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Naloxone saves lives, and it’s critical that we get naloxone into the hands of as many people as we can. In this podcast, Dr. Phillip Coffin and I will discuss the risk factors associated with opioid overdose, the different naloxone formulations, who should be prescribed naloxone, and how we as clinicians can promote the availability of naloxone in our communities. 

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Published On: 03/24/2022

Duration: 18 minutes, 58 seconds

Referenced Article: “Naloxone Prescribing,” The Carlat Addiction Treatment Report, July/August 2021

Noah Capurso, MD, MHS, and Phillip Coffin, MD, have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Transcript:

Dr. Capurso: Naloxone saves lives, and it’s critical that we get it into the hands of as many people as we can. In this podcast, Dr. Phillip Coffin and I discuss naloxone formulations, who should have access to naloxone, and how we as clinicians can promote the availability of naloxone in our communities. 

Welcome to The Carlat Psychiatry Podcast. This is a special episode from the Carlat Report’s Addiction Treatment team.

I’m Dr. Noah Capurso, the Editor-in-Chief of The Carlat Addiction Treatment Report. I’m an assistant professor of psychiatry at the Yale University School of Medicine and practice at the West Haven Veterans Administration Hospital.

I’d like to turn our attention to today’s guest, Dr. Philip Coffin. Before we begin, would you please introduce yourself?

Dr. Coffin: So I’m a physician boarded in addiction medicine, infectious disease, and internal medicine. I am the director of substance use research at the San Francisco Department of Public Health, and on faculty at UCSF. I do mostly research into substance use. I try to find older medications that may help people to cut back or stop using methamphetamine. We do some alcohol, cocaine research as well and HIV prevention work with people who use drugs and hepatitis C work. A large focus of my work for the last couple of decades has been around overdose initially involved in some of the efforts to develop overdose prevention programming and over the last ten years more of a focus on the research side of it trying to understand how these programs function and develop novel ways to address overdose focused mostly on opioids but with a growing interest in acute stimulant toxicity as well.

Dr. Capurso: Let’s briefly talk about tolerance and how it relates to overdose risk. It’s important to realize that loss of tolerance to opioids happens much faster than what we might be used to for say alcohol. What sort of time frame should clinicians keep in mind? 

Dr. Coffin: Interesting question and something I’ve explored in research in trying to find out what length of a period of not using is meaningful in the development of heightened overdose risk. I generally go down to as little as three days when I’m thinking of a heightened risk. I don’t think of one day as a significantly heightened risk; two days not really; three days – if you haven’t used for three days I kind of think of that as a somewhat increased risk. Once you get it out to five days, yeah, that’s definitely a significantly increased risk. So I’m thinking about it in terms of the clearance of the drug from your body. And what happens with abstinence sometimes especially if you’re using a medication like naltrexone which is an opioid blocker, is your mu receptors, your mu-opioid receptors, actually become hypersensitized to opioids. So if you’re naïve mu receptors that had never been exposed to opioids were exposed to x-amount of opioids that would result in an overdose, and then you’re using opioids for a long time and then you stop and let’s say you’re using naltrexone you’re opioids become hypersensitized. So it’s X divided by 2 that would result in an overdose instead. And that’s a really important thing to be aware of and you don’t always know all the details of this, but resuming use after a period of abstinence can be really hazardous and you always need to be cautious and take whatever you think is a safe dose – make it much lower than that.

Dr. Capurso: And which patients should be receiving a naloxone prescription?

Dr. Coffin: Probably the most important people to have naloxone on hand are people who are using drugs purchased outside of the pharmaceutical industry, that’s to say really any street drugs. Most important, obviously being opiates, so somebody who’s buying heroin, fentanyl, or opioid pills off the street. That is the most important population. Those are the people who are most likely to actually use the naloxone to reverse an overdose because they’re the people to be most likely present when an overdose happens. Because they’re the people who when you’re using drugs you tend to use drugs with other people so you’re most likely gonna be around other people who use drugs. So far and away, that is the top priority population and if somebody is going to start prescribing naloxone but they worry about cost implications for the healthcare system or something like that I would say that is the group that you should focus on.

Going beyond that, in the 2016 guidelines the CDC added the additional groups of people who are prescribed opioids, and people who are prescribed opioids they listed off a dose of 50 mEq or greater or benzodiazepine use along with opioids or any history of a substance use disorder or any history of opioid overdose or any other factors that increase risk like certain comorbidities or concomitant medications that might increase overdose risk. So it’s kind of complicated, but basically anyone who’s prescribed opioids in any significant amount or that has additional risk factors.

With fentanyl kind of taking over the market, that is why we shifted going back in time a little bit, but that was why we shifted from just prescribing it to let’s say people who used heroin, to prescribing it to anyone who uses any street drugs because fentanyl is often in the drug supply and mistaken for other drugs so we really want it to be in the hands of somebody who let’s say only uses cocaine because one of these days they are likely to buy something that they think is cocaine but that is actually fentanyl.

So we’ve got the people who use any street drugs, the people who are prescribed opioids in a significant dose or with other risk factors, and then the third group is people who are at risk of witnessing an opioid overdose. And most states authorize this; we call it “third-party prescribing. And it’s an important category and this can include let’s say the parents of somebody whose child has an opioid use disorder and they want to have naloxone. This is authorized in most settings and it’s important. It gives a sense of comfort. There are far too many stories out there about a parent finding a child who just overdosed in their room and calling the ambulance and waiting 20 minutes when they could have potentially saved the life then. 

Dr. Capurso: I’d like to pause here to go over the various formulations of naloxone.

We have an IM injection form, a nasal form, and an auto injector. 

The IM injection is the most basic, just a vial and a syringe. An advantage of the IM is that you know exactly how much naloxone is going into the patient’s body and it acts almost immediately. 

The nasal spray, known by its brand name Narcan, is the most commonly prescribed formulation because it is easy to use and widely available. The cost is around $150. While that’s not trivial, it is covered by many insurance plans. A generic intranasal naloxone has been approved but isn’t yet available.

As a side note, there is a new high dose nasal spray on the way called Kloxxado, which was approved by the FDA earlier this year. This formulation contains 8 mg of naloxone compared to the 4mg in Narcan. Click the link in the description to check out our recent podcast called “What You Need to Know About Kloxxado,” to learn more.

Finally, the auto-injector delivers naloxone subcutaneously. It’s a self-contained device that talks you through the administration. Unfortunately, it costs hundreds of dollars and has since gone out of production.

Dr. Capurso: So, Dr. Coffin, how is naloxone accessed by patients?

Dr. Coffin: So when you think about the two models of getting naloxone out there, one is prescription which is what we’re used to in the medical system and that relies upon pairs and so those pairs can absorb a little bit of cost. The other is the distribution model and this is really the classic one and frankly this is the workhorse of naloxone in terms of overdose reversal. Most of the reversals are coming from naloxone distributed through the distribution model which is generally through syringe exchange programs most often. And with contracts they’re able to get this product cheap enough that they can hand it out in the thousands of doses and reach a wide number of people that are around overdoses all the time. It is not too common to prescribe this version; I’ve had to once or twice. There are some Medicare Part D plans that wouldn’t cover the nasal and I had to prescribe the vial and syringe. I don’t see an issue doing that for patients that are comfortable with injecting medications or drugs. But for most patients it’s not the optimal way to be dispensing the medication.

Dr. Capurso: And can you describe what a standing order is?

Dr. Coffin: A standing order is a way of providing naloxone that’s been authorized in multiple states. And that is essentially a physician writes an order; this is usually more of a legal document and not just a one-line order that authorizes a product to be dispensed under their license without them authorizing each individual dispensation. It’s been used in other settings before. Given that naloxone is not a controlled substance, which is a really important issue, there’s not so much of a concern about a standing order like this, but it is nice to have it specifically authorized by state law or in some circumstances in the past it had been authorized by local public health emergency.

The standing order is generally used to allow naloxone to be dispensed from a place like a syringe exchange. So I issue the standing order for the drug overdose prevention and education program in San Francisco and they order naloxone and send it to the syringe access programs where it is dispensed to the clients of the program. And those clients, we have unique ID’s for them, they’re unnamed. This is not billed through insurance; this is done sort of outside of the traditional health care system, and it is made to reach people in a much lower threshold manner.

Dr. Capurso: The bottom line is, when in doubt, prescribe. The more naloxone out there the better. If you are seeing a patient who warrants a naloxone prescription, just prescribe it. There is no need to wait. If you don’t have the ability to write a script yourself, provide a list of places where patients can get naloxone. Tell them about the standing orders that Dr. Coffin just described. 

Although it may seem counterintuitive, be especially sure to prescribe to patients not injecting opioids. Injecting is the highest risk form of use, but people who inject opioids are more likely to have access to naloxone through a needle exchange program.

Dr. Capurso: So far we’ve covered the pros and cons of each naloxone formulation and how we can make naloxone more available for the public. But we also need to emphasize the importance of educating patients and families on how to use naloxone. In the vast majority of cases patients are not reviving themselves, so it’s essential that they become naloxone educators for those immediately around them. 

With that being said, how should we discuss naloxone use with our patients, Dr. Coffin, is there specific language you recommend?

Dr. Coffin: Sure, and I’d love to cover this on a couple of points. So the first thing I’d like to discuss is the language to use when you’re offering naloxone to a patient in general. So the terminology “overdose” which I use all the time is problematic because most people when they suffer what we call an overdose they aren’t doing it on purpose. And people think of an overdose, especially people who are taking prescription opioids, they think of an overdose as when you swallow your whole bottle of pills or you go up and you shoot a bunch of dope. They don’t think of an overdose as having too much opioid in your body in a given moment in time for your body to handle. 

And there’s a wide variety of reasons that can happen to somebody. There is genetic distribution of sensitivity to the respiratory depression effects of opioids, so that accounts for a third of the variation in respiratory depression. There are some people out there who will stop breathing before they get any relief from opioids, so those people are obviously at extremely high risk of overdose even if they’re doing exactly what their provider tells them to do. There are also changes in your body that happen with age: comorbidities that emerge whether it’s sleep apnea or lung disease or cardiac disease that may make you at higher risk for an overdose. They may also be starting other medications that lower your tolerance for opioids and make them at higher risk for an overdose. So there are lots of reasons that somebody can have an overdose that have nothing to do with breaking the rules of your medications.

So we try to, especially people who have been prescribed opioids, we really try to stay away from the terminology of overdose, and we use phrases like “bad reaction,” medication safety, opioid safety. “Your medications can cause a bad reaction where you can stop breathing and that can be fatal. This is a medication that can reverse that.” In fact, when we interviewed patients that had been prescribed naloxone almost half of those who had overdosed denied an overdose, but admitted to a bad reaction where they had to be revived by paramedics. So people think of it as toxicity not as an overdose. 

It’s a little bit different for people who are using street drugs. They tend to identify more with the terminology of overdose, so you have a little bit more liberty with language in that domain. So that’s that part.

The second part in terms of when you’re prescribing it to somebody who themselves are at risk for an overdose, you do want to make sure that they alert other people as to where it is. There are rare cases – they do happen – where people administer naloxone to themselves. This happens especially when somebody hasn’t been using in a long time and they use and they feel like they’re gonna stop breathing. They feel like they’re going too deep. They may administer naloxone to themselves. This may also happen with let’s say a patient who is being tapered off of their opioids and goes back to their standard dose because of the distress that they’re feeling. I’ve heard cases of this: they then self-administer naloxone because the effect just feels too strong that it’s coming on. So it does happen, but it’s uncommon and the vast majority is administered by somebody else in the event of an overdose. 

Fortunately, the nasal spray comes with really nice simple patient instructions as does the auto-injector that makes it easy to look at it and figure out what to do. 

So the most important thing to do when you’re prescribing naloxone to somebody who themselves is at risk is to make sure that they let somebody else know where the naloxone is. And this applies not just for themselves but also for somebody else. So I may prescribe naloxone to somebody who has a bunch of opioids at home but I don’t think they’re at risk for overdose, but I do think they have a lot of opioid medications at home and they’re unlikely to keep them in a locked safe and they also have grandkids, and maybe their grandkids are gonna access the opioids and maybe they’re not gonna be home when that happens and their son is gonna be there. So you want to make sure that everyone knows where the naloxone is. And how to use it is frankly really easy with the nasal spray and auto-injector; you don’t really need much instruction there. If somebody is not breathing, you give it to them, and you call 911 and you try to wake them up however you can try to wake them up. So it’s not a complicated education but the most important piece is just to make sure they let other people know that it’s there and that they should use it if somebody is not responsive.

Dr. Capurso: Opioid use disorder treatment legislation varies by state. So, as a provider, it’s important to be aware of your local laws. 

Dr. Coffin has recommended some resources in order to do that; SAFEProject, which stands for Stop the Addiction Fatality Epidemic, and the Legislative Analysis and Public Policy Association. Finally Temple University has a website called LawAtlas that maintains a registry or laws relevant to mental health providers, including naloxone prescribing. The printed interview is available for subscribers to read in The Carlat Addiction Treatment Report. Hopefully people check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits. 

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As always, thanks for listening and have a great day!