Hello, everyone. Today we're going to be talking about methadone and buprenorphine-associated drug-drug interactions. My name is Dr. Andrew Saxon. I am an addiction psychiatrist at the University of Washington School of Medicine in Seattle, and I also work at the VA Medical Center in Seattle. And with this presentation, I do want to acknowledge Eleanor McCance-Katz, who was instrumental in doing a lot of the research that provided the background and also in developing some of these materials. So I will let you know that I did receive a consulting fee from Indiviewer, which is the company that makes some brand name formulations of buprenorphine, but this financial relationship has been mitigated. The target audience for today has to do with the overarching goal of the provider's clinical support system, which is to train healthcare professionals in evidence-based practices for the prevention and treatment of opioid use disorder, particularly in prescribing medications, as well as for the prevention and treatment of substance use disorders. So for today, we have some specific objectives. So we're going to go over some of the epidemiologic data on drug-drug interactions between opioids and other medications. We're going to give some of the background on what the causes are for drug-drug interactions. We'll describe the physiological and pharmacokinetic basis for these adverse drug interactions, and we'll look at how we as healthcare clinicians can mitigate some of that risk. So we're going to start with the background epidemiology and looking at what are the leading causes of death. And of course, as healthcare clinicians, one of our major goals is to help our patients to live long and healthy lives. And if they die at a young age, obviously that doesn't happen. So we're looking at data from 2019 on the leading causes of death of essentially young people from age 25 to 44. And you can see very clearly that about a third of these deaths are due to unintentional injuries, which does include poisonings and overdose. And on the next slide here, you can see the trends in the subtypes of unintentional injuries that relate so much to what our topic is concerning today. So if we go back 40 years, you can see back in the 1980s, really motor vehicle accidents were by far the most common cause of unintentional injuries. And then about 20 years ago, poisoning, the vast majority of which is drug overdoses, started to creep in and take that over. And by 2020, you see not only in that particular year, possibly related to the coronavirus pandemic, there's a big jump in the number of poisonings, but you can see that poisonings are now far outweighing all the other causes of unintentional injuries. So that's the focus today is finding ways to prevent some of these poisonings. Going specifically to overdose deaths in the United States, looking over the last seven years, we can see this increasing trend in overdose deaths. And this information obviously is pretty current, up to a year ago. And it looks like there might be a decrement, but that probably is going to turn out to be a reporting issue. From everything we can tell, the rates of overdose are still going up. And most of the, we're going to be talking primarily about opioids today, and most of the overdoses, probably two thirds of overdoses or more are due to opioids. And you can see some important trends here. During the early 2000s, the types of opioids that were prescribed, which are represented by this bluish gray line, really dominated the overdose scenario. And in the 2010s, that really began to change where we first saw that heroin was becoming much more frequent. And we think that had to do with the fact that around 2010, 2012, there was a reduction in prescribing of opioids for chronic pain. And some of those patients who could no longer get prescription opioids turned to heroin, and also heroin just became more plentiful. Then you also see, starting around 2015, this rise in synthetic opioids other than methadone, which is primarily fentanyl. And we know by now that in the last few years, the vast majority of opioid overdoses are related to fentanyl. Now, methadone line is interesting, and we're going to be talking a lot about that today. So what you can see is there wasn't much issue with methadone 20 years ago, but when more methadone started being prescribed for chronic pain, we saw this little uptick maybe between 2003 and 2009. And then when the dangers of methadone, particularly in the hands of prescribers who were not really familiar with many of its important characteristics, the fact that methadone is a very long-acting medication, the fact that its duration of action is highly varied among individuals, the fact that it can build up in people's systems over a period of days and suddenly get to be too much. And so it requires a lot of skill to prescribe that. So when the dangers became known, the prescribing of methadone went down, and we have seen this little slow downturn in methadone-related overdoses. Now, just in the last few months, some data have come out suggesting that in 2020, methadone overdoses went way up. And we think that it's hard to know for sure what caused that, but we do know with the coronavirus pandemic that the opioid treatment programs that dispense methadone for treatment of opioid use disorder had to lessen their regulations in terms of how often people had to come in to take methadone under observation, and they began giving out more take-home doses. And it's possible that those take-home doses of methadone out in the community are potentially causing more methadone overdoses. So we're back having to, as the topic of this talk today, we're back having to be concerned about how do we reduce the potential harms from methadone while still using it because it's a very valuable medication for the treatment of opioid use disorder. So we've already talked about how overdose can occur from opioids, but as you'll see in a moment, most opioid overdoses are not caused by opioids alone. In the majority of overdoses, especially those involving methadone, there are other drugs or substances involved. And so you can be more likely to get an overdose when you're combining medications. So sometimes those are other opioids such as fentanyl or heroin with methadone or with buprenorphine, but there can also be sedative medications, antidepressants, antipsychotics, or alcohol. And these are the interactions that we need to be concerned about. I'm showing this slide, which is very similar to the one that I previously showed, but this is really the only point in the talk where we're going to be mentioning stimulants because stimulants combined with opioids can increase the risk for overdose. And what we see here is that looking at the red and gray lines, that's red is cocaine and gray is other psychostimulants, which is primarily methamphetamine. And we can see that they are causing increasing numbers of drug overdose deaths. And oftentimes we see them combined with opioids, whether that be methadone, buprenorphine, or opioids that people might obtain without a prescription. So here are some examples of the types of drugs and medications that we see associated with methadone overdoses or methadone deaths. And you can see, as I already mentioned, only about a third of these overdoses are methadone only. And so we see a lot with alcohol, with sedatives, with antidepressants, gabapentinoids, other opioids, antipsychotic medication. And so these are all drug-drug interactions that we need to be aware of and try to avoid for our patients. And we're mostly going to be focusing on methadone because overdoses from buprenorphine and even drug-drug interactions with buprenorphine are far less concerning than with methadone. But there can be drug-drug interactions. And you can see from this slide that the things that we're concerned about are very similar to what we have seen with methadone. In this case, we're seeing reports from, we're not seeing deaths, we're seeing reports from emergency department visits that were associated with buprenorphine combined with other medications. So people come in with side effects or problems or even an overdose that's non-fatal and with buprenorphine. Because with buprenorphine, the chances, because it has a ceiling effect on its ability to produce respiratory depression, the likelihood of an overdose in adults with buprenorphine even combined with other medications is much, much less than with other opioids. But nevertheless, we do see these adverse events and we want to avoid them. So what are some of the underlying reasons that we are seeing a lot of drug-drug interactions? Well, we talked about the fact that in general, our healthcare system in the U.S. is providing many fewer opioids for chronic pain than what we used to do 10 years ago. But nevertheless, we have still a large number, several million, what we call legacy patients who were started on opioids years ago and continue on them. And they clearly are at risk for drug-drug interactions and adverse effects. And these patients often have other medical disorders besides pain and mostly and almost all of them have psychiatric disorders. So they are likely to be prescribed antidepressants or other medications for psychiatric disorders. And there's a belief among patients that if it's prescribed, it's fine. It's not dangerous. And even if they take a little extra, that shouldn't be a problem because they're safe medications. So we all do need to take responsibility for talking to our patients and educating our patients about the risk of the medications that are being prescribed to them and also about the potential for drug-drug interactions. So there are two concepts important to the pathophysiology of drug-drug interactions. The first is the pharmacokinetic and that's what the body does to the drug. So that has to do with the protein binding, the metabolism, the transfer of drugs across membranes, and the excretion of the drugs. And you'll see, we're going to be giving specific examples. You'll see that sometimes with drug-drug interactions, we can give someone on methadone another medication that's going to change the pharmacokinetics of methadone. And then there are the pharmacodynamic effects. And so that's what the drug does to the body, not what the body does to the drug. So that has to do with the drug binding to receptors and causing an effect. And we'll see that as we've already alluded to, many of the interactions occur because the drugs have overlapping or similar effects that are additive. So that might be two opioids combined or even an opioid and a sedative combined where both have respiratory suppressant effects and overall brain suppressant effects and sedative effects. And so that pharmacodynamic effect can suddenly become synergistic and cause a very serious problem. So let's just look at an example of the pharmacokinetic interactions. So what are some of the things that can happen? The absorption could be changed by one drug to another. This protein, P-glycoprotein, is a protein that exists in our membranes, like in our gut or in the blood-brain barrier. And this protein moves molecules across these barriers. And the activity of P-glycoprotein can vary based on both genetics and environmental effects. And also some of the environmental effects can be other drugs that compete for the P-glycoprotein. A very prominent reason for the pharmacokinetic interactions is inhibition or induction of metabolism. This usually occurs through the P450 CYP enzyme systems of which there's many different enzymes that we'll be talking about in just a couple minutes. And so one drug can either inhibit or induce those enzymes that's going to change the metabolic rate of our target drug. In this case, it would be primarily methadone. And so you can get an increase or decrease in exposure to the drug, even to the point of inducing opioid withdrawal, particularly in patients on methadone. And so here is one specific example with buprenorphine. And this buprenorphine was combined, and Dr. McCance-Katz did this study, was combined with the antibiotic rifampin, which is an antibiotic often used in the treatment of active tuberculosis. And so with square symbols, what you're seeing is a buprenorphine plasma levels over 24 hours. In the squares, and so you're seeing that pre-rifampin, we're getting the buprenorphine peak of one hour, about seven and a half nanograms per ml. And the buprenorphine stays in the system over 24 hours. And at the end of the dosing period, it's about two nanograms per ml. When the patients are given rifampin, they're getting a pretty decent peak, but very rapidly that because the metabolism had been induced, their buprenorphine levels drop. And you can see the area under the curve after rifampin is about less than half of what it is pre-rifampin. So in the case of buprenorphine, as you'll hear, buprenorphine has some characteristics that make this interaction clinically less meaningful than it would be with methadone. But nevertheless, we are seeing this big reduction in plasma levels. And it could, in certain instances, lead to withdrawal symptoms. Turning again to the pharmacodynamic interactions. So drugs can have both pharmacokinetic and pharmacodynamic interactions, but the pharmacodynamic interactions can occur in the absence of the pharmacokinetic interactions. So we've got, again, two drugs that are doing similar things to the receptors or overlapping things. And it's not, the metabolism hasn't been changed at all, but because they're having an additive or synergistic effect, they can increase their toxicity. And so a common example of that is opioids and sedatives. And the specific example is alprazolam with methadone or opioids and alcohol as well. And so turning specifically to methadone and why we're seeing a lot of interactions, the metabolism of methadone is very complex and not even completely understood, but you can see here that there are at least four or five different CYP450 enzymes that are involved in the metabolism of methadone. So every individual person is going to have different activity levels of these various enzymes based on genetics and environmental exposures. And so it's very, very hard to predict with methadone, whether someone will be a slow or poor metabolizer or a rapid metabolizer. And that can even change over time for an individual patient. But there are many, many other medications as we'll go over that can have effects on these enzyme systems and thus on drug-drug interactions with methadone. Buprenorphine is a little bit simpler. It's mostly metabolized by that one enzyme. And again, because it has an active metabolite, if its metabolism should be increased, as we saw in the example with rifampin, it's being turned into its active metabolite, which is still acting like buprenorphine, whereas methadone only has inactive metabolites. So if it's metabolized more quickly, the effect of methadone is going to be potentially greatly decreased. And so common antidepressants like selective serotonin reuptake inhibitors and some antipsychotic medications can affect these enzymes. So one example is the SSRI antidepressants fluoxetine and fluvoxamine can inhibit two of the enzymes that are active in the metabolism of methadone and could lead to increased methadone levels. And other SSRI medications inhibit one of the enzymes, CYP2D6, that could potentially have the same effect depending on the patient. Also with methadone, methadone does block potassium channels that can lead to a prolongation of the QTC interval on the electrocardiogram. And we know when that interval gets excessively prolonged, it can set someone up for the potentially life-threatening arrhythmia to, it's a ventricular arrhythmia disorder. And so there are many, many medications, as you know, that also lead to QT prolongation. So if we combine methadone with those other medications, we are having the risk of a serious event or even a death due to an arrhythmia that is another cause of drug-drug interactions other than an overdose. And we also know that the higher the methadone blood level, which is partially correlated with dose, the more risk we're incurring both for QT prolongation and for overdose. And in the era of fentanyl, we're seeing, because fentanyl is so potent and we're trying to take people off of fentanyl and get them stabilized in methadone, we're seeing higher and higher methadone doses being used in recent years. And a point that we're going to talk about in just a minute is there can be risk if we're giving another medication that induces methadone metabolism, we therefore increase the methadone dose when that other drug is withdrawn, metabolism returns to normal, and suddenly the person has too much methadone on board. So we have to be cautious about that as well. So how do we avoid some of these? We need to think about them all the time. Very few of us can keep all these potential interactions, which are so numerous in our brains. So basically if we're adding any medication or another clinician is adding medication to our patients receiving methadone or buprenorphine, it behooves us to look up the potential interactions so we can stay on top of that. We certainly want to talk to our patients and their families about the potential for interactions and what to be observing like increased sedation or slowed and loud breathing. They are going to need some medical attention if those kinds of effects are occurring. And of course we want to possible choose medications that are less likely to have interactions with methadone and buprenorphine. Overall, if a patient can be successfully treated with buprenorphine as opposed to methadone, we're going to have much less worry as you'll see about the drug interactions. That doesn't mean that we should take people who are doing well on methadone off of methadone and transfer them to buprenorphine, but if we have a choice, all other things being equal, there's a quite a bit of safety margin with the buprenorphine. So now we're going to spend the next part of this talk going over in detail all of the possible methadone drug-drug interactions. So we're going to start with antiretroviral medications that are mainly used to treat HIV infection. And the fortunate thing is that most of the ones that have serious drug-drug interactions are older antiretroviral medications that are not often used anymore. So the newer antiretrovirals used to treat HIV, we are not seeing a lot of drug-drug interactions. So we're a lot better off in that regard than we were 10 years ago, but we'll nevertheless go over these. And the ones that are most significant are highlighted in yellow, so pay particular attention to those. So the medications, efavirenz, lopinavir, nevirapine, and vitrigavir do induce the enzymes that are responsible for methadone metabolism. So we can see clinically meaningful opioid withdrawal when these medications are combined with methadone. And what we would typically see is three or four days after the medication started, the patient starts complaining of withdrawal or even showing signs of withdrawal like sneezing, runny nose, goose flesh, nausea, vomiting, diarrhea, those sorts of things. And so if the patient's going to stay on that antiretroviral, we would need to increase the methadone dose. And then again, we need to be alert to the fact that if they go off one of these antiretrovirals, we need to again reduce the methadone dose with the right timing. So we've got several antiretrovirals listed in the next box that may reduce serum methadone levels. And that's primarily through induction of the 3A4 enzyme. And typically that's not enough to cause clinically meaningful symptoms, but nevertheless, we want to be alert to that happening. And then methadone can affect the, some of, methadone has an effect on a few of these antiretrovirals, again, that are not commonly used anymore, but methadone can cause a reduction in didanasine or stavudine levels, which would mean that the HIV is not being fully properly treated. And with the very first antiretroviral zidovidine, we can see an increase in the plasma concentrations when combined with methadone. I don't think that medication is ever prescribed anymore. So it's not, it's of historical interest, but not really clinically pertinent. And then we have delavirdine, which can potentially inhibit the 3A4 enzyme and could increase methadone levels, which has the theoretical potential of toxicity. For the most part clinically, for the medications that might increase methadone levels, we don't often see that getting up to a level of serious toxicity, but still we want to be alert to that and monitor the patients. And then we've got a couple more. We've got the runavir and inhibit the 3A4 enzyme and increase methadone levels. And then a couple more, rilpiravine and miraviroc cause QT prolongation. And we talked about the fact that if we combine methadone with other medications that prolong the QT, we can get a risk for arrhythmia. And so basically, and we'll be talking about this with other medications as well, if we are adding a medication to methadone that could prolong the QT interval, it's probably in most cases, a good idea to get a electrocardiogram if that's possible. So we can assure ourselves that the QT interval is not prolonged. And if it is prolonged greater than 500 milliseconds, we probably need to do some clinical intervention, either change medications or make sure that the patient doesn't have any electrolyte abnormalities, the patient isn't using any illicit drugs like stimulants that could also affect the QT interval. But we don't want to leave the patients in that risk zone. Now, the last thing I'll say about the antivirals is very current, important information. So with the COVID pandemic, we now are fortunate to have a couple of different antiviral medications that can dramatically improve the course of a COVID infection. The common one is Paxlovid, which is a combination of two different medications, Nimetrelvir and Ritonavir. The main reason that the Ritonavir is in there is to increase the blood levels of the Nimetrelvir. And Ritonavir does that by inhibiting the 3A4 enzyme, but it also induces the 2B6 enzyme. So, and we don't know very much about the effects of Nimetrelvir. We know it's a substrate of 3A4. We don't know if it's an inducer or inhibitor. So it's possible that Paxlovid could affect methadone levels in our patients on methadone. And we don't necessarily want to withhold this medication from them, but we want to monitor them carefully. And I can just tell you, anecdotally, we've heard from at least two of our patients that they got on Paxlovid for their COVID infection. And within about two days, it's only a five day course, but within about two days, they were starting to feel withdrawal from methadone. So they stopped the medication and they were fine. There weren't any really serious clinical effects, but it's something where if you're going to treat a patient on methadone with Paxlovid, you want to be aware of it and potentially warn the patient about that. So moving on to the antidepressants, all of the tricyclics are going to have some pharmacodynamic effects that can cause problems with methadone. So we know that these medications can add to the constipation and sedation that patients experience with methadone. But more important, like with some of the antiretrovirals, they increase the risk for acute T prolongation. So again, if you're going to... And that's not to say that you shouldn't use these medications with methadone. Some people need them for pain control or depression or anxiety, but it's usually a good idea to obtain an electrocardiogram if you're going to be prescribing that combination. And generally it would be safe. The SSRIs we already mentioned might more likely increase seromethadone levels or increased risk for serotonin syndrome. Serotonin syndrome is very rare. What we typically see if they do increase methadone levels, the patients are really not reporting and we're not observing that there's any serious toxicity. But again, it's good to be alert to it because there could be exceptions to that. Monoamine oxidase inhibitor class, increased risk for serotonin syndrome. And these are medications that are very effective antidepressants, but really should only be used by people who are very experienced in their use. And they can be combined with methadone, but that would be a rare situation. And make sure there's an expert in prescribing of the monoamine oxidase inhibitors involved. And then we've got the SNRI, serotonin norepinephrine reuptake inhibitors, duloxetine, desvenlafaxine and venlafaxine. So again, we have to be concerned about serotonin syndrome, but primarily QT prolongation and the same cautions apply what we've mentioned with other medications that could cause QT prolongation. We have some antibiotics that can both increase methadone serum levels and increase risk for QT prolongation. So we've got one case report of sedation with ciprofloxacin. And so we don't typically see a problem, but clinical monitoring is strongly recommended. We're coming back here to our old friend rifampin, which again is an antibiotic often used in treatment of active tuberculosis. And this is a clinically important and meaningful interaction. We saw in an earlier slide what rifampin does to buprenorphine blood levels. And we said, even though the levels are reduced because buprenorphine has an active metabolite, it probably doesn't have that much clinical impact, but the clinical impact with methadone is very substantial. And we typically would see a pretty severe withdrawal syndrome within a few days of starting rifampin. So there might be alternatives for tuberculosis like rifabutin, or if we need to use rifampin, we're going to need to increase the patient's methadone dose as long as they're on the rifampin, which tends to be many months of treating tuberculosis. But then remember when the regimen of rifampin has been completed, that we probably are gonna have to drop the methadone dose down again where we could get methadone toxicity. And several antifungal medications do increase methadone serum levels through the 3A4 mechanism, but we just don't see any clinically meaningful toxicity from those medications. Back to some that can really cause concern. So two anticonvulsants, phenytoin and carbamazepine, strongly induce 3A4, and we're going to see severe opioid withdrawal. I think there's a lot of newer anticonvulsants around. These aren't often used that much anymore. Carbamazepine may be used more for bipolar disorder, but that's also a situation which we, if the co-occurrence of bipolar disorder with opioid use disorder is not uncommon. So there could be potential for using carbamazepine in that situation, and we'd have to be prepared for withdrawal and increasing the methadone dose. And then we've got the antiarrhythmic medications that also affect the QT interval. And within the case of amiodarone may inhibit 3A4, even making this problem worse. So if we're prescribing antiarrhythmics, we probably do have electrocardiograms that we're monitoring. But again, just a reminder to do that carefully. And if the QTC is over 500 milliseconds, take some action. Now we're going to move into primarily pharmacodynamic interactions. And most of these are pretty obvious. Benzodiazepines with methadone are going to have additive CNS effects, and there's the potential for overdose. So this is not to say that benzodiazepines can never be prescribed with methadone if there's a good indication, but clinical monitoring is important. And same issue with barbiturates, which are used much less now, but there has been a resurgence of using phenobarbital for alcohol withdrawal. And so we can have patients on methadone who also have problematic alcohol use and might be needing to be withdrawn from alcohol. And so they probably be getting benzodiazepines or phenobarbital. So we just need to monitor that carefully. The antipsychotic medication, ketiapine, it's also used and also is used for psychosis or bipolar disorder, but often used off-label as a sleep aid or an anxiety treatment, a treatment for PTSD. And there's even some evidence it might be helpful for PTSD. And that is an inhibitor of 2D6. So it requires some monitoring and also is sedative in its own right. So we could see some combined sedative effects. Cimetidine, which is a histamine two blocker used for acid reflux. We have better, newer medications. So cimetidine is around, but I don't see it used too often, but it could increase the methadone levels by inhibiting 3A4. And then we've got naltrexone, which is a new opioid antagonist that's prescribed either for opioid use disorder in patients who've been completely withdrawn from opioids, but it also has an FDA indication for alcohol use disorder. So for patients on methadone, we can't give them an opioid antagonist. That's pretty obvious, but you could see someone just sort of forgetting about that and the patient on methadone has alcohol use disorder. Naltrexone is prescribed, and we have a terrible case of precipitated opioid withdrawal. So naltrexone is completely contraindicated. And finally, a very new point, we have cannabidiol or CBD, which I think everyone knows is a component of the cannabis plant. And this has become very hot as a self-prescribed antidote for a lot of different ailments and is actually legal in most areas of the US as long as the THC content is less than 0.3%. And so being widely used by people who get it from dispensaries or order it online, and that the cannabidiol does inhibit 3A4 and 2C19. And so there could be potential for methadone toxicity. I doubt that's gonna be hugely clinically meaningful, but we just don't know yet. So it's something to keep an eye on. Now, after going through that extensive list of the methadone drug interactions, we'll talk briefly about buprenorphine. And as we already said, we don't see a lot of clinically meaningful interactions fortunately. It's not on the slide, but it goes without saying that naltrexone is also contraindicated with buprenorphine and less being used in a research context. So we've got some of the antiretroviral medications used to treat HIV. And Dr. McCants did a study that showed that the atazanavir did cause a reduction in buprenorphine levels, but that didn't seem to be clinically meaningful. It doesn't do anything to methadone levels. Oh, we have the rifampin that we already mentioned, just like with methadone, benzodiazepines or other sedative medications can have a pharmacodynamic interaction with buprenorphine. And among the very few overdoses, fatal overdoses that have been reported in adults where buprenorphine was an agent, the most common other substance in there is benzodiazepine. So it is possible to have a combined benzodiazepine and buprenorphine overdose. Again, this is not to say that benzodiazepines are contraindicated with buprenorphine. If they need to be prescribed, it just requires careful monitoring. And then we have an antifungal that could increase buprenorphine through 3A4 inhibition. And we might see the same interaction with cannabidiol that we were just mentioning with methadone. So the reasons that some of which we've already mentioned, we'll go over them again, why buprenorphine might not be as susceptible as methadone. Buprenorphine does bind very tightly to the mu receptor. So blood levels are less reflective of the pharmacodynamic effect it's having. We already mentioned it's active metabolites. So if it's metabolized more rapidly, it's just producing another drug that activates the mu receptor. And because it's a partial agonist, the dangers of combining it with other sedative drugs are not as great as they are with methadone. And buprenorphine does not prolong the QT interval in a clinically meaningful way. So we don't have to worry about the arrhythmias with buprenorphine. But there's a lot of specific drug-drug interactions that have not been studied with buprenorphine. Good news. As you all know, many patients with opioid use disorder who have injected drugs have high rates of hepatitis C. We have great treatments for hepatitis C and anyone who has active chronic hepatitis C should be treated. The newer medications are extremely well tolerated and they have no clinically meaningful interactions with methadone or buprenorphine. So patients who are on methadone or buprenorphine who have chronic active hepatitis C should be treated and that can be done very safely. So again, what can we do to mitigate these potential drug-drug interactions that can cause adverse events or even fatal events? We want to use non-opioids for pain treatment as much as possible. We want to reduce the number of medications that we're giving patients. As I said earlier, if you have a patient on methadone or buprenorphine and you're starting a new medication, look up the potential interactions. And of course we need to educate all healthcare clinicians, all society in general, our patients, their families about the concerns for drug-drug interactions like don't share your medications, how to dispose of their medications and we'll hope that that message gets out. And of course we have the providers, we have the providers clinical support system which can give you more information on all of these topics. So we have some references here and I'll finish by describing the PCSS mentoring program. I would like to make you aware of two resources offered through PCSS that may be of interest to you. First, the mentor program is designed to offer mentoring assistance to those in need of more one-on-one interactions with one of our colleagues to address clinical questions. You have the option of requesting a mentor from our mentor directory or we are happy to pair you with one. To find out more information, please visit our website using the web link noted on this slide. We also have the PCSS discussion forum. PCSS offers this forum which is comprised of our PCSS mentors and other experts in the field who help provide prompt responses to clinical cases and questions. We also have a mentor on call each month. This person is available to address any submitted questions through the discussion forum or even through direct contact with clinicians who request it. You can create a new login account by clicking the image on the slide to access the registration page. This slide notes the consortium of lead partner organizations that are a part of the PCSS project. Many medical professionals and many of the PCSS project, many medical and healthcare specialty organizations. Finally, please look at this slide for our contact information website and Twitter and Facebook handles to find out more about our resources and educational offerings. Thank you very much for your attention today. And I hope that information has been helpful to you and will help you to provide better care to your patients and avoid dangerous drug-drug interactions with methadone and buprenorphine. Thank you.

Dr. Andrew Saxon

addiction psychiatrist

drug-drug interactions

methadone

buprenorphine

Eleanor McCance-Katz

healthcare professionals

opioid use disorder

epidemiological data