you know, benefit discussion. This is how I would approach it. First of all, we need to look at what indication he was using it for that was GERD. And as I said earlier, the appropriate duration of PPI used for this, you know, population, this indication is four to eight weeks, and he's been on it for three years. It is definitely time to de escalate,

Dr. Sean Kane  33:40
you know, in terms of the benefit. So why is he taking it? He's effectively met the benefit. So he had GERD three years ago. He hasn't had any recurrence since then. It is possible he doesn't need the PPI anymore. In terms of harm, he does have harm. So he has an anemia related to b 12 deficiency and iron deficiency. Again, both of those are likely related to poor absorption of B 12 and iron in his diet. And for that reason, instead of just giving him b 12 and iron, which he needs anyway, to kind of correct that deficiency, the underlying cause may be his ppi, so he is being harmed by being on a PPI for too long, and it would definitely be worth revisiting. The need to continue that.

Dr. Khyati Patel  34:23
PPI, yeah, and patient preference, you know, we definitely want to do these things in in concert with patients and shared decision making. You know, approaches need to be employed. And this patient's coming to you asking you to get rid of some of the unnecessary medication. So that kind of gives you one easy step to kind of climb, and, you know, go to the next step. And so for him, as far as the de escalation, or de prescribing efforts, we could consider that he go from 40 milligram once daily to 20 milligram once daily, and then kind of reassess it in four weeks to. To, you know, see where he's at. We know where how his symptoms are, like he said he's not had another episode in the three years. But maybe we need to still reassess and not just completely abruptly stop him.

Dr. Sean Kane  35:13
You know, another approach could be that we go from 40 to 20 milligrams a day of pantoprazole for two weeks, and then when we're at that 20 we go to every other day for two weeks and then try to stop. And that would be our kind of four week reassessment point there as well. That would be another potential avenue that we consider.

Dr. Khyati Patel  35:32
Yeah, and as we discussed earlier, the importance of lifestyle modifications, you know, definitely come in play. So if you are doing a full interview and find out what are some of their trigger foods, or, as he is, you know, kind of dealing with obesity issues, perhaps you know discussion about how to promote weight loss if he needs help from dietitians or nutritionist or even personalized exercise prescriptions can also be given in order to help him lose weight. So all of these are possible approaches to consider, again, putting patient at the center and having a good shared decision making.

Dr. Sean Kane  36:11
So Dr. tell in terms of some key concepts, I think one thing is recognition of the problem, right? So PPIs are very frequently used by patients for a variety of conditions that help with gastric pH, but frequency or the incidence of undocumented indications for PPIs, where patients don't even really know why they're taking a PPI is actually fairly common in the US,

Dr. Khyati Patel  36:34
and even for those indicated condition you know, like legit conditions, the PPI needs to be used at the lowest dose possible for the shortest duration. That's, you know, approved by the FDA on the labeling.

Dr. Sean Kane  36:48
And another thing that comes to my mind is that PPIs are not benign therapies. You know, when you take it for the 14 day OTC, course, very few side effects, right? But when you take something that suppresses gastric acid secretion over many, many years, we do have evidence that there's at least an association, if not causation, of chronic PPI use with things like not absorbing magnesium, B, 12 iron causing anemias, certain infectious complications like C, difficile, diarrhea, pneumonias, potentially chronic kidney Disease getting worse. And then, of course, the big one is that if you're on it for a really long time, when you try to stop it, you can't, because you have these rebound symptoms. That alone is a problem that I think goes under appreciated as well. So the

Dr. Khyati Patel  37:33
various options we have for limiting PPI is, you know, abrupt discontinuation, although this shouldn't really be done because of the increased risk of that rebound acid hyper secretion that can occur. Those are the gastric acid levels, but somewhat more appropriate approaches, such as, let's reduce the dose. Go from standard dose to low dose. Maybe consider on demand therapy, although there is not a whole lot of evidence for on demand as needed therapy, maybe slowly prescribing. So going from bid to once daily or every other day therapy could work. And alternatively, we can consider changing it completely to another agent, such as h2, receptor blocker.

Dr. Sean Kane  38:16
And then, as we said, there are guidelines out there that are evidence based, guidelines for what are potential approaches? There is not a perfect best approach here, but generally speaking, decreasing the dose, either fewer doses per day, higher dose to lower dose, or even going from once daily to every other day. There's a bunch of other strategies that are options, and the guidelines do go through those options and some of the evidence supporting those different pathways, but oftentimes this is going to be patient specific, and it's also going to be driven by your monitoring of the patient in terms of how their symptoms go, based on whatever strategy you choose to use, and then based on that, deciding what the next step is for the patient. Well, Dr. Patel, thank you so much for bringing the topic for today's HelixTalk episode, as I said earlier, I think it's a really pertinent topic that many clinicians are curious about, and I think that many listeners will find this very helpful in their normal clinical practice. For those listeners that want to look at those deep prescribing guidelines or other literature, you can find that at our website, at HelixTalk.com episode 129 where you'll see show notes and some references as well. We love the five star reviews on iTunes, so keep those coming. We're also on Twitter at HelixTalk. If you want to get some of these clinical pearls delivered to your Twitter feed, can subscribe to us and get those in your feed as well. So with that, I'm Dr. Kane and I'm Dr

Dr. Khyati Patel  39:38
Patel, and as always, study hard.

Narrator - Dr. Abel  39:41
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