• 28 Jul 2022
  • 30 min 40 sec
  • 28 Jul 2022
  • 30 min 40 sec

Dr Caroline West, medical adviser and GP, NPS MedicineWise talks to Professor Sarah Hilmer and Associate Professor Charlotte Hespe about the use of oral COVID antivirals in vulnerable people.

Further reading

RADAR: Changes to COVID-19 oral antiviral PBS eligibility criteria – July 2022
Changes expand access to more people with mild-to-moderate COVID-19, at high risk of progressing to severe disease.

Factsheet: Oral COVID-19 medicines

Transcript

Dr. Caroline West:
Hello and welcome. I'm Dr. Caroline West and I'm a GP and a medical advisor for NPS MedicineWise. In Australia, with winter well underway, we're currently heading into the next surge of COVID with around 350,000 current active cases. Now they're official figures, of course, and the true number is estimated to be way, way higher. Omicron BA.5 is now the predominant strain in Australia, and there are concerns that this variant in particular targets the lower respiratory system a bit like Delta did. Obviously, preventing serious infection and hospitalizations are a key priority, and the use of oral COVID antivirals in vulnerable people could literally mean the difference between life and death for some. In a welcome move as of July 2022, access to these oral COVID medications has been expanded. To take us through the latest changes, I'll be talking to two experts. First up on the show. I'll be chatting with Professor Sarah Hilmer, who's a geriatrician and a clinical pharmacologist at Royal North Shore hospital and the University of Sydney. She's also a member of the Guideline Leadership Group of the COVID-19 Clinical Evidence Task Force. Then later in the show, I'll be talking with Associate Professor Charlotte Hespe, a GP and Chair of the New South Wales ACT, RACGP, for her perspectives on general practice with what's happening out there, what's happening with expanded access. There have been no conflicts of interest declared. So first up, I'd like to welcome Sarah to the show. Thanks for being with us. Can I start by asking you, Sarah? I know we talked to you back in February. A lot has changed since then, but where are we at in terms of managing COVID?

Professor Sarah Hilmer: 
Well, Caroline, I think where we're at is that we have a very highly vaccinated population, and we also have a lot of therapies that are actually highly effective for early disease, as well as the therapies that are available if someone does get sick and wind up in hospital.

Dr. Caroline West:
It's interesting to see that access has now been expanded for vulnerable groups. What are the changes to start off with that health professionals need to know about?

Professor Sarah Hilmer:
Thanks, Caroline. So, the access for the two oral antivirals that are available in the community for people who are within their first five days of COVID-19 symptoms has expanded, and those two drugs are Nirmatrelvir plus Ritonavir or Paxlovid and Molnupiravir or Lagevrio. Now the first big change is that there's no longer a requirement to have less than two doses of the vaccine, and this is partly because almost everybody has at least one dose of the vaccine in our community. It's also because it's been shown that addition of the antivirals to vaccination does give additional benefit. The antivirals are now available to all people aged over 70, to people aged over 50 with at least two risk factors for severe disease, to Aboriginal and Torres Strait Islander people aged over 30 who have two or more risk factors for disease and to people with what we call immuno-compromising conditions who are aged 18 and over.

Dr. Caroline West:
I guess the big question is why has this access actually been expanded? What's the thinking there?

Professor Sarah Hilmer:
As I mentioned, there is additional benefit from using the antivirals on top of vaccination. Initially when we had the antivirals, we had one randomized control trial for each sponsored by the drug company. Now we have some real-world data that suggests that they do actually work almost as well as we thought they would. It's other things that have changed, that we have plenty of drug supply at the moment, so we can use them more widely, not just on the absolutely highest risk people but on the second tier of people also at high risk. It's become clearer who really is at high risk from the real-world data. The final point is that our hospitals are really full at the moment, and anything that works even a little bit to keep people out of hospital is considered beneficial.

Dr. Caroline West:
You mentioned there that you've got real-world data on both of these medications that are available for use in Australia. What are the actual numbers looking like? What could a health professional talk to their patients about in terms of, "This is the advantage to you in taking this medication in terms of keeping you out of hospital, preventing serious illness?"

Professor Sarah Hilmer:
Yeah, look. I think it's worth just starting with a caveat. This is real-world data that's not from Australia. It's from Hong Kong. It's from Israel. It's from the US. These are large population studies where people have looked at routine healthcare data in thousands of people and seen what has happened in the first part of this year when the Omicron variants had been circulating. I should also have prefaced with the fact that a lot of this comes from preprints, so it's not peer-reviewed data, but the numbers look pretty consistent and look pretty good. If you look at the data from Hong Kong where they looked at people who were in hospitals, I think they put pretty much everyone in hospital but with mild disease, they found that you could reduce death, invasive mechanical ventilation and ICU as a combined endpoint by about 50% with Molnupiravir and by about 75% with Paxlovid. If you looked in Israel where they only had Paxlovid, they looked at people in the community with early disease. Amongst people age over 65, they could reduce hospitalization by about 75% and death by about 80%. Interestingly, when they looked at people who were 40 to 65, they didn't see a significant impact of the Paxlovid. If you look at the US, where they looked at people aged 50 and over with about a third aged over 65, using Paxlovid, they could reduce hospitalization by about 50%. It looks like in real-world settings; these drugs do work, and they seem to work better in people who are at higher risk of progression to severe disease.

Dr. Caroline West:
That's very convincing in terms of being an argument for considering these medications in vulnerable people. The other thing that caught my attention was I think you mentioned that people in that 40 to 65 group didn't really see benefit from these oral anti-COVID medications. That's useful to know, too, because I get asked, "Well, I'm 50 years old. I don't have any other risk factors, but why can't I get this drug as well?"

Professor Sarah Hilmer:
Yeah. I think the answer is that based on the evidence we have; it doesn't look like it would help you. Your risk of winding up in hospital is so low that this is unlikely to make a difference. It's also important to note that the absolute risk of going to hospital amongst people who take Paxlovid is less than 1%. We're not talking about a big absolute risk, but for an individual who's high-risk, that risk reduction is really important. On a population level, that risk reduction is really important.

Dr. Caroline West:
What other things do health professionals need to consider when they're managing people at home in the community with their COVID? Where do they draw the line with what other options could be considered apart from these medications?

Professor Sarah Hilmer:
Look, I think it's really important that GPs recognize that these two oral medications are an excellent start, but there are some patients who might actually need other options. There are other options available through your local health districts, through the hospitals. The big group that we see are people who have early mild disease, are at extremely high risk of progressing to severe disease and are not able to take Paxlovid because of either terrible renal function or critical drug interactions. The main groups, they really are the people with terrible renal disease who are taking immunosuppressants and some people with hematological conditions. It's worth bearing in mind that those people might be able to get intravenous Remdesivir through the hospitals, which seems to have similar efficacy to Paxlovid. Now it's not easy to organize. You've got to go into hospital for an intravenous infusion for three days in a row, but at the same time, if you've got someone who really is very high risk, who you can't give Paxlovid to and you think they need something more potent than Molnupiravir, it is an option, and you should talk to the person's treating specialist and the local health district.

Dr. Caroline West:
That's good advice. I'd like you to just pop your clinical pharmacology hat on for a minute, Sarah. Could you take us through some of the interactions, particularly with Paxlovid? I guess that GPs often will pull up the interaction list and go, "Oh good grief. There are just so many things on this list. Surely it's too high-risk for me to prescribe this medication because I'll just be creating more trouble." You talked about this back in February. Can you recap what your main messages are there to give us a bit of confidence with our prescribing?

Professor Sarah Hilmer:
Thanks, Caroline. I think there are two main groups of interactions to think about. There are the interactions which occur because the person is already on a CYP3A4 inducer, and there are the interactions that occur because the ritonavir blocks the CYP3A4. Let's talk about the inducers first. So, if someone is on a drug that induces CYP3A4, that will mean that they've made more enzyme. It takes a couple of weeks to make that enzyme, but then it also takes a couple of weeks for that enzyme to break down. The common drugs that would induce the CYP3A4 would be a lot of the anti-epileptics as well as St. John's Wart, which a lot of people are on over the counter and may not tell you about. Now if someone is on an inducer, then they really should not get Paxlovid because the Paxlovid won't work. The CYP3A4 will be so ramped up, and that extra enzyme will take so long to break down that they'll never get an adequate level of the Nirmatrelvir in their blood and the Paxlovid won't be effective. So, if someone's on inducer, Paxlovid is not a good option. It won't work. However, if someone is on a drug that is metabolized by CYP3A4, and you are going to give them the Paxlovid which includes the Ritonavir that blocks CYP3A4, you might be worried about the fact that they will then wind up with very high levels of their CYP3A4 substrates. Now that is an issue, but it's an issue that's quite manageable because a lot of the time, the drugs that people are on that are metabolized by CYP3A4 could just be dose-reduced or withheld for the five days that they're taking the Paxlovid. There's really detailed advice on the TGA product information and also on the Liverpool Drug Interaction Checker that we talked about last time that takes you through those processes. So just because someone is on a drug that's a substrate for CYP3A4, even if it's a drug with a narrow therapeutic index, you don't need to panic. You don't need to think, "Oh, they can't take Paxlovid." You just need to see what the management strategy is. A lot of the time it's simply a matter of withholding or dose-reducing that interacting drug.

Dr. Caroline West:
So given that expanded access now includes people in younger age groups, what is the story in terms of thinking about side effects? I know that these medications can't be used in pregnancy or with breastfeeding. What else do we need to think about?

Sarah Hilmer:
As younger people use these; we need to think not only about pregnancy and breastfeeding but also about conception. With both the Paxlovid and the Molnupiravir, you should use contraceptives while you are taking the medication and for I think four or five days afterwards. However, the Molnupiravir is unusual and has unusual implications for male conception. I mentioned last time that Molnupiravir works by inducing fatal mutations in the virus. It can also induce mutations in sperm, and sperm take two or three months to develop, so that means that men need to have strict contraception methods or not conceive for three months after they finish taking the Molnupiravir.

Dr. Caroline West:
I'll be talking later in the show to Charlotte Hespe who's a GP. It will be interesting to get her perspective on planning because what I'm hearing is that these conversations do take some time. It's a matter of going through somebody's medication list. Is there an opportunity in advance for GPs and other medical professionals to be looking at the medication chart now, seeing what's relevant, what could perhaps be deleted from the medication charts, no longer necessary? What are your thoughts?

Professor Sarah Hilmer:
I think that's a really good idea. Firstly, a medication review is never a waste of time. You'll always find something that either is no longer needed or actually something that's missing or something that could be optimized in terms of dose or formulation. I think being prepared for this is really important. At the moment when someone finds out that they have COVID, they're feeling sick, they're feeling worried. They need an immediate consultation. You have to squeeze them in for a tele consultation. It's not the time to go through a detailed list. Having a detailed medication list, going through those medications, thinking about what the COVID plan is, as well as thinking about how else you can optimize the medication list would be a really worthwhile consultation.

Dr. Caroline West:
Yeah, I like that, thinking of a COVID plan. It's a bit like the fire drill or talking to somebody if they've got heart disease and what happens if they get chest pain. These are the steps you need to take. I think that's a really important message about being proactive. Also, those that don't have a GP, being aware of whether they fit into the groups that actually can get access to these medications and set about to find a health professional who can have that consultation with them to see whether one of these medications would be useful.

Professor Sarah Hilmer:
Agreed. I think that can be really empowering because I think a lot of people with chronic disease who consider themselves or older people who are considered those high-risk are very worried. Having a plan, knowing exactly who to call, what to do, and what's going to happen when the time comes because unfortunately most of us are going to get COVID at some stage is actually very empowering.

Dr. Caroline West:
Fantastic. Well, that's a nice positive note to finish on, Sarah. So, thank you so much for sharing your thoughts with us today on the podcast and all of your expertise. I've been talking with Professor Sarah Hilmer, who's a geriatrician and clinical pharmacologist. Next up on the show, I'd like to welcome back Associate Professor Charlotte Hespe who's a GP and Chair of the New South Wales, ACT RACGP. I'm keen to get her perspective on what it's currently like out there in general practice with COVID and access to oral antivirals. Thanks once again, Sarah, for being with us. I'm sure we'll talk again soon because COVID just keeps keeping us on our toes, so it's very helpful to get this update on the expanded access of oral antivirals. Thank you.

Professor Sarah Hilmer:
My pleasure.

Dr Caroline West:
Now for the second part of our podcast on the oral anti-viral’s for COVID Associate Professor Charlotte Hespe is joining us. Now you may remember Charlotte because she joined us earlier in the year, back in February I believe when these medications were provisionally approved in Australia. Things have changes a lot since then. Associate Professor Charlotte Hespe is a practicing GP. She's the head of general practice at Notre Dame and chair of the New South Wales/ACT faculty of the RACGP. Thanks so much for joining us, Charlotte.

Associate Professor Charlotte Hespe:
Pleasure, Caroline.

Dr Caroline West:
A lot has changed with COVID. I guess a lot of people out there are hoping that it's all going go away. But with Omicron BA.4 and 5, we've certainly been kept on our toes. What's it like from your perspective out there in general practice at the moment?

Associate Professor Charlotte Hespe:
Oh, there's definitely a sense of everybody is over it and a fear of what the future holds if we're still like this two and a half years down the track from when the pandemic started. So yes, I think we're all fatigued, a bit burned out, and really wish that COVID had never come out of where it originated from.

Dr Caroline West:
Yes, I certainly echoed that sentiment. I think we're all feeling that. I guess though, now more than ever with this third wave on its way with winter upon us, COVID surging, it's never been more important to actually stay focused and actually explore the options for vulnerable groups of the expanded access for oral COVID medications.

Associate Professor Charlotte Hespe:
Absolutely.

Dr Caroline West:
What does this news mean for you and your practice?

Associate Professor Charlotte Hespe:
Yeah. No, absolutely. Look, I think that what's really important is remembering that the primary foundations of protection remain the same. So, we need to continue to push vaccination. We need to really push boosters. That two vaccines is absolutely not enough that people need to have three, and then the fourth if they qualify for a fourth. And again, that's been expanded, which is fantastic. And I'll sing it from the top of all of the buildings around me that the vaccine is the most important thing to do and the most protective. Then obviously we also need to do all of our protection about ourselves, which is about masks and hand washing and being appropriately isolated when we have symptoms of an upper respiratory tract infection. Again, people are a bit over masks. But unfortunately, they actually work. And we need to continue to use them and model it, particularly in the setting of general practice where like hospitals, we need to protect both ourselves as the workers, and more importantly in terms of vulnerability, those patients who might be needing to be seen face-to-face in our general practice setting.

Dr Caroline West:
Now, how can general practice actually prepare for the increased need for prescribing of these medications?

Associate Professor Charlotte Hespe:
Great question. I think the biggest thing we can do is actually sit down and think about who those patients might be, what they look like, and try to have some of those conversations more proactively. So how many patients do you have who are over 70 and therefore will automatically qualify to get a prescription if they get COVID? And how do we manage that as a practice in terms of communicating that to them, helping them have an increased health literacy around the need to be both rapidly diagnosed if they get a respiratory tract infection to whether it is COVID and therefore whether they need to be able to add the extra benefit of the antivirals, and what that might mean in terms of what other medications they have, what to do after hours, et cetera? Know your number in the first place. Then basically again, thinking about how you might do it is you might send out an email to everybody in that group and say, "This is what it means, and we would like you to come in and have a conversation about your choices, because there are two." We know that's Paxlovid or versus Molnupiravir. And it's really important that Paxlovid is actually considered as the first and the best option for everybody. And so, you need to have a conversation. Is that the right option for me as a patient? Or do I actually have medications that absolutely contraindicate me taking it? Or do I have renal function that means that I'm at risk? If that's the case, then I need to have a conversation about Molnupiravir. But much larger number of patients actually qualify for Paxlovid than I think. Some people thought, they it was a bit too hard. But once you get used to looking and doing a checking about what medicines you can and can't prescribe with it, and a lot of them, you can just defer. So, for instance, some statins. You can very easily ask somebody to stop taking a statin for five days. And it's much easier when somebody's not sick to actually have that conversation and maybe have a printout ready to go that actually gives them that information. And you may choose to put the prescription already there, ready to go to. I've been doing that for the conversations I've been having, because certainly I had a lot of people this week coming and saying, "Okay, so what happens if I get COVID? Which medicine and how do I get it?" So, we've gone through, we've chosen the right one for them. I put the script there ready so that if I'm not in the surgery, somebody else can easily see what that patient is ready and raring to use, and that they've actually already been educated about how to do it.

Dr Caroline West:
What about the scenario where a person is in the vulnerable risk group? So, they're eligible, but they don't have a regular GP and it's a Saturday morning. What are your thoughts on how they could access a script and a conversation?

Associate Professor Charlotte Hespe:
Okay. So again, it's about how do we educate the general public out there about A, the importance of having a regular GP? I think I've been well-known for standing there, waving my big flag of how important it is for healthcare, for people to have their own GP. And that doesn't just need to be your own GP, but pretty much the general practice that you go to for everything. If you don't have one, then now's a good time to do a bit of that planning. GPS are really hard to access at the moment, so it may be good to actually think, "Well, where have I been in the last two years? Which place do I think is good?" And being able to select them, find out what their access is. So again, it's called being prepared rather than waiting to get the infection. If, however, you aren't prepared and it is Saturday afternoon that you get that diagnosis, there are obviously easy-to-access general practices around the place, well easier, and/or acute care setting places, which hopefully people can either access. Or if there's not that long a timeframe and you've only just started getting symptoms, then maybe you're going to have to wait till you can actually get into a practice on a Monday. There's five days from when symptoms arise to starting the medication for it to be effective. We know it's better the sooner it's gotten. But actually, if somebody's sick, can't go searching for a general practice, it may be more appropriate to actually find a place that can see you on the Monday by telehealth rather than making it worse for everybody trying to find that place in the next day and a half.

Dr Caroline West:
How are you actually talking to people about what value there is with the oral antivirals?

Associate Professor Charlotte Hespe:
In terms of the benefit for antivirals? Yeah, I suppose when I'm having that conversation is that we are seeing an increased number of people needing to go into hospital and ending up in intensive care beds. We know that the biggest risk factor for that is actually age. So being aged in the 70s means that you are much higher risk of that happening. And similar to me encouraging everybody to go off and have a vaccine, I know that if we give you some medication, then the likelihood of you getting that much sicker is decreased again. It's not nearly as big a benefit as through the vaccine, but there is definitely a benefit to be had.

Dr Caroline West:
Yes. And I mean, the numbers are quite staggering. I know when we talked, it's only a matter of months ago, the numbers were way lower. I think the official number's up to 8 1/2 million Australians have officially had COVID now. The number's obviously way higher than that. But it's quite extraordinary how many people have now been infected by this virus and will probably be repeatedly infected with this virus.

Associate Professor Charlotte Hespe:
Absolutely. And so it's really great to know that we've got this feel like it's that backup buffer thing of, "Yes, I know I'm protected with the vaccine. I didn't want to get the virus. I've got it. Let's then just add that bit of extra insurance policy to keeping me out of hospital, and in particular, keeping me out of an intensive care unit.

Dr Caroline West:
Yep. And I know it's been a really tough time for everybody in the community. But clinicians in particular, you mentioned at the beginning, are really feeling it because there are a lot of demands on your time. How are you pacing yourself at the moment, Charlotte?

Associate Professor Charlotte Hespe:
Well, it's like anything, isn't it, Caroline? We can only do what we can do. And there's no point in getting overly anxious. Planned care is better than reactive care, so think about the things that keep you well and healthy. For me, it's about keeping up my exercise pattern, making sure I keep running, that I make sure that I've got enough time in the day to have a bit of a debriefing and family time, et cetera. So, I think everybody needs to remember that. You can never be responsible for everybody. And so, you just have to do what you can do. But systems really help. I'm a great advocate for systems of care. And that means that it's not just my responsibility, it's my whole practice. So, we, as a whole, are sending out these emails to our patients. They love it, can I say? They love getting something from us. And they love it because we're doing it in a language that lets them know both what is the current scenario, and how we as a practice are going to help them navigate these times and what they need to do. And we put it often in quite explicit steps about just, "These are the things you need to do. If it's out of hours, this is what we recommend you do," et cetera. And a couple of not too many emails, but just enough. So, you make sure that people have seen them. Same thing, make sure our reception staff are okay, because they're in the firing line. They get the anger and the frustration of people when they can't get easy access to care. And how do we make sure that they've got a backup? Where do they put the patient when they don't know what to do? And that we've always got somebody who's behind them to help them when they're feeling frazzled.

Dr Caroline West:
Yes. Very, very wise advice. So, thank you so much, Charlotte, to you and all the other GPS around Australia and the frontline workers, including as you say, reception staff, nursing staff. There are so many layers to providing wonderful care. So much, much appreciated. And thanks so much for your time too. I know that things have changed. They're going to continue to shift and keep us surprised and, on our toes, I think.

Associate Professor Charlotte Hespe:
We continue on that rollercoaster ride, Caroline.

Dr Caroline West:
We do continue on the rollercoaster ride, so I'm sure we'll touch base again into the future. But thanks for those really practical tips, particularly around planning. That really resonated for me, that idea of getting prepared, contacting your patients with clear lines of communication, so that when and if they do become unwell, that they know what to do.

Dr. Caroline West:
Thank you so much, Charlotte, for being with us on the show today. It's been fantastic to get your insights. What I've heard again and again is this importance of planning for COVID, talking with our patients early on in the piece before they have COVID to really get a sense of what they're currently taking, what would be an appropriate choice of medication if they're indeed in a vulnerable group. Of course, with expanded access, we'll need to be having more of those conversations to give people the best chance of reducing rates of hospitalization and serious infection. Thank you, too, to Professor Sarah Hilmer, who joined us earlier in the show for her perspectives as a geriatrician and a clinical pharmacologist. It's great to really get a sense of where we are going with this because so much is changing since I talked to both of our guests earlier in the year. Now, if anybody would like to get access to CPD points for this podcast, then please go to our website. Of course, NPS MedicineWise also has a terrific range of resources to help you understand what the changes are. To give you prompts to discuss with your patients, go to our website and look at our resources under Consumers and Health Professionals. Once again, thank you for being with us on this podcast today. I'm Caroline West. Bye for now.