Push for more detail on COVID-19 oral antivirals impact

They were hailed as a potential ‘game-changer’ when the first clinical data came through.
 
But in the ever-evolving field of COVID-19 treatment, a group of senior pharmacists and clinicians involved in pandemic response have highlighted a ‘crucial’ need for more understanding of how new COVID-19 oral antivirals are performing.
 
Their editorial in Australian Prescriber, entitled ‘Oral antivirals for mild-moderate COVID‑19: a panacea or a logistical and clinical conundrum?’, was published this week.
 
It comes a little more than two months after the Therapeutic Goods Administration (TGA) gave provisional approval to the two new COVID-19 oral antivirals: molnupiravir, which is sold as Lagrevio; and nirmatrelvir plus ritonavir, which is sold as Paxlovid.
 
The medications became available last month, initially through the National Medical Stockpile, then molnupiravir was added to the list of medications funded on the Pharmaceutical Benefits Scheme (PBS).
 
The authors highlight how the drugs are now being used among a very different population to those who took part in the clinical trials, which showed a high efficacy in preventing hospitalisation.
 
‘The evidence of clinical effectiveness was mainly from a patient cohort that now forms only a small part of the community – unvaccinated people infected with the Delta variant,’ they write.
 
‘These rapid approvals create a situation where post-marketing surveillance is crucial to ensure any benefits are derived without harm.’
 
The initial clinical guidelines for both antivirals suggested that the medication should be targeted at unvaccinated recipients shortly after the onset of symptoms to prevent less severe COVID from progressing.
 
However, the guidance indicates the treatments can also be used irrespective of vaccination status for those at ‘high risk of severe disease on the basis of age and multiple risk factors’.
 
The authors state that the drugs are now being used among patients who have had two COVID-19 vaccine doses but who have not yet had a booster.
 
‘It is unknown whether the drugs will remain clinically effective or cost-effective in these people,’ they write.
 
The editorial pushes for greater understanding of treatment outcomes for this wider range of recipients, with the writers describing it as ‘essential’ to ensure the medications are put to the best clinical use.
 
They say the TGA approval and PBS listing are leading to ‘a significant shift’ in the management of COVID-19 patients but warn it could increase ‘the risk of medical misadventure’.
 
‘Comprehensive guidelines and decision support for GPs and community pharmacists are required to ensure the safe use of these oral antiviral drugs, particularly in relation to drug interactions,’ they write.
 
It is also suggested that the rapid early distribution of the drugs to vulnerable populations could have caused harm due to a lack of oversight.
 
The authors reference a shift in prescribing the oral drugs from specialised COVID-19 units to primary care to improve access in regional, rural and remote areas of the country.
 
‘The PBS criteria ideally should complement the national evidence-based COVID-19 Living Guidelines to prevent inequity of access and the use of drugs in patients who are unlikely to benefit,’ the article reads.
 
‘However, the rapid distribution of oral drugs directly to residential aged care and health services for Aboriginal and Torres Strait Islander people, while intended to enable immediate access for vulnerable patient groups, may also have increased risks through a lack of guidance and education to support appropriate prescribing.
 
‘These risks need to be mitigated.’
 
The authors also highlighted the lack of head-to-head studies on the efficacy of the two oral antivirals, which they say would ‘guide treatment recommendations and delineate which patient groups should have priority access to the new oral drugs’.
 
In a Good GP podcast episode dedicated to antivirals recorded on 15 March, the role of general practice in prescribing was described as ‘quite crucial’ by infectious diseases physician Dr Claire Italiano.
 
‘These medicines are intended as early treatment, with the intention they will prevent or minimise the chances of progressing to severe disease and hospitalisation,’ Dr Italiano said. ‘So it is really in that community setting that we would want to be getting in early with these treatments.’
 
She said the oral antivirals are targeted at symptomatic, ‘at risk’ patients.
 
‘The actual at-risk group of people is evolving a bit because the early studies were only done in unvaccinated people, and obviously now in Australia fortunately we have a highly vaccinated population who may not be at risk as much as when they were unvaccinated.’
 
Immunosuppression and comorbidities such as diabetes and heart disease are among the risk factors, she said.
 
‘We consider the Paxlovid to be superior to the molnupiravir in its efficacy,’ Dr Italiano said, while highlighting a number of contraindications, including certain drug interactions that could prevent the use of the oral antivirals.
 
The podcast contributors also said the Department of Health, which is overseeing the supply of the oral antivirals, had asked state-based providers to report on their use, including whether patients had improved or needed further escalated.
 
A total of 500,000 courses of nirmatrelvir plus ritonavir, which was developed by Pfizer, have been ordered by the Federal Government.
 
Meanwhile an order of 300,000 courses of the Merck-developed molnupiravir was confirmed in October.
 
This week, the National COVID Clinical Evidence Taskforce released a new risk classification tool for those with COVID to help guide treatment.
 
A guide featuring information GPs need to know about the oral antivirals was published by newsGP last month.
 
The RACGP has a regularly updated online list of COVID-19 resources, including relevant information for each state and territory.
 
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antivirals COVID-19 Lagevrio molnupiravir nirmatrelvir plus ritonavir Paxlovid