Activity Transcript

Steven Stanos, DO: Hello. I'm Dr Steven Stanos, pain management specialist at Swedish Health System, Swedish Pain Services, in Seattle, Washington. Welcome to this program titled, "Making the Case for an Opioid Action Plan: The Role of Naloxone."

Joining me today are my colleagues, Dr Kathleen Hanley and Dr Kevin Zacharoff. Dr Hanley is an associate professor in the Department of Medicine at NYU Grossman School of Medicine in New York City, and Dr Zacharoff is faculty and clinical instructor and course director of pain and addiction in the Department of Family, Population, and Preventive Medicine at the Renaissance School of Medicine at Stony Brook University in Stony Brook, New York. Welcome Kathleen and Kevin.

Kevin Zacharoff, MD: Nice to be here, thank you.

Kathleen Hanley, MD: Thank you.

Dr Stanos: Well, besides the devastating and unprecedented impact coronavirus disease 2019 (COVID-19) has had on our communities, families, and patients, we really can't forget 2 other related public health challenges. One, the growing number of deaths related to the drug overdose epidemic, and second, the increased prevalence of chronic pain in the United States, by some estimates, impacting 20 to 50 million Americans at any given time. Now, central to this complex challenge is balancing providing patient-centered care while decreasing the morbidity and mortality related to prescription and illicit opioid use and opioid-related overdoses. Naloxone is an opioid antagonist and can be a critical tool in reducing opioid-related overdoses.

Kevin, let's begin with the epidemiology of pain and overdose.

Dr Zacharoff: I think it's important for us to remember the fact that pain is often a component of a number of different chronic medical conditions. If we look at 2016 data, chronic pain affected somewhere around 50 million adults in the United States alone. So we have to consider the fact that when we're thinking about how we treat these patients for pain, opioid analgesics are frequently used as a component of the treatment plan. We also need to consider the fact that, if we look at 2017 data, there were somewhere around 145,000 emergency department visits for nonfatal overdoses involving non-heroin related opioids in the United States. So that means that when we prescribe these opioids to these millions of people, we need to consider the fact that the risk of overdose exists.

Now, when we consider that fact, if we look at just one example of a local study that was done in a small town by a health system in Wisconsin, they looked at electronic health record data in 2016. What they found was that in approximately 1500 -- it was exactly 1490 -- overdoses that they saw for emergency department visits and hospital admissions, 40% of those overdoses were unintentional.

Basically, what's happening around the country is that people, as we will talk about today, are trying to identify situations where there is high risk. One of those situations is high-dose opioid therapy, especially chronic high-dose opioid therapy, which is typically identified as ≥ 90 MME/d. We need to also consider the fact that, very often, patients may be coprescribed other sedatives or other medications that may suppress the patient from a neurologic perspective, such as benzodiazepines; they may be consuming alcohol, and they may even have a history of overdose. These are important things to consider when we take into account the fact that opioids are often used as part of a pain management plan.

Dr Stanos: Kathleen, Kevin just did a nice job of explaining some of the epidemiology about overdoses and some of the risk factors in general with those patients who may overdose. Can you tell us more specifically about naloxone, and how this works?

Dr Hanley: Naloxone is a prescription drug that rapidly and temporarily reverses the effect of any narcotic medication, so anything from prescription opioids to illicit street drugs. It's an antidote for opioid overdose. It was available in several formulations but now is available for use by laypeople, as well as first responders, in a nasal spray. There was an autoinjector that was similar to an epinephrine type of pen injector that has recently been discontinued. Right now, there's a 4-mg nasal spray that can be prescribed ,and it's extremely effective in reversing opioid overdose, from 75% to 100% effective. It's really an important component of reducing mortality from overdoses of opioids.

Dr Stanos: Now, because of the increasing rates of opioid overdose, federal agencies have proposed naloxone use and developed various recommendations through a number of guidelines and strategy reports. Kevin, can you tell us more about some of these guidelines and strategy reports that have recently come about?

Dr Zacharoff: I think the one that comes to the top of my mind are the Centers for Disease Control and Prevention (CDC) guidelines. Most of us are probably familiar with the "CDC Guideline for Prescribing Opioids for Chronic Pain" in a non-expert setting. They probably were the first group to really shine the spotlight, if you will, on the importance of considering naloxone when prescribing an opioid analgesic. But we look at other federal agencies, like the Centers for Medicare and Medicaid Services, which has their own opioid strategy. We can look at a recommendation from the United States Surgeon General who came out with an advisory on prescribing naloxone for people to prevent opioid overdose, and even at the level of the White House, the President's Commission on Combating Drug Addiction and the Opioid Crisis -- there are very many common threads that exist. One common thread through all these federal agency recommendations is increased dissemination and increased consideration of naloxone to prevent unintentional overdoses.

This all led to a recommendation from the Department of Health and Human Services (DHHS) in December 2018, which basically recommended that clinicians should strongly consider coprescribing or prescribing naloxone when patients who may be at high risk of opioid overdose are prescribed an opioid. The recommendations included patients receiving opioids at dosages ≥ 50 MME/d; patients who may have comorbid conditions, such as chronic obstructive pulmonary disease, obstructive sleep apnea, and obesity; any patients who are coprescribed benzodiazepines -- which I really strongly recommend against -- regardless of whether or not there's a high or relatively high dosage of opioids used; and even patients who have non-opioid use substance use disorders (SUDs) who report excessive alcohol use or have a mental health disorder. In those situations, regardless of the opioid dose used, the DHHS recommended that naloxone be strongly considered.

Dr Stanos: Related to that, Kevin, in July 2020, just this past year, the FDA released a Drug Safety Communication, which is a pretty important document to help reduce the risk of death from opioid overdoses. Can you tell us about that guidance?

Dr Zacharoff: That guidance was really the culmination of a lot of discussion going on internally at the FDA with respect to what the best methodology would be. Should there be a mandate at a federal level that every single time an opioid is prescribed that naloxone should be coprescribed along with it? Or could there possibly be some more logical approach? When this came out just this past July, the endpoint of all of those discussions was that healthcare providers should consider the fact that naloxone should be potentially coprescribed and take into account the fact that we needed to consider not only patient-level risk, but we also need to take into consideration the fact that there could be household-level risks. Children could get their hands on an opioid that was prescribed to someone else in the house or other close contacts who could potentially accidentally ingest and ultimately overdose on opioids.

Again, this guidance from the FDA reinforced the notion that people who are on medication-assisted treatment for opioid use disorders (OUDs) should be at increased risk. The take-home message at the end of the day should be that the clinician who's prescribing an opioid, whether it's for acute or chronic opioid therapy, needs to think about the fact that they document in the medical record that naloxone was either considered to be appropriate or not appropriate. When somebody goes back to look at that medical record, they want to see in 2021 that naloxone was either considered to be appropriate or not.

Dr Stanos: Despite the call for coprescribing of naloxone with opioid analgesics, how frequently is coprescribing done? I wanted to turn that over to Dr Hanley.

Dr Hanley: What we do know is that while rates of naloxone coprescribing have increased substantially, and there were over a million naloxone prescriptions written in 2019 compared with 6500 in 2015, it's still an underutilized medication. Data from the National Ambulatory Medical Care Survey & National Hospital Ambulatory Medical Care Survey datasets indicate that from 2014 to 2015, for about every 8,000 visits where an opioid was prescribed, there was 1 naloxone coprescription. In 2018, the rate of naloxone prescriptions per 100 high-dose opioid prescriptions was about 1.5, so truly a very small proportion of folks who are receiving even high-dose opioid prescriptions are being coprescribed naloxone as part of their safety plan.

Dr Stanos: I agree, Kathleen. On the other side is to remember that these are hopefully one-time scripts that a patient can have for 1 or 2 years, but there's so much work that needs to be done to increase the availability of naloxone for patients. Thank you for that.

Dr Hanley: Absolutely, that's true. Also, it is hard to know whether perhaps people are obtaining them under a prescription where they can just be dispensed at a pharmacy without a one-to-one doctor's prescription. Also, in some states, what we've seen is that at least one of the ways to increase prescribing is that some states do mandate opioid patients to receive a naloxone coprescription from their prescriber, and this is something that we all need to keep on top of because it's constantly changing and does vary from state to state, and also from type of prescriber, differing for physician assistants, nurse practitioners, and physicians.

Dr Stanos: Before we go into more of the details around naloxone prescribing, I think Kevin had mentioned the CDC guideline for opioid prescribing that came out in 2016, and I think that's a good place to base ourselves. They talked about considering a naloxone prescription when patients have a history of overdose, a history of SUD, those patients on higher opioid doses, which the CDC recommended any patient ≥ 50 MME/d, or concurrent use of benzodiazepines. We know there is a really significant increase in overdose deaths with the concomitant use of opioids and benzodiazepines. I throw in the whole question of naloxone prescribing with those patients that are on opioids, especially with other centrally acting agents, including benzodiazepines -- that can really put you at higher risk for overdose.

What are the other medical conditions or risk factors that can put you at risk for overdose? Any sleep-disordered breathing, COPD, other respiratory problems, or renal or hepatic insufficiency, especially in our older population -- they may not be able to excrete opioids and metabolites as well, and this puts them at a higher risk for toxicity. Patients over 65 years of age have a number of other risk factors that could increase their risk for opioid toxicity and potentially opioid overdose. Patients that are morbidly obese -- again, another medical condition that can definitely put a patient at risk. I think sometimes there's a false sense of security with just looking at the opioid dose -- those psychosocial risk factors, as well as those medical comorbidities and other medications they're taking, can be very important. And like Kevin mentioned, it’s really important that you document that as well in your discussions with your patients.

There's been some other literature reviews that looked at extended-release/long-acting opioids, with some of those studies showing an increased risk, sometimes a greater risk for overdosing while you're titrating patients, so that's important to remember as well when you're thinking about, is a naloxone prescription going to be an option for your patient, and is it important right now. Again, the presence of an SUD and mental health disorders. Patients can have significant anxiety and depression, and they may be at high risk because of that one month vs when they're more stable they may be at lower risk -- so always looking at the psychologic factors that a patient has had. What's their psychologic functioning? Because those also could put them at higher risk and these patients, again, may benefit from having naloxone in their house so it can be available in case they overdose.

Kathleen, I wanted to turn to you to see if you can explain how, in your practice, you evaluate patients, and some of the other factors that you may look at when deciding if a patient's going to be at greater risk for overdose.

Dr Hanley: That was a pretty encyclopedic list that you already gave, but in essence, yes, I think it's really important to assess the patient for other medications that they might be taking that you might not know about, so asking people about prescriptions from psychiatrists, from other physicians. Also, in most states we now also have a Prescription Drug Monitoring Program (PDMP). Looking at that to verify what medications a patient might be receiving from other prescribers is super important to evaluate them from risk at overdose, thinking about all the medical comorbidities you discussed.

Of course, I do treat people with OUD with buprenorphine, and anybody who is in treatment for OUD should be considered to be at risk for an overdose and certainly should be prescribed naloxone as a matter of routine, not necessarily for themselves, even, but because they tend to know other people who have OUDs and who are at high risk for overdose. I've had quite a few patients who have actually saved other people's lives with the naloxone that I prescribe to them.

So thinking about all the things that you discussed is important. We also, of course, in primary care screen all patients for SUD, so that would also tend to pick up people who drink too much alcohol and who would be at much higher risk of an opioid overdose if they were prescribed opioids as well.

Dr Stanos: You bring up a good point. I think a lot of times we forget the simple part of the social history about alcohol use. Many times patients are not going to tell us about that unless we ask. Like you said, that can put them at high risk, separate from any opioid dose that they're on or any morphine equivalent, so I'm glad you brought that up about other substances. And I agree that the PDMP -- most states have those -- really gives you a lot more insight in what medicines patients are getting from other providers. It also a history of what they've taken, especially new patients that you may inherit, what medicines and controlled substances that they've been given.

Kevin, would you like to add to that? How do you look at, with your patients individually when you're seeing them with regards to their risk for overdose? How do you determine that?

Dr Zacharoff: One of the things we really focus on is the stratification of risk of an aberrant drug-related behavior. As we heard Dr Hanley mention, there is an increased risk of overdose in patients who are identified to be in that moderate-to-high risk situation. When I think about other factors, one of the things that I really focus on is either the patient's past or present history of an SUD and other members of the household who may have a past or present history of SUD. If we take into consideration the fact that many prescribers don't even ask a patient if they have a history of overdose prior to the current opioid prescription, we would be very surprised about those facts.

In addition to the comorbid conditions that you were referring to, Steve, I think it's really important for us to dig a little bit deeper and have much more of an understanding of the context of the situation that we're introducing the opioids to. In the framework of naloxone, I often think of it as having a fire extinguisher in the household for either the patient or other members of the household. That would be what I would add to what Dr Hanley said.

Dr Stanos: Thank you. I like your analogy of the fire extinguisher, and you brought up a good point about we as clinicians really need to have these directed questions like, “Have you overdosed before?” I think sometimes we want to skirt around these questions, but really, just coming forward with patients and having that dialogue is going to be so important. And like you said, too, documenting the responses -- a lot of times, we're just meeting these patients for the first time. They have a whole history that you really need to get a better understanding of where they've been, especially a previous history of substance abuse and alcohol, like you talked about.

I wanted to touch a little bit upon -- I know in our own state, and I think we all can agree, practicing in different states -- there is state guidance. In our state of Washington, we have risk stratification. Risk stratification needs to be done with any patient on chronic opioids, and even patients that have subacute chronic opioid use, which is more than 6 weeks long. Within that, we decide if the patient is low, medium, or high. Based on if we're an MD, a DO, or a nurse practitioner, there are different rules within the state if you're going to prescribe naloxone or you should consider naloxone. In our state, if you're a nurse practitioner and the patient is on ≥ 50 MME/d, there needs to be a discussion based on the pain rules about naloxone. For DOs, it's if the patient is on higher doses, and for MDs, it's if they are considered high risk. They also include based on your individual assessment. We can use some of these guidelines and risk categories, but you also need to consider just the medical issues and those patient-specific issues that we talked about.

Kevin, would you want to comment on your state? Is there specific guidance? Or what does your state use?

Dr Zacharoff: I would say that in New York state, they really hug the CDC guidelines pretty closely. I think they want us to consider the fact that any patient who is prescribed at least 50 MME of an opioid a day should, at a bare minimum, have a clinician consider the fact that opioids should be coprescribed with naloxone. At the most minimal level, in 2021, I would advise all of us to make some notation in the medical record about the fact that naloxone was considered and deemed not necessary to be coprescribed, or it was considered and then deemed necessary to be coprescribed. The New York State Department of Health is really trying to push us to do that. I can say with a high level of confidence that if there is a chart review in our state, they will be looking for this in 2021 moving forward to be part and parcel of "appropriate” prescribing of an opioid.

Dr Stanos: I want to shift this back to Kathleen, too, because you brought up a good point about the conversation. How do you start the conversation with a patient about naloxone and if they're going to use that in the home?

Dr Hanley: I think it's really important that it is part of a bigger conversation about general safety, that these are dangerous medications. We were talking earlier about how some people think, "Oh, I don't need that." “Well, it's not personal, and I’m not singling you out -- these are dangerous medications, and there is a medication called naloxone that can reverse an opioid overdose if it happens.” And then, like so many ways we educate patients, to ask them if they've heard of it, or what they know about it, and to say that I would recommend that they should have this in their home if they're getting a prescription for an opioid, and how extremely safe and easy to use it is. Then we just talk about how to use it and ways of recognizing the signs of an opioid overdose, which, obviously, they are not going to recognize in themself as the patient. But, hopefully, you would have the opportunity, if you're prescribing opioids, to involve a significant other, household member, or family member who would likely be the person to administer the naloxone should your patient experience an overdose. They should be educated in recognizing an unarousable person who has shallow breathing and cyanosis and other signs of opioid overdose and how to administer the medication.

Dr Stanos: How would you explain how the medication is actually given? I know a lot of this can also be done by the pharmacist as well.

Dr Hanley: Yes, the pharmacist, or in our case and in many practices, I do think that there are nurses and laypeople who work in the community that can be trained. It’s super simple: The naloxone comes in a nasal spray. If the person is not already on their back, they should place the person on their back, take the nasal spray out of the box, and then just hold it with their thumb at the plunger. Place the nozzle in the person's nostril, tilt their head back supporting their neck, and just insert the tip and spray the nasal spray into 1 nostril. Then lay the person on their side in the recovery position, because as we know, people who receive naloxone can have symptoms of withdrawal, which might include vomiting, and we don't want someone aspirating when they vomit.

Either immediately before or immediately after doing this, call 9-1-1 and call EMS. As Kevin said, when you use a fire extinguisher if you have a fire, you're going to call the fire department. We're going to call EMS because the nasal spray will reverse the overdose, hopefully, but the person could still be in danger. This can be repeated every 2 to 3 minutes until you see an effect, which would be the person regaining consciousness. Most of the kits with naloxone include 2 nasal sprays, so a layperson who has a naloxone prescription would get to do this twice. Presumably, if it didn't work, EMS would be there by then.

Dr Stanos: You bring up a good point that many times, depending on the type of opioid that they're on and the potency, this may just be a transient response to naloxone. You may need to repeat the dose, and obviously the importance of calling 9-1-1 and getting additional medical help --

Dr Hanley: -- can’t be overemphasized. If you need to give someone naloxone, you must call 9-1-1.

Dr Stanos: I know the guidance we give, too, is that it could last for 30 to 90 minutes, but that's just kind of an approximate range, so people just need to understand that.

Dr Hanley: Even if we are pleased that we've reversed the overdose and the person seems fine, they still need medical attention and monitoring.

Dr Stanos: Thank you. Now, going back to Kevin: Despite the discontinuation of the naloxone autoinjector, it is still available for use until supplies run out. The autoinjector was typically used in the field by EMTs, police, and firefighters. Can you describe how it was used, even though I know there's probably going to be a limited supply?

Dr Zacharoff: It's a pretty sophisticated little device. The autoinjector has automated voice instructions to guide someone through each step of the injection, starting with removing the autoinjector from its case, removing a red safety guard, and then placing the back end of the injector against the outer edge of the thigh, even through the clothing if there is clothing, and pressing firmly and holding in place for 5 seconds. After that, you will hear a distinct clicking and hissing sound, which means that it has been effected. As Dr Hanley mentioned, in a best-case scenario, someone is alerting EMS simultaneously as this is happening. If you're all by yourself, you could engage EMS after you give the first injection.

Similar to what Dr Hanley described with respect to the nasal spray, if symptoms return after an injection, you could give additional injections with a new autoinjector (it's important to note that the autoinjector is single-use only) every 2 to 3 minutes until EMS arrives. Reiterating what Dr Hanley said, continue to closely watch the person until EMS arrives. Lastly, the only other important point, which we as clinicians are taught as a basic premise, is not to put the autoinjector back in its case or re-cap it in any way and dispose of it as if it were a used medical-grade needle.

Dr Stanos: Kevin, can you discuss the adverse events that can occur with naloxone use? 

Dr Zacharoff: Sure, Steve. I think it's really important for us to consider the fact that if someone is physiologically dependent or not opioid-naive, which means that they might go into withdrawal if their opioid was suddenly unavailable to them, they will likely experience withdrawal-like symptoms if they are given naloxone. Those could include anything ranging from, as Dr Hanley mentioned, nausea and vomiting to severe agitation, confusion, all the way up to seizures. So while naloxone is a very safe medication, it's really important to warn people that if somebody is dependent physiologically on opioids, they will likely experience some range of withdrawal-like symptoms, and it shouldn't take them by surprise.

Dr Stanos: Thank you, Kevin. There are some things I wanted to also touch upon so we can complete our understanding of naloxone with basic pharmacokinetics and storage. You should not freeze or expose naloxone to excessive heat greater than 104 degrees. You should keep the nasal spray in its box until it's ready to use. Dr Hanley explained how they usually come with 2 bottles in each package. You want to protect it from direct light. You want to replace the naloxone nasal spray before the expiration date, so be aware of that. And keep naloxone nasal spray and all medicines, controlled substances, out of reach of children -- it is really important and something we didn't have a lot of time to go through, but it is really critical for us to understand the risks associated with accidental exposure to these medicines. You want to dispose of naloxone in a place that is away from children as well.

With that, I wanted to turn it back to Dr Zacharoff and Dr Hanley for any final comments they may have about naloxone prescribing and where that fits in with better patient-centered care with opioid management.

Dr Hanley: I think it's important to emphasize that naloxone is just one component of safely prescribing medication. As we talked about, assessing people's risk before prescribing, really trying to avoid coprescribing medications such as benzodiazepines with opioids or prescribing opioids to people who are on benzodiazepines. And to have a discussion about safety that includes safe storage of opioids, not lending them to other people, where do you keep them in the home, and thinking about who lives in the home. Then, prescribing naloxone as a component of safety. To me, it's an extremely safe medication, so there's very little downside, and it opens up a conversation about safety in a bigger way.

Dr Zacharoff: What I would add to that is that we all need to recognize is it’s not a coincidence that the different federal agencies I mentioned include naloxone as part of a much larger plan. I think there's a sense of urgency, certainly at the federal and regulatory level, that naloxone is going to be the silver bullet. But I think it's important for us as clinicians to know that there really is no single silver bullet. Back in 2014, the thinking was that the PDMPs that Dr Hanley mentioned before were going to be the be-all and end-all solution. Right now, it's accessing the PDMP, it's utilizing naloxone, it's making documentation, it's our considering appropriate prescribing.

Lastly, we need to consider the fact that the likelihood of a patient ever administering this to themselves is extremely low. So educating the patient about it is not likely going to be the end of the story. If they live with someone else, that person or those people need to be educated about it. Maybe there needs to be something on the refrigerator about it. It's really important for us to just not consider the fact that patient-level education is going to play a significant part when we think about naloxone's role as part of our action plan.

Dr Stanos: Thank you, Dr Hanley and Dr Zacharoff. I really appreciate your insights into this. All of us as prescribers need to be aware of our state guidance and our state pain rules. Many times these are changing on a month-to-month basis, so be aware of this within this realm of safe opioid prescribing. Understand the rules in your own state or jurisdiction around naloxone prescribing, as well. Within that, there are a lot of resources, websites, and other information that you want to have access to that can also be helpful for you as a prescriber, and information you can give to patients so they can have for themselves and their family members.

I want to thank Kathleen and Kevin. I really appreciate this discussion. Thanks again. I want to thank all of you for participating in this activity. Please continue on to answer the questions that follow and complete the evaluation. Thank you very much for your time.

This transcript has been edited for style and clarity.