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Presentation: Over the counter, down the hatch: OTC codeine use

Codeine up-scheduling workshop, Melbourne, 28 November 2017

16 January 2018

For further information about changes to medicines containing codeine, see the Codeine information hub.

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Presentation

  • Presented by: Dr Matthew Frei, Head, Drug and Alcohol, Monash University
  • Presented at: TGA workshop: Codeine up-scheduling, 28 November 2017
  • Presentation summary: This presentation provides an overview of OTC Codeine usage and pharmaceutical opioid addiction.

Transcript

Over the counter, down the hatch: OTC codeine use

Dr Matthew Frei
Clinical Director, Turing Point
Treatment - Research - Education

TGA workshop: Codeine up-scheduling, 28 November 2017

We are delighted to have Dr. Matthew Frei who is as the slide shows from an organization known as Turning Point, which is linked into Eastern Health here. Mow Matthew also has linkages with Monash University and is past president of a chapter of addiction medicine, and has also published and written more generally on codeine dependence. So, I think it's a good segue from the earlier talk about approaches to do with opioid using patients to actually focusing more specifically on the issue of dependence. Thank You Matthew.

Thanks for inviting me and thanks Pene and Malcolm's presentation. So, I'm I'm aware of time so some of what I talk about has been covered which is gratifying that nothing that's on my slide is contradictory to what anyone else has said. But it also means I can skip over and we can move closely to a discussion I guess.

So, I'm going to talk a bit about... I'm going to be nostalgic about codeine, talk a bit about pharmaceutical opioids, but again, I knew Malcolm would be here and cover most of that. Talk a bit about over-the-counter drugs because it's a really interesting area. Got a lot of pharmacists here as well and talk about management of codeine independence.

So, look I just wanted to reflect and when you're saying John before of the media on codeine, I mean codeine is like the issue that keeps on giving, I mean, in my work, I'm  moving on towards retirement, and looking at the stuff that I've done and what's asked, what gets asked about? And I worked in doctors' health and worked in methamphetamine and harm reduction. All anyone ever wants to talk about whenever there's a media inquiry to Eastern Health, and we get a lot of media inquiries to Eastern health. It's always about over-the-counter codeine. No one wants to talk about anything else in the media. I've done media training at Eastern Health just to cope with the codeine. Anyway, I can't think of anything that's more interesting to the general public than codeine, over-the-counter codeine, so it's going to be kind of sad when it goes. I won't have anything to do. I'll go into withdrawal.

So, it's still legal in the UK, over the counter in the UK. So anyway, I wanted to reflect going back about a decade and what happened back then was, we were seeing people coming. The hospitals all worked out as an addiction specialist and they were coming in with various gastroenterological conditions and sometimes renal conditions. And they were called by the gastroenterologist as an NSAID toxicity related presentation, and there was a really characteristic picture or fingerprint of how these people looked.

And there were a few things, and I'll go through some of the biochemistry that was part of these presentations. And the other thing was, they were coming and this guy's taking 24 over the counter or 48 and this was back in 2007. And this was of course related to pack size at the time of the popular product on the market, ibuprofen and codeine product. And this was the typical presentations.

Often it was a woman, but it was a middle-aged person or someone in their 50s who came in. Usually they're pretty grey and pallid and tired, and they were taking a lot of non-steroidals as I mentioned. And they usually started self-treatment of a chronic condition or a headache or something like that. And the gastros would say, it's this odd chap, and they would eventually get to drug and alcohol, but he's got an insert related gorosion, and this funny picture of overuse of non-steroidals and we don't know why he's taken so many non-steroidals. He's just taken this product called Nurofen Plus.

And this was the typical picture and I'll point to the potassium level. So, classic was like a low potassium, a blood loss anaemia and I'm taking 48 over-the-counter painkillers a day. So, it got to the stage where I'd only have to see the biochemistry and the FBE result and it became like a parlour trick. you know, that's a Nurofen Plus user. So that was the typical picture and I'll talk a bit more about this. They did really well on buprenorphine- naloxone. They did really well on Suboxone.

But before I talk a bit more about codeine, I just I don't think it's possible to discuss this without kind of looking at the whole issue of pharmaceutical opioids. And I won't go into great detail but I'll frame it first of all in the context of addiction medicine being an incredibly fascinating field and constantly changing and constantly moving and dynamic.

And what's happened in the last 15 or so years. And what's happened is people have gone from supporting one team to being multi drug users so you're not just a heroin addict and you don't use psychostimulants or alcohol or smoke pot. You use everything. So, polysubstance abuse has become the norm as people will know who work in drug and alcohol will camp come across drug and alcohol patients in the last five or so years.

There's been a growth psychostimulant use, crystalline methamphetamine that you will have seen on the news. There's a big change in cannabis. That's a whole presentation in itself and I won't talk about that but people used to roll joints in the old days and smoke joints. Now, if you go on the internet, you'll see the technology for using cannabis is absolutely extraordinary. It's become a whole science and that's probably driven by the United States and that states that have gone legal on medicinal cannabis and have gone legal on cannabis.

There's new devices because consumption, this is all a fascinating field. If I was talking to potential registrars, I'd be selling this much more. But there's new devices for consuming drugs like e-cigarettes and various vaporizers for using cannabis. There's growth in these drugs that you order over the internet or buy in sex shops which are called various things, such as novel psychoactive substances, which is this so-called synthetic cannabis, which is really just some foliage with some sort of weird offshore formulated drug of unknown constituents and potency sprayed onto it. But those formulations become very popular and they try to skirt around the law. And of course, there's pharmaceutical drugs of which opioids I'll just talk a bit about.

Andon the back of this, and for people like me working in drug and alcohol, what's happened in the start of the century is, we've gone, as people old enough to remember. I remember from a period in the nineties of abundant, especially in the east coast of Australia, the abundant cheap street markets of potent heroin that was killing about a Victorian a day, to at the start of the century, you can see a massive drop in overdose deaths, and there's some debate whether that's going to come up. And certainly, the discussion about what's going to happen with heroin often comes up when we talk about pharmaceutical opioids. Because people might know the experience in North America is as soon as real-time prescription monitoring and regulation and tamper resistant formulations, whatever, locking doctors up in jail for prescribing for murder and whatnot. When those things started happening and since those things started happening, the use of pharmaceutical opioids has decreased but the use of heroin, Mexican heroin particularly, has skyrocketed in the United States and there's great deal of concern.

What's the number of total deaths?

In the number of total deaths? I'm not sure. I when you add up heroin deaths and pharmaceutical opioid deaths, I think the Americans are very concerned about that. But you're talking about with regulation, the total number of deaths might have dropped. Yeah, sure. I certainly think we're seeing a change but it's a bit of a balloon squeezing I think, and there has been a boom in heroin, in a certain group who and American's got slightly different drivers, so I don't if we'll see it here, such as private insurance and so forth so people can't afford pharmaceutical opioids is the usual thing that people say, so they go to good old cheap heroin, and I think it's almost the opposite here.

So anyway, we've seen a drop in heroin deaths and around this throughout the century, and we've seen, and I know those charts look confusing, but we've seen basically a different …and I've seen this working in hospitals, a different proportion in the nature of presentations for opioids. And so, at the start of the century, you'd see opioid users come into a hospital into a hospital emergency department, most of them will be heroin overdoses, heroin related and poisoning, but now the majority are pharmaceutical periods and that's really all the take-home message from those charts is.

So that's a change. And this is like one slide to summarize really much more elegant and detailed way of what Malcolm discussed pharmaceutical opioids. And I'm not one of those people that think there's absolutely no place for pharmaceutical opioids in management of pain. However, for me, drug and alcohol work has changed a lot.  I work in a pain clinic in Caulfield and it's changed a lot since the management of pharmaceutical opioid dependence became a large part of our work and it's really challenging. It's burnt at least one of my colleagues out because this is a challenging group to work with in the drug and alcohol sphere, the people that present with pharmaceutical opioid addiction.

So, I'm biased and I see obviously the pointy end and the difficult end, and the times… You know I don't see people coming in… I have no problems, my doctor's happy, I'm happy everyone's happy with my use of opioids at a low dose. Managing my pain, I'm going to stop them next week. Everything's good, I only see the really horrible cases.

So, you know what I think it's fair to say is there's not a great deal, and you point out Malcolm, a great deal of evidence for the benefit of a long term pharmaceutical opioids at high doses in the management of chronic pain. There's not a lot long-term studies, I should say. And who wants to do long-term studies? I mean, you want to get your PhD over and knock it off in a short time. And it is a problem throughout medicine I think, particularly in drug and alcohol.

And the quote, I really like this quote. I saw this quote from the ex-director of the CDC, and I think it really sums up… but again I'm looking at it from maybe a jaundiced perspective.

So, from that, I just wanted to talk about the fascinating area of misuse of over-the-counter medications and then go on to a bit about coding and codeine treatment. And when I started looking, back in 2007, these people started wandering in, and good old Malcolm Dobbin tapped me on the shoulder and he said, you know you're seeing a lot of these. This is a really big issue. And I said, are you sure Malcolm? And my colleagues said to me, over-the-counter, it's not the big issue, why are you interested in this? And as I said, it became the most popular discussed issue in my career really.

So, before I before I did a study, and I'll go through it briefly in a moment, I started looking at the history of over-the-counter opioid use. And people may know this. The misuse of dextromethorphan, there's a bit of literature about that antitussive and and the ability for it to put you in some sort of stupid if you drink a super therapeutic amount of it. There's a lot out there about tampering. I don't know whether people have heard of cold water extraction, particularly with codeine combination formulations, so there's quite a hot science and fascination in the community around what you can do with over-the-counter medications. There's even now reports dripping in, the toxicologists tell me, about misuse of Imodium.

So, taking about fifty times the regular dose of Loperamide is supposed to have some of euphoria associated with it. And then the other things, other than conversion of pseudoephedrine  into methamphetamine, is the conversion of codeine products into morphine, a crude form of morphine, which is not so popular in Australia; it has been done but  certainly the New Zealanders love to do this. They're very clever at doing this stuff because they don't have heroin in New Zealand.

So, that's my summary of the world of over-the-counter ingenuity, and this is a  picture… and I've shown this picture in various forums before. This fellow came into the ED at Box Hill actually, and he'd been ordering diphenhydramine gel caps. So this was a guy that was injecting. So, if Malcolm Dobbin lobbies with the TGA to get  Temazepam gel caps taken off the market, what else have you got but diphenhydramine gel caps? So, people are yet very ingenious in the way they misuse over-the-counter drugs.

The other thing I want to say is we've got a very strong history in Australia of over-the-counter, a bit like the English, and the New Zealanders. It's a colonial thing I guess. As people may know, we've had some ground-breaking work done by Priscilla Kincaid-Smith in analgesic nephropathy from Beck's powders back in the 60s, from phenacetin. So, it's a culture tradition in Australia is what I wanted to say.

And this is just some national household drug survey statistics, again supporting the idea that Australians are very keen on non-medical use of opioids and over-the-counter opioids in particular with codeine being very highly represented in the National Household drug survey as a drug that people report using in a non-medical way.

And again, in order to get through my presentation, you might see things on the slide that I don't go into and I'm happy to answer questions about it, but I will keep moving.

So, what about codeine? And again, I think Malcolm mentioned that codeine is methyl morphine and it's a mild opioid. I would consider it a crap opioid, a mediocre opioid and I think Pene was talking about the number needed to treat, and again Malcolm gave me these…Malcolm Dobbin gave me this information, and a lot of what Malcolm would have submitted, along with myself and other people who are interested in this issue when the TGA came to review scheduling of coding, was the idea that codeine wasn't much better in doses that are available over-the-counter than  simple analgesics than paracetamol or paracetamol and ibuprofen or ibuprofen.

And it's already been mentioned that there's the other issue with the mediocre opioid that is codeine, I think, is that it's not very potent, is there's variations in the way people metabolize that. As Pene was saying, there's concern with children in Eastern health with their pain? We've been through a pain Advisory Committee that I sit on. We've been through a process of taking codeine off the formula for kids. ? been involved in that, and that's based on the information, I think that was presented earlier on, and the fact that children, don't use it for children, and again going to codeine being an issue that evokes a lot of passion as I think we've heard throughout the evening. That was a really controversial… you would think well let's pull codeine off the formula for kids. The children's done it, there's all this evidence, the resistance that we got, particularly form emergency departments was extraordinary, so  it is an issue that evokes some  passion and anger.

So, a lot of the information, a lot of the research evidence about codeine goes to case studies, and there might be more than this now. And where I got involved was, as I said, with a study with Susie Nielsen and Malcolm Dobbin and Claire Tobin and myself. We collected some cases and we've got 27 cases together, the largest case study I think since then in looking at over-the-counter codeine. And it was all the one product and there was some characteristics. They're a bit like the pathognomonic sort of case that I presented earlier. This group tended to be people that started codeine for management pain.  More women, it was a different opioid presentation group than the traditional illicit opioid users because that's about three to two males to females. This was almost equal gender distribution. They were a bit older, they had little treatment contact before, and they had sort of three broad groups. A third had some sort of significant renal disturbance, a third had bleeding in the gut, and a third the primary presentation was, I'm addicted to codeine,

And as I mentioned, they had a good response to buprenorphine naloxone. And I used to say back then it's not actually so much about the codeine, it's about the two drugs mixed together. When we talk about ibuprofen codeine, it's about the combination. I don't know if people even know who Hall & Oates are, but all I can say is they were a music group back in the 70s, and they were generally considered better together than on their own, or more potent together and more influential.

And the coroner, and one of the drugs on the real-time prescription monitoring list, I think is codeine combination products, and this is in part because the literature review found that codeine is really well represented in multi drug toxicity deaths, and the coroners commented on it.

How am I going for time? I think I'm doing all right.

So, I just wanted to finish up talking a bit about the treatment of codeine dependence. And I've sort of talked about this and I've alluded to this idea that codeine users, and I think it's important coming into up scheduling, that we might see the people involved in a therapeutic clinical contact with this group, might see a slightly different group than maybe we're traditionally sort of expect from an opioid addicted person, an opioid dependent person. They tend to be a bit older, more often women. And the real interesting thing was this group often struggled to get into drug treatment because they had little contact with the drug and alcohol treatment services. They tended to be people who had never injected drugs, never used illicit opium. Some of them had never smoked a joint. They were very illicit drug use naive and treatment naïve.

They often, as I mentioned, self-started treatment for back pain or headaches or dysmenorrhea or whatever, and had a very good response to buprenorphine. And I think the reason I always thought people did well on Suboxone for codeine dependence and I imagine as people start to continue to present to treatment after up scheduling, they will continue to respond to buprenorphine therapy with therapy with buprenorphine naloxone or Suboxone. I think because the usual concerns about this therapy and it's much of an issue. It is cost competitive with buying a packet of codeine over-the-counter combination analgesics every day or two, and the inconvenience of going to a pharmacy every day is not a big issue for Suboxone because people that use over-the-counter codeine are often doing that to different pharmacies. And it's well-tolerated, particularly in compared to super therapeutic doses of ibuprofen containing analgesics, very well tolerated.

And I put that last point the risk of tapering, and again with up scheduling, it mind not be an issue. Often, people say to me, isn't one way of management of this getting people to taper down, and coming up to up scheduling, maybe that will be raised if they work in drug and alcohol. What about tapering and just reducing the dose? I usually caution people about that because I know of at least one death happening from that, because of course, if you're going from say 40 ibuprofen to 30, you're still at this toxic dose. And the death that I'm aware of with somebody who started to get abdominal pain while they were tapering and they were still taking massive doses and they had a perforation and died. And everyone just thought, oh they're just getting a withdrawal from the reduction in codeine.  So, I think that a better approach is to substitute buprenorphine-naloxone or methadone.

And so yes, we're up scheduling again and this is probably going to be the last time unless codeine combination products are made Schedule 8, and one of the reasons, I think is after the 2010 moved from S2 to S3, the move from the bargain bins and sold by anyone in the pharmacy to behind the counter was not in my experience, didn't make much change to presentations. There was a sort of still pretty much the same number of people. The only thing that changed was the pack size and the multiples of the pack size that people presented using.

And in the last couple of slides and the use of maintenance therapy or substitution therapy as I keep saying. I've said about a half a dozen times, really good response to buprenorphine-naloxone in this group. It seems just a very good therapy for people who are over-the-counter codeine or codeine.

I've spoken about cost and there's still an issue of stigma, and I think that's probably what makes Suboxone a bit more appealing to this group who are treatment naïve. Illicit drug use naïve perhaps and coming to a drug and alcohol service sometimes feels a bit uncomfortable being commenced on methadone, even if there's a clinical indication because of the stigma attached with methadone, which doesn't appear to be the same with Suboxone.

I've talked about the restrictive programs again with people going to a chemist every day anyway, it's probably not as much of a concern. The big issue since I started working this area, the big issue with pharmacotherapy prescribing and treatment is the number of prescribers in the community in rural, regional areas. It's also probably the number of dispensing points, but the real pressure point is on the number of prescribers. The point of those pictures is we've got a distorted system where there's a few big high-volume prescribers of these medications, these opioid substitution medications: Suboxone or buprenorphine and methadone who carry most of the state's cohort of people on this treatment. The good news about that is people who are general practitioners may know or may be involved in the fact that the policy in Victoria now allows you to have up to five patients without doing all the fancy training in opioid pharmacotherapy, prescribing five patients on Suboxone. So, the rules in Victoria the guidelines or policy in Victoria say you don't have to do a lot of training to prescribe up to five people in your practice Suboxone. Anybody can do, it any GP can do it.

But we still have a distorted system as it happens, even though that policy has been around for some years, and I was involved in the development of that policy. It hasn't been taken up and so there's still that small cohort of doctors who are getting older, and I don't think that they're getting old, they're looking towards retirement, and I don't think we've got a succession plan, so it's all it's going to take is a few of those doctors to drop out and I think we're going to face some real challenges in Victoria.

I'll finish up there. It's a Victorian audience and so just people are familiar with Drug and Alcohol Clinical Advisory service. We get a lot of calls, that's part of Turning Point so it's part of my responsibility. So that's a 24-hour phone advisory service on drug and alcohol, completely free. You can ring at any time, any clinician in Victoria can ring any time to get advice on what to do about any sort of drug and alcohol related issue. And that's maybe what you're referring to Malcolm when you said there's a drug and alcohol phone service but no phone pain service. We get a lot of pain calls again and we do we audit the calls every month, and we often say, where's the addiction issue? Well there's no real addiction issue but they're on a very high dose of Fentanyl or something like that. So, anyway that's DACAS and if you don't know about it, you do know about DACAS now.

So, look, I'll finish there. Malcolm has already touched on tamper resistant or abuse deterrent forms of opioids, and I don't think they've been a big game-changer either. I think what will be a game-changer is what's going to happen in the next year or two. I think it's already happened in the United States, is a depot form of buprenorphine, so that's really going to change a whole lot of things around buprenorphine therapy. But the positive side is, it's going to give us a lot more options anyway.

I've mentioned the regulations and the fashion in the United States to go hard on opioid prescribers in the medical profession, and I think the other big game-changer is going to be real-time prescription monitoring that Malcolm's mentioned. So, I might finish up there and I think we've got time for a question or two perhaps.

There's another panel at the end but why don't we stay here, please Matthew. Any questions for Matthew?

[Question partly inaudible] We have this fear as a GP that we're going to be inundated by people walking in who are taking 50 over the counter tablets. What are they going to do now? This is our greatest fear. So, I still don't have a sense of how many patients… [Inaudible]…because I think there'll be people that we don't know about, that none of us know about. How many of these people go around to different doctors and pharmacies. And so, we're very worried about, what are we going to do with these people who are on 50 codeine tablets? What are we going to do with them? [Inaudible] This is the problem. We're really concerned that the people we usually get advice from or refer people to…[Inaudible] I might be a catastrophiser in this situation…

I personally… I if I was to bet on it, you know gamble on this issue, Turning Point is also a gambling centre so I don't gamble, but I don't think …I think it'd be great if … you know cause a revolution and I honestly don't think you'll be inundated. It'll be a trickle, it'll be like turning a big ship but that's my view. Look, I might be wrong, part of the new guidelines, the policy for opioid pharmacotherapy, was to change the culture of prescribing take away doses. That was part of the role of the revision of the Victorian policy on pharmacotherapy, and I think they're similar. That was going to be a slow culture change. Look, I might be wrong on this, I don't think suddenly someone's going to wake up on the 2nd of February saying I've got no codeine left and rush to their doctor.

But in answer to your question, I think prescribing Suboxone is very straightforward, it really is if you've prescribed a full opioid agonist. I really think prescribing it. The doctor's role is very straightforward. I think it's a very easy. forgiving drug to prescribe. and I think the behaviours surrounding dependence is very challenging, but the pharmacology of that drug is very straightforward, and if you can prescribe a Schedule 8 opioid, it's very much easier to prescribe that particular Schedule 8 partial agonist drug.

But I don't think you'll be inundated. That's my view. People might differ, I can see people shaking their heads, but just from my experience, the human behaviour is such that people will stockpile. People will detox before the date and so there'll be a change in the culture of the nature of codeine use and the way people present to GPs around that issue, but it won't happen in in February. It will happen over years.

[Inaudible question]

Yeah but I'm sure I think that's different.

Can I do a .. for the pharmacotherapy based networks. So, Victoria is divided up into five networks. It covers the whole state of Victoria and our role is to support GPs in prescribing Suboxone and supporting them with managing dependence. So, depending on where you are, there's a pharmacotherapy network that covers you so it would be good to perhaps link in with them. And some of them are here tonight.

You need to go the government website… [Inaudible] and then you'll find everything on pharmacotherapy, and you'll find the networks. [Inaudible]. And there's a four- page cheat sheet on telling doctors what's been done before. There's plenty of resources [Inaudible]

And Maureen would agree that it's not surprising that not everybody knows about the five. It's a small government department and it's probably up to Maureen to tell every GP in the state.

[Inaudible question]

And also, ? have their own website too so you  can just in your postcode and it will tell you who your support person is. So, I'll send the TGA guys a link and they can give some feedback.

So, we can add a whole host of other links we already have on the codeine information hub that we have to other external parties so we can reference some other information.

There's a question here.

I hate to admit this but I recall those APC issues very, very well so that tells you a few things. I've been in the drug regulatory business for pretty well my adult life, and I think I can say pretty confidently that codeine was never much of a problem until it was combined with ibuprofen, not with codeine, with paracetamol, and we see this today that despite the fact that there's a larger amount of codeine phosphate in Panadeine extra, it's the ibuprofen combination that attracts more problems. What is it about that combination that has caused this huge upsurge? I think the genie was let out of a bottle when it was in Schedule 2, and as you said quite rightly, when it went to Schedule 3, it made a little bit of a difference initially but picked up again. So I don't know why it is that particular combination is being attractive to so many. Is it because [Inaudible]

Yeah it could be the Hall and Oates phenomenon and the combination is particularly appealing. I've had people that say I've had Oxycodone as Oxycontin and I prefer Nurofen plus to somebody who's Nurofen Plus dependent which was extraordinary. She said, I don't want Oxycontin any more, I'd rather be taking mega-doses of Nurofen plus, so I think if ibuprofen is more forgiving in chronic higher doses. It seems to be more tolerable and even though it's dreadfully damaging, people seem to have discomfort about taking high doses of paracetamol every day. But I don't quite know what the reason is but you're right, it wasn't until that combination came along but it was marketed well and it was pushed by a company that you is renowned for pushing.

Go straight to the side of pushing.

[Inaudible question]

From an acute pain perspective, there is an advantage of high-dose non-steroids. It penetrates the brain, the neuro inflammatory component and is quite effective as an analgesic in high doses. It prevents dementia. It takes out your gut but you've got a good brain to go with it.

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