So now we're going to talk more specifically about how to prescribe buprenorphine, how we can have an increased comfort level prescribing buprenorphine for people who have limited or no prescribing experience before for that. So during this talk, we're going to look a little bit more into some of the pharmacology of buprenorphine, some of the regulatory issues that surround this medication, and talk about different strategies to start taking this medication and to kind of troubleshoot some of the problems that come up in early treatment with buprenorphine. So I want to work on reframing the perspective of buprenorphine therapy. Are you folks able to see my complete slide, or do you see like a toolbar that's overlying the… We can see the whole thing. Okay. All right. Okay. Finally, it went away. It was blocking my screen. Sorry about that. So the old perception of buprenorphine is that this is a high-risk medication and it requires this very specific specialized in-depth training to be able to prescribe it properly, and you have to have lots of integrated behavioral health support in order for patients to succeed in taking this. And that was in the context of over 20 years ago when this medication was provided in which we had no context. There was nothing like this before. All we had was methadone. And so essentially, you know, initially when buprenorphine was released, a lot of the recommendations and the monitoring and things were framed in the sort of way of which we think of methadone as very tightly regulated, highly prescribed, tightly controlled sort of program. And what we have learned over the last 20 years of utilizing buprenorphine is that it's not that complicated. This medication is a very safe, very effective medication. It's the gold standard treatment for deadly disease, and all providers should be comfortable in prescribing this medication. And that is the reason why they took the waiver away is because we realized that that is not necessary to be able to help people with this medication. So we just went over this here. Again, there really is no excuse to not prescribe this life-saving medication. And although there isn't any specific educational requirements to prescribe buprenorphine, when every provider goes to renew their DEA, if you have not done so since July, this started in the next three years, everyone's DEA will come up for renewal, and you will need to attest to having taken eight hours of education in addiction medicine to renew your DEA. And this is completely unrelated to prescribing buprenorphine, but it is, again, kind of the goal of the government to help people better understand about how to help people with addiction to treat addiction and to avoid, you know, inappropriate prescribing of controlled substances. So it's important when we think about buprenorphine treatment that every day that a patient takes buprenorphine, even if they're not perfect with taking their medication, every day that they take buprenorphine is a day that is going to reduce their risk of overdose, death, and use of other opioids. And really, there is almost no situation which a patient has opioid use disorder that we shouldn't be comfortable in providing them with buprenorphine if that's something that they want to take. Even if someone's in the emergency room in the hospital, even if we don't have a specific follow-up appointment scheduled for a warm handoff for that patient, we should still prescribe buprenorphine and work to do whatever we can to provide that warm handoff. When we're discharging someone from a hospital, we should always give them a prescription for buprenorphine to continue. And again, not prescribing buprenorphine means that you are not following the standards of care and clearly results in worse outcomes. So changing that perception of providers that this is a risky thing to prescribe to really the opposite, that this is very risky to not prescribe this medication, and not prescribing is not following the standard of care guidelines. Which providers should prescribe buprenorphine? In almost every specialty, almost everyone interacts with patients with opioid use disorder in their specialty. So even if they're a person that doesn't normally treat people chronically with addiction, it doesn't mean that they can't help that person, at least temporarily, to bridge them to care. In primary care, even if we don't provide ongoing opioid use disorder treatment, they can start someone and bridge them to treatment until they can get in with another provider that provides chronic care. There is an increasing trend following new CDC and VA guidelines. If patients are on chronic opioid therapy for pain, other opioids switching to buprenorphine can reduce their risks in that situation. In the emergency room, we use it for patients who have experienced an overdose, who are in withdrawal, to manage a withdrawal in the hospital. Whether they want to continue as an outpatient or not, we can still treat them when they're in the hospital. Surgeons can use it for patients with post-op pain. It's used in adolescents, and greatly underused in adolescents, so pediatricians. It's becoming increasingly used in palliative care for patients who either have a history of substance use disorder or are experiencing intolerable side effects from their chronic opioid therapy. Really, anyone can prescribe buprenorphine, even if it's only a temporary bridge to bridge patients to that chronic care. We already talked about the pharmacology of buprenorphine, but again, it has a sealing effect on respiratory depression, so it is very safe in that sense. It stays on those receptors for a long period of time. It's a long-acting medication. There are a number of studies that really demonstrate how incredibly safe buprenorphine is. This is a study that is looking in patients who are opioid naive, so patients who do not have any opioid tolerance at all, who are given a single dose of 32 milligrams of buprenorphine, which is double the average dose that most patients with opioid use disorder would be commonly prescribed. Even in those patients who have no opioid tolerance, they do not experience respiratory depression when given very high doses of buprenorphine. We also see similar studies from the emergency room with giving doses of up to 40 milligrams or more of buprenorphine. There is absolutely no sign of any respiratory depression or significant alterations in important vital signs, so it is an incredibly safe medication. It is essentially impossible for an adult to overdose on buprenorphine by itself. Generally, less than 4% of overdoses nationwide involve buprenorphine as being present in the patient at that time, and essentially, in all of those cases, there is another drug that was responsible for causing the overdose, like fentanyl, not the buprenorphine. It is possible for small children to overdose on buprenorphine due to issues with the blood-brain barrier in very young children. There are a number of formulations of buprenorphine. The most common formulation that we see is this combination buprenorphine naloxone film. One of the brand names is Suboxone, but there are many different generic formulations, and it comes in many different strengths. Eight milligrams is the most common strength, but it also comes in two milligram films, which can be really helpful sometimes for starting folks if we're doing a low-dose start. It also comes in tablets that have buprenorphine and naloxone in them as well in two milligram and eight milligram strengths. Plain buprenorphine tablets have just buprenorphine and no naloxone in them. That historically has been used commonly in pregnancy, although that is not always true anymore. It can also be used in patients who just have side effects and don't tolerate the naloxone due to nausea or headaches that are persistent. Buprenorphine comes in an IV form that can be given in a hospital if someone is not able to take medications under their tongue. For the last almost six years now, we've had a monthly injectable form of buprenorphine that comes in two doses, and then just in September was released another long-acting injectable form of buprenorphine that comes in various doses, both in weekly and monthly formulations. There are forms of buprenorphine that are FDA-approved to treat chronic pain, so that is transdermal buprenorphine, only one brand that's called Butrans, and a buccal formulation called Belbucca. These medications actually are not allowed to be used to treat opioid use disorder. They are very, very low-dose formulations of buprenorphine that is not sufficient to treat opioid use disorder. You may not legally use these formulations of buprenorphine to treat opioid use disorder. The other is not true in that it is perfectly legal to use sublingual buprenorphine to treat chronic pain, although that's off-label use. It is legal and it's commonly done, so you can use sublingual buprenorphine to treat chronic pain, but you cannot use the formulations FDA-approved to treat chronic pain to treat opioid use disorder. Why is naloxone included in most of these sublingual buprenorphine products? There is a lot of misunderstandings about this, both by patients and providers, on why it is. The naloxone is in there solely as an abuse deterrent. It has minimal absorption when taken as prescribed under the tongue and essentially has no clinical effect. A very small amount of it is absorbed, but remember naloxone is a very short-acting medication. Whatever is absorbed is essentially metabolized and excreted out of the system within an hour. Naloxone is not altering the effectiveness of the medication. It's not the cause of precipitated withdrawal, and it does not block opioids. It has no clinical effect. Really, the only reason they put it in there is to reduce the misuse of the product, specifically to reduce the IV injection of buprenorphine products. If the combination product that has naloxone in it is injected, in certain cases it can trigger precipitated withdrawal or it can partially block the effect of the buprenorphine. There is some data, very limited data, that prescribing the combination product can reduce this misuse of the product. However, that data is quite limited. There is increasing reports and arguments for more consideration and more flexibility with switching to the plain buprenorphine product for patients who don't have persistent ongoing intolerance to the combination product. What we'll typically see with that is a patient report said about an hour after they take their sublingual buprenorphine naloxone that they have nausea or have headaches that is persistent, regardless of how long they're on that medication for. Patients and those who are experiencing those circumstances may be an indication to switch to the plain product or to switch to long-acting injectable buprenorphine. There are, I think, some advantages of the films in particular. They are very easy to cut. If you need to take a half of a dose, it's easy to do that. They come in many different strengths. They are inherently abuse deterrent because all the films have naloxone in them. They're the generic and most widely available formulation of this medication. They're also very easy to count and transport. They're individually wrapped in kind of childproof wrapping containers. So patients, you know, you could put a film like in your wallet with you. It's very easy to count them. You don't have to worry about touching the medication or, you know, when you're counting them. So that's some nice things about the films in particular. We already talked about the fact that we cannot use the Butrans or Belbucca pain formulations to treat opioid use disorder. And it's also, you know, illegal to use any other opioid agonist to treat opioid withdrawal in the outpatient setting. So we can't prescribe, you know, someone methadone, morphine, tramadol, things like that to treat outpatient opioid withdrawal. However, in the hospital, we can use any formulation of opioid that we want to treat opioid withdrawal. And that is sometimes required. Sometimes patients who are in the hospital do need medication like fentanyl to treat their opioid withdrawal when they're in the hospital. And that is completely legal to do. So let's talk about the kind of initial assessment of a patient who's presenting, requesting treatment for opioid use disorder, kind of what the bare minimum is for assessing a patient to start on buprenorphine. So in the history, we want to get your standard medical history and mental health history. But with special focus on certain parts, like the substance use history, how are they using? What are they using? How much? And, you know, what's worked for them before? What hasn't worked for them before? And really looking specifically at that social history of what is their living situation like? Do they have employment or want employment? Do they have transportation to get to the pharmacy or their clinic? Do they have open legal issues that could, you know, are they at risk for reincarceration? Issues like that. Are they living with other people who are using drugs? These are all really important factors that can have huge implications on kind of how their treatment will progress and succeed. Prescription drug monitoring, most states require providers to check these. And again, this can be helpful to kind of reveal other things maybe that a patient hasn't shared with you about maybe prescriptions that they're getting from other providers. Again, so we can counsel patients on interactions that might occur between some of the other medications that they're taking. The initial physical examination can be really very limited. And again, you know, intake, we do almost all of our intakes for buprenorphine over telemedicine. So you don't have to have an in-person physical exam to safely initiate buprenorphine. But if you have the opportunity to have that person in front of you, specifically looking for things, you know, some of the physical effects related to addiction. So signs of endocarditis, of skin infections, looking for screening for infections like hepatitis and HIV. For laboratory testing, kind of the most important testing, if we're able to get it, if we're able to get a drug screen, it's great to get that baseline. If we're able to do that, again, it's not absolutely required. There is almost nothing in that initial urine drug screen that is going to change whether you're going to prescribe someone buprenorphine or how much, other than possibly the presence of methadone that could kind of complicate starting a medication as far as the risk of withdrawal with that. But remember, fentanyl isn't going to show up on the drug screen. So you could have a drug screen that has no opioids in it on your rapid drug test, even though the person is using fentanyl every day. So the utility, it can help provide information about what's going on in that patient's life, but it's not required necessarily to be able to start taking the medication. For women, we would like to get a pregnancy test, if possible. Again, it's not absolutely mandatory, but people may not know that they're pregnant, and that's especially in terms of making sure that they get connected to the care that they need and counseling on what their medication options are. It's not required to monitor liver drug testing, liver function testing on buprenorphine anymore, but it can be helpful to see, especially there's such a high incidence of hepatitis C, that often we'll see that there are some issues with liver function tests in patients who have hepatitis C, and then that can motivate patients and us to get that treatment started for the hepatitis C. So we're really kind of looking at some of these comorbid conditions so that we can treat them down the road. However, we should not delay treatment of medication initiation because we're waiting for lab results or because we haven't had a complete physical assessment yet. Encouraging patients on education on taking buprenorphine, these are some of the most important things to make sure we explain to patients, that discontinuing buprenorphine increases the risk of overdose death upon return to illicit opioid use. Again, we can't control patients' behaviors on whether they take their medication or not, but we can make sure that we provide them with that informed consent that you need to keep taking this medication, and if you stop taking it, that your risk of return to use and risk of death goes up, that people understand that they have that informed consent. Again, the same thing, informed consent, that it can increase risks to take alcohol and benzodiazepine with buprenorphine. Again, it's not a contraindication, but we want to counsel patients that it does increase their risk, and we want to make sure that they have training and access to naloxone. To make sure that they know when people stop using drugs, women who stop using drugs may be more likely to become pregnant because they can be healthier and ovulation can return. So, offering them contraception and making sure they let us know if they become pregnant so we can help them to get the care that they need. And then also making sure that they keep us informed if they're going to have a procedure that may require pain medication, if they know they're going to be having a surgery, or if they end up in the emergency room with a traumatic injury, so that we can help them to make a plan to manage that pain so that they don't stop taking their medication or return to use because of uncontrolled pain. This is a really great patient handout that gives educational components for patients about buprenorphine, about some of those possible side effects and benefits, things, important things that they need to know. So, it's a nice one-page educational document that's free and available online that you can print out to give to your patients. An important thing when prescribing buprenorphine to know is that lower is not better. There are so many things in medicine that we say, well, we're going to start at a low dose and titrate up. That's the opposite with buprenorphine. What we know with buprenorphine is that low doses are not effective in many cases at either stopping or reducing opioid use, and also they are not effective in blocking fentanyl. So, the minimum required dose for those early in treatment is 16 milligrams a day. Now, there have been a number of reports that have come out this year that really indicate that for a number of patients who have heavy, especially ongoing chronic use of fentanyl, these potent synthetic opioids that they actually can do better on higher doses of buprenorphine. So this was one study that came out this year showing that patients who were prescribed 16 milligrams of buprenorphine were 20% more likely to discontinue treatment than those that were prescribed 24 milligrams of buprenorphine. So that higher dose has an improved retention and treatment. Also, this is a very excellent article about buprenorphine dosing safety and needs and the setting of fentanyl use. And that when we look at some of the testing on people who are on buprenorphine, looking at plasma drug levels, and looking at how effective the buprenorphine is at blocking the liking effects of hydromorphone. So hydromorphone is also a very potent opioid agonist with similar potency to fentanyl. And what we see is that there's kind of a variety of dosages that suppress the liking of hydromorphone, but that liking of hydromorphone is best suppressed when the serum drug level of buprenorphine is greater than three nanograms per milliliter. And to get serum drug levels that are that high can require doses of up to 32 milligrams a day, or a stable treatment with high dose extended release monthly buprenorphine. So there are a certain subset of patients, especially patients who have a very high level of tolerance on high potency synthetic opioids like fentanyl, who are going to benefit and have better control of their withdrawal symptoms, better control of their cravings, and a better blockade of fentanyl at the higher doses of buprenorphine. And this is from that article that I would highly recommend reading. It gives a lot of great information about kind of comparing the outcomes with these different higher doses of buprenorphine. Also, a study just came out showing that for patients who inject opioids, that they do better in treatment when they're being treated with extended release buprenorphine, that they do better staying on the high dose of the extended release rather than switching to the lower dose. So the higher dose long-acting injectable buprenorphine can be more effective, especially for people who have very high levels of dependence and who are injecting drugs, which of course increases their potency. So how dosing sublingual buprenorphine? Buprenorphine is a very long-acting medication, and it stays on those receptors for 24 to 48 hours. And so the package inserts for the sublingual products say that they can be dosed once a day to control drug cravings and withdrawal. However, most patients really prefer to split their dose, BID or TID, when patients are having chronic pain as a comorbid condition. Interestingly, the analgesic effect of buprenorphine only lasts about six to eight hours. So it can definitely make sense, especially in patients who do have chronic pain, to split that dose up three times a day or more often. The trouble we get, we know that it is very difficult to take a medication multiple times a day. So there is, again, the balance of the risks and benefits for that person, that if they decide to split their dose, they need to make sure they do it in a way that they can stick with taking that same dose in that same way every day and not missing doses. The more often you're dosing a medication during the day, the easier it is to either forget a dose, miss a dose, or accidentally take too much because you forgot that you took it already and you take an extra one. So there are positive and negative things about once-daily dosing versus split dosing of buprenorphine. And it really comes down to what works best for that patient so that they can do it the same day every day and feel as well as possible. It's important to explain to patients the proper way to take their medication. And you shouldn't assume that even in patients who have taken buprenorphine before that they actually know the correct way to take their medication. I surprised every day by patients who actually weren't aware of how to properly take their medication, which can make it, of course, not be as effective. So we want patients to make sure that their mouth is moist, have a drink of water, avoid smoking before the dose because that reduces the circulation and can be drying to the oral mucosa. They're going to put the film or the tablet underneath their tongue. If they have two films or tablets, you can put one on each side of your tongue and allow that to dissolve for 15 to 20 minutes. It doesn't taste good. People hate it. Especially the films might dissolve quickly and then people want to spit it out and rinse their mouth out after it's only been in there for 5 to 10 minutes, but that's not a sufficient length of time for the medication to be fully absorbed. And we want to counsel patients, don't eat, drink or talk or smoke during that 15 minutes while the medication is in your mouth. They can spit out any excess saliva. You don't need to swallow this medication and, you know, counseling people especially don't swallow the tablets. It can be really confusing. Like it's a tablet. I should swallow it, right? But, you know, less than 5% of that is going to be absorbed if you swallow it. So there's no reason to swallow the saliva. It does not help in any way to swallow saliva. And some people think it can increase the incidence of nausea. So if there is excess saliva that can be spit out and then after the 15 minutes, we encourage people to rinse and spit out any residue that's left. There's some concern that the sublingual buprenorphine can be kind of irritating to the enamel of the teeth. So it is recommended now that patients should rinse their mouth out after they take their dose of buprenorphine. And it's a pretty quick acting medication. So we should see the effect of the medication within an hour of taking it. There are some side effects that are very common when patients first start taking buprenorphine. The number one is headache. Patients, many patients, sorry, the number one is nausea. Nausea is so common when people start taking buprenorphine that we prescribe all of our patients on Dancetron just in case they need it. And we counsel patients that it really is a side effect that almost always goes away once you adjust to the medication. So it's generally a short-term side effect. Headaches as well, usually those tend to go away. All opioid agonists can cause sweating in some patients. And some patients when they're first starting taking their medication, especially if they've been abstinent from opioids for a while, sometimes can feel a little over sedated or over medicated when they first start taking their medication. Again, this will resolve quickly as their tolerance develops, which will happen quickly. So generally, over the course of two weeks, generally most of these side effects will go away for most people. Constipation is really the one side effect that is chronic. It never goes away or gets any better and is really important to monitor for because sometimes the constipation can be so severe that people actually want to stop taking their medication. So really counseling people on the proper management long-term of constipation with a good bowel regimen is really important. Precipitated withdrawal. So this is really our main concern when the person is starting to take their very first dose of buprenorphine. Well, we really, we want to avoid precipitated withdrawal if at all possible. So precipitated withdrawal occurs when people still have a lot of opioids in their system, typically fentanyl or heroin, and they take the wrong dose of buprenorphine too soon after their last dose of fentanyl. And precipitated withdrawal occurs very rapidly. It's generally in less than an hour after they take their very first dose of sublingual buprenorphine, and it's a very rapid and severe onset of opioid withdrawal symptoms. And we can hopefully avoid this by really counseling patients on how important it is to wait until they are in adequate withdrawal before they take that first dose of buprenorphine. Now, the use of fentanyl now as the opioid of choice for most patients with OED has complicated this picture. And these blue fentanyl pills are kind of ubiquitously available in many areas, and for many patients have become their drug of choice, you know, versus other. But fentanyl can also be in a powdered form, and really there is no such thing as pure heroin anymore. All heroin has fentanyl in it, or sometimes actually no heroin at all and just fentanyl. And people think that they're getting heroin, but they're not. So essentially all patients who present now who are using opioids that they're painting off the street, almost everyone is using fentanyl now. And although we think of fentanyl as being a short acting medication when we use it in the hospital, if you chronically administer fentanyl, it's very lipophilic, so it is stored in the fat in our bodies, and so people can store up high levels of fentanyl, and it takes it a long time for it to be eliminated. So that fentanyl can take, you know, up to a week or more to be completely eliminated after you stop that use. So, you know, that can really mean that in this first couple of days, you know, a person's the levels are dropping, and a person is feeling that they're in withdrawal, but they still have very high levels of fentanyl in their system. And this can cause an increased risk of precipitated withdrawal when people take their buprenorphine because they don't realize how much fentanyl is actually really still in their system, and it could potentially trigger precipitated withdrawal. So fentanyl withdrawal can start sooner, can last longer, and can be more severe than a withdrawal from other opioids, and can have an increased risk of precipitated withdrawal when we're starting people on buprenorphine. It also can require, because it's such a potent opioid, it can require, especially in the first couple days of treatment, significantly higher doses of buprenorphine to manage that withdrawal. And when we look at the some of the emergency room studies that have come out in the last two years, you know, we're seeing doses sometimes up to 40 milligrams a day the first couple of days required to manage those fentanyl withdrawal symptoms. However, you know, many patients, in fact most patients, even who are using fentanyl, will be able to start buprenorphine without having any issues. So this was a great study that came out last year that was looking at, you know, patients who were starting on buprenorphine while they were in the emergency room that were using fentanyl, and precipitated withdrawal in that setting is actually very rare. So it's scary, we hear about it, patients hear about it, they're scared of it, but it's actually quite rare for it to happen when people follow the instructions on how to take their medication. So it's really important to talk to patients about what their previous experience is with prescribing buprenorphine. So we want to talk with them about, you know, have you tried buprenorphine in the past? And most people that will present for care will have tried buprenorphine in the past. In fact, often, you know, they've tried non-prescribed buprenorphine, their friend has given them some in the past when they're in withdrawal. So saying, you know, what was that like for you before? Did it help you to feel better or did it make you feel sick? What dose did you take in? You know, how long did you wait to take it? Were you able to initially succeed and get on the medication? And getting that information can tell you a lot about, it can really help you to make a plan for initiation with that patient that's going to be the right fit for them. If a patient tells you, you know, everything went great, I took a strip, I felt better, I ended up taking, you know, I needed two strips a day, I needed three strips a day. You know, you can really use that information to guide, you know, that patient should be just fine with kind of standard, simple medication initiation versus a person that says, hey, you know, every time I try to take buprenorphine, it makes me violently ill and I'm really scared to start taking it. Those may be patients that we need to plan out for some different approaches to starting taking their buprenorphine so that they can do it successfully. Now, most of the instructions that you read about starting buprenorphine will say, you know, calculate a cow score and we like the cow score, the opiate withdrawal score to be, you know, greater than 10, greater than 13, depending on the situation that you're looking at. However, you know, patients aren't going to be calculating a cow score on themselves when they're at home. So, when someone's at home, how do they know when there are enough withdrawals? So, you know, first of all, waiting long enough. You tell people kind of to wait 12 to 24 hours from the last time that you used opioids. Some people need to wait longer to be able to experience significant withdrawal than that. Some people need to wait 36 hours and to wait until you have at least three or four symptoms that, you know, you have a runny nose, sweating, tearing, upset stomach, restlessness, creepy crawly feelings. You're having multiple of those symptoms and they are becoming unbearable. So, essentially, wait until you feel like you can't possibly wait any longer and that is usually the right time to start taking your buprenorphine. And at that first visit, we want to make sure that people have those prescriptions that they need to get started and to treat kind of the most common withdrawal and side effects. So, typically, we're going to give a prescription. It may be only a few days. If a person lives very close by or you're very concerned about them and you want them to check that shortly, maybe you'd only give a three or four day prescription medication. If a patient, if you're less worried about them, maybe they live farther away, it's hard for them to get there, then we're probably going to give them a longer prescription, like up to a week at their first prescription for their buprenorphine. And again, the minimum dose should be 16 milligrams a day. But if we have someone who has a very high level of tolerance or they've had difficulty with managing withdrawal in the past, then it's safer to prescribe them a higher dose of buprenorphine, at least for that first week, so that it's always better to have extra, to have more than enough, than not to have enough and then fail because the symptoms are not adequately controlled. I prescribe all of my patients anti-nausea medication on Dancetron because nausea is so common when we're first starting to take buprenorphine. Also, it is one of the most common effects, symptoms of withdrawal as well. And then clonidine can be really helpful in that first week to help with the kind of the restlessness, the creepy crawly feeling and the sweating during that time period when people are making this transition. So those are standard prescriptions that I prescribe with everyone. And we want to make sure that everyone has access to naloxone that we see who has an opioid use disorder in our office. And then there can be other medications too that can be helpful for withdrawal. So really asking people like, what are the most uncomfortable withdrawal symptoms for you that you experience when you stop taking opioids? For some people, it's the sleep. That's that is what gets them and drives them crazy. I can't sleep and that's what makes me go back to using. So a non-narcotic medications to help manage insomnia can be helpful. Tizanidine is an interesting muscle relaxant for muscle spasms because it also, like clonidine, it's an alpha agonist like clonidine. So it also can help with some of those withdrawal symptoms along with kind of helping with the muscle spasms, managing diarrhea. Hydroxyzine can be helpful non-narcotic for anxiety and insomnia as well. So we want to make sure that we kind of try to plan for that for that medication initiation, that patients have the medications that they need to treat their common symptoms so they're more likely to be successful. And then also not, you know, calling, trying to call after hours or whatever, you know, I don't know what to do because I'm throwing up or I don't know what to do because I'm having diarrhea, that we plan for that ahead of time. And also at that first visit, if a patient's going to be on getting long-acting injectable buprenorphine, that would be a time when we would order that because it needs to get shipped to our office. So common standard instructions for starting buprenorphine would be for patients to wait until they're in withdrawal, again wait until they can't wait any longer, and to start with about eight milligrams of buprenorphine for the first dose. Patients who have are currently abstinent from opioids but are having cravings like that would be someone maybe who's released from incarceration or residential treatment they haven't been using. They may need to start at much lower doses to, it's not a safety issue, it's simply a matter of reducing side effects from the medication. We want to reduce that nausea, reduce that feeling of feeling over-medicated, dizziness, that sort of thing. So in those patients, they may be started at lower starting doses of two to four milligrams. And then patients can repeat, you know, another four to eight milligrams every couple hours as needed. Again, typically the minimum dose we should be trying to get to is to 16 milligrams. However, we definitely may see the need for higher doses up to 24 milligrams or higher in order to control both the withdrawal symptoms or the cravings. I'm going to mention briefly two alternative dosing strategies for patients who, you know, struggle with starting to take their buprenorphine. So one is a low-dose overlapping start or what you'll hear patients call micro-dosing sometimes. So in this strategy, the patient actually continues to take their drug of choice. So typically that would be fentanyl. So they're actually continuing to use the fentanyl the way that they normally would and they start taking their buprenorphine but they start with a tiny, tiny little baby dose. So we give them a two milligram strip and tell them to cut it into a quarter and just take one quarter of that, which is one half of a milligram of buprenorphine. And then essentially they double that dose every day while they're continuing to use fentanyl until they get up to a therapeutic dose of buprenorphine, 60 milligrams or more, and then they stop taking the fentanyl or whatever other opioid that they're taking. And this has become, we've had a lot of case reports and much larger studies of this and knowing that this seems to be a very successful approach for certain patients and can be a very comfortable way to start buprenorphine without having to stop the fentanyl first and without experiencing precipitated withdrawal. It can be good for patients who are switching from long actings like switching from methadone. If they have that chronic fentanyl use, people who have severe acute pain, let's say they're hospitalized because they were in a car accident and they have multiple broken bones, this can be a great way to make that switch over without having to stop the opioids that they're taking for pain at the same time. And if they've really struggled with precipitated withdrawal in the past, this can be a good alternative approach. This is kind of a nice handout for patients that explains to them how to take that dose and how to gradually increase that dose over the course of a week until they can get onto a full therapeutic dose of buprenorphine. Again, most patients are not going to need to do this. The downside to this is that it's obviously it's much more complicated. It requires patients to be able to follow instructions, to be able to keep track of what day they're on, to take the right amount every day and to stick with taking that. So it requires a pretty high level of motivation for patients to be able to follow these instructions. But for some patients, it can be very helpful when other attempts, other approaches have not been successful for them in the past. The other approach, which is actually a much simpler approach, is a high dose initiation. And this is the approach that we actually recommend in our office for most patients to utilize when they're using fentanyl. So what we really want to avoid with buprenorphine is we want to avoid this no man's land when it comes to the initial dose. So when we look at this is, you know, When the opioid receptors all have opioids on them, it only takes a small dose of buprenorphine, like four milligrams is the classic dose that's going to cause precipitative withdrawal, because four milligrams is actually very effective at displacing all the fentanyl off the opioid receptors. But four milligrams absolutely is not going to help someone to feel better. So it's like the worst case scenario of you're kicking all the fentanyl off the receptor, but you're not getting enough opioid agonists to help people to feel better. So again, for most patients who are using fentanyl, the minimum starting dose should be eight milligrams. But if we can give them a much higher dose of buprenorphine, then we can get that agonist effect that we need to relieve the withdrawal symptoms. Really, the only way people's withdrawal symptoms are going to be relieved is with more opioid agonist effect. And the only way to get that is very high doses of buprenorphine or for the person to continue to use fentanyl. So, you know, when we think about, you know, we used to try to like gradually work up on the dose over two, three, four, five days. And, you know, what we know is that people, you know, are going to need, they're going to need this, this therapeutic dose. That's the goal, you know, of 16 or more milligrams. So why not get there in two to three hours instead of two to three days, you know, get that, get that protection and that control of cravings and control withdrawal symptoms on board as soon as possible. We don't need to drag this out, just make it happen quickly. So this, these instructions also by the Bridge to Treatment Program are the standard instructions that they give to start people, for people to start buprenorphine from when they leave the emergency room. So they're made to be very simple, very easy to read, but still have some flexibility kind of built in. And this is a high dose protocol. So essentially it says, you know, for that, if you, if you have a fairly high tolerance to opioids, then you can start out with the first dose, your initial dose of 16 milligrams of buprenorphine. And then repeat another eight to 16 milligrams every hour until you feel well, you know, up to, you know, and these studies in emergency room are looking up to 40 milligrams for that first day or two of treatment may be required to control withdrawal symptoms and people that have, you know, a very, very heavy amounts of tolerance. So, and this also talks about, you know, hey, if you don't, if you're not using that much and you have a less of a tolerance, then you could go with the lower dose instead. But these are very nice, very straightforward instructions that you can print out and give to patients to take that really kind of simplify process. If a patient does experience precipitated withdrawal, additional doses of buprenorphine are the standard treatment for precipitated withdrawal. And that can be really hard for patients to wrap their heads around like, hey, you just took this medication that made you feel incredibly sick. So in order to feel better, I want you to take a whole bunch more of it. You know, that is, it's not a logical thing for patients. So really explains them like, like this is a partial opioid. The only way you're going to feel better is if you get more opioid in your system. So you need to take a much higher dose of buprenorphine to relieve those symptoms that the best way to feel quick, to feel better quickly is to take more buprenorphine. So really counseling patients that that's what they need to do. If this happens to them again, it doesn't usually happen, but if it happens to you, this is how you treat it. So we actually give patients these instructions on like, if you experienced precipitated withdrawal, you immediately put two more strips of buprenorphine under your tongue. We allow patients to take up to 40 milligrams in that first day, if they need to, along with taking ondansetron and clonidine. And we actually have patients recommend patients who have experienced precipitated withdrawal in the past to premedicate themselves with ondansetron and clonidine, like about a half an hour, hour prior to taking that first buprenorphine dose. So they can have that prophylactically on board. So I'm going to talk a little bit now about long-acting injectable buprenorphine and how that works and how it's a little different from the way that we use sublingual buprenorphine. So long injectable buprenorphine has a number of advantages to it. So for one thing, as far as from a practice management and case management perspective, it really simplifies the management of these medications. We don't have to worry about diversion because the patient's getting their shot in the office. So we don't have to worry about is the patient taking their medication every day? Are they sharing their medication? We don't have to worry about, you know, doing drug testing to check to see if they're taking their medication. So it really can simplify that workload, you know, on the office, on the case managers, on the providers, because we don't have to worry about that part. It also reduces the risk of withdrawal and relapse that's related to prescription interruption. So, you know, some patients, you know, again, if they're struggling to keep their appointments, if they're struggling to get their refills, if they're on and off and on and off their medication, they're going through those frequent cycles of withdrawals, which can trigger that return to use. And so the nice thing about the long-acting medication is that it doesn't just suddenly wear off when the month is done. It wears off very slowly and gradually. So we don't have that acute onset of withdrawal that can be very triggering for people. And it gives you much more flexibility to kind of schedule and reschedule and be able to get people back into the office for their next shot without worrying about that kind of dangerous, you know, rapid onset of withdrawal if people are running out of their sublingual medication. Also, it provides, you know, a very effective blockade of other opioids, because it is a high dose and that blockade can last for a long time. So when people are, you know, losing access to their medication, you know, if they move away, they become incarcerated and they don't get their medication, they're away for work, these kinds of things, that they're going to be protected for a much longer period of time than they would, you know, if they had lost access to their sublingual buprenorphine. So this is a study looking at the effectiveness of buprenorphine to reduce the respiratory effects, depressive effects of fentanyl. So in this study, they're looking at a patient who didn't have any buprenorphine on board. This is their ventilation. They're giving them increasing doses of fentanyl, up to 800 micrograms of fentanyl. And what we see is, we see, you know, very dangerous levels of respiratory suppression occurring in these patients, which it would be expected. However, when we see that the blocking the effects of fentanyl is dose dependent with buprenorphine. So the higher dose, the higher the serum drug levels, the more effective it is at blocking those respiratory effective depressive effects. And when we look at patients who have very high levels of serum buprenorphine, and these are level 5 nanograms, 5 to 6 nanograms per milliliter. These are the levels that we would see when someone is stabilized on high dose extended release buprenorphine, that they don't have any respiratory depression related to the fentanyl. So it's very good at blocking that. But what they did in this study, they tested all different levels of buprenorphine. And we see when that serum drug level drops down below two nanograms per milliliter, that is when we start to lose that blockade of fentanyl. That is so important, you know, to keep people alive if they return to use or inadvertently exposed to fentanyl. So, and that level of two nanograms per milliliter, that's a level we can see, you know, patients who are taking 16 milligrams a day, if they miss a dose, or if they take their dose in the morning, even by the evening time, those levels can drop down below two nanograms per milliliter. So that's why, you know, one of the reasons why 60 milligrams is kind of the bare minimum to block fentanyl. And the more, the higher buprenorphine you have in your system, the better it's going to be at protecting you against fentanyl. So again, higher doses are better protection against fentanyl. The other thing that's really nice about this medication is the really extended blockade after the medication is stopped. So for patients who stabilize on the low dose, and this is on sublocate, we don't have the same data on the new medication, that's come out yet. But if people are stabilized on the low dose, the 100 milligram dose, after their last injection, they will maintain levels above two nanograms per milliliter for about eight weeks after their last injection of the 100 milligram monthly shot. If patients are able to stabilize on the 300 milligram dose, and their medication is interrupted, they can maintain therapeutic drug levels above two nanograms per milliliter for up to five months after medication interruption. So again, a very long lasting protection against fentanyl for them. This medication also has, you know, good evidence. It has a very high patient satisfaction rate. And so patients, they really love this medication for the most part. Not everyone loves it, but most people really, really like it. It's just much easier for them to take. And also, this is a drug company study here, but that they had good outcomes after medication was stopped in that many people were able to remain abstinent. It is important to understand though, that this medication takes time to stabilize, and that the first month of injection is not going to be enough to produce therapeutic serum drug levels for many patients. So if we look at the serum drug levels that you get from taking 24 milligrams a day of sublingual buprenorphine, that serum drug level is going to be, you know, average, you know, around two to three nanograms per milliliter, although it will drop down below two nanograms per milliliter at certain times of the day or in between doses. However, if we look the 300 milligram that first month of injection, you are not, you know, you're getting, you know, an average of about two nanograms per milliliter, but less than you would get if you were on 24 milligrams a day. And also, the levels can drop well below two nanograms per milliliter at the end of the month. So it's really important to counsel patients that that first month on long-acting injectables, they are likely to not have a high enough dose to control their cravings or to block fentanyl. So this is the reason why that first month, especially on long-acting injectable buprenorphine, people also may need to take sublingual buprenorphine supplementary, especially the last two weeks of the month when that medication is wearing off. But we see once we reach steady state that even at the minimum, at the end of the month, those levels are going to be maintained over two nanograms per milliliter. And again, at the high dose, really between five to six nanograms per milliliter consistently, you know, whether you're at the beginning of the month or the end of the month, you're going to have therapeutic drug levels all month long. So people, but it takes time to stabilize. And if we look at the package insert for long-acting injectable buprenorphine for the monthly formulations of sublocade, it asks, it recommends that people take buprenorphine, sublingual buprenorphine for a week before they get their injection. However, in real life, kind of what we see is that people often can get started, you know, with only taking buprenorphine for a few days, or maybe not taking any at all, depending on, you know, what that patient's experience is with buprenorphine in the past. The new weekly Bruxade injection is specifically meant to be able to give people who haven't taken buprenorphine before. So the labeling on that one is a little bit different. Also, we can just, we can keep people at the higher doses, we don't need to reduce the dose. The package insert says, give two 300 milligrams as a loading dose, and then you can switch to 100. But there's no reason that you have to go down to 100. Again, if you keep people at that 300, you're going to end up with much more protective serum drug levels that are going to allow for a much longer therapeutic activity of the medication. So it's important to counsel patients on, you know, what they should expect so that they have reasonable expectations for what early treatment is going to be like on these long-acting injectables, to understand that they're not going to feel 100% great the first month. It's normal the first month to have some uncontrolled cravings and use, especially at the end of the month. And so that's where, you know, taking the extra supplemental at the end of the month can be really helpful for the first month. Occasionally, again, at the second month, generally not required after that. And that if people stay on, the longer they stay on the medication, the better that they're going to feel, especially if they stay on that higher dose, that it takes four to five months to reach the maximum steady state of that medication. So every month that they stay on it, they're going to feel better. Their cravings are going to be better controlled. And even patients that struggle at first with ongoing use, the first couple months, if people stay on the injection, almost everyone will extinguish use if they stay on it. And that also to counsel people those first couple days after they get their injection, the medication levels are pretty high the first couple days. And so it's normal to experience some side effects like nausea, sweating and drowsiness the first few days after an injection, especially if they don't have a very high tolerance to opioids. But that is something that the body adjusts very rapidly to. And so it will not be recurring with every month. It's just the first month that people experience those side effects. So essentially every shot that they get, they feel better and better and more and more normal. They kind of get to the point where they just feel the same all day, every day, which is one of the things that people love about it. They just wake up feeling normal every day. And people love that. The other thing that's tricky about this though, is that especially once someone gets stabilized, is that they might not feel it wearing off. Patients love that, that they don't feel it wearing off. But that can also be a little bit dangerous if people, they feel so well, they're doing so well. Maybe they missed their appointment. They don't really feel any withdrawal symptoms. And again, I'm doing fine. I'll just keep pushing it off and pushing it off and pushing out the appointment. And three or four months later down the road, it has worn off. And then that's when cravings can return. And if people return to use, they can have a lower tolerance and still increased risk of overdose. Again, much less so than on sublingual buprenorphine. But still, if people stop, it's going to take much longer for those cravings to come back. But to counsel them that it is wearing off, even if you can't feel it wearing off. And eventually, if you don't keep getting your shot, people are almost always going to return to use, which can be dangerous. But the nice thing about this medication is that it allows us to have the flexibility that people can get their injection no matter what else is going on in their life. So, really counseling people that no matter what other drugs you're using, no matter what is going on in your life, you can always get your injection no matter what. And so, that really simplifies things for people that have been struggling with traditional care. Monitoring people for ongoing chronic treatments. When people come in for their checkups, we're going to check the PDMP. Drug testing can be helpful. And again, confirmatory testing, if that's needed, to talk with people about what's going on in their life. We want to confirm with people how are they taking their medication? How much are they taking? Are they able to take it every day or are they struggling to take it every day? Are they having cravings? And if so, what's triggering their cravings? Are they having side effects, specifically addressing constipation and helping people learn how to manage that? And then find out, you know, do we need to adjust the dose? Do we need to think about changing to a different medication? We want to address, you know, some of these comorbid issues that are going on, like their depression, anxiety, and their chronic pain, to reduce, you know, some of these triggers that they are experiencing. The typical with sublingual buprenorphine, typically we're seeing people weekly until they're able to stabilize their dose and stop their use, and then every two weeks, and then eventually switching them to monthly visits once they're stable. And again, when we think of length of treatment, really kind of a minimum of two to three years, and longer is better. So we want to really encourage people to stay in treatment for the long term and really work to try to discourage people from stopping taking their medication too early. When we think about tapering these medications, you know, when is it the right thing to do to taper those medications? So first of all, it should always be patient-led. So we should never, as a provider, be telling patients like, oh, you've been on this for a long time. I think it's time we try to taper you down for a lower dose. That's never appropriate. And most of the time, I think often when a patient is asking to taper medication or stop their medication, it's really not a good time for them. They're not in a good place to be able to do that. So we have to work hard to try to counsel them to stay on their medications. But we want to make sure that at a bare minimum that people have been free of any illicit drug use for at least a year. They have a stable life. You know, their housing, their family life, their social situation is stable. You know, they're not at risk, you know, for incarceration. They don't have open legal issues and financial stressors that are weighing them down. Their mental health is stable, and they really have, you know, a good recovery network supporting them. And it should always be patient-initiated, and it should always occur ideally very slowly over, you know, six months to a year to have a good chance of success with a taper. And we want to work very hard to counsel patients against stopping taking their medications when they're during high-risk time. So if they've been taking their medication for less than a year, if they are pregnant or in the postpartum period, they're experiencing a lot of stress in their lives. We don't want them to stop before they have surgery. And really, again, like, we want to get to the root of the reason of, like, why do you want to stop taking your medication? Like, and when you start to someone about that, you know, hey, it's working well for you. You're staying healthy. Your life is so much better. You know, now you're feeling your health is better. Why would you want to stop taking this medication? And when you get down to the root of that, for a lot of times with patients, it's because of some other outside influence. A family or friends are saying, hey, I don't think you should take this medication anymore. Or they just feel like they don't need it anymore. You know, they're doing so well, their mind tricks them into thinking that they don't need it anymore, just like we see with patients, you know, with mental health issues on their medications. The medications help you to feel so well. And after a while, you feel so normal and you're doing so well, you think you don't need the medication anymore. And your mind can really trick you into thinking that. So patients can need a lot of support and counseling to help them to be able to stay on their medications. And these are some really good resources that I recommend checking out. So again, the Bridge to Treatment resources have those patient educational handouts and instructions that are, you know, they're already fully vetted, they're in wide use already, and they're very up to date. So I highly recommend utilizing those resources rather than necessarily trying to recreate your own. There are also some quick start guides to help providers, kind of quick reference to starting buprenorphine on patients. And they have like a little pocket guide. And again, these updated clinical, ASAM clinical considerations that just came out this year, to really how we need to rethink the way we treat, use buprenorphine, the doses we're using, the way we approach treatment in patients who are using fentanyl is different than it was years ago when they were lower potency opioids. So that is probably one of the more important articles that has come out in this last year that is very much worth reading.

buprenorphine

prescribing

safe and effective

opioid use disorder

formulations

naloxone

dosing

side effects

healthcare settings

long-acting injectable