Speaker 1 00:05 Alright, 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 HelixTalk Episode Five. I'm your co host, Dr. Kane. I'm Dr. Patel and I'm Dr. Schumann. And before we get into today's topic, I wanted to update our listeners on an inaccuracy that we had in one of our previous podcasts regarding the novel oral anticoagulants, or noacs Speaker 2 01:07 in particular, Pradaxa generic Dabigatran, and one of our listeners Dr. Sean Kane 01:12 actually let us know that when Pradaxa was first approved by the FDA, it was only approved in the bottle for an expiration date of four weeks, but that expiration date has now been extended to four months. So again, instead of four weeks for the expiration it's now four months with Pradaxa. Speaker 2 01:28 However, it's still to be kept in the original container to protect it from the moisture. Dr. Sean Kane 01:32 And with that said, if any other listeners have any questions or comments regarding any of our episodes, please visit us at HelixTalk.com for our contact information. We absolutely love the five star reviews that we've received on iTunes, so keep those coming. So today's topic for Episode Five is going to be on smoking cessation. We're going to talk a little bit about the pharmacotherapy of smoking cessation, but really focus a lot of our attention on some of the nuances with one of the newest medications, varenicline, or Chantix. So we'll get started with some background information. So I think it's interesting to think about how common smoking is, in terms of how many Americans are smokers, versus, let's say, a few decades ago, Speaker 3 02:13 one of the first thoughts we look at currently is one in five Americans is an is an active smoker. And that seems like a very large number, 20% but that's actually down from about 44% in the 1960s and that was prior to some of the famous surgeon general warnings, and the first one that came out in about 1964 Dr. Sean Kane 02:31 and although it's one in five Americans are smokers, it's about five out of five Americans on reality TV shows are smokers. So Dr. Patel, do we know about the treatment to prevent someone from relapsing from smoking or to even have an initial quit attempt. Speaker 2 02:46 So we have two different things going on, and we are trying to help a patient quit smoking. First thing is, obviously the medication, which we will go over briefly. The second thing, and very important thing, is counseling. And when we talk about counseling is behavioral modification, and what we have found is that counseling, plus the medication therapy, is more effective than just using them either by themselves. Dr. Sean Kane 03:13 So it's interesting. What you're saying is that medication therapy, it's not a magic pill, but it also requires some form of counseling, whether it be a telephone hotline or in person counseling to a patient, the combination is more effective than either agent alone. Speaker 2 03:28 That is true. And I've sat through one of these counseling sessions, and they tend to be more of a group counseling sessions, or group discussion sessions, where patients come along and they discuss about their triggers and little tricks that they have used to modify their cravings. Dr. Sean Kane 03:46 If I'm not mistaken, I believe there's a very strong dose response effect, so the more intense your counseling, so the more contact hours, the better. The chances are that a patient will maintain abstinence with smoking, Speaker 2 03:58 and that is very true. The established smoking cessation programs do register patients in into these counseling programs and make sure they complete the sessions if they need to. Dr. Sean Kane 04:08 So Dr. Schuman, I know that it's very difficult to quit smoking, but can you give me some idea of how successful a patient is if they receive no counseling, no medication, versus any of our best attempts at providing pharmacologic or non pharmacologic therapy, Speaker 3 04:23 sure, so, so those individuals who have no counseling, no medications, quit rates are about 10% or sometimes even less than that. So what we can consider is counseling alone. What does that do? That's about 15% quit rate there, and then that's compared to if you just did the medication, no counseling, but just given a medication. Say, Here, take this, and you know this is going to help you quit smoking, about a 20% quit rate or abstinent rate there. And then if you combine the two medications plus counseling, you get an extra 5% so you get about 25% quit rate there. So again, we're still talking numbers that aren't as stellar as we'd want. You know, we're always going. Per 100% so maybe one in four individuals, based upon these numbers, is going to have a long standing successful quit. From that, from that initial Dr. Sean Kane 05:08 trial, I think it's really important to emphasize that these trials are generally randomized trials of people who are being enrolled in a study to quit. So these patients are going to be highly motivated to attempt to quit, as opposed to, let's say, the outpatient setting, where you say, Do you want to quit? And they say, Sure, their quit rate is probably going to be lower than someone who enrolls and goes through the process of a clinical trial. Speaker 2 05:32 And you made an excellent point there. So in clinical practice, in my clinic, too, I let the patient know to come to me when they are ready, when they're absolutely ready to dive into quitting, because we know that if the initiative is not coming from the patient, the outcome is not that great, absolutely. Dr. Sean Kane 05:49 So we're going to talk a lot about the medication therapy in a minute here. But what is the best evidence in terms of what are the most effective medication plus counseling therapies that we can give a patient, Speaker 3 06:01 a few of them is, is combinations end up being one of the best things we can do. For example, a long term therapy of a nicotine replacement patch, plus an as needed on top of that, for what we say, breakthrough cravings. I when I counsel individuals on it, I tell them it's a lot of times we have conditions, pain, anxiety, other conditions, we have a medication you take for a long, a long term, you know, on a daily basis, then you have medications, whether it's for breakthrough pain, breakthrough anxiety, or here for breakthrough crave, nicotine cravings. You have something to go on top of it, because we can give you, what we think is that is the best dose of, say, a nicotine patch. But then if you still have craving on top of that, if you're going through a stressful time, or you're hanging out with individuals who in the past, when you were with those individuals, you've smoked, or in situations where you may want to smoke, to have something there that can help you. So that combination, or another one to combine the nicotine replacement as well as Bupropion, so a medication that works on a couple neurotransmitters, for example, dopamine and norepinephrine, the two of these we believe in particular dopamine, so that if you're getting the dopamine from there, you may be less likely to self seek it through through behavior such as smoking. So again, that kind of one two punch there can also be beneficial. Dr. Sean Kane 07:15 I know one concern that many patients have regarding nicotine replacement therapy is it seems counterintuitive to them that you're going to help them quit smoking by giving them nicotine. There's a number of reasons that we're accepting of this practice, and probably the biggest is that as far as we know, based on the trials that we've done, nicotine replacement does not have cardiovascular effects in terms of making patients at higher risk for having cardiovascular events, and it is safer in the sense that they're not inhaling carcinogenic smoke and having that kind of a habit perpetuate, as opposed to a medication that we can provide them. Speaker 3 07:52 And I think a lot of it too, is that the controlled nature of the nicotine replacement, whereas with smoking, if you're borrowing somebody else's cigarettes versus your own brand, or, depending on how you inhale it, how deeply you inhale it. There's so many other factors involved there. But with with the smoking, we can tell you that that you know, that patch is a certain controlled release, milligrams per day. And so then by doing it and I graded or bringing it down from time to time, we can have a little bit more control over what doses you're on. And so thus bring it down to a point, and then once your body's gotten used to it, then being able to kind of go from there to maybe either not being on the patch or just continue with that lower dose. Dr. Sean Kane 08:30 So Dr. Patel, what are some of the dosage forms of nicotine replacement? Which ones do you prefer for yourself? Speaker 2 08:35 Well, see, there are many different combinations available. We got the nicotine gum, we got the inhaler, the lozenges, we also have nasal spray. And then most commonly used is the patch. If I were to pick one over the other, I probably would go with the patch. Once again, it's because easier for its application. And also, most of the clinical trials that are done using NRT or done using the patches. And I Speaker 3 09:02 think individual preference is something that we can't emphasize enough with this. As Dr. Patel said, that she has one particular idea for herself. But again, for those listeners who are interested in quitting themselves, or for their patients, you really have to look at some of those other factors. Is somebody, you know, would they again prefer a patch? Or there's, is there been in the past, you know, issues with with the rashes, say, with patches? Is there? Is it, again, something where it really is that hand to mouth, somebody that says, Well, I tried a toothpick for a while, and that helped, but then I still was craving so that individual, maybe that nicotine inhaler could be beneficial. And then again, there's, I've had individuals that say they do not like the taste of the gum, or they do not like the taste of the lozenge. I'll often hear the same complaint about one, but then the other one was better, and I've heard it flipped both ways. So it's going to be a lot of those just individualizing and encouraging the individual. Speaker 2 09:52 So with the recent initiative of, you know, healthy life and helping people quit, most of the insurances will pay for the therapy, especially. The patches and the inhalers that are available via prescriptions too, but things like gum and lozenges are not covered because they're over the counter. So you kind of have to play around with what patients can afford as well. One thing you also have to consider that you put the patient on the appropriate dose of either the gum, the spray or the lozenges or the inhaler or the patch, because if there's if they're smoking a whole pack, and if you start them out on seven milligrams of the patch, they're going to have craving and they're going to fail. So make sure you follow the manufacturer's recommendation as to how many milligrams of nicotine replacement they should start out with based on what their current use of cigarettes is, and a cup another very important advice you want to give patients, which sometimes, to my surprise, patient tell me, at times they were not told, is that they cannot smoke while they are using the nicotine replacement therapy. So please, please, please, tell them to not smoke. And the biggest reason you can give them that they can't because it increases their risk of side effects such as myocardial infarction. Dr. Sean Kane 11:02 So moving on from nicotine replacement therapy, one of the first oral agents that came out for smoking cessation, that's really one of the main line therapies, is Bupropion. The brand name for this under the smoking cessation label, is Zyban. Speaker 3 11:17 So as I stated before, Zyban again, it also, you may hear it by the name of Wellbutrin, which is the brand name for the product, as it's approved for treatment of depression, works on a couple of those neurotransmitters, those chemicals in the brain, and just in the same way, it increases them in depression, and can kind of increase, you know, for a low energy form of depression, can have the benefit in allowing an individual to maybe, you Know, not you know, who may use smoking as either a coping mechanism or weight again, to get some of those neurotransmitters going, that dopamine, this can be a way to augment that without going to something like smoking, so those individuals, you know, maybe have less of an impulse to then smoke over time and again. This is when, you know, at the facility where I work at, this is one of the first line medications we start with. And can, can be a very good one. You start at at one tablet, or 150 milligrams every day, and then you increase to 150 milligrams twice a day. I believe after three days, the one thing with this medication is that we counsel on is a couple things. One is that you really want to take the second dose at least before 5pm we usually say around three to 4pm just because it is activating. And so compared to other medications, again, for pressure, for example, but here it can sometimes lead to insomnia, and if that's an issue, again, not for everyone, but if that's a concern, or you notice that, then kind of pull back when you take it, but still make sure to give yourself about eight hours for when you take it. So if you take your first dose at 8am you can maybe take your second dose about 4pm or so, and again, you can move that about we just want to be given at least eight hours, and yet you don't want to take it so far away that it's going to cause insomnia. And then we also want to monitor for things like changes in mood. If the individual has a history of depression, bipolar disorder, there's concern about a switch to mania or so that increased impulsivity. If that occurs, we have to be careful. And then also really want to be careful with somebody who has history of seizures, this medication can lower the seizure threshold, so that that is one thing that for those individuals, we generally do not recommend this medication. But then the other thing people do like about it is it's a favorable effect on weight gain. A lot of times, people say that when they quit smoking, they start to gain weight. And this medication, because it can be weight neutral to even cause a little bit of weight loss, that can be something that for some individuals, that that's a really big concern. I don't want to quit smoking because I like my weight then we can offer this as an alternative. Speaker 2 13:37 And if I'm not wrong with bupropion, you can set up a quit date early on, and then start the Bupropion the week before the quit. Yes, yes. Speaker 3 13:48 Usually that, and then this and the next medication we talk about. That's one other thing we can discuss with our patients, is that they want to go ahead and start the medication and then give themselves a week of taking the medication before they quit to again allow the medication to be in the system and working before you go ahead and quit. Dr. Sean Kane 14:04 With timing in mind, I think it's important to think about how long you continue any of these oral therapies before you say, you know, maybe this isn't working very well. So at least in the package insert for Zyban or Bupropion, it says that generally, if patient is not successfully quit after about seven to 12 weeks, so roughly, you know, about three months, then it's unlikely that the patient will successfully quit after that, while continuing Bupropion or Zyban therapy. So that's another consideration to think about in terms of duration of therapy, whether you're having success or Speaker 2 14:38 not, and if you do decide to withdraw the therapy, then you have to make sure it's an antidepressant, so you have to taper it down. Dr. Sean Kane 14:47 All right. So moving on to the third agent. The generic is varenicline, and the brand name is Chantix, and this is the newer agent to the market. Kind of has a unique mechanism of action and some interesting controversy surrounding. Speaker 3 15:00 So this medication, what it does is it works at some of these nicotine receptors, the alpha four, beta two receptor is it works as an agonist at some nicotine receptors, but it also blocks others. So it gives you a partial effect of smoking, and yet, what it does by doing that is it kind of blocks some of the overall effects of it. So then, by getting a little bit of stimulation, but not to the full effect, it kind of almost discourages somebody from continuing to smoke. So it's very unique in how it works. Not really a lot of medications quite like it. Speaker 2 15:32 So Dr. Schuman, with your expertise, I would like to ask you, what type of patients would you target this particular medication to? Speaker 3 15:39 Again, that's a good question with a lot of patients, again, in my in our facilities, because of some of the effects we'll get to in a second, it's usually we start with somebody who has failed both the nicotine replacement and the zybra, the Bupropion, and then once, once you've had the failures on those, or if they've used this one in the past, for example, to come to us and say, it's been beneficial, then we'll look at it. One of the things we do look at is going to be psychiatric stability. One thing with this medication, this is where it's gotten. A lot of of press, both good and bad in the last few years, has been about things like psychiatric disturbances or causing changes in dreams. So for example, very vivid dreams, as well as sedation, have been have been two concerns with it. So I believe that, especially in early on, it's still, I believe is the case for a lot of companies, that if you have a job to where you need to be focused, or you need to be alert, then they usually don't recommend it just because of an increase in sedation. So we want to be kind of aware of some of those concerns. But then, as I said, psychiatrically, well, the one thing that we emphasize is that if somebody has a history of depression, that doesn't mean they can never use this medication. Just means somebody who is not stable on their medications, maybe has been on and off taking their medications, or hasn't been seen in a while, then this may not be a good medication, at least at that that point in time, give that individual time to stabilize their psychiatric care, and then give this medic this medication can be an option. Speaker 2 17:00 That's a really good statement you just made, because I had a patient recently in the clinic who was on a mood stabilizer and was seeing a mental health provider for her bipolar disorder. And the provider referred her to me to see if Chantix would be a good option, because she had failed all the previous therapies, first line therapies, and so my recommendation was to a first get a clearance for the mental health provider to make sure patient is stable. Enough to get started on the treatment, and I also let the patient know to maybe have a frequent follow up with that provider, so they can also track the mood changes. One important thing I've also heard is to let the patient's family member that the patient's living with know so they can also effectively monitor any changes in the patient's behavior or the mood Dr. Sean Kane 17:44 so Dr. Schuman, in addition to the vivid dreams and the issues with mood stability, I know that one of the controversies with varenicline Chantix is the issue of seizure threshold. Would you mind just kind of discussing what the controversy is and how significant the issue with seizures with varenicline, sure it was Speaker 3 18:02 one of those issues where there was, when they were initially testing it, I believe there may have been one or two patients who had developed a seizure. So when the packaging first came out, it mentioned things like, they mentioned the sedation. They said, you know, neuropsychiatric effects. So sedation and seizures were all were placed in there. And so the Institute for Safe Medication Practices did an analysis of about 3000 individuals, and within those there were 86 reports of seizures, and which sounds like a fairly substantial number, but note that they noted that two thirds of those patients were on additional medications, as well as 10% taking greater than nine medications, so a very large number of medications which some of the patient and hard to decide, you know, which particular medication it could have been leading to. And so then other governments have done the same thing, because, again, you don't want to give a medication to treat one thing and then cause an outbreak of some very serious side effects. And so in Australian government, they have the Therapeutic Goods Administration, which is their equivalent of the FDA, and they looked at about 210,000 prescriptions. So a very, very large number had about 339 adverse reactions. And of those 15 were seizures. And even within that number, they're not sure how many of those individuals even had a history of seizure and so and again, they the medication history was not there either. Dr. Sean Kane 19:17 So it sounds like this adverse effect was born out of some preliminary data, and it's kind of been propagated over time, but really, the data either shows that the risk of seizure does not exist, or if there is a risk, it's a very, very small risk, Speaker 3 19:30 certainly, and so at our facility, it's still mentioned within the within the information to provide, but it's not a contraindication. It is just you let the patient know. Speaker 2 19:40 So in order to summarize today's podcast, I'm going to go ahead with nicotine couple things that you need to remember, that you need to start the patient on a proper dose of the nicotine replacement based on the current numbers of cigarettes they're smoking in a day. And second, very most important counseling point for the patient would be to not. Smoke while they were using the nicotine replacement therapy because of the side effects such as myocardial infarction. Dr. Sean Kane 20:06 So the second agent that we talked about today was Bupropion. And for smoking cessation, the brand name is Zyban. But for depression, the brand name is Wellbutrin. Keep in mind that Bupropion is an activating medication, so patients may have problems falling asleep at night if they take it too late in the day. So an important counseling point is to have them take it before 5pm so that they're not up all night because of the activating effect of the Bupropion Speaker 3 20:29 and then the final agent, varenicline, or Chantix. Main points with that one is, as I stated early on, is that this is a medication that started seven days before you go ahead and have your quit date. So once you have the quit date in mind, go ahead and start the medication. The medication to give it time to get up to the to the final dose, and so it's in your system and then with it. As I said, it's not a complete contraindication. Or there's no rule that says you cannot use it if you have seizure or if you have history of mental illness. These are things that just need to be discussed and monitored for. Dr. Sean Kane 21:00 That concludes episode five of HelixTalk. Again, please give us a positive review on iTunes or visit us at HelixTalk.com with that, I'm Dr. Kane and Unknown Speaker 21:10 I'm Dr. Patel and I'm Dr. Schuman. Speaker 2 21:12 That being said, I hope you all students will study hard. Narrator - Dr. Abel 21:18 Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com you.