Thank you all for being here. I want to introduce you to a team that Dr. Lane and Dr. Ray and I have been working with for a couple of months now to review our OBOT policy and also to explore offering sublocate or long-acting buprenorphine at the clinic. I want to acknowledge that Dr. Taylor started this process a really long time ago, so this is really a continuation of her foresight that this was going to be an important thing to include in our tools in the clinic. I want to hand it over to Emily to introduce our speaker, Dr. Sarah Spencer, who is an addiction medicine doctor, and say a little bit more about their program. But just in case anyone has this question up front, we aren't currently able to offer sublocate, but we are hoping that we'll be able to move in that direction. So this is in advance of that. All right, Emily, I'll hand it over to you. Thanks. Thanks, Kate. Good morning, everyone. My name is Emily Mossberg, and I am a Tribal Specific Coordinator with the Opioid Response Network. I want to acknowledge that funding for today's presentation was made possible in part by a grant from the Substance Abuse and Mental Health Services Administration, or SAMHSA. The SAMHSA-funded Opioid Response Network assists states, tribes, organizations, and individuals by providing free training and technical assistance on topics related to prevention, treatment, and recovery for opioid and stimulant use disorders. We work with consultants in all 50 states who can respond to local needs. Anyone can submit a request for assistance on our website at opioidresponsenetwork.org. And the Opioid Response Network is honored to be partnering with Lundy Tribal Health to bring you today's training on sublocate. This training will be led by our consultant and trainer, Dr. Sarah Spencer, who I am happy to now introduce. Dr. Spencer is a family addiction medicine specialist who has been providing treatment of substance use disorders in rural Alaska for over a decade. She is the volunteer medical director and founding member of Megan's Place, the first rural syringic access program in Alaska. She also partners with the State of Alaska's Project HOPE, and she currently works at an Inuit community clinic as an addiction medicine physician. And with that, I will go ahead and pass it over to Dr. Spencer. Okay. Hi. Are you able to hear me? Okay. Okay. Yes. All right. All right. We'll get started. So we're going to, today we're going to cover, we're going to just learn a little bit about long-acting injectable buprenorphine, about some of the ways in which it's different, especially the pharmacokinetics than the sublingual buprenorphine. We're going to talk a little bit about some of the logistical issues with that medication, comparing some of the different formulations of that medication that are available, and talk about how we can actually initiate and administer and monitor continuing that medication. I don't have any financial disclosures. So this, I've been using long-acting injectable buprenorphine since it first came out, supplicate came out just about six years, six years ago, I think this month. And, and we, we started using it right away and it has really, really dramatically changed our practice of treating opioid use disorder. It's been really, really an incredible tool to have in our tool belts, especially when helping patients who have, who really are struggling, who have really severe, severe substance use, or really a lot of, you know, other psychosocial complications that make it difficult for them to access and continue on to care. So I've, I mean, I've probably given like over a thousand supplicate injections. So we, we more than half of our patients who are on bup are on the long-acting injectable form. So some of the advantages that we have really seen to utilizing, and I, and I work in a rural area of Alaska, I work for tribal health clinic, but we serve the general community as a whole. So one is it kind of, it really simplifies the medication monitoring as far as monitoring for compliance and diversion risks, because that's just not really, completely takes that out of the picture. So kind of the extra work that goes into monitoring medication compliance, you know, like doing, doing medication counts, doing, you know, drug testing specifically to monitor for if someone's taking their medication or not. We don't have to do those things with this medications and in, in many areas, the, you know, offering sublingual buprenorphine there can be a lot of stigma around the fear of diversion of sublingual buprenorphine. So that, that can also help in those areas to expand treatment to areas that maybe haven't been willing to offer that treatment before. It, it because it's a long acting medication, it reduces the risk of withdrawal and return to use if medication is interrupted. So if a patient is taking sublingual buprenorphine and they miss their appointment, they run out of their medication, something like that happens. And, and, and they stopped taking their sublingual buprenorphine pretty quickly, generally, you know, within 48 hours, they're going to experience withdrawal symptoms. And often people, this will trigger cravings and return to use if people don't get back on their, their sublingual buprenorphine. So the nice thing about the long acting formulations is that they wear off really slowly. And so it gives you much more wiggle room and in that the timing of those follow-up appointments, if they don't come in at the four week mark, they're going to be okay. You know, the medication is going to wear off slowly and they're not going to have an acute onset of withdrawal. And it's going to give you more time to get that patient back into treatment, you know, to get their next, their next injection without, without as much risk of kind of acute onset of withdrawal symptoms. And it currently, if you utilize the high dose formulations of at least the sublocade, it gives you serum drug levels that are significantly higher than what you can get with 16 to 24 milligrams of buprenorphine a day. So those higher serum drug levels can provide a better blockade of fentanyl and again, a blockade that is long lasting. And so again, when people, if people have their, their care interrupted for some reason they're still going to be protected for a while, depending on how, how they've, if they've stabilized on the medication or not. So we can get more of an extended protection against overdose in the, if a patient experiences medication interruptions. So who are patients that might benefit from switching from sublingual buprenorphine to extended release buprenorphine? So certainly people who have really struggled with medication continuity, maybe, you know, they, they when they take buprenorphine, it helps them, it works for them, but they just can't stick with it for whatever reason. You know, they're on and off and on and off and continuing to return to use. And then they just can't stick with taking a daily, it can be really difficult to take a daily medication, especially when it requires, you know, frequent visits, frequent refills. There's, there's frequent opportunities there for medication to be interrupted for those people. So, especially in our area, because we work in a rural area, we have a lot of patients who just, they really struggle to attend frequently scheduled appointments. They, they don't have transportation or they live off the road system. Some of them work in jobs where they're away from home for weeks or even months at a time. And also other people that, you know, for other reasons are at risk for medication interruptions and a common that can happen in the case of a patient being incarcerated, sometimes their buprenorphine is not continued when they are incarcerated or moving or they lose insurance or issues like that. So protecting people in that situation where medication might be interrupted. Patients who tend to do better on higher doses of buprenorphine in, in Alaska here right now, we're, we're limited unless we tried to do a prior authorization to utilizing 24 milligrams a day of buprenorphine. And there are definitely patients that, that really still struggle even at 24 milligrams a day and need kind of higher serum drug levels. So this can provide higher, higher levels than you'd see, see with that. Some patients just don't like taking sublingual buprenorphine. They hate the way it tastes. It makes them nauseous. They just don't like doing it. Some people have difficulty keeping their medications secure. They might be in situations where, you know, maybe they're unhoused. Maybe they're living with other people who are actively using drugs. Maybe they're in, you know, situation with a partner who's using drugs and kind of being pressured to share with those people or domestic violence situation. You know, there's lots of situations where it can be difficult for people to secure their medication. And people who generally are at, you know, really high, high overdose risk and, and maybe, you know, in addition to that, you know, are struggling to take an adequate dose of buprenorphine to protect themselves against overdose. You know, if they're, they're using other substances with buprenorphine and we, and we really are continuing to intermittently use fentanyl, we're really, really worried about their overdose risk. And certainly patients maybe who have been kind of kicked out of treatment in the past due to having issues with diverting, diverting their buprenorphine. So, and, and this medication really can be used in lots of different situations, other than just the, your, your outpatient clinic. It's a, it's a great place to reach out to people who are at really high risk for, for being lost to follow up, like, you know, like, you know, homeless outreach, giving this in the emergency room, giving this to people who are incarcerated before they leave. It really is, it's a great way to try to bridge people to care and reduce that people falling through the cracks here in between episodes of care. This medication has a high patient satisfaction. The, a number of studies that have looked at this have shown that, that patient satisfaction was over 80% for this medication. And also that it improved a number of quality of life measures. And, and then both the patient satisfaction quality of life measures improvement were, were somewhat higher on long acting injectable buprenorphine than they were for sublingual buprenorphine. Sublingual buprenorphine also has a high patient satisfaction and obviously improves patient quality of life, but extended release seems to work even a little bit better in that way. This is just one of the, one of the exam, one of the articles that looks at patient satisfaction and quality of life on, on the extended release buprenorphine. And the kind of things that we hear from our patients, the things that they really like about this medication. So, so one of them, you know, they, they, they really like the fact that they don't experience acute withdrawal if they, they run out of their medications like they do with sublingual buprenorphine that, and that is, you know, a barrier to some people, you know, just not wanting to be on sublingual buprenorphine because they, they hate that, that they experience withdrawal when they're, when their therapy is, is interrupted. And people, you know, a lot of people just love, they love just being able to wake up feeling normal every day and not having to kind of deal with the hassle of taking an everyday medication. It's really, it's very convenient for patients. There are some regulations related to this medication that, that are, that are a little, little different than what we deal with the sublingual buprenorphine. Since this medication, this medication cannot be, can never be in the possession of the patient at any time. And, and so there is a REMS surrounding this medication. And the, the reason for that is because when this medication is injected into the body, it turns into a solid depot mass. And so the, the danger with it being in the possession of the patient is that if the patient were to inject this intravenously, that it could cause a massive embolus. So, so because of that, the REMS program is really the, the goal of that is to ensure that the medication is kind of kept in a secure way, either at the clinic or at a specialty pharmacy. And, and that it's, it's not in possession of the patient. There are, there are two different ways to, to get long-acting injectable buprenorphine for a patient. One is to order a patient specific medication. If a patient has insurance, if they have Medicaid or private insurance, then you can order the medication for the patient to be shipped from a specialty pharmacy to your clinic. And in that situation, the medication comes and it's already paid for when it comes. So, so the clinic doesn't have to deal with billing for the medication. So this is the most common, most common way that most clinics do this because they don't necessarily want to take on the financial risk of buying this medication and then trying to get reimbursed when they are billing for the medication. But that using ordering that medication this way does come with significant limitations in that you can only use that medication for that patient. That patient owns that medication. And, and unfortunately, if the patient doesn't come in within six weeks for that shot, it actually has to be disposed of, which is, which can be a horrible waste. We, we wasted, you know, many, many thousands of dollars worth of medication every year due to patients not showing up for their appointment. So the advantage of, of the other option, which is called buy-in bill, is that the, the clinic or the clinic's pharmacy buys, you know, buys the medication, whatever amount that they need and whatever doses that they need, and just keeps it as part of their medication clinic stock. And that medication can be used for any patient at any point in time and can be kept until the expiration date, which is generally more, it's more than 12 months, generally like 18 months on the medication. So, and then, but then the, the clinic is responsible then for, for billing to get reimbursed for that medication. And it is, it is a very expensive medication. So on average, it costs about, about $1,700 a month for this medication. And the, the newer, that's the sublocated, the Brixati is a little bit cheaper, maybe a hundred or $200 cheaper, but very, very similar in cost per month. There has been a study that came out recently that showed that this is still cost-effective when it's used for people who have severe opioid use disorder because of, you know, reducing complications and increasing retention and treatment. So just like with storing any controlled substances, it needs to be kept in a secure manner, and you have to keep logs of all the, the ins and outs and disposals of that medication. This is just a link to the, to the buy-in bill. And also if your, your clinic has, actually has a pharmacy on site, which I understand yours does, your pharmacy can actually get registered to actually be a specialty pharmacy, which, which simplifies things even more. It's a little bit more hassle as far as getting signed up to do that, but, but the pharmaceutical companies can assist the pharmacies with that process of getting signed up to be a specialty pharmacy, kind of making it easier to just have it on hand, so for whenever it's needed. This medication can only be delivered to a location where there is a provider who is registered with the DEA as practicing at that address. So if you have a patient that, that moves or traveling is going to another, going to be at another clinic, you, you actually can have that medication directly sent to another clinic to be administered wherever the patient needs to have that administered. You just need to have the contact information for the, the DEA registered provider who's going to be receiving that shipment. And this is really, really helpful for, for us in Alaska, because, you know, we do a lot of telemedicine and a lot of times, you know, patients are kind of located in, in areas that are far away from us that they can't necessarily easily get to our clinic to get their injections done. Another, you know, in general, this medication is not, once, once it's assigned to a clinic or assigned to a specific patient, it's not supposed to be transported someplace else. It's supposed to stay there. So if the patient, you know, if the patient goes and switches clinics and you have their dose of medication here, you can't just courier it to the other clinic. It's supposed to stay at your clinic. Now there are some exceptions to that. So on a, it's called the black bag exemption. So on an kind of as needed and random basis, the provider can take that medication and bring it to the place where the patient needs to get that injection. So that example of that might be home visits. It might be a patient maybe is in residential treatment nearby and you're going to do a visit to, you know, where they're at in the residential treatment to administer that medication. You know, maybe, maybe they're in the hospital or they're in skilled nursing, you know, it's called a place like that where they don't have access to that medication there, but you have their, their dose of medication and you can bring it to them. So when it's a random as needed situation that that medication can be transported to a different location for that patient. So that's, that's, that's it for the, the boring regulations around that medication. So just this fall in September, the, a second formulation, a new, another brand of long-acting injectable was released called Brixadi. And this actually has been utilized in some places like Europe and Australia for a number of years, just as long as we've had sublocate here. But, but kind of dealt with some issues around manufacturing and clearance here in the United States. So, so just was approved, just was, was actually started to be released in September. I haven't utilized this medication personally myself, but we're going to talk a little bit about kind of what some of the differences are between this Brixadi and between the, the sublocate brands. So one of the advantages of the Brixadi is that it doesn't require refrigeration. It, some, some places have kind of limited places in their refrigerator to be able to store medication. So that, that can be nice that you don't have to deal with refrigerating the medication. Although the sublocate starting this spring or the summer, they're changing the packaging to allow it so that it actually can be kept out of the refrigerator for up to 12 weeks. So, so it doesn't necessarily always have to be refrigerated depending on this situation, the clinic circumstances. It can be given at alternate sites once the patient reached steady state. So sublocate can only be given in the sub-Q tissues of the abdomen. But the Brixadi once they recommend after the, by the fourth injection, so it, which would they say is, you know, reaching steady state at that time, then it could be given in sites like the upper arm and the thigh where the absorption can be a little bit reduced, but but once they're stable, that's fine. And the Brixadi comes in, sublocate only comes in two doses. It comes in the 300 milligram, which is generally the starting and loading dose. And for many of our patients, they continue on that dose and then a smaller dose, the 100 milligram, which for some patients that are lower risk is their continuing dose. However, Brixadi comes in a wide range of doses. I think they have four different doses, both for their weekly and their monthly formulation. So lots of different choices with doses. And it also comes in a weekly formulation, which can be helpful, especially when you're first starting the medication, you're not really sure, you know, what dose the patient's going to need, or they're a little apprehensive about starting a monthly medication. The weekly formulation is proportionally less expensive because it's only one week supply. So it can be nice having that, you know, it can be kept in the emergency room or hospital to be given and not have such a financial investment in the medication. One thing to consider with comparing these two medications, the highest dose of the monthly formulation of Bruxadi that is available is their 128 milligram dose. And if you look at the average serum drug levels when stabilized, it's more similar to the blood levels that someone would have when they stabilize on the 100 milligram sublocade. So it doesn't have, it isn't able to reach as high serum drug levels as you can get with someone staying on the 300 milligram sublocade, which we'll talk more about why that might be important for people. It also has a little bit shorter half-life than the sublocade. So especially in the situations of medication interruption, you're going to have to assume that it's going to wear off a little bit faster than the sublocade would wear off. Otherwise, the REMS regulations, the ordering procedures, the cost is very similar between the two medications. And for pregnancy, the substrate, the kind of inert substrate of the Depo for Bruxadi is different between the weekly and monthly formulations. The monthly formulation has the same substrate as sublocade does, NMP, but the weekly formulation has actually a very small amount of ethanol as substrate, like a tiny, tiny microdose. There's some concern that the NMP substrate in the sublocade in the monthly Bruxadi in kind of rats experiments might be associated with some teratogenic effects. So when we look at these medications being used kind of worldwide in other countries, that weekly formulation of the Bruxadi tends to be the one that is more preferred in pregnancies since theoretically we think it might have less teratogenic effects, but there really is no evidence in humans either way for that. This is a nice table that compares the doses and the serum drug levels that you get between these different formulations. So this column is looking at sublocade, this column at Bruxadi, and then this column at the sublingual buprenorphine. So we can kind of compare the average steady state serum drug levels that you get between these medications. So if you see on buprenorphine, someone who's on eight milligrams of buprenorphine has a serum drug level of buprenorphine around one, this is nanograms per milliliter, versus getting close to three if they're on 24 milligrams per day. The 100 milligram steady state for sublocate is very similar to what you would see if someone was taking 24 milligrams of buprenorphine a day. However, you see if someone actually stabilizes on 300 milligrams, they actually get to more than double that of five to six nanograms per milliliter as their steady state, versus the monthly formulation of Bruxadi doesn't get quite that high. Still gets high, but just not quite as high as the sublocate. However, we're gonna talk a little bit more that that's the steady state. The first dose is a little different. And I don't like about this table is it doesn't have the troughs at the first dose, the dose which I think is actually the most important thing to consider. So we'll look at that here in a couple other slides. Again, the half-life here with the Bruxadi is about half what we see the half-life with the monthly sublocate. And again, comparing the substrate of the depot here. If you are switching a patient who is already stabilized onto daily sublingual buprenorphine, and you want to switch them over to monthly injectable buprenorphine, this is a table that kind of shows you what doses are likely recommended for that. And so for the typical way, if you look at the package inserts for sublocate, it recommends giving two doses of 300 milligrams and then switching to 100 milligram. However, that is not required. You don't have to reduce the dose to 100. But patients who are taking lower doses of buprenorphine could be switched more quickly to 100 milligram. They could switch to the second dose if they're already stable on lower doses of buprenorphine. And there isn't great data around this, but empirically and in practice, we do see some people using just the 100 milligram for patients who are on low doses of buprenorphine, like less than eight milligrams. The package insert for sublocate does say that if essentially any delay of, you can give it up to every 26 days, but delays of the injection for up to six weeks, two weeks are generally well tolerated. So it's kind of a four to six week dosing period. Although I think especially with that second injection, it's really important to try to get that on time and not have that delayed since they really only have the one depot. They're not stable at that point in time. If someone is on 100 milligrams, but they might be missing a dose, then you can give them a 300 milligram instead to allow them to basically skip a month completely and still remain stable. And this is a similar table for how to change someone over to Bruxadi. And again, here we have many more dosing formulations available to try to align with the dose of sublingual buprenorphine. Another difference with the Bruxadi is it does have this really low dose that it can be given, the lowest dose can be given to someone who does not currently have an opiate tolerance at all and who has never taken buprenorphine before. They recommend giving one dose of buprenorphine before you give it just to make sure they tolerate it okay. So that's one of the main reasons that it has been utilized a lot in studies in the emergency room is that the labeling already is there to give it immediately without having to have loaded someone with sublingual buprenorphine. The labeling of sublocade does recommend that a patient take buprenorphine for a week before they get their injection. In practice, we'll talk a little bit more about in practice that really isn't always practical nor is it probably necessary. And I know that the company has done some studies and is doing more studies right now to kind of try to get that labeling change so it's more similar to the Bruxadi with being able to start it quickly without needing that week long lead-in of sublingual buprenorphine. Another kind of off-label way that this medication is utilized is actually to assist with tapering or withdrawal management in a patient who has been on buprenorphine, they've been in long-term recovery, they haven't been on buprenorphine for a really long time and they're on a really low dose, they're trying to taper off but they're getting down to four milligrams or so and they just kind of get stuck and they're not really tolerating well tapering beyond that but they really want to and it's medically appropriate for them to do that. So there's a number of case studies that look at actually just giving a single injection of low dose extended release just to assist with that taper process and it appears to be well tolerated by people. So I'm gonna talk a little bit more about the serum drug levels in the first month of treatment. So it's really important to understand that, so this depot, especially the sublocate here, this depot, it doesn't just dissolve in a month, it takes like three to four months or longer for the depot to dissolve. So that first month you only have one depot in your system and the second month you have two, the third month you have three, so the levels are building every month and becoming more stable. But that first month, it is not stable the entire month and if you look, if you compare the serum drug levels of a patient taking 24 milligrams of sublingual buprenorphine to that first injection, you're gonna have levels that are significantly lower than that, especially at the end of the month. And what's really critical here is that we know that to effectively block the respiratory depressive effects of fentanyl, kind of the minimum serum drug level is two to do that. So the end of that first month, those patients don't have adequate protective levels as far as the blockade. Some people do fine with that, they don't have cravings, they're great, they feel fine, but other people do have significant cravings because this is not a therapeutic level for them. And then they do have breakthrough or continued use that first month. We see that a lot, especially in our patients who are kind of really already struggling with really severe use disorders. So we certainly recommend, the package insert doesn't recommend this, but we certainly recommend to our patients that if they are having breakthrough cravings, especially the last half of the first month, we prescribe them sublingual buprenorphine to take in addition to that first month to help to protect them, especially for safety reasons, if they're having cravings of breakthrough use to give them a better blockade against fentanyl. Similar for the Brixadi, the blood levels can drop down below. This is the stable troughs. The stable troughs are two, but if you kind of look down here at the fine print, it's a little complicated, but essentially those first month's levels can drop quite low down below one as well. So it's very normal for people to feel like their cravings and their use is not controlled in that first month and also when they use to feel like they're not blocked. They're not, they're still being able to feel the effects of the fentanyl. The administration technique, these are both given subcutaneously. The refilled syringes are a little different between a Brixadi and the sublocade. So this is the Brixadi. It has a syringe that screws together here, and it has a little bit of a shorter needle. So it's given, you pinch the skin and you go directly down at 90 degrees to administer the medication. The sublocade, the needle just screws onto the syringe and then you pinch the skin. And this one is a little bit longer of a needle. So it's given at a 45 degree angle. And it is important to, these are subcute needles. They're meant to be, you know, go all the way to the hub and inject there. There is some concern or some reports when it is injected too superficially, like if it's accidentally injected like dermally instead of subcutaneously, that that can put a lot of pressure on the dermis and can cause necrosis, kind of pressure necrosis of the dermis overlying the implant can actually be extruded. I've seen that two times happen with people. It wasn't injections that I did, but it's felt to be related to injection technique where it's injected superficially rather than subcutaneously. Anesthesia for sublocade, I highly recommend some form of anesthesia. Apparently the Bruxade is a much smaller volume. And so people from what I've heard that have experienced giving that, it's actually appears to be a less painful injection. So maybe the anesthesia is not as important, but I can tell you I've had many patients who have had the sublocade administered and anyone that's had administered with and without anesthesia, you know, they won't let anyone give it to them again without anesthesia. Cause it's a 19 gauge needle and it's a one and a half milliliters of this thick, like honey thick viscous liquid. And so it hurts. And it's like this intense kind of burning that goes on. It's limited, you know, but it's a couple of minutes. And especially when you have people that, you know, they're afraid of needles, it's a very boring, you know, your stomach is this very vulnerable area to be injected in. And so I think it's trying to make that experience as positive as possible for people to provide the adequate anesthesia. So what we do in our clinic, we, you know, trial and error over the years of what has worked best for us is we have the patient, we give people a little ice pack and we have them put it on. This is as time as our, we generally like five minutes prior. So the nurse, the MA, when they check them in, they give the patient the ice pack, they put it on. By the time I get in there, it's been on for a couple of minutes already. I chat with the patient just for a couple of minutes. And then I inject a milliliter of plain lidocaine into the site, kind of at the same angle and same depth that I'm gonna be administering the depot to. And then I let that, I put the ice pack back on and let it set for another five minutes or so as I'm talking with the patient and doing my documentation and we're having a little chat. And then I administer the supplicate. I've had patients who were, you know, certainly not all medical personnel are able to administer lidocaine. So often, you know, MAs, nurses, other medical staff, and in Alaska we have community health aides, they're not actually generally allowed to administer injectable lidocaine. And so in those cases, using just the ice or other, you know, topical anesthesia may also be effective. Before that first dose of buprenorphine, of supplicate or brisadi is administered, you know, if you're looking at the package insert for supplicate, it says, you know, that you should test their urine and they should be negative for opioids and they should be positive for buprenorphine. But in reality, you know, most of the patients who we are using this medication in, again, tend to be folks who have pretty severe use disorders and they oftentimes are using opioids kind of right up until the day of their injection. So ideally, they have been taking buprenorphine before their injection and their urine is positive for buprenorphine before that first injection. But we actually, in our clinic, don't require any urine drug testing prior to administering any doses of long-acting injectable buprenorphine. We, you know, we do utilize it off-label as far as giving it to patients who haven't taken their subliminal buprenorphine ahead of time with their consent when they're just not able to do that. And in chronic kind of long-term continuing doses, you know, I don't really care what's in their urine. It doesn't matter what other drugs we're using. And most of the patients, you know, kind of our target population for using this medication is the patients who are really struggling with ongoing drug use and a lot of polysubstance use. So patients generally are very honest about what they're using for drugs, but we don't have to require them to give a urine test in order to get this injection. And that is also a big positive for some patients. You know, patients that have, you know, legal issues going on, child welfare issues going on, a lot of times they are very apprehensive about providing a urine sample. They may be willing to talk with you about their use, but they don't really want it kind of documented in an objective way that maybe, you know, could be subpoenaed to court for evidence and that sort of thing. So that makes it easier for patients to access that we're not having to do. We always offer urine drug screening prior to administration, but we don't require it. So it's one less barrier that they have to do. Hey, Dr. Spencer, I just wanted to mention, they actually have to start seeing patients again at 11. So we do have a, it's tough in a couple of minutes. Okay, let me skip through this here real quick. And there was also one quick question in the chat from Zoe, do patients experience withdrawal if they just use fentanyl before the injection? So, first of all, there's no studies on that. We're working with a study with UW that they're looking at that right now. In general, and there's some slides in here about rapid starts, and that generally appears to be well tolerated. From what we can tell, it's no more likely than someone, you know, who is using fentanyl and starts sublingual buprenorphine. But the studies haven't, a lot of the studies haven't actually come out yet. But the emergency room studies that were done on patients who use fentanyl, who, and they were given like, you know, one test dose of sublingual buprenorphine before, but they had a very low, like only two to 3% incidence of precipitated withdrawal. This is just looking at the ability of fentanyl to block, ability of buprenorphine to block the respiratory depressive effects of fentanyl, and the higher the serum drug level, the more effective that is. Sorry, sorry to interrupt. We do have some people that are going to have to leave to start seeing patients in about five minutes. And I'm wondering if it would be okay if we just open the floor to their questions and then the people who are able to stay longer could hear the rest of the presentation. I'm really sorry about the late start. This is all such valuable information and we're all curiously taking notes here, so. Yeah, and it will be recorded too, so people can go back and watch the end of it if they missed it. But yeah, if we want to take a couple of questions. Hi, Sarah, I'm Tina Perez. I can't remember what the name of the company was before Indivior took over Sublocade, but they came to New Mexico where I was doing addiction medicine. We decided not to go with Sublocade. And so I'm really interested in how you've made this successful. We've had a couple of issues. One, you brought it up in terms of the pre-steady state. And levels. And we actually found that even in kind of steady state, we couldn't get to a 24 kind of milligram sublingual kind of efficacy. And so, especially now with fentanyl, so back then it was all heroin. Back here, we're dealing with fentanyl and fentanyl powder. Yeah. And I'm wondering how, if you're finding that folks at 300 a month, if you're able to eventually kind of cover- Yeah. Those. Yes. Yeah, so in addition to providing that supplemental sublingual dosing the first couple of months, we actually empirically keep the majority of our patients, probably 80% of our patients, just empirically stay on the 300 milligram dose. We don't even try to drop them down to the 100. If they're still that second month, if they're still having cravings and breakthrough use, we know for sure that they're gonna need to stay on 300. And it does take about five months at the 300 milligram to get to those maximum, to get to that six nanograms per milliliter a day. Again, about twice the level that you're gonna get with 24 milligrams a day. So most patients were able to stop sublingual supplementation after the first or second month, but the people who really struggle, which is the minority of patients, sometimes will continue to have like low doses of supplemental and ongoing months beyond that. But, and we've had really great success with much, in that subgroup of patients that really struggles with ongoing use, even on 24 milligrams a day, that most of those patients do much better once they stabilize on the 300 milligrams. But getting them to keep coming back for the injection can be a challenge, and it really requires a lot of support. It requires a lot of really counseling the patient ahead of time, which we'll talk about that more. But on kind of what to expect those first couple months, that the first couple of months aren't gonna be perfect, but you can help them through that, especially by administering additional sublingual. And we found that it's, in our situation it's it's really excellent for the patients you know who who are using fentanyl that they get a significantly you know better blockade if they're able to stay on it and get enough support to be able to stay on it. Okay yeah I think that's the piece that we were able to do and they were quite pushy on going dropping to the 100 after those first two injections. Yeah yeah there's really no reason to do that. How much of sub how much of the supplemental are you giving on average? I would say the the first the first it really is dependent on the patient what they're kind of what they're feeling for cravings what their use was like beforehand so so it depends but you know I think for people who are really struggling who have very very high levels of fentanyl tolerance you know towards that end of that first month you know we may we may initially say hey just try you know try you know doing short prescriptions first of all and seeing what works for that patient and understanding that especially the first month the levels are going to be going down so each week they might need a higher dose so we might start out the second week or first week with like just like an additional four milligrams or so but by the end of the month we could easily be giving an additional 16 milligrams of sublingual to those patients it doesn't you know it doesn't matter insurance for us pays for both at the same time and so you know it's better to have too much than to have too little yeah and it's a temporary thing and so really and just remembering that the beginning of the month is going to be better the end of the month is going to be worse for at least the first two months super helpful thank you so much I have a question so I know you said that like they have to have it every 45 days but would it be like a good idea to maybe schedule their next appointment like for the 45 days or does it have to be 45 days no it's allowed so it's every 26 days that that it can be so we we schedule every 28 days every four weeks just for kind of simplicity their you know insurance varies as far as how soon they will allow you to you know how closely together but because the packaging says every 26 days that's what the limit for most insurance that they will allow there's no danger in giving it sooner if your insurance allows to give it sooner but the spacing it out to every four to six weeks is really kind of once they're stable not early in treatment you want to keep them close together early in treatment if at all possible and actually the company is actually doing and doing a study right now looking at giving the second dose a week after the first one for the patients who have really high levels of tolerance I have a patient right now who you know switched over from 175 milligrams of methadone a day to buprenorphine and like amazingly we were able to keep her out of the hospital but you know she got you know she was taking she's been taking that this first couple weeks you know after supplicate you know like you know 30 milligrams of buprenorphine in addition to her supplicate and we're giving the second dose like at the second weekend so but but insurance is what limits that I'm not seeing any other questions and we've still got about four people in the room here and a few people online too so I'm going to mute it up and you might okay um so this this is you know one of my favorite things about this medication is how long if you know if you can get people to stabilize on the medication that they and then they they fall out of treatment or they they move they become incarcerated whatever it is they lose access they had their medication is interrupted they have a really extended period of therapeutic serum drug levels after that happens so and another reason to keep people who are at risk for medication interruption to keep them on the 300 if the 200 is if the 100 is interrupted they'll maintain their serum drug levels for about a month after their missed shot or two months after their their last shot versus four months after their missed shot potentially for patients who have stabilized on the 300 so again much very extended protection in the situation of medication interruption this is also why it's used to help people taper off sublingual buprenorphine because it it you know it's it's coming down you know this is over you know the course you know essentially of a year it's slowly slowly slowly coming out of their system it's a very natural gentle taper for which most people don't experience any significant withdrawal symptoms and this study just came out kind of comparing the efficacy of the high dose versus the lower dose of sublocade and it did find that for patients who had more severe disease and who were using injection drugs that they do have better retention and treatment if they stay on the 300 milligram which again that's what most what we're doing for most of our patients with severe disorders. There's not a lot of information about how quickly the medication comes out of the system if they only get one or two doses or kind of what that what that blockade looks like necessarily but this is in the package the package insert for sublocade is this example of when two injections are given here and the liking effect of 18 milligrams of im hydromorphone so in this situation you can see that this is where the third injection should have been given but was not so a month after that missed third injection they still have significant blocking of the liking effects of high dose hydromorphone which is similar in affinity to the mu receptors that fentanyl has. Um something to make sure that you counsel patients about before they get their um first injection is that they if they discontinue the um long-acting injectable they will have very very prolonged positive um urine drug testing for buprenorphine um and it can be um easily can be a year and we have seen it for more than a year there's actually another place in the package insert where it says it's even been document up to like 30 months in some patients still having positive tests for buprenorphine so this can come up with um especially if patients are on you know probation or parole and for some reason have stopped taking their buprenorphine it wasn't given them and we hope that wouldn't happen but in cases where it does where patients you know aren't taking their medication and they're being monitored with drug testing um or they're being monitored while they're incarcerated and they're not being given their medication essentially what we see over and over and over again is that patients get um accused of taking illicit sublingual buprenorphine because they're still testing positive so long after the injection has been discontinued but this is clearly documented to be a known um a known you know fact um with with sublocate so it's something to let patients know that they're they're going to be positive for a very long time after they stop and the you know in the real world use of this medication the vast majority of us who use this medication um really realize that that we can be much more flexible in the way that we use this medication than what we're seeing kind of in in the package insert so most of us are using this in the long term for patients you know with severe disorders you know we're starting it much faster than the seven day we're not requiring a seven day lead-in we're keeping people who um who need it at the 300 we're not even trying to go down to the 100 and and giving that supplemental buprenorphine in early months to to really really help those people who are struggling more so there have been a number of studies looking at starting this medication without that seven day lead-in with a very short lead-in um essentially they're all still looking at administering like one at least one test dose of the buprenorphine before before giving the sublocate um we we don't we don't require that in our clinic i mean the way i think about it is you know if a patient's been you know i we always meet with people the week before we give them the week prescription for their sublingual buprenorphine to take but say you know come in no matter what happens still come in still come in and i was even if you haven't been able to start your buprenorphine still come in and so we have patients that you know despite being given that prescription um come in and they just haven't been able to start they mean to i'll do it tomorrow i'll do it tomorrow right and they're not able to do it um and which is why they need this medication because they're not able to take the sublingual and and then when you think of you know um of for those folks of um so if you give them a test dose of sublingual buprenorphine and they have precipitated withdrawal you know what are you going to do not give it to them they're already in precipitated withdrawal you've already done it um if and if they they're not taking they're already not taking their sublingual then they're not going to continue to take their sublingual they're just going to go back to using again the whole reason they need this is because they can't take sublingual so we counsel our patients that you know if they are not able to take their sublingual um and they come in and they want to get this injection that we will still give it to them but we with the um informed consent that they understand the risk of precipitated withdrawal and we teach them about how to treat precipitated withdrawal um and for um for these patients it's um they they greatly appreciate this like they just struggle so much nothing has worked for them they haven't been able to stay on treatment they understand that the end for most of these patients these are patients that get sick every single time they try to take their sublingual they just can't successfully get on sublingual because of the the precipitate withdrawal they're experiencing because of fentanyl and so they understand that they might be sick that first day but it's totally worth it you know if if they um you know after that they're sick for they're sick for a day but then after that by 24 hours almost everyone feels better and then and then they then they're on treatment they did it they got some place they got something out of it um and they don't have to ever go through that again versus if someone gets precipitated withdrawal on sublingual you have to keep forcing yourself to take that medication that just made you so violently ill and no one wants to do that and so they just fall out of treatment so um you know as a form of harm reduction off-label use for those patients who just struggle and they just are not able to take the week-long lead in um again we offer that with informed consent and when you think about the risk of precipitated withdrawal with this medication and the pharmacokinetics of this medication kind of the difference about with sublingual buprenorphine it hits you hard and fast in one hour you're getting this peak concentration so you get the rapid onset of precipitated withdrawal versus with the long acting injectable it takes you know it slowly comes up to therapeutic levels over the course of 24 hours so it's a little bit gentler onset and so we find with our patients there that they most people tolerate this eat really well even if they've recently used fentanyl the minority of people experience precipitated withdrawal and those that do um it's a rough first day but they're so glad that they did it after the fact because now now they're on their medication that they need to be on so we really try to make this medication as accessible as possible and remove as many barriers as we possibly can to accept excuse me um to accessing this medication so again um we give it to people no matter what they've been using for drugs we don't require them to do drug testing we really allow a lot of flexibility and when they come in to get their injection um we allow walk-in appointments for their injection which can be done by the nurse if the provider is not available which gives a lot more flexibility and you know if people are missing their appointments gives more flexibility in that um again doing the rapid starts providing that supplemental supplementation and we do use it in pregnancy and patients who have failed uh being able to take the sublingual buprenorphine with with consent that it's not studied in pregnancy so this this is the things that i think it's really important to counsel patients on to really get you know so they have realistic expectations about what to expect and are more willing to continue on this medication you know again like from from using this medication for six years with so many different patients and seeing what they're going through so we tell them it's totally normal to not feel like this medication is working that great the first month because it probably isn't it's okay it's normal um it's okay if you're having breakthrough use and cravings we really encourage people to please let us know if that's happening so that we can give them supplemental supplement uh uh supplementation for people who we know have struggled in the past we just give them the prescription up front we don't even wait for them to call and ask us it can be really good to schedule a follow-up at the two-week mark especially to really assess that are the cravings coming back are they needing that supplemental um supplementation especially those first two months is the most important time for that and we tell them you know every month um for the people who stay on the 300 which is most of ours that every month those medications are going to continue to rise so every month they're going to feel a little bit better a little bit better controlled and you know there was a poster presentation at ASAM a couple years ago that was looking at this group of patients who really struggled with breakthrough use like who just continued to use the first couple months um despite getting their shots but if you follow those people the people that continued to get their shots by six months in almost all of those people extinguished their use so it really does get better and so we just people don't get discouraged it's okay if you're still having some breakthrough use this medication is giving you at least some level of protection even if you're not you know being able to achieve abstinence yet if you just stick with it and and make it as easy as possible for people to get those injections um most people will be able to extinguish use because of the much higher serum drug levels and protection that they're going to get we also you know caution them about side effects so some people because those first couple days after the injection um there are really quite high serum drug levels of buprenorphine the first couple of days and that can cause symptoms that sometimes people confuse with withdrawal symptoms um especially if they've been used to taking subliminal buprenorphine or making that switch over they can be very apprehensive and anxious about that and very worried about withdrawal so sometimes when they experience the symptoms like nausea and sweating um and just feeling kind of blind out of it they think that that's withdrawal symptoms when you generally it's side effects from very high levels of buprenorphine so that really is just the first month it doesn't continue to happen again you know with subsequent um we make sure that everyone has anti-nausea medication when they start this because nausea by far is the most side effect common side effect of high dose buprenorphine the other thing that's really important to caution caution patients about that the thing that patients love about this is also the danger kind of inherent in this medication is that you don't feel it wearing off a lot of times especially once stabilized if you only get one shot you're going to feel it wearing off at the end of the month but if you've gotten multiple shots and you've stabilized remember that graph of how slowly it wears off patients oftentimes do not feel it wearing off you know they're they they miss their appointment a couple weeks go by they intend to reschedule it maybe they miss it again they reschedule and they miss again but they just feel so good like i don't really need to go back i feel great i'm doing great and then three months go by four months go by and then even though people don't feel it wearing off it is wearing off and they're losing that blockade and they're losing that protection against um fentanyl so we warn people that um it's wearing off even if you can't feel it wearing off if you even though you feel like you're doing great at first if you don't keep getting your shots almost everyone is going to return to use and when you do return to use you're going to you know be in that situation like anytime you go off your medication that you don't have that blockade and you don't have so much tolerance and you're going to increase risk of overdose um and we really make sure that patients understand that that um that we're going to make sure that they get in their injection no matter what if they show up to the clinic we're going to make sure that somehow we get them their injection no matter what drugs they've been using um you know uh no matter what we're going to make sure that that they get their injection to make it as easy as possible for them to get it so that is the end here so i'll see if we have any other questions from anyone else have you noticed um any patients that say that they're allergic to suboxone and have been okay on the supplicate or how do you treat those and say you know i didn't have very good side effects on the suboxone so um so in part it depends on you know some patients you know if you're if you're if you're you know utilizing the term suboxone to mean combination buprenorphine naloxone like some people don't seem like they just don't tolerate the naloxone in the combination product really well you know like they're getting headaches they're getting nausea they just they just hate it and they want plain buprenorphine but some places just won't prescribe plain buprenorphine it's against their their um you know policies or whatever so in that kind of situation if people have tolerated plain buprenorphine well but they haven't tolerated the combo product well then that's a no-brainer like well great you're going to love this because it doesn't have any naloxone in it um if patients truly like every time that they try to take even plain buprenorphine have a reaction like what is the allergy is it actually precipitated withdrawal that they're experiencing like okay and then we can fix that is it that like you know i took tried to take plain buprenorphine i tried taking it for weeks and weeks at a time and still feel horrible and it doesn't work for me then i don't know that this is going to work any better i mean ideally like like you know if we're gonna we ideally you want to give this to a patient who you know that buprenorphine has been helpful for in the past ideally and that's one of the only reasons in my view to make to have them try taking buprenorphine before they get their shot is to make sure they like it because you can't take it out once it's in actually i had one patient and like the thousand plus patients i've given this to i had one patient who actually said that that that every time i try to take this i get horribly sick i've tried over and over and over and we just figured it's precipitated withdrawal and so you say okay well let's just try this nothing else worked i mean he literally has had like had 10 admissions to inpatient withdrawal management in the last year and left a man like the second day every single time we'll just try this and see how it goes um he so we did it he went into precipitative withdrawal and then um he showed up at the emergency room demanding that they cut it out and we really encouraged him to like just admit him like give him fentanyl give him anything you need to and he absolutely wouldn't have it and he would not leave the hospital until the surgeon cut it out so that's the only person you know but again he was a person who never ever ever had tolerated buprenorphine so you know that's the only time i've ever had someone that that did that and it was a very very unusual case so you can cut a depot out if it's the first depot and it's been there for less than two weeks the package insert says that you can have a surgeon cut it out that would probably be the only situation in which that would be appropriate yeah yeah i don't know davis do you have any questions uh no thank you uh dr spencer that's a great presentation i don't have any have any questions um thank you very much this was great thank you i think that i think the thing to remember about this medication is that i think i think for anyone who's used it and used it long enough to get comfortable with it um that it's just an indispensable tool to have to treat patients who are struggling with severe opioid use disorder and it really it's much easier um in the long term it's a lot less monitoring that's needed it's a lot less appointment that's needed it's easier for the provider's schedule it's easier for the patient's schedule um it made just such a dramatic positive impact in our practice when we added this medication in and i could not i can't imagine practicing without this medication i just i cannot imagine it it's made such a dramatic positive impact in having this available for our patients so even though it's a little scary to use something that you haven't used before you know there are a few things you need to know to use it the more you use it the better you're going to get at it and you're you're going to be able to serve a population of patients that you've never been able to successfully serve before so it's 100 worth it to to figure out you know the logistics of how to do it dr spencer what i'm just curious what percentage of of your patients um are on sublocate um so it varies um it's kind of gradually increased over the over the years um i would say now it's it's more than half it's probably two-thirds we serve a very high risk population you know we're like the only addictions specialist for 200 miles so everyone who gets kicked out of all the other practices comes to us but i can tell you i would say three out of four of every phone calls we get for intakes are patients saying i want to come get the shot because my friend told me how great it is and i want to get it too and because they have never succeeded being on sublingual so we don't we don't need to advertise this once you get it going and you get patients that are happy um they are coming asking for this medication um straight up front and we we talk obviously we offer talk for cover all the treatment options make sure that that's actually appropriate for them um but um but really based on patients um patients liking this medication so much that is really what has driven us in the simplicity of it to now being the majority of our patients who utilize it okay thank you and then my other question uh besides the already known um patients that we have to be careful with using these medications but what specific would be a contraindication for the sublocate you know i think the only contraindication would be probably that situation we talked about before of a patient who had like severe adverse reactions to buprenorphine and has never tolerated for like really giving that like that's that's like really the only kind of and you know a patient maybe like a patient who's like on super high doses of methadone and you haven't tapered you haven't made that switch over to sublingual yet like you really got to do that switch over sublingual first before you give the injection um you know it's um you know you might um you know we don't consider pregnancy a you know contraindication but we we try to avoid it in the first trimester we try to make sure that people who um who are on contraception when they're on sublocate that they understand their you know the unknown risks you know of potentially get you know getting pregnant um the the um the the biggest release of the nmp is the first couple days after the injection even though the buprenorphine stays for a really long time um so in theory um you know if someone finds out they're pregnant when on it you may you know the studies just aren't out there but um so that you know might be considered a relative contraindication i think really the only absolute contraindication is like a true allergy to buprenorphine which is just so just intolerance you know to any formulation of buprenorphine is probably only um like true contraindication great thank you um anything else no thank you so much this is i look forward to getting this going at our clinic

long-acting injectable buprenorphine

substance use disorders

medication monitoring

withdrawal risks

patient satisfaction

administration techniques

dosing

patient management

quality of life improvements

tapering off sublingual buprenorphine