Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk, Episode 127, I'm your co host, Dr. Kane, Dr. Khyati Patel 00:36 and I'm Dr. Patel, and in today's episode, we are going to discuss naloxone. The title of our episode is Naloxone to the rescue, opioid overdose treatment and more. And we're kind of hoping to cover basic pharmacology and the use of naloxone. What different formulations are available in the market, what's its use for effectiveness and in general, what are some of the Naloxone related pharmacy management and regulations that our audience would need to know? Dr. Sean Kane 01:07 Great. Well, Dr. Patel, why don't we just start with the basic pharmacology of naloxone. So naloxone is an agent that we use to reverse opioid overdose, so it's actually competitive opioid antagonist. So in patients overdose an opioid, this prevents that opioid from binding to the opioid receptor, and it reverses the pharmacologic effect of whatever they overdosed on. Dr. Khyati Patel 01:29 This is used to reverse, you know, overdose from your prescription opioids or non prescription opioids, aka street drugs like heroin and Dr. Sean Kane 01:41 Dr. Patel, what would be some indications in terms of signs or symptoms of an overdose that may be amenable to Naloxone to reverse that overdose? Dr. Khyati Patel 01:51 Yeah, some of the common things that we can look out for would be things such as pinpoint pupil, you know, you finding patient unconscious, bradypnea, vomiting, inability to speak, so aphasia can be there lower heart rate, bradycardia, kind of limp responses, muscular responses, so limp arm and legs and then signs of hypoxia, if the patient has been down for a long period of time, such as Very pale skin or even like purple lips or fingernails can be spotted. We'll talk Dr. Sean Kane 02:25 more about the kinetics of naloxone in a little bit, but it's important to recognize that naloxone is a temporary treatment, so this is something that buys some time, potentially given by a police officer or a family member before more comprehensive medical intervention is available. And even once you get to the hospital again, as we'll talk about, with its half life, sometimes we have to redose it or even use a continuous infusion, depending on the opioid that was taken, right? Dr. Khyati Patel 02:53 And with these street opioids available there are laced with other products and stuff, which increases the strength of the opioid overdose, requiring very, very large doses of naloxone to reverse the overdose impact and effects and stuff. And so we will cover different formulations that are out there, but all of them, if you look at their, you know, pi, it says you give the first dose, and the next thing you do is call the emergency services and be ready for, you know, more doses that you might need to give to the patient if they don't come back Dr. Sean Kane 03:27 Well, Dr. Patel, I think most of our listeners are probably familiar with the injectable form that we'll talk about in a second. But you know, a lot has been done in the last five years or so related to nasal spray of Narcan. So what can you tell us about availability of these nasal spray products on the market that would be more for the non healthcare provider or kind of EMS, type services? Dr. Khyati Patel 03:51 Sure this Narcan, a nasal spray product is basically your prefilled, needleless device. This was actually the first naloxone product developed by the National Institute on Drug Abuse, funded research, and so we call it NIDA for short, and that was made available for, you know, community use of naloxone, you know, like the injectable ones, is mostly used in the hospital side but and this Narcan, the nasal spray, it's available either in a single dose, two milligram or four milligram doses. And the idea is that the four milligram dose, when it comes to its bioavailability and other pkpd parameter, it's very close to the injectable version that's used in the, you know, er or EDS or hospitals. And so really, it's given as a four milligram single dose spray in one nostril. And like we discussed earlier, patient may require additional doses, and they can be given every two to three minutes in the alternative nostril until the emergency services arrive and the patient is revived or taken to the ER and in terms. Dr. Sean Kane 05:00 Of how this is given. So Dr. Patel, you mentioned you start with one nostril. If you redose, you go to the other nostril. The prefilled syringe is very similar to what you might see from an oral syringe or an injectable where you're holding the syringe in your first two fingers and using your thumb to kind of push the plunger in. You're going to tilt the patient's head back so that any drug is going to go not out their nose, but kind of down the back of their nose. And then you're basically going to push it down and you're done. So once you give that first dose, you're going to call 911, to get emergency services available, potentially prepare another dose if you have one, depending on the patient's response. And then hopefully by that time, you'll start seeing reversal effects if the patient truly did have an opioid Dr. Khyati Patel 05:42 overdose, right? And the beauty about this formulation is that that spray is actually absorbed by the nasal mucosa, so it doesn't require any inhalation response from the patient. Obviously, in majority of these cases, patient is either unconscious or to the point where they're, you know, a respiratory system has been depressed, and so they can't breathe very fast. And so this, this formulation doesn't require that response, which is a good thing. Dr. Sean Kane 06:11 Then, of course, as I mentioned, injectable naloxone is very common in the kind of hospital environment. So this is a single dose or multi dose file. Typically will give it IV. But if a patient doesn't have IV access, it can be given intramuscular or even subcutaneous. Typical dose is point four to two milligrams, and you're going to repeat it, depending on what dose you pick, initially, every two to three minutes. Generally speaking, the lower doses are going to be used in those that have known opioid dependence or opioid abuse problems, basically, to prevent the patient from going through florid opioid withdrawal immediately versus a higher dose would be more appropriate for someone who doesn't routinely take opioids, and we suspect that they have a high dose or high burden of opioid, and we want to reverse all of it as soon as possible because of a life threatening reaction The patient is having, or something to that effect, yeah, Dr. Khyati Patel 07:03 and last, but not the least, you know, there's, this is the newest formulation out of our Naloxone it's evzio. It's basically one of those EpiPen, like voice assisted auto injector that can be used to administer Naloxone via im route. It's available as a two auto injectors. So two, two milligram auto injectors, again, additional one is provided to reduce the patient in the next two to three minutes, if the patient's not reliable and basically, just like your EpiPen goes through, you know, your jeans or pants that you're wearing, it's injected in the anterolateral aspect of the thigh, and you know, it goes through the clothing if need be. But yeah, you basically pull out the outer cover, pull the little red safety guard from the bottom, and then the the injector side. You press it against the skin or the clothing on the thigh, and then press it and then just basically hold it for about five seconds, and the dose will be delivered. Sometimes the manufacturer says the the talking technology doesn't work, but as long as the three simple steps are followed, you can say that the dose was administered to the patient, and again, you're going to call the emergency help right after administering this first dose. Dr. Sean Kane 08:22 And as we mentioned earlier, from a kinetic or pharmacodynamic standpoint, the onset of naloxone is fairly quick. So if you give it IV, im or sub q, these injectable routes within about two minutes, maybe a little bit more than that is your onset. Intranasal is a little slower, so we're looking at eight to 13 minutes. So maybe we call it about 10 minutes on average. And interestingly, there are other ways that you can give it that have been described, mostly as case reports. The one that I think is kind of interesting is nebulized version. So you can actually nebulize Naloxone as well. So lots of different cool ways that we can give this drug, right? Dr. Khyati Patel 08:57 And depending on, you know, as we said this, it's a quicker acting but also a shorter acting agent to reverse the opioid effect. And so depending on the route of administration, we can, we can anticipate the duration to last anywhere between 30 to 120 minutes. Obviously, IV is going to be shorter than IM because of the absorption, but most of these patients, as we mentioned earlier, will require repeated doses, and which can be given every two to three minutes. Dr. Sean Kane 09:27 And you know, if a patient does make it to the ICU or emergency department, depending on their response and depending on how much drug they took and the type of drug, some of these patients will actually be indicated for a continuous infusion of naloxone, where the half life of what they took is so long, as opposed to the nurse coming in, and every 30 to 60 Minutes re injecting the patient, they actually have a continuous infusion of naloxone to maintain the blockade of the opioid receptor for some period of time. Dr. Khyati Patel 09:54 And as far as the metabolism goes, it is a hepatic metabolism, but it doesn't go through the. Sip, it goes through the glucuronidation, and obviously IV or im is going to be 100% bioavailability, but when we compare the intranasal product, it has anywhere between 43 to 54% bioavailability, and that's why that emphasis is on there for that four milligram dose. Dr. Sean Kane 10:17 And what's kind of interesting is that you know from an oral standpoint, Naloxone has really poor bioavailability. Basically, you don't absorb it. So manufacturers have actually taken advantage of this in a really cool way. So if you look at a drug like Suboxone, which is buprenorphine with Naloxone, the naloxone in the tablet of Suboxone actually has no therapeutic effect if you take it orally in a normal fashion, but if you crush that suboxone and try to inject it, now you're injecting Naloxone that you absorb all of it because you inject it, it prevents the patient from getting high by abusing or misusing that product that has naloxone in it, which is intended only to be taken orally. Patel, basically, from a side effect standpoint, we're effectively inducing opioid withdrawal for these patients, if they are not naive or if they have an opioid abuse problem. So what are some of the symptoms that are associated with quick reversal, or effectively opioid withdrawal by giving Naloxone to a patient. Dr. Khyati Patel 11:22 Yeah, so a lot of these side effects we are going to talk about are kind of side effects of, not really the drug Naloxone, but really that those withdrawal symptoms, so things such as, you know, sweating, nausea, vomiting, diarrhea, abdominal cramps, you know, cardiovascular rise. We can see variations in blood pressure, mostly increased blood pressure, and then even tachycardia and V tax have been reported as well. So those are with pretty much any product. And again, these are kind of general symptoms of withdrawal. In addition to that, some other symptoms of withdrawal could be irritation, agitation, irritability, disorientation or anesthesia and hallucinations, etc. And some Dr. Sean Kane 12:06 of the kind of neat ones that I've seen include things like yawning, which is kind of a random one, also goosebumps, or pilo erection on the skin, and even like kind of tearing of the eyes is another symptom as well. So it really runs a gambit, depending on you know, how severely tolerant the patient is of their opioids and what dose you give them to effectively induce withdrawal for that patient. Yeah. Dr. Khyati Patel 12:32 And interestingly enough, the nasal product is known to cause toothache out of everything, and constipation too, in addition to some nasal irritation, dryness, congestion, edema, headache, etc, perhaps too close to the CNS, you know, proximity. When this product is used in neonates, for you know, withdrawals, there's some additional side effects that have been seen, such as excessive crying, some convulsions as well as hyper reflex, yeah, so kind of watching out for those symptoms in the little ones. Dr. Sean Kane 13:07 So Dr. Mattel, you know, it's great to have Naloxone available, right? But the intended administer of the medication is actually not the patient who takes the opioids, right? So it's really someone else who will be giving it to the patient who has excessive amounts of opioid on board. So who are the typical people who may be administering Naloxone to a patient with an overdose? Dr. Khyati Patel 13:32 That's absolutely right. Dr. Kane, I would just like to make one distinction. However, though those who are on opioid therapy for chronic pain and stuff. Still can be advocating for themselves to have their family members be provided such rescue options or be taught on how to do the rescue option. Obviously, patient themselves might be unconscious. You know, when this happens. So really need to have surrounding folks be equipped with this. So most commonly, we're going to see first responders such as the emergency med techs or police officers using naloxone. There's about 2500 law enforcement agencies across the country that report that their officers have been trained and carry Naloxone to rescue their patrons in the community. That's great. Yeah, that's actually really neat. And I think more and more trainings are being offered by the Bureau of Justice, agency and department, and grant is available for, you know, police officers and PDS to kind of get enrolled in it. It's fairly a new approach. We don't have a whole lot of data, but there is one county in Ohio that looked at the effectiveness of such officer training, and they found some decrease in overdose mortality in that particular county. So small data, but I think it's really helpful for the first responders to have access to these. Dr. Sean Kane 15:00 Yeah, then, of course, we kind of alluded to it already, but healthcare providers, obviously, in the hospital setting itself, will be giving this medication. And Dr. Patel, you mentioned your family and loved ones. Can they give this legally to a patient, or are there implications, because it's a prescription product, it Dr. Khyati Patel 15:18 is a prescription product, and this answer depends on the state you're looking at, and as more awareness about you know, Naloxone access and the laws are changing across the country. More and more states are allowing loved ones and families to carry Naloxone as well as administer it. Majority of these states allow these loved ones and family members to be immune from any criminal or civil liability. I mean, taking Illinois example, you know, lay a lay person, quote, unquote, is actually exempt from any criminal or civil liability when they are going to administer Naloxone. Dr. Sean Kane 16:00 That's great. I think that that really lowers the bar in terms of access for patients to and their family members, to be able to give the drug without kind of litigation worries and things like that, given that this is a potentially life saving intervention to someone with an overdose, right? Dr. Khyati Patel 16:17 And more so than the overdose to just the possession of opioids or opioid related paraphernalia. There is many different Good Samaritan laws out there, and the extent of these laws across the state varies from somewhat punitive to very forgiving. And this This has actually been done to let down the stigma that's affiliated with substance use disorders and actually getting the people the right help that they need. And so there is lots more out there. We do have an excellent website that breaks down what the current law is according to your state. It's a prescription drug abuse policy system, and we have that linked in our references. Dr. Sean Kane 17:00 That's wonderful. So we kind of covered who can give it. But I guess maybe we should take a step back and ask the question like, how do you actually get naloxone? So if you're a family member or police officer or a patient, what is a typical pathway for you to actually get the prescription medication and have it available, right? I think the Dr. Khyati Patel 17:21 emergency response team, as well as the police officers, have affiliations with local health departments and community based distribution programs. That's where they receive their products. When we talk about loved ones and family members obtaining Naloxone, couple different avenues are available. One is that their healthcare providers a co prescription of naloxone along with opioid prescription is actually advised. We have some excellent data that may show that CO prescribing actually can reduce the risk of death even if the Naloxone prescription has not been filled, and in some cases, there's been evidence for fewer ER visits because of opioid related emergencies in chronic pain patients, when co prescribing Naloxone occurred by healthcare providers. It's very interesting. We'll talk a little bit later as to what providers and what type of healthcare providers tend to prescribe Naloxone more than the other, or prescriptions by those providers have been have been dispensed more so than the other. But in general, this healthcare provider should be considering prescribing Naloxone to a patient. If a patient is using high doses of opioid for chronic pain management, they are on maybe rotating opioid medication regimens, kind of like on and off, or they're taking certain extended release products or long acting opioids. Or we know that they're recently discharged from a hospital, from, you know, an overdose or treatment facility, and now they're clean, or there is a period of abstinence. Maybe it's, you know, their post long term treatment, or maybe they just got out of a prison, you know, and they remain clean during that time. These are the patients going to have the highest instance of overdose, because now they come back and they, you know, use the same amount as they used to use before, and that could be actually lethal for them. Dr. Sean Kane 19:22 And in terms of, you know, just availability at a pharmacy, obviously, if you have a prescription, you can pick it up. But depending on the state laws, and we'll talk more about this, there are certain states where you don't even need a prescription, that you could actually get your Naloxone at the pharmacy without a provider's prescription that you have in hand, and you could potentially get a medication that way. Dr. Khyati Patel 19:43 Yeah, and this is part of the movement for nanoxone access across the country. So all states have some sort of naloxone access laws in place. Various different mechanisms are used, but one of the ways they have done so is collaborating with pharmacies and allow. Allowing pharmacies to dispense these products without prescription. Dr. Sean Kane 20:04 And Dr. Patel, you mentioned that the show notes for episode 127, available at HelixTalk.com that you'd have a link to a website. Could you just verbally mention the website URL for those that want to know more information about obtaining Naloxone, right? Dr. Khyati Patel 20:20 And so, you know, I mean, you have to have, like, the community knowledge of where you know these products are available. But just like you know, finding where your sharps, you know will be taken, there is actually Naloxone finding site. And so you can go on www dot get Naloxone now.org and find a nearby either the health department, community based distribution programs, pharmacies that would facilitate Naloxone product. Dr. Sean Kane 20:53 So kind of switching gears a little bit. So we've talked about how patients and their family members can obtain Naloxone from the pharmacy side. What are some considerations in terms of being able to dispense that Naloxone to a patient or a family member? Dr. Khyati Patel 21:06 Yeah, so as we mentioned that there are laws that allow pharmacies to dispense these without individual prescription, and this mechanism is facilitated by a few different things. It could be either just direct legislation. Efforts could be protocol or standing orders could be collaborative practice agreements in about nine of our states, pharmacists have direct prescriptive authorities, so they don't have to worry about any of these. They can dispense Naloxone using that prescriptive authority. So if you take kind of like Illinois, Illinois has a standing order for Naloxone dispensing, which is renewed every year. We take Illinois example, there are certain requirements that need to be followed. Obviously, these requirements are different for each state, but those can include annual renewal of the standing order, a particular registration is required. Pharmacists are required to complete training and education initially, as well as you know, every so often. And then this rule actually requires pharmacists to educate the patient and the caregiver who comes to pick up the product properly and kind of document that the training has occurred. And then all of this data for dispensing and education needs to be reported to the Illinois prescription monitoring system. Okay? Dr. Sean Kane 22:25 And you know, just like what we talked about earlier, in terms of liability to a lay person who administers the Naloxone, do we have kind of a similar liability immunity for pharmacies that are dispensing this through any of these mechanisms that may not be an individual prescription for a patient. Dr. Khyati Patel 22:43 Yeah, I think the number is a little bit different depending on what type of liability we are talking about. For most states would offer criminal, civil or professional liability, immunity to a Naloxone dispenser like a pharmacist. And if I recall, Illinois is a state that offers all three of them, which is wonderful. Dr. Sean Kane 23:02 So you know, Dr. Patel, it's great that we have availability. It's great that we know who can give the naloxone. It's great that we know which patients are kind of indicated to have either co prescription of an opioid plus a Naloxone or whatever mechanism cost. So cost drives so many different things in life. What can you tell us about the cost of getting that naloxone? Who is paying for that? Dr. Khyati Patel 23:27 Yeah, and, you know, you're absolutely right, Dr. Kane, you know, on one hand, we have a prescription that could cost, you know, a certain dollar amount, and then the other hand, we have a human life, you know, and it's kind of hard to put a cost on the human life, but different products have different costs affiliated with that. I was able to kind of venture into some of the CDC data that they were collecting between 2012 and 2018 dispensing, and what they found is most of the Naloxone products were covered by insurances, commercial insurances, Medicaid and Medicare, and the billing through the pharmacy. Through these insurances actually facilitated by the standing or protocol orders or the collaborative practice agreements, or the fact that the pharmacist has prescriptive authority in given state, so pharmacies dispensing don't have to worry about, you know, eating up the cost if patients' insurance were not to pay for it. There are certain pharmacies in the high risk communities that offer discounted programs for Naloxone, and obviously, some of your health departments or local organization as well as emergency responders are going to provide Naloxone for no cost at all. Dr. Sean Kane 24:47 Dr. Patel, the cynic in me, says, okay, so it's it's covered by insurance, but that doesn't necessarily mean that it's still affordable based on out of pocket costs, which would include co pays, deductibles, things like that. So can you. Give us a sense of like, what would be a typical out of pocket cost for a patient, even if it is covered under insurance? Dr. Khyati Patel 25:07 Yeah, I would say the typical out of pocket costs were below $50 you know, in that CDC data that looked at dispensing between 2012 and 2018 about 24% of patients paid less than $10 about 22% of patients paid anywhere between 10 to $50 there were some patients who ended up paying more than 50 but that was like about 6% and I bet any money that the those who paid more were probably getting evzio, because the average wholesaler price for evzio, it's it's a little bit more than either the nasal spray or the injectable, generic injectable products. Dr. Sean Kane 25:50 Okay, so it sounds like it's reasonable, because this is not something that a patient, hopefully is going to use every month or every two months. Hopefully, this is kind of a not very common instance. So it's not like that's a monthly cost that we're looking at with that out of pocket cost. Dr. Khyati Patel 26:06 Yeah, you're right about this. And unlike the EpiPens, which tends to have very short shelf life, Naloxone life tends to be a little bit longer, so the product is not used, but it's stored at the right temperatures and conditions, it could easily have a two to three year shelf life. Dr. Sean Kane 26:24 Wow. And I think that that's, as you mentioned, comparing it with an EpiPen that's really important to think about in terms of that cost is going to get you, let's say, two years worth of naloxone, assuming, hopefully you don't need it. So I think that that helps put the cost into perspective a little Dr. Khyati Patel 26:40 bit, absolutely, it does. And it's kind of cool to see what is the dispensing like, right? We have these access laws put in place, and now pharmacies are dispensing it, you know, under these protocols and agreements and stuff. But what, what is the trend been? And what I can tell from this pooled analysis from from CDC, is that the number of prescription dispensed of naloxone overall has dramatically increased. We're talking about, you know, 1300 some prescription in 2012 to 556 some 1000 prescription in 2018 and this was increased by 106% from 2017 to 2018 alone. Dr. Sean Kane 27:23 So this is definitely a moving market. In terms of more and more patients are taking advantage of this opportunity compared to roughly 10 years ago. Dr. Khyati Patel 27:33 Then that is right. But when we kind of compare a Naloxone prescription for a high dose opioid prescription. There's only one Naloxone prescription being dispensed for every 69 high dose opioid prescriptions. If you think about it from that perspective, that's not a whole lot. Dr. Sean Kane 27:53 Yeah, that's interesting, because at least in my mind, I'm thinking, does a patient already have a Naloxone prescription already, and they don't need to fill it because it's working for a couple years or Dr. Patel, I actually don't know what my number would be in terms of how many high dose prescriptions per Naloxone I'd like to see, but I certainly would agree that there's still opportunity for improvement, right? Dr. Khyati Patel 28:16 Yeah, and this data may suggest that, you know, majority of the people who are getting the Naloxone save out there are getting it from either, you know, from the emergency services, from the first responders, or them just, you know, showing up or being brought to emergency rooms and hospitals, if that's where we are with the dispensing data. Dr. Sean Kane 28:38 And that also kind of begs the question, you know that that data 556,000 dispenses of naloxone in 2018 are there any patterns in terms of who is more likely to take advantage of a Naloxone prescription versus less likely? Yeah. Dr. Khyati Patel 28:54 And you know, as we, as we kind of break this between, you know, Metropolitan more urban population versus some of your rural population, there is more use of opioids. And you know, abuse reported in those metropolitan areas. So rightly so, the dispenses of the Naloxone were also high in those metropolitan areas, and the least high in rural counties. And this is not true of you know, when I speak that opioid use and abuse is more common in urban population. It's not true when we think about some of the rural counties, such as Appalachian, you know, overall use of opioid abuse, and that's actually in Appalachians, it's really, really high, but nearly not enough dispensing of naloxone in those communities. Dr. Sean Kane 29:45 What about regionally within the US? So, are there certain regions that are more or less inclined to have a Naloxone prescription? Dr. Khyati Patel 29:53 Yeah, and this may have to do with either the stigma or just the just the common, you know, medical problem. Practice. But yeah, there were higher dispensing rates in the southern states of the United States compared to, you know, the least number was in Midwest region. Actually interesting, okay, yeah, and demographically too, we found that more, more dispenses occur to female patients than they occurred to male patients. And if kind of breaking these patients down into different age groups, the dispenses were highest in the age group between 60 and 64 Dr. Sean Kane 30:30 What about prescribers? So we talked about patients, but what about the prescriber component of the equation? Dr. Khyati Patel 30:36 Yeah, this kind of ties back to our discussion about CO prescribing opioid products along with Naloxone prescription. And it was really interesting to see that. Again, this is dispensing data from the pharmacies and what provider is listed on those prescriptions. So highest dispenses occurred from prescriptions that were provided by psychiatrists, addiction medication specialists and Dr. Sean Kane 31:01 pediatricians. What about the lowest rates? Then Dr. Khyati Patel 31:05 you're ready to hear that it actually occurred from surgeons, pain medicine providers, which is really hard to believe, physician assistants, primary care providers and nurse practitioners. Dr. Sean Kane 31:19 So it sounds like the people who are more inclined to be dealing more with the opioid abuse side of things are potentially more in tuned than like your typical provider who is more in tune with treating pain as opposed to treating addiction, then, Oh, that is correct. Yes, in terms of what is dispensed, you mentioned evzio being a little bit more expensive. I'm assuming we're not dispensing as much evzio versus the other formulations. Then correct, that Dr. Khyati Patel 31:45 is correct out in the community. Most of the Naloxone distributed is that Narcan, I'm using the brand name, but basically your nasal spray Naloxone, as opposed to evzio, which is that voice-assisted auto injector. Dr. Sean Kane 32:01 So, Dr. Patel, this is all wonderful. You know, we've seen a dramatic increase in the amount of naloxone prescriptions over roughly the past 10 years. We've seen a dramatic increase, from a legal standpoint, different ways to get that prescription product into the hands of a patient or their loved ones. Is this working? Is this an effective therapy to help with our opioid epidemic, including opioid overdose related deaths? Do we have data that really supports that or not? Dr. Khyati Patel 32:30 And you know, Dr. Kane, you're absolutely right. This is like a million dollar question that you must ask. We are doing everything possible to raise awareness, to change laws. There is numerous hours of advocacy that's happening at national as well as local level for these laws to go into in effect. But is it working right? And unfortunately? Unfortunately, we have some data, but unfortunately, it's not enough. In my opinion, if this movement, which is so massive and so loud, we need to see more data, and so we hope to see more data in future, but the little data that we have available does show some indication of decrease in opioid deaths, for example, Abouk, Pacula and Powell in 2019. This more recent study looked at differences between these naloxone access laws, and what they found is that in in in the states which had direct pharmacist prescriptive authority, so significant decrease in overdose deaths, and this was measured about three years after installation of the law in the Naloxone access law and in the States, and what they found is that opioid overdose related deaths lowered by an average of 34% and the non fatal ER visits increased by 15% now it sounds like the non fatal ER visits increased by 15% is a bad thing, but if you think about it, it's not it says non fatal. So patients didn't present to er in a fatal overdose conditions, they were taken to the ER after giving some rescues with, you know, a few initial doses of naloxone, and that Dr. Sean Kane 34:18 was with the direct pharmacist authority. What about a standing order? Did that have any impact? Dr. Khyati Patel 34:24 Unfortunately, this particular study found that the standing orders or the protocols or the CPA led mechanisms had little effect, and we're not sure exactly why that was the case. Is there more training requirement, the reporting requirement, additional registrations and stuff that prevented pharmacies from actually registering, versus if you and I, Dr. Kane had authority to prescribe Naloxone, we'll pull out our pad and, you know, prescribe Naloxone and save a life. So I think that's that's probably why they're seeing this difference. But this is the first of the study that kind of come. Pair two different mechanisms, Dr. Sean Kane 35:02 and Dr. Patel, do we have any other data besides that 2019 study? Dr. Khyati Patel 35:06 Yeah, you know, 2017 and 2018 a couple different groups, looked at decrease in opioid deaths and found anywhere between 9% to 14% reduction there. But the most controversial report came out from another 2019 study by Doleac and Mukherjee that actually produced opposite results. They found that these Naloxone access laws have resulted into more ER visits, more opioid related deaths, and so no reduction in the opioid death. And you know, this has stirred some controversies in the medical community as well, as, you know, in news community, but there's been some healthy debates about, what are we doing by increasing the naloxone access laws? Is it really effective in preventing deaths, or is it really allowing people to use more opioids and kind of conduct these opioid overdoses, knowing that there there is plenty of naloxone out there if they needed to be saved, and we don't know the answer to that yet. Dr. Sean Kane 36:13 What about data related to pharmacy implementation of these new laws and things like that, is pharmacy pulling our weight in terms of getting Naloxone into the hands of patients so that we potentially could see a benefit by giving this drug to patients that need it. Dr. Khyati Patel 36:28 Yeah, and they know on paper, the states can say, Yes, we do have this Naloxone access law. Yes, we do have this, you know, prescribing authority, or, you know, collaborative agreement where patients can get it from the pharmacy. But is that implementation really happening? Is there clear communication to the pharmacies? And what we found based on some secret shopping studies that this wasn't the case, the rollout hasn't been as as good as it should be. For example, about 24% of 1100 some California pharmacies, which is, by the way, the state that has Naloxone access law dispensing via pharmacy available. Only 23% of these pharmacies knew that Naloxone available to be dispensed via without prescription. So again, this was kind of like ignorance on the side of pharmacy staff that they didn't know that that was allowed. For example, in Pennsylvania, out of the 682 pharmacies, only 45% of the pharmacy had Naloxone to dispense under such authorization. Two thirds of the staff couldn't really answer the questions correctly. And when they asked what would be the price that they would pay for Naloxone, they were given quotes anywhere between $50 to $4,000 Dr. Sean Kane 37:46 oh my gosh, $4,000 Come on. Dr. Khyati Patel 37:49 So that tells you that the information is not sustained. There needs to be more improvement on whether it be pharmacy board or whether it be legislative bodies or public health departments that are working with pharmacies to implement such access laws, to have a clear communication and expectations. Dr. Sean Kane 38:08 And then, Dr. Patel, you know one other study that I know that you had mentioned to me earlier was in New York City, that about 38% of the 270 New York City pharmacies said that they had naloxone in stock and were willing to dispense it without a prescription. So again, more data showing that throughout the country, Pennsylvania, California, New York, despite having the laws in place, there is kind of a delay in having the pharmacy pick up slack and be able to be well informed and implement these laws that are on the books. Dr. Khyati Patel 38:43 That's true. And you know what? It really takes more so than having these communications and implementation kinks worked out. It's really, truly community partnership, and I'm going to toot our own horn, but we have an excellent program in our Lake County, Illinois area where our University is located, program that's supported by the Lake County Health Department called a way out. It's basically a non judgment free of cost program for patrons of Lake County who have opioid use disorders, who are willing to come clean and wanting to get help, medical treatment, they could come to any of the Lake County sheriff's offices or participating police departments in the county to seek help, in addition to health department as well as, you know, police departments, we have the District Attorney's Office, local treatment providers, local disposal agencies like swallow, which is the solid based agency of Lake County, research partners like departments of pharmacy and psychology at you know, Rosalind Franklin University are involved in this process, and overall, we are hoping to kind of collaborate and make a difference in. In this epidemic that we have been dealing with. Dr. Sean Kane 40:03 I think that's so important, because, as we've kind of alluded to, just having a lot on the books may not be enough. Having the prescription of naloxone being given to a patient may not be enough. It's probably a multimodal approach, which is kind of what you're saying, is that you need these programs that have lots of different arms to them, to really address the problem in a lot of different ways, and that's really the way that we're going to get out of this problem. Dr. Khyati Patel 40:28 Yeah, and just being involved from the research perspective, you know, with this program, I could tell that it really is a multimodal approach, and the problem as we know it is vast and rooted deep in our community, and it takes more than just one department or one organization to take care Dr. Sean Kane 40:48 of it. So kind of wrapping up today's episode. So some key points from today. Dr. Patel, what is your first key take home point that you'd love our audience to remember? Dr. Khyati Patel 40:59 Know that Naloxone, which is available in various different formulation, is a quick acting opioid reversal agent that's approved for use in opioid overdose cases. Dr. Sean Kane 41:09 And one thing for me that I didn't know that much about was that there are Naloxone access laws that are state specific, that allow patients or caregivers to get Naloxone and even administer Naloxone, potentially without even having an individual patient specific prescription. So there's a lot of different ways that a patient can can get that. Dr. Khyati Patel 41:28 Yeah, and these access laws would allow pharmacists to dispense Naloxone to patients without that individual prescription. And this is facilitated by either prescriptive authorities in the individual states, or mostly it's standing orders and protocol orders, as well as collaborative agreements, depending on the state. In order to implement this, there might be different requirements for registration, training, education and reporting. Dr. Sean Kane 41:56 And then finally, you know, dr, you mentioned you'd love to have a little bit more data, and I totally agree with you, but of the data that we do have, it would appear that we have some room for improvement in terms of getting more Naloxone out there in the community, as it relates to comparing it to the number of high dose opioid prescriptions that are given out. And of the data that we have, these new laws and new implementations probably do help to reduce opioid overdose deaths, but the data is a little bit muddy there. As you said, you'd like to have a little bit more data. In addition to that, we also see that implementation of these laws does have some opportunity for improvement, specifically related to educating pharmacies about these new laws and helping them implement these changes again, to get more Naloxone out there into the community, and Dr. Khyati Patel 42:41 that's absolutely right. And to our listeners, if you are interested in learning more about some of these laws, how to find Naloxone, some of the examples of such Naloxone protocols, we have references listed in the show notes. So please do visit those helpful sites, Dr. Sean Kane 42:57 and that's at HelixTalk.com and today's episode is number 127 so you can find it there. We're also on Twitter, at HelixTalk, and we love the five star reviews and iTunes. So keep those coming. So with that, I'm Dr. Kane Dr. Khyati Patel 43:10 and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 43:14 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store, search for HelixTalk and place your review there Narrator - ? 43:25 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.