Top 10 drugs 2020-21

Welcome to Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

I'm Dhineli Perera, your host for this episode. And it's a pleasure to be speaking to Dr John Dowden. John is the Editor in Chief of Australian Prescriber. He's also a Founding Director of Therapeutic Guidelines Limited. He's here today to chat about the top 10 drugs for 2020 and 2021, which have been published in the December edition of Australian Prescriber. John, welcome to the program.

Hello.

So John, this is a bit of a rolling tradition each year for Australian Prescriber to publish the data for the top 10 drugs. I thought we should firstly touch on what each table represents and where the data comes from.

Thanks Dhineli. At this time of the year it's always good to reflect on what's been happening in the world of prescribing and Australian Prescriber's now been publishing the top 10 lists since the mid-1990s, and should probably begin by acknowledging our colleagues at the Department of Health who supply the data from the Pharmaceutical Benefits Scheme and the Repatriation Benefits Scheme.

So the information is presented as top 10s, first by prescription count (so the number of prescriptions), by cost, and then defined daily dose per 1000 population. Now that last unit of measurement is a maintenance dose of the number of people per 1000 who are taking a regular dose of a particular medicine each day during the day. So the reason we have defined daily doses is that, if you think about antibiotics, you're probably going to get a course of a week. So they may be frequently prescribed, but they wouldn't show up in the defined daily doses per 1000 population because people aren't taking them every day throughout the year.

Right. So that's for antibiotics. And I guess there are other medications that fall into that bracket as well.

Sure. It's interesting, Dhineli, looking back over the years we've been doing this, that when you look at defined daily dose per 1000 population that there's not a single drug which was on the top 10, when we started publishing these lists back in about 1994. There's not a single drug still in the top 10. So back then it was drugs such as salbutamol and frusemide (or furosemide), whereas now the top two are statins.

Yeah. It's definitely been a big shift and that's coming up to 30 years since then. So I guess that's not too surprising that there's been such a dramatic shift, especially when it comes to cost as well. And comparing tables one and two at a glance, there are some obvious similarities. The statins for example, atorvastatin, rosuvastatin sort of rule the roost on both of them. Are there any surprises for you there?

Well, the statins were also top last year by prescription count. And you'll see from the figures that this year there're over 14 million prescriptions for rosuvastatin and over 11 million for atorvastatin. So there's a lot being prescribed. The prescription count positions 3 and 4 are taken up by proton pump inhibitors. Also in the top 10 there's another two cardiovascular drugs plus metformin. One change from last year is that amoxicillin has dropped out of the top 10 by prescription counts.

Was that amoxicillin on its own or with clavulanic last year?

That was on its own.

That's interesting. So one of the standout differences I noted was that the PPIs were quite high on the list by prescription count, but didn't make it to the top 10 ranked by DDDs. Why do you think that might be the case?

Well, I’ll have to speculate a little bit there, Dhineli. The defined daily dose isn't necessarily the recommended dose. It's a sort of estimate if you like of the average maintenance dose. So with the PPIs, it's possible that you get a lot of prescriptions just for short-term use.

Yeah. And PRN usage as well, I'd assume this too as well?

Yeah.

Yeah. So I guess that's one way to help listeners to really differentiate between the DDD table as well as the prescription count, where you've got sort of a difference between regular daily doses versus PRNs or short courses and things like that.

And the other classes that have similar positions on both lists are the ACE inhibitors and AT2 inhibitors. Besides their use in hypertension, which comorbidities in your opinion, do you think really drive their frequency of use?

Well from the statistics on utilisation, we don't really have information on the indication. There are obviously other databases that can give us some information about indications, but the ACE inhibitors and the statins have a broad range of indications. I think hypertension's probably going to be the main use still, but they're also used in heart failure for reducing progression of renal disease and also for managing risk cardiovascular events. There's quite a broad use. So when you put it all together, looking at prescription counts, you've got the statins there, you've got drugs for hypertension, heart failure. So prescribers are seeing a lot of cardiovascular disease.

Yeah. And I guess that pattern's not changing. It'll be interesting to see how that does shift or if that shifts in the next decade or two as well. When you compare, as you've said to 1994, where they weren't really making as much of their presence felt and when they didn't exist some of them. And so it will be very interesting to see if there's a shift.

Yeah. While we're speculating, in the prescription counts, I noticed this year compared to last year there'd been a change in antidepressant prescribing. So escitalopram and sertraline have both moved up the list of top 10 by prescription counts. For escitalopram prescriptions went up from 4.9 million last year to 5.4 million this year. With sertraline, that increased from 4.7 million to 5.1 million. So there could be a variety of reasons for these changes, but you could speculate that during the pandemic in lockdown, has there been increased prescribing? So that might be something for a pharmaco-epidemiologist to look at. But you'll see that sertraline also made it into the top 10 by defined daily doses, so 27 people per 1000 population per day taking sertraline.

Yeah. Well, it wouldn't be surprising would it, when you remember the amount of coverage we did see explaining that the demand on services for mental health supports really did increase over the last two years. So yeah, very interesting to see whether it shifts back down again or persists and plateaus out over the next 12 months. And I will put my antimicrobial stewardship hat on for a moment and say I'm relieved to see that there are no broad-spectrum antibiotics that have made their way to the top 10 lists. If we wound back a few decades ago, would that have been a different story? Was there many more antibiotics that made an appearance in the top 10 lists?

Sure. As I said earlier, amoxicillin has dropped out of the top 10 and cefalexin is still there, but the number of prescriptions has fallen. If we go back again, as we did earlier to 1994, in the top 10 by prescription counts, number 1 back then was amoxicillin. And also in the top 10 was amoxicillin with clavulanic acid and also doxycycline. So now as you can see, there's only one antibiotic in the top 10 by prescription count.

So the drug that takes out, I guess the undesirable position of most expensive drug to the government is aflibercept. And it's used for different types of macular degeneration. Does it surprise you to see an ophthalmic drug take out first place?

No, because it's been there over a few years now. I think the number of prescriptions is relatively small, but it's obviously expensive. But we have to say about the cost to government top 10, that this is, if you like, the headline cost because behind the scenes there's various agreements about risk sharing price volume agreements. So although we're publishing the total cost, there may be rebates involved depending on how the drug has been used and what terms have been negotiated. So the true cost might not be the published cost.

So the actual out of pocket cost is different for the government perhaps than what we can see. And I guess the fact that 7 out of 10 of the most expensive PBS drugs are monoclonal antibodies, and that would be a less surprising fact, when did you first see these agents make their appearance on this list and has it been a gradual shift or more abrupt?

I think it's been gradual. When I've looked back at the data, I think we first saw the monoclonal antibodies appearing in the top 10 by cost around about 2009, 2010. Rituximab, for some of the rheumatic disorders, was one of the first and another one is ranibizumab, which is still in the top 10 today, which as you know is also used in treating macular degeneration.

And so then you've got apixaban standing out as a lone-soldier NOAC in the middle of the top 10 drugs by cost. What do you think sets this agent apart from the other NOACs, which don't seem to make that same appearance?

Yeah, again, that would require some speculation as to why that particular drug is where it is. Clearly in guidelines it's recommended for its role in prophylaxis, say around the time of orthopaedic surgery. It can be used in atrial fibrillation, it can be used in the treatment of venous thrombosis, and it has the advantage of being oral. Why it stands out from its competitors in terms of the top 10 by cost, I'm not sure. Apixaban is the most prescribed of all the drugs in the top 10 by cost where it had over 3 million prescriptions.

I wonder again, speculating from my end, whether it's got to do with the fact that interactions are a bit less with it. And there's options for dosing in renal impairment and the elderly and some of the other NOACs have that as well. But just from on the ground experience, I do note that apixaban tends to be a little less interacting with the other drugs, which is why we sometimes have to shift people across to it as well. But it would be interesting to see whether that maintains its place in that list.

And over the years, John, have you seen drugs on the top 10 list that were consistently prescribed frequently that gradually or suddenly disappeared? So I think you've touched on things from 1994, like salbutamol and frusemide (furosemide), but in more recent years, have there been shifts that you'd like to comment on?

Well, one I would like to mention is change over the last few years. And I think this is where you can view expenditure on pharmaceutical benefits as an investment. And that's in the antiviral drugs for hepatitis C. They appeared in the top 10 by cost over a number of years, but they've now disappeared. And it would be good to think that that's because that investment has paid off in that we're now seeing less hepatitis C and therefore there's less need for the antiviral drugs. And hence they've dropped out of the top 10.

That's a very good point. I'd be interested to see data on the incidence of hepatitis C over those sort of years, especially overlaying that cost and investment, as you've said. And John, what do you think are some of the changes you predict will be seen in the lists for the next year?

Well, I can confidently predict that we'll be seeing more high-cost drugs. Back when we started publishing these lists, the cost of the Pharmaceutical Benefits Scheme was about $2 billion. It's probably over $12 billion now. So there's certainly been a move to these high-cost drugs. So a new entry in this year's top 10 is ocrelizumab, which is used in multiple sclerosis. So although the headline cost was $175 million, there are only actually 10,000 prescriptions. So that gives you an idea that these new drugs, particularly the mabs, they are expensive. But they may only benefit a small number of patients. And I think increasingly if you read the New Drugs section of Australian prescriber, you'll see that there are a lot of monoclonal antibodies being approved for use in conditions, which are quite uncommon. So the likelihood is that there'll be low volume, but potentially high cost.

That's the sort of change that we've seen over the 25 years or so that we've been doing this. The original top 10s were high-volume drugs which cost the most because they were the most prescribed. Whereas now we've seen the high-volume drugs not really appearing in the top 10 by cost have been replaced by low-volume, high-cost drugs. So I would predict that that trend will continue that when we're talking next year, the top 10 by cost will still be mabs, monoclonal antibodies. And I would suspect that the figures for prescription counts and top 10 by defined daily dose per 1000 population will be pretty much the same because we'll still be treating a lot of cardiovascular disease next year as well.

Yes, of course that's unlikely to shift, isn't it? But one thing, I guess it would be amiss to not mention drugs used for COVID. Because they're not on the PBS and they're sort of costs that are borne by the hospital, they're not going to be captured in these lists, are they? So things like sotrovimab, tocilizumab for COVID versus rheumatoid baracitinib, remdesivir, those drugs won't appear on this, given that they're non PBS drugs, is that correct?

They may not appear because also the numbers probably aren't going to be great. To get in the top 10 by prescription counts, you've got to have over 4 million prescriptions. So it's unlikely that there would be... and we hope that it's not the case that we have millions of prescriptions.

Yeah. It would be interesting data to pull in as well, given that, as you've said, they are the high-cost, low-volume groups of drugs that we seem to be using more of. And it also sort of explains the complexity of the PBS. And it's not just as simple as this is the cost, this is your co-payment and everything else comes out of the government. It's far, far more complicated than that.

Yes. People who want to find out more about these sort of expensive and hard-to-pronounce drugs are very welcome to go to the Australian Prescriber website and read about how they work and what their role is. As you know, every issue we review the new drugs which have been approved for use in Australia. So it's always worth checking out to see what's coming.

Excellent. Thank you, John. Thanks so much for your time.

Thank you, Dhineli.

[Music]

The views of the hosts and guests on the podcasts are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.