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 151 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is deep dive into diltiazem, pharmaceutics, medicinal chemistry, the FDA Orange Book and more. So clearly today we're talking about diltiazem, all things. Diltiazem kind of a potpourri of topics that we think the audience will get a lot of value out of all of these different aspects of the drug and how it relates to clinical practice. Dr. Khyati Patel 00:59 And Dr. Kane, if I'm not wrong, this was one of our listener requested topic because they wanted to understand the difference between all different formulations of diltiazem that are out there Dr. Sean Kane 01:11 exactly and it's actually really confusing. I would say, prior to preparing this topic, I actually didn't have a full understanding of all of the differences and the nuances for those dosage forms. So we will absolutely be covering the confusing state of diltiazem dosage forms. But we're also going to go beyond that and cover kind of the top 200 drug-esque facts about the drug and a variety of other topics as well. Dr. Khyati Patel 01:35 So kind of kicking us off to discuss the background or the basics of diltiazem. You know, there are multiple different brand names, but we'll, we'll call it Cardizem for right now. And it belongs to a drug category of non dihydropyridine type of calcium channel blockers. As we know, there's two different Dr. Sean Kane 01:55 types, yeah. And we'll talk more about the medicinal chemistry behind that kind of drug class or nomenclature in a little bit from a mechanism standpoint, Diltiazem is a calcium channel blocker, so it's blocking the calcium channel, which just means that it makes it harder for calcium to get into certain cell types. In this case, those cell types are in the smooth muscle vasculature, so this is going to cause vasodilation and decrease blood pressure. So as we'll talk about it, it is an antihypertensive, and also it decreases calcium influx into certain cardiac tissues, specifically the conductal tissue of the heart. So this is your SA node and your AV node and things like that. And by making it harder for calcium to get into those tissues, it will decrease your heart rate, and it will also decrease the forcefulness of contraction, or the contractility of the heart as well, in terms of indications. So we're thinking of a drug that slows down your heart rate, how forcefully contractions occur, and it decreases your blood pressure. So it shouldn't be surprising that we use diltiazem for angina, chronic stable angina. We also can use it for a couple different kinds of arrhythmias, mostly for atrial fibrillation, to decrease the feeling of palpitations, or the tachycardic response that we see in afib. And technically it's also proof for hypertension as well. Dr. Khyati Patel 03:19 Yeah, this is interesting. Dr. Kane and I still get to see some patients on diltiazem for purely hypertension use, so they don't have afib, they don't have angina, where we are trying to reduce the contractility and heart rate. And it's, it's a little bit of my pet peeve, to use it as a purely as an anti hypertensive, while we do have alternate, you know, guidelines, and this is not considered as a mainstream anti hypertensive and Dr. Sean Kane 03:47 Dr. Patel. Probably the easiest way to remember this is that we don't use drugs that decrease your heart rate just to decrease your blood pressure too. So if we think of beta blockers and diltiazem and verapamil, these drugs do decrease your blood pressure, but they also decrease your heart rate, and heart rate is not a target in someone who doesn't have other medical conditions that just has hypertension. Dr. Khyati Patel 04:09 100% agree, and I think this is an easier way to remember. I guess the confusion really stems from the fact that there are so many different formulations out there, right? So yes, we do for the inpatient side, have an intravenous formulation. We do have the IR tablets. And things get really confusing when we talk about the longer acting tablets or capsules. There are plenty different brand names and release mechanisms that we're going to talk about later. Yeah. Dr. Sean Kane 04:39 And in terms of kind of big things to know about diltiazem from a Warnings and Precautions standpoint, one of the things that always comes to my mind is that we should not use diltiazem chronically in patients who have heart failure with reduced ejection fraction, also called systolic heart failure. And the reason for that is that there was a study done in patients that. Had heart attacks that had reduced ejection fractions, and their mortality was higher if they got diltiazem versus if they did not get diltiazem. So for chronic use, we don't use diltiazem in that patient population. Another reason we don't use it is that that patient population should be on certain kinds of beta blockers, and if we combine diltiazem with beta blockers, the heart rate could get too low and we might not be able to maximize that beta blocker. So kind of two reasons why we don't use diltiazem in those with reduced ejection fraction heart failure. Dr. Khyati Patel 05:29 And aside from those warnings, some of the common side effects we get to have with this drug is prophyladema. Now prophyladema happens with all calcium channel blockers, whether they are dihydropyridines or non dihydropyridines. And this seems to be more of a dose dependent side effect, but as contractility decreases and the heart rate decreases, bradycardia is one of the side effects, and this could lead to blockade of the AV node as well. Dr. Sean Kane 05:59 Yep, and it shouldn't be surprising, this is an anti hypertensive it causes smooth muscle relaxation in your vasculature, so it can cause hypotension, and just having low blood pressure in general can cause symptoms like syncope or pre syncopal episodes where someone feels like they're fainting or they actually do faint. Also they could just get dizzy or light headed, especially when they stand up too quickly. Obviously, all of those are related to its anti hypertensive effect, Dr. Khyati Patel 06:23 and some of the rare side effects are headache, hepatotoxicity and rash and other type of like cutaneous eruptions and hypersensitivity reactions. These hypersensitivity reactions seem to be rare, but with diltiazem, they're a little bit more common than other calcium channel blockers. Dr. Sean Kane 06:40 channel blockers, and from a drug interaction standpoint, diltiazem uses your liver for metabolism, mostly through the three a four pathway. So any drugs that induce or inhibit the three a four pathway could impact the kinetics of diltiazem. Diltiazem is also a P-gp substrate, so substances like grapefruit juice can interact with diltiazem and make you absorb more diltiazem than you normally would. So it's susceptible to drug interactions with three, a, four and peak lipoprotein, but it also causes drug interactions too. So it actually inhibits cytochrome, 2d, six and also three, a, four. So it can actually increase drug levels of any medication that uses 2d, six or three, a, four and three, a, four is by far the most common enzyme that is involved in hepatic metabolism. So we can see a good number of interactions with diltiazem, right? Dr. Khyati Patel 07:32 And then there are some additive drug interactions, meaning, you know, if you're using other drugs that also reduce heart rate, then you could have increased risk of reduced heart rate or bradycardia. An example of these drugs are, you know, your beta blockers. And the other additive drug interaction is the antihypertensive type. So we know that this, you know, causes vasodilation in the periphery and decreases the blood pressure. And if there are other medications, antihypertensives, on board, it can lead to further blood pressure reduction. Dr. Sean Kane 08:05 So Dr. Patel, I feel like we have a pretty good overview of kind of the nuts and bolts, if you will, of diltiazem. Why don't we move on to the medicinal chemistry and the pharmacology? And specifically, a very common question or misunderstanding that I observe, especially with student learners is one, they cannot pronounce dihydropyridine, and then two, they can't, kind of explain the difference between a dihydropyridine and a non dihydropyridine calcium channel blocker. Dr. Khyati Patel 08:31 And I think this is an important distinction to be made. So, as we discussed earlier, there are two different types of calcium channel blockers, the dihydropyridine and the non dihydropyridine, there are few more dihydropyridines out there than there are non dihydropyridines. The examples of the dihydropyridine calcium channel blockers are Amlodipine or nifadapine or phyllodipine. Some are more commonly used than the other, such as Amlodipine. Some are not as commonly used, such as nifada pin or phyllo to peen. Now talking about dihydropyridine, the thing that is common among these ones that are ending in p, i, n e, that they share a similar chemical structure, dihydropyridine. Dr. Sean Kane 09:19 And then for the other class. We just call them non dihydropyridine because they don't have that dihydropyridine drug class or that structure to them, but they're different from each other. So there's only two non dihydropyridine calcium channel blockers, diltiazem, which we're talking about today, and verapamil. And the reason that we call these non dihydropyridines, as opposed to some other drug structure is that the structure of diltiazem and verapamil are actually dissimilar from each other, so I'm going to butcher this, Dr. Patel, but diltiazem is a benzo thiazepine, kind of like benzodiazepine, but benzo thiazepine And then Verapamil is a phenylalkylamine. So they are different from each other, which is why we just call them non. Pyridines Because they don't share a similar structure to each other. Dr. Khyati Patel 10:03 And kind of the cheat sheet I give my students to differentiate these two, Dr. Kane is again looking at that common ending. So again, think about the those ending in p, i n, e, are your dihydropyridines, and the other two, dotaz, I'm in rep meal, they just sound different. They are your non dihydropyridines. Dr. Sean Kane 10:24 That's great. So Dr. Patel, I love that mnemonic, and I think it'll help a lot of learners out there, aside from just knowing, hey, there's a chemical structure difference. Why does it matter that we know that? How does that inform something to know about the drug clinically? Dr. Khyati Patel 10:39 Well, I think it does, because it tells you where the drug works and what kind of pharmacologic effect we are getting out of these drugs. And so one established fact is that these are both calcium channel blockers. They particularly block the L type calcium channels. And so, as you explained earlier, Dr. Kane, it's going to stop the calcium influx into the cells. Now there's cells. We're talking about two different types of cells, the vascular smooth muscle cells, such as the arteries that you know, obviously carry the blood vasodilation in these muscles are going to result into decreased blood pressure. And both of these, the dihydropyridine and non dihydropyridine calcium channel blockers, can do that. However, when it comes to the calcium mechanism into the cells of the conductive cells of the heart, that mechanism is particular to non dihydropyridine meds. And so this is going to decrease the heart rate, decrease the contractility, and only the veropamal and diltiazem, the non dihydropy calcium channel blockers, do that, the amyloidopine, the nifati pain, those peens, DHPs, they don't have this effect. Dr. Sean Kane 11:59 So clearly, Dr. Patel, if your goal is to decrease only blood pressure, you'd be reaching for the dihydropyridine like amyloidopine. But if your goal is to decrease heart rate only, diltiazem and verapamil, the non dihydropyridines, only those drugs can actually decrease your heart rate, and they also, in fact, do decrease blood pressure. But 99% of the time we're reaching for these because we want to decrease heart rate. Dr. Khyati Patel 12:23 And I think it's a good way to remember, you know, not only the mechanism, but where, where do we use these medication, right? So it all the way from chemical structure to pharmacology to the drug effect to the use in practice. That this is why medicinal chemistry matters. Dr. Sean Kane 12:41 So medchem is interesting. Really, the reason that we reached for this episode from a listener request was the pharmaceutics, which is another field of pharmacy that's present in probably every pharmacy school in America. And really the question was, why are there so many different dosage forms of diltiazem, and what does a clinician need to know about the differences? Dr. Khyati Patel 13:03 Well, I guess the confusion really comes because there are very many different extended release products, and we're gonna spend good amount of time talking about that. I like to grab the low hanging fruit first, and that's your IV formulation. You know, we have it available such that we can deliver it in IV push or IV drip or IV infusion fashion in hospital settings, typically in patients who have AFib or rapid ventricular response. We're going to use IV version because it's going to have a Dr. Sean Kane 13:39 quicker effect. Yeah, Dr. Patel, I see this all the time. We use this very frequently in the inpatient setting. I also see a good amount of immediate release diltiazem. We don't see a lot of this on the outpatient side, because immediate release you have to take it three to four times a day. So tid or QID diltiazem itself has a really short half life, which is why we have so many extended release products where they take advantage of the pharmaceutics to be able to have an extended release, as opposed to the chemical structure. We can't change the half life of diltiazem. It is what it is. So typically, I'm seeing immediate release diltiazem in nursing home patients where they they have to crush their medications because of swallowing issues or because they have to have a feeding tube, because you cannot crush extended release products. And I also see it when we're kind of transitioning patients. So we might start with IV, give them immediate release where we can kind of titrate the dose very fairly frequently. Then once we find the perfect dose of diltiazem for that patient, we might then bridge them to that extended release product. Dr. Khyati Patel 14:44 And I will tell you, you know, those are two good examples of where we use or see immediate release tablets. Dr. Kane, because in my am care or outpatient practice, I don't see patients normally on immediate release tablets. They're usually using one of those extended. Release products out there, Dr. Sean Kane 15:02 absolutely so related to those extended release products. Dr. Patel, I assume you don't have to take these as often. But specifically, what is the advantage of these er products, and why do we see so much of that versus the immediate release Dr. Khyati Patel 15:14 Well, as you said earlier, Dr. Kane, but the immediate release tablets, you know, you you're asking patients to take it three or four times a day, and then we know as the frequency of medication increases, the adherence decreases from literature. And so it's not usually ideal for patients to be on three or four times a day dosing. And therefore manufacturers have come up with this extended release product where we can minister them in more once daily or or twice daily fashion. Dr. Sean Kane 15:42 And that would be one difference, I suppose, between the products is that one product on that used to be on the market that really isn't on the market anymore, was called Cardizem SR. That one, because of how long the extended release product lasted for, you had to take that twice a day. Not surprisingly, Cardizem SR, the bid dosing version is not commonly used, and eventually was discontinued, because all of these once daily products made it to the market, so we don't really see Cardizem SR used anymore, because why would you pick it if you can use a once daily product? Dr. Khyati Patel 16:15 And that makes sense. And aside from you know how many times patients have to take it. There is another difference to discuss here. Dr. Kane extended release products. Then further, have two formulations that are available in tablet but also available in capsule. Yeah. Dr. Sean Kane 16:33 So there's really only one tablet version of extended release still ties in and it had the brand name of Cardizem LA, so that one is unique just because it's a tablet versus a capsule. And really, all of the other extended release products on the market are er capsules, and because the dosage form is technically different between a tablet and a capsule, we'll talk about this later, you can't switch between the two without contacting the provider, right? Dr. Khyati Patel 17:00 And so when we talk about capsules, which are kind of like the more common extended release formulation of diltiazem, what is really so unique Dr. Sean Kane 17:10 about them? Yep. So the main one that we have on the market is just the traditional extended release capsule product. There's nothing crazy about how it becomes extended release. It's not using like that laser drilled hole that we see with auros technology. It's just normal extended release capsules. So this is Cardizem CD and Cartia XT. These are actually therapeutically equivalent to each other, so they're interchangeable. We'll talk more about that later. But then we also have another extended release product with brand names of Tiazac and tastia XT, Dr. Patel, have you seen these in your clinical practice? Dr. Khyati Patel 17:47 You know, not as much. I've seen Cardizem CD and Cartia XT, a little bit more. Most of the patients who can, you know, swallow the capsule as whole, are okay using that. But yeah, Tiazac and Taztia XT are also very interesting, and tell us why. Dr. Kane. Dr. Sean Kane 18:04 So these are interesting because unlike most extended release capsules, where the extended release technologies in the capsule or the tablet itself, this is where the sprinkles inside the capsule are coded in the extended release technology. We've covered this in previous episodes where we've talked about different technologies to produce extended release products. But basically, as long as you don't crush the sprinkles inside the capsule, you can open up the capsule, sprinkle it onto applesauce, or even dissolve it in some water and then drink it quickly or put it through a tube. As long as you're not crushing the sprinkles inside the capsule, it will actually maintain its extended release kinetic profile. And again, just like Cardizem CD and Cartia XT, those are interchangeable. Tiazac and Taztia XT are also interchangeable with each other. Dr. Khyati Patel 18:54 And so I can imagine Dr. Kane, somebody who has following difficulty the tizak and tastia XT would be more appropriate to use, because you can mix it with foods like applesauce Dr. Sean Kane 19:06 and then just take it once a day, versus if you took the immediate release, where you can crush it, that's, again, three to four times per day. Dr. Khyati Patel 19:14 Well, and also, it seems like we have quite a few other products that have been eventually removed from the market. And so I guess it's better for us to and less confusion. But some of those brand names were Dilt-CD, Dilacor XR, Diltzac, Teczem, and Tiamate Dr. Sean Kane 19:33 and I think that this is probably where most of the confusion comes from with these diltiazem extended release formulations, is that you read about all of these different brand names and things like that, and you assume that they're on the market, but they're actually not. They've been discontinued by the manufacturers. So even though you might see some of these brand names and drug information resources, they're not used in clinical practice anymore because the manufacturers no longer make them. Dr. Khyati Patel 20:00 So moving on from the different products and formulations, let's talk a little bit about interchangeability. And I have a hypothetical scenario to ask of you, Dr. Kane, let's say, you know, we receive a prescription for Cardizem LA, 360 milligram once daily. Remember, this is our extended release version of diltiazem. We don't have the Cardizem LA, but we do have other extended release product, including Cardizem CD. Can we just go ahead and fill Cardizem CD? What do we have to do here? Dr. Sean Kane 20:36 Yeah, and you know, Dr. Patel, this is a perfect example of when a pharmacist would use what's called the orange book. And the actual term for the Orange Book is the approved drug products with therapeutic equivalence evaluations. But that's a long title, and when they used to print it, it was a big orange cover, so we just call it the orange book instead. Dr. Khyati Patel 20:57 And I imagine all of the FDA approved drugs are listed in this book. And really, as you said earlier, the purpose of this book is to find medications that have therapeutic equivalents and evaluations done for that. And so the listed product will tell you whether there is a true therapeutic equivalent, interchangeable product available, yeah. Dr. Sean Kane 21:22 And you know, before we talk about the what are called A B codes, or a B compatibility, before you even get there, to make sure that something is interchangeable, it has to have the same active ingredient, so diltiazem has to have the same dose. 360 milligrams has to have the same dosage form. So tablet is not the same as capsule as an example. Also, extended release is not the same as immediate release, and it has to have the same route of administration. So that would be oral typically, is what we're looking at. But you can convert between a tablet and a patch, for example. And then finally, those things all being equal, can make the the equivalence claim, if you have data, pharmacokinetic data, and they look at AUc and the C max, or the maximum serum concentration between two products, you actually have to run a study showing that these kinetic parameters are within 20% of each other, between dosage form a and dosage form B. And if they are, then we provide this claim of therapeutic equivalence. Dr. Khyati Patel 22:26 And in addition to therapeutic equivalency, as you explain, some of these criterias, Dr. Kane, the bioequivalency kind of come and play a role as well, right? So if the two drugs are bio equivalent, you're going to find them listed an orange book as an entry with a B next to them, Dr. Sean Kane 22:45 yeah, and if you see that, unless the prescriber wrote, dispenses written or da W, the pharmacist, then can switch from Product A to product B without contacting the prescriber. And this is good for patients, because it might mean that they get a cheaper drug. And it's good for the prescriber, because then they get one less phone call about something that they probably don't care that much about if they didn't write DAW dispenses written on that script. Dr. Khyati Patel 23:09 Yeah, and I think most state laws allow pharmacists to make this change, as long as you know they're following the rating in the orange book. Dr. Sean Kane 23:18 So if we kind of deep dive into the orange book for diltiazem. What you'll actually find is 193 diltiam entries. Of those 193 that's including IV stuff and oral stuff and immediate release and extended release, all that different manufacturers of the 183 110 products, do have an AB rating. So 110 of the 193 have some equivalence code where you could potentially switch them between each other. Well, that's Dr. Khyati Patel 23:47 a mind boggling number, Dr. Kane, and not to talk about the different type of AB related classifications to make things even more confusing. Yeah. Dr. Sean Kane 23:58 So if you think about it with 110 products, you're going to have a situation where five of the products are equivalent to each other, but then seven other products are equivalent to only those seven other ones, and you have these different silos or categories where not all of those AB rated ones are equivalent to all other 110 AB rated ones. So the way that the orange book tackles this is that they start just by classifying drugs that are therapeutically equivalent as a classification of a B, and once they have a new equivalence silo or category, they call it a b1 so that means that any drugs that have a B on them can be switched, and any drugs that have a b1 can be switched with other, a b1, drugs and actually with diltiazem, they went through a B, A b1, a b2, A b3, and a b4, which means that there are actually five different categories in terms of being able to switch between products, but you have to stay within that same silo or category. So for example, if Cardizem LA is A b3 you can only switch it with another A b3, code and the orange book. Dr. Khyati Patel 25:07 All right, so I hope our audience is still with us, because this gets even more interesting. Talking about this five different A B related classification. Most of our diltiazem products are kind of writing in that A b3 category. We're talking about 40% of the A B related oral diltiazem products are in that A b3 category. An example of these include the card is m, c, d, the cardiac st and the generic versions of extended release capsules. Dr. Sean Kane 25:38 Yeah. And then after that, it's pretty uncommon. So a b, without any number. This is your Cardizem and other generic versions of Cardizem that are just immediate release. And then this is also where we have Cardizem LA and generic versions of Cardizem LA. And then we have a b4, category. This is our Tiazac and tastia XT, and then generic versions of that. That's where we have the sprinkle technology inside it. Dr. Khyati Patel 26:06 And so I take it that with with a b3, and a B and A b4, being common, a b1, and a b2, as regards to diltiazem, are uncommon. Less than 10% of formulations are falling in these Dr. Sean Kane 26:21 two categories. Yeah, this is kind of like the uncommon formulations, or formulations that are no longer really on the market. Most of these at this point are just generic, extended release capsules that aren't really worth talking about. I think the most important thing here is that A, b3, in the orange book would be for the really common Cardizem CD and Cartia XT. And then we have some other AB ratings for some of those other slightly less common diltiazem products. Dr. Khyati Patel 26:48 And then there are products that are not AB rated at all. And some of like you said, Dr. Kane, some of these products are not in the market. These are Cardizem SR, Dilacor XR, Dilt-CD, Diltzac, Teczem and Tiamate, and most of these are extended release capsules or tablets, Dr. Sean Kane 27:06 yeah, and again, I think a lot of the confusion here comes from those brand names, where we assume that they're still on the market and patients may take them, but they're not on the market. So at least for me, I see no value in memorizing those brand names because we don't use those products and they are no longer on the market, right? Dr. Khyati Patel 27:27 So kind of going back to our hypothetical prescription switch question. Dr. Kane, we got a prescription for Cardizem LA, going through all these a B ratings, we found that this one has the code A B next to it in the orange book. And what we have in the pharmacy is not Cardizem LA, we have Cardizem CD. You look up orange book and you find that that has a code A b3 next to it. And as we discussed, A B is not the same as A b3 you could interchange A B with a B. You cannot interchange AB with AB three. So technically, these two are not interchangeable, and that means pharmacists must call the doctor to get the prescription changed. Yeah. Dr. Sean Kane 28:10 And you know, for the listeners, most formulations on the market do not have this degree of like AB one, AB two, AB three, most of them just have AB or nothing. But there are certain products, like levothyroxine is a great example, and diltiazem is another good example, where they've been on the market so long and there's been so many different formulations, we do have to have different ways to describe which products have been proven to be similar to each other and not and that's where this somewhat confusing, but still not that confusing, a B rating comes from, right? Dr. Khyati Patel 28:42 And so imagine, you know, the complexity of reviewing the orange book for various formulation of diltiazem. Here we were just talking about extended release. Item one was tablet. One was capsule. In our example, we get it. But are there other formulation related med safety issues that could occur with diltiazem? Absolutely. Dr. Sean Kane 29:01 So. Dr. Patel, this actually came up in my clinical practice not that long ago, where we had a patient that was admitted to our ICU with bradycardia and hypotension. And what ended up happening was that this patient was on diltiazem CD, the long acting version 360 milligrams a day. And when the prescriber effectively renewed their prescription, they typed it into their electronic health record. They typed in diltiazem. They clicked on the first one. They ended up e‑prescribing diltiazem, but without the CD or the ER. And what they ended up prescribing then was immediate release diltiazem, 360 milligrams once a day, as opposed to the extended release product, and you can quickly appreciate why this is confusing, because it says diltiazem, but those are actually completely different products and has a huge med safety implication. Dr. Khyati Patel 29:51 And so if we kind of dive into why this was dangerous, we know that the extended release, the 360 milligram. M would be given over 24 hours versus IR, 360 milligrams would only last for four to six hours. And if you think about it, patient would get all of this 360 milligram dose in four to six hours. And that makes a lot of difference. That's a lot of drug concentration and exposure to drug over a short amount of time versus 24 hours. Dr. Sean Kane 30:24 Yeah, if you do the math, they're getting basically in a given in that first period where they take the drug, they're going to get four to six times higher drug levels of diltiazem by this dosing error, where they take the entire dose in a four to six hour period, as opposed to the entire dose over 24 hour period. And of course, being exposed to four to six times more drug is going to cause hypotension, bradycardia, AV block, and in this case, they had to be admitted to the ICU and receive vasopressors to support their blood pressure and their heart rate until the effects could wear off. Dr. Khyati Patel 30:58 And I can totally see, you know, Dr. Kane patients being turned off by such an issue where, you know, they're like, oh, this drug caused that to me. I'm never gonna take it. And then, then, sure, you know, you know, they tell this to 10 other people, and those 10 other people go to their doctor and like, Nope, I'm not gonna be on this medication again. But really, the issue was that there wasn't an appropriate transition or switch between these two products, you know, Dr. Sean Kane 31:21 yeah, and it's really kind of the honest mistake that is typical with med errors. So it was an honest mistake by the prescriber to pick diltiazem instead of diltiazem ER or CD. And then it was maybe a less honest mistake that this was filled by the pharmacist, because the pharmacist should know that immediate release is never given once a day, and that would be too large of a dose for immediate release anyway. So it's kind of that Swiss cheese model where different errors happened subsequently that resulted in harm to that patient. Dr. Khyati Patel 31:50 Well, this is where proper review by pharmacists come in play, and it's really important to understand this nuances while filling the prescriptions for meds like diltiazem and Dr. Sean Kane 32:02 Well, Dr. Patel, I feel like that kind of wraps up our deep dive into diltiazem. You know, one thing that really stands out to me that's really important for especially newer learners of drug therapy is that diltiazem is a non dihydropyridine calcium channel blocker. It's in the same category as verapamil, and it will reduce both heart rate and blood pressure, whereas those dihydropyridine calcium channel blockers like amyloidopine, they only reduce your blood pressure, not your heart rate. Dr. Khyati Patel 32:31 And for me, the confusion really stems from the type of different formulations that are out there. It's good to have different formulation for patients who want to use one over the other, but this also results into some med safety issue. And it's important to remember that the current extended release formulations that are in the market are dose ones daily versus the immediate release tablets are always dosed more frequently, like three or four times a day. Perfect. Dr. Sean Kane 32:58 Well, I think that wraps up today's episode nicely for the listeners. If you have any listener requested topics like today's topic, you can reach us at HelixTalk.com and find our contact information. We love to hear from our audience of what you'd like to hear more of. We're also online at HelixTalk.com where you can look at older episodes. We're on Twitter at HelixTalk, where we release clinical pearls from previous episodes. And then finally, we have a mailing list. So if you want to get an email every time, every third Tuesday, at 6am when we release our new episodes, we have a mailing list where you can get the most recent episode and the show notes for that episode right in your inbox. And you can sign up for that at our website, HelixTalk.com so with that, I'm Dr. Kane Dr. Khyati Patel 33:41 and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 33:45 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 - ? 33:56 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.