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. This podcast is Narrator - ? 00:12 provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 165 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is Cutie and the Beast managing medications that prolong the QT interval, and Dr. Patel today, we're obviously talking about QTC prolongation, and really how the typical clinician can evaluate Whenever a patient is at risk for Qt prolongation, what that actually means, and how to manage those kinds of adverse drug reactions or drug interactions. Dr. Khyati Patel 01:03 And I'm sure we see this all the time in practice, especially for us pharmacists, there is that drug–drug interaction popping up saying, hey, this drug increases QT risk. Or, I'm sure on the, you know, prescribing side, that flag goes up in Epic, which is a lot of the time ignored or consulted to a pharmacist, saying, What do I do? Dr. Sean Kane 01:22 Absolutely, and Dr. Patel, I just want to mention that this was actually a listener requested episode. So for the listener, if you have any episode topics that you'd like us to cover, you can reach out to us. Our contact info is at HelixTalk.com and related to the website, because of kind of a university pause on the website right now, we actually can't update it until July, so we'll still release our episodes, and the show notes are actually in the episode description in your podcast app, so you can see the references and things like that. But we won't be able to actually update the website until early July, so stay tuned for that, Dr. Khyati Patel 01:54 and to kind of set the stage, Dr. Kane, you know, perhaps my knock at the wood type of a case. Let's say you are an outpatient pharmacist filling a prescription for a Z‑Pak, which is our azithromycin for five days for a 50‑year‑old male patient, and the computer system flags an alert that there is an interaction between the Z‑Pak and the patient's chronic escitalopram, which is Lexapro, and that flag is for an increased risk of QTc prolongation. So as a pharmacist, how should you approach this? We cannot come back to the case at the end. Before that, though, let's start discussing what is the Qt or QTC, which is corrected QT interval, and why that prolongation is kind of the concern. Yeah. Dr. Sean Kane 02:44 From a literal EKG standpoint, we have our P, QRS and then T and a QT interval literally means the beginning of the QRS complex, which is where the ventricles depolarize, all the way to the end of the T wave, which is when the ventricle repolarizes. When we talk about a long QT, what we're talking about is that that process of ventricular repolarization is taking too long. And during that period where the ventricle is sitting there, not doing anything, waiting to repolarize, it's at risk for certain kinds of arrhythmias. The main one is called torsade point, and the way that you pronounce it is without the s at the end. So torsade de point is how they would say it in French. But the American version, I guess, is torsade point, or TdP for short. Dr. Khyati Patel 03:30 And as you said, Dr. Kane, the TDP is, you know, not good, because it's fatal, and it's a type of ventricular tachycardia, where the heart rate goes really fast and it doesn't allow ventricle to fill fully with blood, and patient can go into a cardiac arrest because of that. Yeah. Dr. Sean Kane 03:48 So this is a form of ventricular tachycardia. And sometimes ventricular tachycardias can be stable or unstable, meaning that the patient can kind of lose their pulse or be very unstable from a vital sign perspective, and the name itself actually is kind of interesting. So obviously it's French, and it stands for twisting of points, and it's it describes how the EKG looks during this polymorphic ventricular tachycardia, where it almost looks like twisting around the isoelectric line, or kind of a party streamer. Ask, look where each of the different QRS complexes are different size and shape because it's a polymorphic or different sized ventricular tachycardia. Dr. Khyati Patel 04:26 And this Qt prolongation could be drug induced, as we are kind of focusing on, but it could also be congenital. So this syndrome is also called Long QT syndrome. We're going to focus more on the drug induced aspect of the Qt prolongation in this episode, as it pertains for more to the pharmacist Dr. Sean Kane 04:45 role and Dr. Patel, like you mentioned earlier, we have Qt and QTC, and when we talk, we actually are almost always talking in QTC. This C stands for corrected, meaning that we actually correct the Qt length and the. Seconds for how fast or slow the heart rate is. So normally in humans, as your heart rate gets faster, your QT interval naturally shortens. Remember, the Qt is how long it takes for the ventricle to repolarize. So if you're going really fast with your heart rate, that interval is going to naturally get shorter. Or if you have a really slow heart rate, that interval is naturally going to elongate. Dr. Khyati Patel 05:21 So basically, from what I understand, Dr. Kane, is that the correction is kind of averaging this heart rate out. So correcting the QT interval, Dr. Sean Kane 05:30 yeah, it's a way to normalize it so that we're always speaking the same language in terms of a QTC above 500 milliseconds, for example, is prolonged, and that 500 milliseconds is independent of the heart rate because it's been normalized or corrected for heart rate. There's a bunch of different formulas. The Bazett formula is the most common, but there's a bunch of other ones out there, and there's different ways that you can mathematically correct to turn a QT to a QTc, which is the normalized or corrected version of that. Dr. Khyati Patel 05:59 So Dr. Kane, what is normal QTc, and how do we know if your patient's QTc is prolonged? Dr. Sean Kane 06:06 So it's kind of weird. It depends on who you ask. So most references will say that a normal QTc is around 400 to 440 milliseconds. Then there's kind of a gray area, and then many sources say around 470 to 480 is prolonged. Some sources will actually say that men have a naturally shorter QTc compared to women. And maybe for men, anything above like 450 is prolonged. And women, 460 is prolonged. Regardless, there are normal variations where some people have a little bit longer, a little bit shorter. But really, all references are going to say that anything about 500 milliseconds is a clear risk factor for this arrhythmia, TDP, torsade point, and in those patients where that QTC is more than 500 that's where we really start to get worried. Dr. Khyati Patel 06:55 So that's one way of looking at QTC prolongation. Is an absolute number anything about 500 but then there is another way of looking at it. Is like that percent change from the baseline. So you look at the patient's baseline, and then once a medication is added, you know, then consider how much, how many percentage change you're making, and that's an example. Is 15 to 20% increase from the baseline, or add like 60 milliseconds to the patient's baseline QTC, and that's considered a prolongation. Dr. Sean Kane 07:28 And the typical scenario with that, Dr. Patel, would be when we start certain class III antiarrhythmics like dofetilide as an example, and those patients actually have to be admitted to the hospital, and every time they get a dose, they get a new 12‑lead EKG to look for their QTc interval. And we're looking for both, is it prolonged, defined as being more than 500 milliseconds, but we're also looking from the change from baseline to your point, 15 to 20% increase, or about 60 milliseconds, and either of those scenarios where it's prolonged more than the baseline by above a certain amount, or if it's more than 500 we'll actually back off, or even discontinue that therapy, because we are worried about this ventricular tachycardia called torsade point. Dr. Khyati Patel 08:13 And then that's that's one way of looking at right that absolute increase or percentage increase, but looking at the risk value attached to certain medication. FDA then categorizes this Qt prolongation risk into like three different categories. Can you elaborate a little bit on that? Dr. Kane, Dr. Sean Kane 08:33 yeah, so the FDA actually has a guidance document that is referenced in our show notes, where they basically tell manufacturers that they want new medications to be evaluated for Qt prolongation, and in phase three trials, if they show that the mean QTC change is less than five milliseconds, that they don't care and you don't have to say anything or do any more testing, if it's between five and 20, they might ask for more data or maybe even A warning in the package insert. If it's more than a mean change of 20 milliseconds, the FDA gets more worked up about that they may require special monitoring. Definitely it's going to be in the package insert. So just again, remember, clinically, a change of more than 60 milliseconds is considered dangerous in terms of torsade risk, but from the FDA standpoint, they're much more conservative in the package insert in terms of when they might add a warning about Qt prolongation, really, anything above about five milliseconds of change, which is clinically insignificant, could prompt the FDA to do something in the package insert. Dr. Khyati Patel 09:35 And I would say the ondansetron, brand name Zofran, is a perfectly good example. So you look at the package insert for Zofran, you will find that Qt prolongation is listed in the warning precaution section as well as in the adverse effects section, and then it kind of describes the mean changes that the you know, QTC that happens after a single dose of IV and dosage. On. So again, this is a dose based effect. So for example, eight milligram of dose would cause about six millisecond change in QTC, versus a 32 milligram dose can cause the change for about 20 milliseconds. Dr. Sean Kane 10:17 And again, from a clinical standpoint, we don't get too worked up unless that changes at least, like 50 or 60 milliseconds, that's what we would consider clinically relevant. But from the FDA standpoint, they're trying to be more cautious, which I think makes complete sense. So anything more than five millisecond change, it could make it into the package insert as a warning or precaution or extra monitoring or something like that. So if you think about that, from an ICU perspective, we typically give four milligrams of ondansetron, which is almost certainly not going to change that QTc interval very often. But when a provider types in ondansetron, most drug interaction checkers are not smart enough to know that it's a dose‑dependent risk and that we're giving a low dose versus a high dose, and in those circumstances it doesn't know that we're giving the safer dose. From a QTc prolongation standpoint, we're not giving 32 milligrams. So for that reason, you do have to evaluate something like that alert that would pop up and realize or recognize that you're giving a very low dose, compared to 32 milligrams of ondansetron, which is where most of that warning honestly came from. Dr. Khyati Patel 11:28 And that's a perfect example of how this can be drug specific. But if you were to lump all these drugs together to say these are the drugs that cause QTc prolongation, what would be some of the common offenders here? Dr. Sean Kane 11:43 So by far and away, and there's no doubt about this, everyone agrees the worst drug class for QTc prolongation are the Vaughan‑Williams class III antiarrhythmics, specifically dofetilide (Tikosyn), dronedarone (Multaq), and sotalol (Betapace). And these are agents where, when you start them on someone who's never been on them, they actually, again, have to be admitted to the hospital and have routine EKGs every time they get their dose to make sure that they don't have QTc prolongation. Or the other, honestly, reason that they're in the hospital, aside from the convenience of the EKG, is that if they do go into torsade, someone is there to shock them out of it. These are hugely associated with QTc prolongation and torsade risk, and for that reason, we're extra careful when we initiate these in patients who are naive to that therapy. Dr. Khyati Patel 12:30 And some other examples outside of these anti arrhythmics would include macrolide antibiotics, such as our patient who is now taking azithromycin, azole antifungals such as fluconazole, or quinolone antibiotics such as levofloxacin. Dr. Sean Kane 12:47 Then for some psych medications, you'll see typical anti psychotics like Haldol or Haloperidol can do this, and then only certain SSRIs are more implicated. Citalopram and it's s enantiomer es citalopram are the two that are more implicated from an SSRI standpoint. And especially remember, all of these Dr. Patel are dose dependent. So if someone was to overdose on an SSRI, for example, if they were to overdose on citalopram or escitalopram, we are much more worried about QT prolongation than if they were taking Zoloft or sertraline as an example. And then our last one is methadone. And there's actually a ton of other drugs out there, but we've kind of listed the most common and most notable ones from a QTC prolongation standpoint. Dr. Khyati Patel 13:30 So you know, some of the drug based property, or the drugs pkpd, can make drugs more prone to having Qt prolongation. We talked about higher the dose, higher the risk. The other things to look out for is patient's renal function. So if you have a renally eliminating drug, but then your patient is experiencing renal impairment, that drug is going to accumulate, aka exposed patient to more dose of the drug, and that could increase Dr. Sean Kane 13:59 And then, of course, if there's a drug interaction that increases the blood level of a QTc‑prolonging drug, that means that QTc‑prolonging drug level is going to go up, therefore a higher risk of QTc prolongation and torsade. Dr. Khyati Patel 14:13 And then last, but not the least, you know, adding more than one drug that has potential to cause QTC prolongation could also increase the risk. And again, Dr. Kane, you know, here we're going to look at individual drugs and the doses to interpret, like, what is the perfect example of how many drugs can you add, or what combination of drugs are added, to say how true risk for QTC prolongation, the combinations can bring. Dr. Sean Kane 14:42 And you know, for the listeners, you know, we've listed a handful of potential QTC prolonging therapies, the main website that's going to have other agents is going to be credible meds.org or Qt drugs.org, it'll go to the same place. And this website is nice because it does describe QT risk as a known risk where there's clear evidence of QTc prolongation and torsade, a possible risk where the QTc is prolonged but we don't really know if that correlates to torsade risk, and then conditional risk, which is where in certain circumstances like overdose or electrolyte disturbances, there appears to be a risk of torsade. And on that website, at least in the US market, there are 41 meds that are known risk. So examples would be like ondansetron, sotalol, azithromycin, quinolones like ciprofloxacin. There are 119 meds with possible risk. A couple examples would be ranolazine, some of those newer antipsychotics like lurasidone, iloperidone, clozapine is on there, which really has never been on my radar. Tramadol – most of these are false alarms, in my opinion, where there might be a case report where QTc was prolonged, but we've never really seen that correlate to torsade risk. And then there are 48 meds that have a conditional risk, where in certain circumstances we could be worried about torsade, that would be risperidone, paroxetine, and again, there's 45 other meds out there. So suffice it to say, the benefit of the website is that it does list a bunch of meds that are potentially implicated in prolonging the Qt, but it also lists a lot of meds that probably are not super worrisome from a Qt risk standpoint, because maybe there's only one case report, and maybe there are other things going on in that case report that also predispose that patient to Qt prolongation. Dr. Khyati Patel 16:31 And just like the medications, inherent risk for causing this Qt prolongation, we have to also consider patient specific risk factor, which is like external to medications, right? So one good example is, as you mentioned earlier, too, looking at patients electrolytes, and we're going to focus mainly on potassium and magnesium. So hypokalemia, or hypomagnesemia, can increase the risk. Dr. Sean Kane 16:59 And another risk factor is the patient being bradycardic; the slower their heart rate is, the more likely they are to go into torsade. And actually, one of the treatment modalities for torsade, and there's a bunch of things that we do for these patients, but one thing we can do is actually pace the patient, where we force their heart rate to go faster. And by doing so, we can make it so they're less likely to go into torsade. Dr. Khyati Patel 17:22 That's a pretty neat way of resolving the situation. The other population that could be at a higher risk is in case of cardiac ischemia, so a patient coming in with MI or they have increased troponins. Those are kind of like the signs or markers to look out for. And then actually, Dr. Kane, can you explain it? There is actually a calculator available where you can evaluate patients risk based on all these factors. Can you walk us through that one? Dr. Sean Kane 17:50 Yeah, so there's something called a Tisdale risk score, and this is a very basic calculation to describe a patient's risk of having QTC prolongation when they're in the hospital, when you're giving them a Qt prolonging medication. So this was only validated on the hospital side, so hospital pharmacists like myself could potentially use this on the outpatient side. Is this not validated for that? So it's still something you could think about doing, but again, it's more validated for the hospital patient, and it incorporates many of the risk factors that we've talked about. So if you're older, if you're female, if you're getting the loop diuretic, which can produce electrolyte problems, if your potassium is low, if you already have a long QTC that was shown on a 12 lead EKG, if you have cardiac ischemia, like you've been admitted for a heart attack, you have sepsis, heart failure. Then also the number of drugs that are known to prolong the QT. Obviously, the more drugs you have, the higher the risk is. Dr. Khyati Patel 18:46 And basically, you know, the results would be interpreted as if the number is less than six or less than that, then the risk is low. If that value is between seven and 10, then patient has a moderate risk, and 11 or more puts patient at a higher risk for QTC prolongation, something to consider, though, the author of the calculator lists out the limitations that again, this is only tested in hospitalized patients, so this is not for your outpatient patients. It does not account for the drug drug interaction, as Dr. Kane you were saying, certain drugs increase the concentration of the Qt prolonging drugs. It doesn't account for that type of drug interaction in here doesn't account for patients renal function or hypomagnesemia, absolutely. Dr. Sean Kane 19:34 And you know, no system is going to be perfect. This is the main one that's out there that is used to quantify risk in some form or fashion, but it's important to remember that the Tisdale risk score, the outcome, the thing that you're predicting is whether that patient is going to have a prolonged QTC. So it does not predict whether the patient is going to have torsade point TDP. And the reason that that discrimination is a. Important is that TDP is actually fairly uncommon, and there's many examples out there where patients can be on medications that prolong the QTC, but even though their QTC is long, that doesn't correlate necessarily with a risk of torsade. Dr. Khyati Patel 20:16 And a good example of this would be patients who are hospitalized, or those patients who are in the ICU. So you're not at the woods where QTC is frequently prolonged, but they're not necessarily all at higher risk for having to Dr. Sean Kane 20:30 resolve Yeah. So in other words, that QTC alone, meaning that a random patient on no particular meds has a prolonged QTC, probably because of their severity of illness, that alone is not really a good predictor of torsade risk. So other risk factors have to be considered. We went through many of those other risk factors through that Tisdale risk score, but another example of this is actually certain meds that will prolong the QTC interval, but don't appear to actually cause torsade. So amiodarone, which is a class three anti arrhythmic, remember, the other class threes are well known for causing torsade. For whatever reason, amiodarone is a substantial QTC pro longer, but its risk of torsade is actually quite low, especially compared to those other class three anti rhythmics like sotilal, dilfetilide, things like that. We don't exactly know why Dr. Patel it could be because amiodarone isn't just a pure potassium channel blocker, which is a class three effect. It also blocks sodium calcium and beta receptors. So potentially, because it does other stuff, it may mitigate some of that risk of torsade. Dr. Khyati Patel 21:37 And as you said earlier, too, Dr. Kane, it just takes one case report for such a medication to be associated with, or, you know, kind of correlated with, torsade point. So, for example, a patient is on drug X, they had increased QTC or prolonged QTC, and then they ended up having to sort but it's the actual causal relationship in reality, is much harder to prove, Dr. Sean Kane 22:02 and that's why there are, like, 200 meds on credible meds.org, that are implicated in QTC prolongation. Is because it really does only take one case report, and because torsad and QTC prolongation are relatively uncommon, it is difficult to show a cause and effect relationship that is strong enough that we can definitively say whether Dan Citron truly does cause torsade or if it only causes Qt prolongation. That's a really hard thing to prove, because the risk of torsade is generally pretty low in most circumstances. Dr. Khyati Patel 22:34 So this is a little bit confusing. Dr. Kane, there's 200 medication, which seems like a very long list of meds that could increase Qt prolongation, but they don't all cause increased risk of torsade. So what do a pharmacist do when you know a QTC is prolonged, or a patient is put on multiple medications that can prolong QTC? Dr. Sean Kane 22:58 Yeah, so there's a really nice algorithm that we're going to link to in our show notes the articles by Noel and colleagues from 2021 if you take a look at figure one, I really like it because it does go through kind of the cognitive process of what a pharmacist or healthcare provider should do when they identify that they're worried about Qt or QTC prolongation. Really, the first step Dr. Patel is making sure that that QTC is accurate. And I know that sounds kind of weird, because what happens is, when you get a 12 lead EKG, kind of in the top middle, it the computer calculates the QTC for you, so you literally just look at the number and it tells you what the QTC is. But there are certain circumstances where that QTC, even though the computer calculates it, that it isn't accurate or representative of a delay in ventricular repolarization. So one example of that is if the QRS complex, which is ventricular depolarization, that is prolonged, then the QTC is no longer accurate, and it can be prolonged in what are called bundle, branch blocks. It's where the ventricles are taking longer than normal to depolarize, also in ventricular pacemakers, where the ventricles are being shocked to actually produce a heartbeat that messes up your QRS, that then messes up your QTC, because the QRS is part of the QTC, so can't rely on whatever the computer tells you the QTC interval is. There are kind of correction or ways that you can get around that, but they're not super validated, so they do exist. And for the listeners, a PubMed search would certainly show you some of those equations or adjustments. But for the most part, you just have to realize that it's probably not going to be very accurate. Dr. Khyati Patel 24:34 Another reason why we have QTC is we are correcting it for the heart rate, right? So we have outlying heart rates, like whether the heart rate is really, really fast or really, really slow. Then again, this QTC may not be all that accurate. Dr. Sean Kane 24:51 Then the third scenario where QTC may not be accurate is an AFib patients. And by its nature, AFib is an irregularly, irregular arrhythmia. Which means that the heart rate itself is changing beat to beat. So if you ever looked at the heart rate on a heart rate monitor, and someone who has afib, it will go back and forth from like 80 beats per minute to 85 to 95 to 120 all the way back to 85 and like a span of 10 seconds. It's because the ventricles are not regularly depolarizing at common intervals. And if you think about it, when you look at a QTc, it's correcting for heart rate. So if your heart rate is all messed up and really difficult to quantify, then your QTc is also difficult to adjust for, because you don't have a consistent heart rate. So in those patients, the QTc can also be inaccurate as well. Dr. Khyati Patel 25:40 So those are pretty good examples of Dr. Kane. You know how to make sure look out for the errors or look out for inaccuracies in the QTC calculation. But let's say you avoided all that. You made sure your QTC is accurate. The next step becomes to assess patients risk factors, and these are inherent risk factors off a patient that we discussed earlier as part of the Tisdale school calculations, such as hypokalemia, hypomagnesemia, older age. You know patients being admitted for like mi or sepsis or heart failure, and that helps you evaluate the true risk for having torsade and not just Qt prolongation. Dr. Sean Kane 26:20 So then, if you get to that point, Dr. Patel, in our kind of cognitive algorithm here, you've established it. You trust that the QTC is accurate. You are worried enough, because the patient has certain risk factors for prolonged QT and or torsade. The next thing is to say, okay, so if I did something about it, so if I didn't give my azithromycin, but I gave an alternative drug. Is the alternative a reasonable substitute? Or by switching, am I actually doing more harm than good? Because sometimes what will happen is that the alternative med is an alternative because it has more toxicities, or it's not as effective, or whatever, and if the patient has a 0.1% chance of torsade with their current regimen, but if you switch it to an alternative regimen that has a 10% risk of angioedema, that doesn't feel like a good trade off to me. So you do have to consider like, How worried are you and if you switch, is the alternative therapy really going to be that much better from a side effect standpoint or from a lack of efficacy standpoint. Dr. Khyati Patel 27:25 And as of course, as a team member in an inpatient side as a pharmacist, you could always request monitoring of EKG as we are dosing the medication, like we do for some of those class three rhythmics after dosing to see if the QTC is getting worse. So that's one way to monitor the patient for this issue. Dr. Sean Kane 27:47 Then, on your side, Dr. Patel, the problem is that you can't just routinely get a 12‑lead on an outpatient basis, so you're kind of stuck with patient counseling. And I see this all the time with pharmacy students, where they want to tell a patient monitor for Qt prolongation or monitor for torsade, a patient can't do that, and that makes no sense to a patient. So instead, you have to provide patient counseling points that are related to, you know, things like unexplained dizziness, palpitations, syncope, things like that, because those may represent a self terminating torsad, where they went into torsade temporarily, and then they self terminated. They got out of it. And even if that isn't torsad, and someone who has new onset dizziness, palpitations or syncope, they probably need to see a health care provider anyway. But if you're worried enough about torsade, really, the only thing you can do on the outpatient side is to have them monitor for that and look for those symptoms that could be associated with an arrhythmia. Dr. Khyati Patel 28:44 And I agree with you. Dr. Kane, it's important to make this communication in a patient friendly and understandable manner. So explaining the symptoms of torsade is better than telling patients that you may experience torsade, and Dr. Sean Kane 28:59 certainly you're not going to tell them. Dr. Patel, you are at risk for a fatal ventricular arrhythmia if you take this medication, because they won't take it, right? So you do have to be careful of explaining to the patient why you're concerned and how rare This is and how they can monitor for that. Dr. Khyati Patel 29:15 Yeah, absolutely. And so kind of tying everything that we discussed so far, Dr. Kane to our patient, just to kind of remind our patient is a 50‑year‑old man who is on chronic escitalopram therapy and now has been issued a new prescription for a Z‑Pak, which is a five‑day course of azithromycin. What do we do? How do we approach it? Dr. Sean Kane 29:38 So one thing you could do is you could go to that credible meds.org, website. And if you do that, and you type in escitalopram, it'll say that drug has a known risk of TDP torsad, and if you type in azithromycin, it will say drug has a known risk of TDP. So in both cases, both of these medications have a known risk of causing torsad. And at face value. That sounds pretty scary and something that you might not want to fill based on that one resource alone. Dr. Khyati Patel 30:06 So then you go to package insert for each of these medications, and you find that azithromycin, the 500 milligram dose, increased the QTC by an average of five millisecond. And as we know with the Z pack, you know, the rest of the four days, the patient's on 250 milligrams. So maybe it's less, because it could be dose dependent. And then, in case of escitalopram, the average QTc shown to be increased by about five to ten milliseconds. And so most patients are on maximum of 20 milligram dose. So you kind of are looking at that range for increase, if it would happen Dr. Sean Kane 30:46 and again, like we get worked up of, you know, QTC changes of 50 or 60. So a change of five or five to 10 is really not that big of a deal, at least on the inpatient side. You know, another thing you could do Dr. Patel is look at the Tisdale score. One thing I like about it is that it does it does give you a list of things to think about in terms of risk factors for a patient. And again, this is risk of QTC, not risk of torsade. And for this particular patient, even though they you know, it's outpatient versus inpatient, the patient score is fairly low. Most of their points come from being on two QTC prolonging meds, as opposed to a history of heart failure or a history of something that would predispose them to QTC prolongation. So the risk based on that score is actually pretty low, right? Dr. Khyati Patel 31:32 And this risk score also, you know, looks at things such as age, patient sex. So this is a male patient, not a female patient, you know patients not admitted for any reasons, right? Patients not at least from what we know on loop diuretics, things such as their potassium level or magnesium level or renal function or EKG, we don't have that information, but if you do yes, you could make even more informed decision on it. And as far as we know, Dr. Kane, this patient is being put on just one additional medicine that has a concern for increased QTc. And so we're talking about combination of two. There are no other medication that we know that could increase either concentration of either of the struct to put at a higher risk for QTC prolongation. Dr. Sean Kane 32:19 So Dr. Patel, at least, in my opinion, I would view this as a fairly low risk of torsade. Maybe the patient's QTC will, in fact, prolong a little bit, but the magnitude of that increase, I would not expect it to be substantial enough that I would really change my therapy. So at least from my standpoint, sure the risk of torsade goes up a teeny, tiny bit. But there are many other drug interactions or adverse effects that we worry about with many other medications that we still fill them. So Lisinopril with angioedema is a good example. We still fill Lisinopril prescriptions all day, every day, even though the angioedema risk is 0.1% and that's a life threatening reaction. So it's one of those things where, if you had an alternative that is just as good as azithromycin, you could consider it. But to be honest with you, I don't even know if I'd go that far, because I think that, in my opinion, the risk is fairly low for this Dr. Khyati Patel 33:12 patient, and I 100% agree with you on the risk assessment here. Dr. Kane, I don't think that patients combination of these two drugs puts them at a higher risk of torsade. But if you are a pharmacist who is, you know, wanting to be extra sure, you could again, do the patient education and ask patient to look out for the symptoms of torsade, such as, as we explained earlier, feeling dizzy, having palpitation, or having any syncopal episode that they need to reach out to their provider? Dr. Sean Kane 33:43 Well, Dr. Patel, I think that wraps things up nicely. A couple key points. One is that QTC interval is the QT interval that has been corrected. That's what the C stands for, for heart rate. So in nearly all cases, when we talk about Qt we're actually talking about the QTC because it's normalized, where we're always talking the same language, from a QTC standpoint, whether the patient's heart rate is fast, so or normal. Dr. Khyati Patel 34:07 And although we define prolonged QTc as a QTc that exceeds the range of 450 to 480 milliseconds, the real danger, which is torsade point, that risk begins to become concerning at QTc above 500 or if you're looking at baseline comparison, we're looking at 15 to 20 % longer than the baseline number, or, you know, add that 50 to 60 milliseconds from the baseline. Dr. Sean Kane 34:40 And then by far, and there's no debate here, the Vaughan‑Williams antiarrhythmic class III medications, like sotalol, dofetilide, dronedarone. These are very implicated in prolonging the QTc and also very implicated in torsade risk. Amiodarone is a class III, and it does prolong the QTc, but despite that the actual risk of torsade with amiodarone is actually very low, which is interesting. We don't fully understand why. Dr. Khyati Patel 35:06 And so for pharmacists, you know, assessing the risk of QTC prolongation and torsade, you have to consider multiple factors, not just the drugs QTC prolonging effect or the patient's QTC interval, you've got to look at the risk score, such as the Tisdale risk score, or even consider risk and benefit of switching the therapy. Kind of take everything into account to make an informed decision. Dr. Sean Kane 35:35 So Dr. Patel, for the listeners, we do have some references that are available in the podcast app in the show notes for the podcast app, and we'll have those up on our website at the beginning of July. So you'll have to stay tuned for those, but they are available in the episode itself. So with that, I'm Dr. Kane Dr. Khyati Patel 35:51 and I'm Dr. Patel, and keep recommending good topics for us to cover, as we discussed, this was a listener recommended episode and study hard. Narrator - Dr. Abel 36:02 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 36:13 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.