Speaker 1 00:05 Lange, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University College of Pharmacy. Narrator - Dr. Abel 00:11 This podcast is produced by pharmacy faculty to supplement study material and provide relevant drug and professional topics. Speaker 1 00:19 We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. Narrator - Dr. Abel 00:27 This is an educational production copyright Rosalind Franklin University of Medicine and Science. Speaker 1 00:32 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 - Dr. Abel 00:47 And now on to the show. Dr. Sean Kane 00:51 Welcome to episode six of HelixTalk. I'm your co host, Dr. tain. I am Dr. Patel, and I'm Dr. Schuman, and today we're talking about the gold guidelines, and we're going to be focusing on kind of an overview of the treatment of COPD, but really honing in on some of the newer agents for COPD that you may not be that familiar with. So to kick it off, I think it's important to at least mention some of the diagnostic criteria for COPD, because I really think it helps emphasize how a patient with COPD feels in terms of their respiratory status. Speaker 2 01:20 So we're considering diagnosis of COPD in any patient who complains of dyspnea, has chronic cough or production and a history of risk factors such as tobacco smoking, exposure to smoke from cooking or heating fuels or occupational dust or chemicals. Dr. Sean Kane 01:37 Really the gold standard. Once you've established risk of COPD with symptoms is to do spirometry, and the way that COPD is diagnosed is based on what's called the FV, one divided by the FVC. What those mean are the forced expiratory volume in one second, so how much air you can blow out in one second divided by your functional vital capacity. So the total amount of lung volume that you have. So in a patient who has COPD by definition, they are not able to expire more than 70% of the total air in their lungs, whereas a normal patient should be able to expire within one second at least 70% of the air in their lungs. And I know Speaker 3 02:19 I had that explained to me when I was a student as difference between something between something that's restrictive and obstructive. So again, that's kind of that clue here is that it's as something obstructive, it's that difficulty getting the air out or expelling it quickly. And so that's where that number is going to show up as that difference, especially in that percentage, and Dr. Sean Kane 02:36 why it would be lower. If you're really trying to think about this, you can kind of mimic the same effect by trying to breathe out through a straw. So if you have a straw to your mouth, and you're breathing out as hard and as fast as you can, you're not going to be able to get as much air out as quickly as someone who doesn't have a straw. In the same effect, someone with COPD as hard as they try to expel air from their lungs, within that one second period, they're going to get less than 70% of their lung volume out. Speaker 2 03:02 And so one of the ways that we define the severity of COPD is looking at the post bronchodilator FEV one response. And so according to the gold guidelines, it's divided into four different categories. We have gold one, which is mild, which is greater than 80% of the predicted FEV one value, gold two, which is the moderate COPD severity, which is falls anywhere between 50 to 80% of the predicted FEV one. Goal three, which is considered severe, and that falls somewhere between 30 to 50% of the predicted FEV one. And then Goal four, is very severe, anything less than 30% of FEV one, predicted FEV one falls into this category. Dr. Sean Kane 03:42 It's important to note that when we say predicted, it's based on the patient's age, primarily in terms of what we would predict their FEV one should be based on their age. And although we're not talking about asthma today, you'll note that these cut offs of 50% 50 to 80% greater than 80% these are actually very similar to what you would see for asthma treatment when we're looking at peak flow meters. Speaker 3 04:05 So that being said, we want to go ahead and jump right into some of the medications. Yeah. Dr. Sean Kane 04:09 So the gold guidelines were last updated in January of this year, 2014 they had a number of small updates, but really the biggest update that potentially could change practice is how they recommended steroid treatment for COPD exacerbation. Speaker 2 04:24 I'm really excited to talk about it, because I've been trying to push this change even before the gold guidelines accepted it based on the clinical study evidence that was available, but none of the providers were ready to listen. So the change, as Dr. Kane mentioned, is that for the COPD exacerbation, the older dosing of oral steroids was 30 to 40 milligrams of prednisone to be given over 10 to 14 days. Now the new recommendation is to do prednisone 40 milligrams, but only five days of therapy. Dr. Sean Kane 04:55 It's important to note that the old recommendation was not born out of strong evidence. For 10 to 14 days. It was primarily expert opinion, whereas the new recommendation saying about 40 milligrams for five days for a COPD exacerbation, they classified this as level B, which is fairly good quality evidence. It was based on one recent trial. Speaker 3 05:14 And for anyone that wants to look up some of the information and get get the further details, it comes from the REDUCE trial, and what they looked at was the five to the 14 days of the 40 milligram prednisone, and it was a non inferiority design. So what they're looking for again is, could they show non inferiority? So what they showed was that five days was indeed non inferior to the 14 days for six month re exacerbation rate. And so what that does, though, is we can reduce the net the amount of the steroid side effects. So things like changes in blood glucose readings, one that could come up in my in my area, with some of the psychiatric effects. So again, changes in mood, agitation, aggression, that may come about from from high doses of servants for extended periods of time. So it's nice to see them fight that, you know, shut cutting it down by about nine days, less of a chance for some of those things to rear up. Dr. Sean Kane 06:03 It's also important to point out that with a five day duration, there's really no need to taper, but at 14 days, that really is getting to that point, depending on who you talk to of whether or not a taper is needed for that prednisone course. So Dr. Patel, in terms of thinking about prevention, what are some of the preventive let's say vaccinations that someone with COPD should absolutely get. Speaker 2 06:24 First and foremost is the yearly influenza vaccine that is must for all the patients who have COPD. And then we have our pneumococcal vaccine that is recommended, that's based on the clinical evidence that the pneumococcal vaccine has shown better benefits in patients who are 65 and older patients who have severe form of COPD and patients who have other cardiac comorbidities and the other non farm therapies that we should consider for patients who have anywhere from severe to very severe COPD, we should consider pulmonary rehab, those are usually run by respiratory therapist, either in the inpatient basis or outpatient basis, where referral can be made, where patients can learn to utilize their medications properly, to utilize certain behavioral therapies and changes, or trigger modifications and things like that, to better control their symptoms. And then third that, when we just talked in our podcast, number five is smoking cessation. So if you are looking forward to helping a COPD patient quit or explain them the risk and benefits of smoking cessation therapy, you can go ahead and listen to the podcast number five. Dr. Sean Kane 07:35 Moving on to kind of COPD specific pharmacotherapy, the first and most recommended drug class are going to be our bronchodilators, and we've got kind of two ways that we can bronchodilate or widen the airways of a patient. One is by using the beta two receptor, so a beta two agonist, then the other way is via anticholinergic or anti muscarinic activity, which also widens the airways, which in effect, increases the patient's FEV one, so we're basically widening the straw that they're breathing out of so that they can breathe out quicker and more efficiently. And then, I Speaker 3 08:08 think it's always interesting, even within the class, such as within those beta two agonists, you even have those labeled as a short acting beta agonist, or a Saba, and then you have the long acting beta agonist, which is the lava. So you have some that can last four to six hours, others that can last 12 hours. And even now, we have newer agents that can even last up to 24 hours. So we have newer therapeutic options, again, that change how they should be used and as well as how many times per day. Speaker 2 08:33 And then we have medications that work on the anticholinergic receptors. So we got the long acting muscarinic antagonist, and then the short acting muscarinic antagonist, the llama and the Asama, if you were to call it. Dr. Sean Kane 08:47 And one thing that the gold guidelines emphasize is that for patients who have more than just kind of run of the mill, infrequent COPD using a long acting bronchodilator, either a llama or lava is preferred over having a patient use only a short acting agent frequently throughout the day, because symptom control, quality of life is going to be better by giving a long acting agent. Speaker 3 09:10 And I think that's one that can be a good education point, because I know we have individuals who have, maybe just at one point, been on a short acting and just use, for example, something like either the albuterol or the epitropion, and just use it, you know, maybe a couple times a day, and they start to see an increased frequency of use. And that would be a great intervention to then start using one of those long acting agents, instead of just having somebody just blow through those Dr. Sean Kane 09:33 inhalers every day. Along the same lines, it's important to counsel a patient for these long acting agents that they aren't used for acute symptoms. They need a short acting agent for that, and also they're not used PRN, meaning that a patient should be taking these whether they feel good or they don't feel good, the way that they work is preventing symptoms, not treating active symptoms. Speaker 2 09:53 Another good thing that goat guidelines mentioned that if the patient's not control on one particular long act. Bronchodilator, you can actually add another long acting bronchodilator rather than increasing the dose of the first long acting bronchodilator. This is because we're attacking two different mechanisms to relieve the straw, like effect and widening the straw, basically. And we will talk about one of the agent that grabbed the gold guideline recommendation and created a combination. Dr. Sean Kane 10:23 The third kind of class of bronchodilator is called theophylline. And for me, I really haven't seen more than one or two patients who have been taking theophylline. Is there a reason that theophylline has kind of fallen out of favor? I think Speaker 3 10:35 part of it is going to be that it's a narrow therapeutic window agents. We have medications that we generally dose a certain way, because if you deviate from those doses too much, you can kind of see somebody with either maybe getting under dosed or potentially getting an overdose. And so medications like warfarin or lithium are considered to be an inner therapeutic window at the opal in it is another one, and with its adverse effects similar to caffeine. So with that, you can get some some jitteriness, I believe then they can lower the seizure threshold. Can be a concern for other individuals, and you may have, again, potentially some anxiety like effects as well, and some effects on the heart. Dr. Sean Kane 11:11 So theophylline is nice that it's an oral agent where you take an actual tablet or a capsule, but it's, as you said, not so nice because of its really unfavorable adverse effect profile, whereas with these local inhaled agents, they have very minimal adverse effect profiles, we don't have to worry about these super narrow therapeutic windows. And while Speaker 3 11:30 we're talking about different inhaled agents, I think one thing that's important is, if you're in combination or just switching from agent to agent, is to know that a lot of these inhalers are going to look a lot differently, and they're going to be used a lot differently. For example, some of them are are inhaled. You just go ahead such a more traditionally, like an Albuterol inhale, where we just use it with or without a spacer, and you go ahead and spray it into the into the mouth, and then open up the airways and take it in that one. Then you have others that you actually crush a capsule. But then there's a medication Tia tropium, or spireva, is one where it comes as a capsule, but that is not a capsule to be taken by a mouth and said, That's a capsule that gets placed into the inhaler and crushed, and then you're going to inhale the dust within there. And so I think for those individuals, again, who are prescribing these to make sure that the patient is aware of the differences, and so in particular, which one they're using, so that if they come up they have somebody else who has inhaler, they say, Oh, I can tell you how to use that one. It may be completely different, depending from inhaler to inhaler. Speaker 2 12:28 Counseling is very important, like you said, Dr. Schuman, but if additional information is needed, you can go on to the particular manufacturer website, and they do have medication use guides with the little pictures on it, and that becomes really helpful for the patient if they forget anything that Dr. Sean Kane 12:42 you mentioned, and even videos too, some of the videos are actually extremely helpful for a patient. So moving on from our long acting bronchodilators, the next drug class that a COPD patient is likely to encounter in terms of chronic use are inhaled corticosteroids. Speaker 3 12:58 And these are medications that generally are used only for severe or very severe patients who have frequent exacerbations Despite long acting bronchodilators, and that's based upon the torch trial that they show milder improvement in exacerbations versus an increased risk of pneumonia. Dr. Sean Kane 13:13 So it's really a risk benefit for a patient if they have to go to the hospital often because of their COPD exacerbations. Based on the torch trial data, we can make it so they have fewer exacerbations. But the downside to that is that because we're giving something that suppresses the immune system, they're at a higher risk for pneumonias. So it's really a risk benefit for a given patient. Speaker 3 13:35 And to jump back to when we talked about prednisone and the five day versus the 14 day, you want to re emphasize the monotherapy with these oral corticosteroids without any inhalers is not a good idea. So when we talk about using them for exacerbations, it should be on top of somebody who is already getting the right courses with their inhaled Dr. Sean Kane 13:51 medications, and on top of that, really, as you mentioned, Dr. Schuman, you know, an inhaled corticosteroid is the cornerstone of asthma therapy. It is not the cornerstone of COPD therapy. So it would make no sense to have a patient on either oral or inhaled corticosteroids and not have a long acting bronchodilator. The bronchodilator is the cornerstone of COPD management. Speaker 3 14:12 As always, you kind of try to focus on some of the, some of the newer agents. So one of the one of the new ones, that's kind of a totally different direction with the mechanism, is one called daily rest is the brain name or refuel. Last is the generic. And this is one. It's a phosphodiesterase Unknown Speaker 14:26 inhibitor. And so how does it work? Dr. Schuman, Speaker 3 14:29 oh, so this one, it reduces inflammation, just as some of the others do, but this one by inhibiting the breakdown of something called cyclic AMP. This is similar to how medications, for example, sildenafil or Viagra works on a different kind of phosphodiestera. So this one is called a PDE for inhibitor, so totally different than those PDE five inhibitors used for other conditions. Speaker 2 14:49 Sounds very fancy, so I'm thinking it's probably not approved for a mild to moderate COPD. Is that true? Speaker 3 14:55 Yes, this is one that it's been shown when it was approved for exacerbations with. Severe, very severe, COPD with frequent exacerbations, and that's despite use of long acting bronchodilators. So either your llama or your lava, Dr. Sean Kane 15:08 and I think it's interesting to think about, not only that, they're approved for efficacy with, let's say, preventing exacerbations, but the actual effect size that you'll see is actually kind of minimal. So for a medication like this, or even kind of our standard bearers, like teotropium or spireva, the actual decrease in yearly exacerbation rates are about 15% so that means that we're going from, let's say, something like 1.3 exacerbations per year to 1.15 exacerbations per year. So the actual effect size is quite minimal. I think it's important to keep that in mind in terms of you know, is a patient ready to take another medication, have another copay, if their symptoms aren't that bad, they stand to benefit less than someone who has very, very severe symptoms. So what are some of the adverse effects? Do we see things like we would see with sildenafil, where we have erections that last more than four hours, or do we have a completely different adverse effect profile because we're working on a different PD enzyme? Speaker 3 16:05 Good question. You. One thing you can notice is with this one is nausea, potentially diarrhea, weight loss is one not really seen with sildenafil or Viagra. One to two out of every 10 patients can lose five to 10% of body weight. So that's a fairly significant number. Again, something you really, really want to educate Dr. Sean Kane 16:22 on that seems relevant to the COPD population. Because oftentimes, when we have a very severe COPD patient, they're not going to be overweight. To me, the typical COPD patient is going to be an elderly person who has smoked for a long time, who weighs something like 50 kilograms, not the 150 kilogram patient. Speaker 3 16:39 And for diarrhea, I know is one that in some of the reviews I've read on this and other medications, it ends up being one that potentially can get patients to stop. So that is one that needs to be discussed up front. Because, again, if you're using this medication and just not taking it because of that effect, we're going to want to make sure that those other therapies are optimized. Speaker 2 16:57 Notice that one of the side effect listed is also anxiety, and that is the reason manufacturer says not to combine it with theophylline but you have to consider patients are going to be on Saba or another long acting anticholinergic, which can also add into things like anxiety. Dr. Sean Kane 17:13 In terms of what we're going to be picking and recommending for our patients, there's kind of four groups that the gold guidelines spell out in terms of what we should be giving our patients. So for patients who are having very few symptoms and have a low risk of exacerbation, they really just need an as needed, short acting bronchodilator, like albuterol or aprotopium. If it's a patient who has more symptoms but they have a low risk of exacerbation, then we're typically going to give them a long acting bronchodilator that could be a lama or lava. And then for the remaining groups, these are patients who have a high exacerbation risk, they're going to be getting a long acting bronchodilator and an inhaled corticosteroid. And remember, we said that that inhaled corticosteroid helps with exacerbation risk. The very last group are the group who has the most symptoms, so very severe symptoms and very high risk of having exacerbations. And that patient group is most commonly going to have a long acting beta agonist, a lava a long acting muscarinic antagonist, a llama and an inhaled corticosteroid as well. So these patients will have a lot of different inhalers that they're going to have to manage throughout the day. Speaker 2 18:26 And just to reiterate, these are the recommended force choices. So if one of your patients cannot tolerate one of the therapies, or also due to the cost reason, you can always pick the alternate therapy that are also listed in the gold guidelines. Dr. Sean Kane 18:40 And as we discussed, there's a number of add on agents, such as the refluma last that is not a first line therapy, but can be added on as kind of a patient specific decision. So before we move on to some of the very new agents, one thing that I wanted to mention are COPD exacerbations. And what the gold guidelines say about COPD exacerbations, aside from the prednisone that we already discussed. Speaker 2 19:03 So as far as the antibiotics go, you know, you have a patient with COPD exacerbation, they come in the hospital, and the first thing physicians want to do is start antibiotics. And that's an issue that's really controversial. So most patients who have the three symptoms, such as dyspnea, increased sputum volume and sputum purillians are the patients who would get the antibiotics. However, the recommendation is to give the antibiotics to patients who come in with the infectious etiology, and not all those patients. Second category of patients who almost always will receive antibiotics is your patients who are intubated or on mechanical ventilation, and if you are in the hospital working on the floors, make sure this antibiotic duration is minimized as much as possible. So the recommended duration is five to 10 days. Speaker 3 19:54 So Dr. Patel, you're saying that if we do decide to use an antibiotic in an individual, again, it's not a rubber. Stamp that should go to every patient who comes in with COPD and maybe a little bit of Unknown Speaker 20:03 dyspnea. That is absolutely correct. Dr. Sean Kane 20:06 So moving on to some of the newer agents, either ones that are mentioned in the gold guidelines or the ones that made it to the market after the gold guidelines were prepared. The first one is called indacaterol. The brand name is Arcapta Neohaler. This is a long acting beta agonist, just like salmeterol or formoterol, but the unique thing with it is that it lasts 24 hours, instead of lasting 12 hours like Speaker 2 20:29 the other two agents. So are you saying that's once a day administration? In that case, it's once Dr. Sean Kane 20:33 a day. I love it, and this is it's important to note that this is only approved for COPD. It's not approved for asthma, and the way it's given is very similar to the way that we give teotropium or spreeva. So there's a capsule that you put in an inhaler, you crush the capsule in the inhaler, and then you inhale the powder. But the cool thing is that the capsule has little micro beads inside of it, and as you inhale, it actually makes a whirring sound as those beads go through the inhaler. And it's one way to give positive feedback to the patient, to let them know that they're truly getting the medication. Speaker 3 21:06 So again, that's a capsule. It's not to be taken by mouth, not to be taken by mouth. Let's just kind of wait for the little helicopter going on inside the little thing, all right. And then I think there's, there's one more aclidinium, or that Tudorza Pressair, and this one is a twice daily LAMA or a muscarinic antagonist. It's like tiotropium, but instead, this one's given twice a day. Dr. Sean Kane 21:27 So why would a patient want to take something like acladinium Twice a day when we have another long acting muscarinic antagonist, llama, like teotropium, that's only once a day. I believe, Speaker 3 21:37 with this one, it's a breath actuated dry powder inhaler. So again, instead of doing it with the capsule, and but it's different in that the one inhaler has a 30 day supply built into it. So it's more like another medication advert, which is a combination of the lava and inhale steroids. So instead of having to have a separate capsule every single day that you're you're putting in there, this medication has all 30 of those doses are ready there. And so if, for example, you don't want to carry around a whole bunch of capsules and your inhale, you can just have one single unit that you can have with you. Dr. Sean Kane 22:08 So it's kind of a give and take. You take it twice a day, but you don't have to deal with the capsules. So there is some advantage, probably a patient specific preference, and Speaker 2 22:16 a couple other medications that have been introduced in the market very recently that have not made their place in GOLD guidelines are Anoro ELLIPTA. It is a combination of a LAMA umeclidinium and a LABA vilanterol. And basically the advantage with this combination is that it's one inhalation once a day. So we are hoping to improve compliance, and it's a dry powder inhaler. So this is Speaker 3 22:41 a dry powder inhaler. Does that mean that mean that this one, like our previous discussion, is another one that you don't have to carry around a whole bunch of capsules with you, but just one single inhaler. Speaker 2 22:49 That is absolutely correct. And the second name in the brand name, ELLIPTA, it's the type of technology, or the device system that the manufacturer has created to deliver the doses. And part of that device technology is what requires once a day inhalation only. Speaker 3 23:05 Okay, so again, this one's probably if somebody was to use it to look a lot different than any other hailer out there. So we probably want to make sure that they're aware of it and have a little bit of a demonstration as to Speaker 2 23:15 how to use it. Definitely, definitely. The second combination of the ELLIPTA technology is Breo ELLIPTA, and that's a combination of inhaled corticosteroid fluticasone and the LABA vilanterol. Again. This is also a dry powder inhaler, just like the Anoro ELLIPTA. This is also one inhalation once a day. And the good thing about this one, it's also used for exacerbation of COPD along with maintenance treatment. Speaker 3 23:43 And so this is one that combines an existing agent, right? I believe that futicosome is something that's already on the market, and then we're combining it with that new or long acting beta agonist. Speaker 2 23:52 That is correct? But the benefit here is, unlike if you were to compare it to Advair, which is a twice a day administration, we can get away with once a day administration, okay, they will still have to wash their mouth after using it, just like they would do with AD wear. Speaker 3 24:06 I think that's a good point that we always recommend just to and to avoid the risk of any sort of an oral infection or an inspection on the mouth a white kind of plaquey stuff, is to make sure to rinse your mouth out if you were to use one of those inhaled corticosteroids. Dr. Sean Kane 24:18 And again, for both of these agents, for Breo ELLIPTA and anoro ELLIPTA, they're only approved for COPD, not for asthma therapy, at least at this time. So to summarize, with our management of COPD, again, the cornerstone of COPD management are going to be bronchodilators. That means either a beta two agonist or a muscarinic antagonist. Speaker 3 24:40 And then another point to make is that, based upon the REDUCE trial, we can do a five day course of an oral prednisone therapy, 40 milligrams, instead of doing a 14 day we can have the same benefit without having all the same long term effects and having to worry about a taper Speaker 2 24:55 going along with the steroids. When, if we are looking at the use of inhaled corticosteroid words, make sure you reserve them just for patients who have severe to very severe COPD who frequently have exacerbations, because we know the data from the TORCH trial tells us that if we use it, we put them at a high risk of pneumonia. Dr. Sean Kane 25:15 So going through some of the newer agents that you may or may not have heard of, the first that we discussed was roflumilast; the brand name is Daliresp. This is a phosphodiesterase-4 inhibitor, which has an anti-inflammatory effect that reduces COPD exacerbations. Speaker 3 25:31 And another one is going to be indicator all, or the arcapta neohaler. And this is another of our long acting beta agonists. But this is one that lasts about 24 hours and has a capsule like the teotropium that you would go ahead and place into the machine. Speaker 2 25:45 The third new agent is acladenium. Brand name is Te Dorsa press air. This is a long acting muscarinic antagonist, just like tiotopium. However, it needs to be taken twice a day, but good thing is that it's built in into the inhalers so patients don't have to put individual pills in and crush it. The fourth new agent, and again, this is not mentioned in the gold guidelines, is the combination of a llama you make claudinium Or a lava and a lava villain throughout in the brand name called a neuro ELLIPTA, which is a new type of delivery device. Speaker 3 26:21 And then the final one is called Brio ELLIPTA. And this is a combination of an existing inhaled corticosteroid called Fluticasone as well as valantorol, again, which is that new long acting beta agonist. And this one is a dry inhaler once a day. Dr. Sean Kane 26:35 And again, both the ELLIPTA products, a neuro ELLIPTA and Breo ELLIPTA are once daily administration, which is fairly unique for inhalers. Speaker 2 26:44 and also, to keep in mind, these agents are only approved for COPD at this point. Dr. Sean Kane 26:49 So with that, that concludes episode six of HelixTalk. Please visit us at HelixTalk.com and or give us a positive review in iTunes. I'm your co host, Dr Unknown Speaker 26:59 King. I'm Dr. Schuman, and Unknown Speaker 27:01 I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 27:06 Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com. You.