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Molnupiravir to be used only as a last resort: Taskforce


Jolyon Attwooll


5/12/2022 6:59:09 PM

Advice has changed for the country’s most prescribed COVID-19 oral antiviral, although access via the PBS will remain in place.

Molnupiravir boxes
Molnupiravir has been widely prescribed since it first became available in Australia. (Image: AAP)

The oral antiviral drug most widely dispensed to treat vulnerable patients with COVID-19 should not be routinely used, the National COVID-19 Clinical Evidence Taskforce has advised.
 
The group updated its listing for molnupiravir (sold as Lagevrio) on Friday, after considering data from the large-scale PANORAMIC trial in the UK, which compared the impact of the treatment to standard care.
 
That analysis, which was published in October, looked at data from 25,000 patients, most of whom were older than 50. The randomised trial also included a group aged 18 and above with co-morbidities that increased their risk of severe illness.
 
Its researchers concluded that molnupiravir did not reduce hospitalisations or deaths among higher risk, vaccinated adults with COVID-19, even thought it did seem to prompt a faster recovery time, as well as reduced viral load.

As a result, the Taskforce said the trial results mean there is now ‘high certainty evidence’ that the treatment does not have an impact on hospitalisation or death in ‘multiply-vaccinated adults with mild COVID-19 and one or more risk factors for disease progression’.
 
It also said the trial underlines its existing stance towards nirmaltrelvir plus ritonavir (sold as Paxlovid) and remdesivir as the preferred antiviral treatments for mild COVID.
 
Professor Mark Morgan, the Chair of RACGP Expert Committee – Quality Care (REC–QC) and a member of the Taskforce’s guidelines leadership group, stressed the importance of using the most effective treatments and noted the implications of the PANORAMIC study.
 
‘In summary, molnupiravir did not work,’ he told newsGP.
 
‘The drug is an antiviral and seems to reduce viral load but that did not translate into saving people from severe disease.
 
‘I hope patients don’t miss out on effective treatments because of ongoing use of less effective treatments.’

The authors of the Taskforce rationale acknowledge evidence is less certain about the impact of molnupiravir in high-risk patients, including those with severe immunosuppression, and in residential aged care facilities.
 
They also noted that the full picture in similar high-risk settings remains unclear for other treatments, including nirmatrelvir plus ritonavir.
 
‘Current evidence provides greater certainty of clinical benefit for other antiviral agents in the broader population; therefore use of these other antivirals agents rather than molnupiravir is preferred,’ they wrote.
 
‘However, there may be specific circumstances for the highest risk patients, where all other treatment options are contraindicated or inappropriate, in which non-routine use of molnupiravir might be considered, in consultation with specialist clinicians where necessary.’

According to the most recent Department of Health and Aged Care (DoH) COVID-19 update, molnupiravir has been prescribed at more than three times the rate of nirmatrelvir and ritonavir overall, with 329,050 prescriptions dispensed compared to 96,020 as of 2 December.
 
While the latter is regarded as the most effective treatment, it also has a significant number of interactions with other drugs that make it substantially more complex to prescribe.
 
Because of this, Dr Anthony Marinucci, Chair of RACGP Specific Interests Aged Care, told newsGP the use of oral antivirals in this setting remains a ‘complicated issue’.
 
‘The PANORAMIC trial was carried out in a different population with a slightly different treatment model – eg specialist clinics for high risk individuals – so one must take care when extrapolating recommendations to a different cohort of patients – ie Australia,’ he said.
 
‘Compounding this, as mentioned in the communique, there is less evidence about the effect of molnupiravir in the highest risk patients and in residential aged care.
 
‘After careful consideration of the risks versus benefits, a shared decision-making process will be made to prescribe or not.’
 
Nonethelss, Dr Nick Simpson, a DoH medical advisor, noted an uplift in recent rates of nirmatrelvir and ritonavir use in the recent COVID-19 Primary Care Update webinar, with recent prescriptions rising to around 30% of the total for COVID-19 oral antivirals.
 
‘Perhaps people are getting more familiar with Paxlovid and when they can cease concomitant medicines that might be causing those problematic drug interactions, so it is encouraging that it is being used slightly more frequently than before,’ he said.
 
Both treatments were added to the PBS earlier this year, with GPs able to access molnupiravir from March and nirmatrelvir and ritonavir from May.
 
The Taskforce also referenced observational studies, including one from the Victorian Department of Health that concludes molnupiravir significantly reduces the risk of hospitalisation and death.

‘The nature of these studies means that their results are open to significant bias – particularly selection bias – and substantial confounding – both the healthy user effect and confounding by indication – and cannot provide reliable evidence to determine the effectiveness, or otherwise, of molnupiravir,’ the Taskforce concluded.
 
‘However, these studies are very helpful in generating hypotheses, particularly about groups most likely to benefit from treatment, for testing in future randomised controlled trials.’
 
Professor Morgan notes that other countries have also changed their advice on molnupiravir, including the UK, where it is no longer recommended for use by the country’s National Institute for Health and Care Excellence.
 
He also said that vaccine boosters should be the mainstay of preventing serious disease.
 
Meanwhile, the Pharmaceutical Benefits Advisory Committee (PBAC) recently recommended expanding eligibility for both oral antiviral treatments to include those previously hospitalised with COVID-19.
 
Dr Simpson said the change would be relevant in the example of a young patient who may otherwise be fit but had a bad experience with COVID.
 
PBAC also recommended expanding eligibility to patients who have received anti-CD20 monoclonal antibody treatment in the past 12 months, as well as softening the requirement for a verified COVID-19 test result.
 
The recommendations are expected to be introduced early next year.
 
The Taskforce has published a prescribing guide for nirmaltrelvir plus ritonavir (Paxlovid) on its website.

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Dr Ian Mark Light   6/12/2022 6:30:38 AM

We will need a dramatic increase of the use of Remdesivir as an infusion either through existing ambulatory infusion units or hospital in the home places .
Also the National Institute of Health in the USA has published an expanded list of medications that can be withheld or doses reduced but Paxlovid still given though there will need to be greater observation of patients .
It applies to statins some anti- hypertensives many benzodiazepines and some anti- coagulants for example .
Declining to prescribing Paxlovid because of interactions has been overdone and now needs to be reassessed so at risk patients do not miss the opportunity of reduced chance of severe disease death .
The Interactions Charts have to be upgraded urgently .


Dr Paul Grenville Smith   6/12/2022 7:44:40 AM

The increase in online requirements eg Death certificates. drivers licences .disabled parking and Proda takes up more consultation time leaving less time for patient care and outcomes = " Beauracratic rigor mortis"


Dr Andrew Carr   6/12/2022 8:51:46 AM

Imagine a Venn diagram of patients who have the co-morbididities making it necessary for an antiviral but are also not taking any medications which may interact with Paxlovid. Not a huge number.
Then for the remainders, add nuance of trying to find evidence of whether or not you can safely stop the interacting medication for 8 days (could you steel man your rationale in a court in front of a family?)
Look at statins for an example. The existence of rebound cardiovascular events in statin withdrawal is a concern, but not certain. Is it safe to withdraw? How can I be sure?
At the beginning of the pandemic, the profession couldn’t even suggest substituting ACE inhibitors for other BP meds in select patients because the decision was supposedly too nuanced. We allowed a blindingly obvious vector for lung cell invasion to go on continuing to be prescribed due to fear of nuance. Yet now, we’re being encouraged to engage with such nuance to prescribe Paxlovid. Why?


Dr Inanch Mehmet   6/12/2022 11:41:53 AM

Does it reduce long covid though ?


Dr Arthur Gordon John Snow   10/12/2022 1:36:18 AM

The emphasis of the article is that molnupiravir does not prevent hospitalization or deaths. I have however found that this "lesser' drug very effective at speeding the recovery of the mild - moderate covid cases I have treated and also markedly reducing long covid. Surely that is a good thing? Whereas Paxlovid is almost impossible to prescribe and I have found that there is often a reactivation of the virus once the course of treatment is complete. My analogy is that Paxlovid freezes the virus and hides it from the immune system where as molnupiravir just slow the virus down, allowing the immune system to do its job. I think the underlying drive is really about the costs of providing these medications and the emphasis on whether patients end up in hospital is the wrong focus. I think there is a far greater long term savings in costs to the community if patients who probably were never going to end in hospital do nonetheless recovery faster with the help of these drugs.