In January, the TGA provisionally approved two oral dose treatments for the COVID-19 virus to be used in the first phase of the illness.
Both oral antivirals are designed to minimise the severity of COVID-19 infections, reducing the risk of hospitalisation and death.
The new anti-virals
The first of these oral antivirals will be sold as Paxlovid (a combination of nirmatrelvir and ritanovir from Pfizer), with the second to be sold as Lagevrio (which is molnupiravir from Merck).
Paxlovid is a “protease inhibitor”. The nirmatrelvir interferes with the virus’s dividing (multiplying) by blocking part of its life cycle. The ritonavir enables the nirmatrelvir to remain in the body longer.
Lagevrio acts on an enzyme that the COVID-19 virus uses to replicate itself. It introduces errors as it copies leading to what is known as “error catastrophe” – a position where there are so many errors in the virus, it dies.
Speaking in a recent edition of ABC’s Coronacast podcast with Dr Normal Swan earlier this month, Professor Josh David, from Infectious Diseases at the University of Newcastle and member of the National COVID-19 Clinical Evidence Taskforce stated that Paxlovid was likely to be of greater efficacy than Lagevrio in the Australian context.
He stated that evidence about the benefit of Paxlovid was superior to that of Lagevrio. The Taskforce, of which he is a member, has noted in its recommendation of Lagevrio that “evidence is limited, effect sizes are small and there are limited safety data”.
Consequently, the Taskforce has recommended on a consensus basis that “molnupiravir [Lagevrio) should only be considered where other treatments (such as sotrovimab or nirmatrelvir plus ritonavir [Paxlovid]) are not suitable or available.”
Although Paxlovid is suggested as more effective, Paxlovid is contraindicated against a large number of commonly used prescription medications, including Amiodarone (blood pressure/heart rhythm medication), Colchicine (gout), simvastatin (blood cholesterol), sildenafil (erectile dysfunction and tadalafil (erectile dysfunction/urinary symptoms of enlarged prostate) and diazepam (anti-anxiety and muscle spasm) amongst many others. This may lead to the use of Lagevrio. Significantly, Lagevrio is not recommended in pregnancy or during breastfeeding.
Interestingly, the evidence supporting both antivirals was conducted in unvaccinated populations and not with Omicron.
Consequently, the recommendation from the National COVID-19 Clinical Evidence Taskforce in favour of these treatments for partially or fully vaccinated patients (or immunocompromised patients regardless of vaccination status) with certain risk factors was issued on a “consensus” basis – meaning it has been recommended based on expert consensus even though its use for these patients is less supported by the evidence.
The Taskforce notes that given “the lower risk of deterioration in these patients, it is unlikely that nirmatrelvir plus ritonavir will be particularly valuable in patients who have received three doses of vaccine, unless the patient is immunosuppressed.”
There is existing laboratory evidence that suggests that Paxlovid is efficacious against Omicron infection.
Can we access these anti-virals when we need them?
The announcement of these oral dose treatments has been widely cited as a justification for relaxing public health measures designed to limit the spread of COVID-19. The theory being, of course, that if the illness from COVID-19 is increasing mild across the population, then there is less need for restrictions on daily life to prevent infections.
With public health measures now being relaxed at significant speed, and winter approaching, we need to understand exactly what progress is being made with these anti-virals. How far have we progressed beyond these initial announcements?
At the current time, the Department of Health (Cth) does not appear to have clarified publicly how many doses will be available or when shipments will be available.
However, the Department of Health (Cth) has indicated that when available, they will be prioritised for distribution to the aged care sector. Any additional supplies will be available from the National Medical Stockpiles.
At the same time, the process is underway for the antivirals to be included on the Pharmaceutical Benefit Scheme by the Pharmaceutical Benefits Advisory Committee – the Committee which recommends medications for listing and the rules for access to the medications.
In Victoria, the Department of Health has just issued a Prioritisation Matrix which describes in some detail which patient groups will be able to access the antivirals before they are PBS listed, according to supply availability – thereby giving us a good idea of how antivirals may be distributed in the coming months.
Based on this Matrix, the highest priority groups will be patients with high-level immunosuppression above the age of 12, unvaccinated persons above 75 years of age and pregnant women (unvaccinated or partially vaccinated meaning they have had only 1 or 2 doses of COVID-19 vaccine). One can expect these patients to access the antivirals when supply becomes available.
In addition, until supply is unlimited and freely available, priority access will be available to:
* partially vaccinated patients (1 or 2 doses only) with multiple high-risk co-morbidities and who are over 75 years of age
* unvaccinated patients over the age of 65 or over 55 (the latter with high or moderate risk comorbidity)
* patients with lower-level immunosuppression.
It is proposed that unvaccinated people with a high or moderate risk co-morbidity will access the antivirals once the supply becomes unlimited even if they are not listed on the PBS at that time.
Partially unvaccinated patients (1 or 2 doses) under 65 with multiple high-risk co-morbidities are prioritised to access the antivirals only when antivirals become available on the PBS.
For the purpose of the Matrix, high-risk co-morbidities include:
* Morbid obesity (BMI >35)
* Diabetes on therapy (not gestational)
* Cerebral palsy
* Intellectual disability of any severity
* Sickle cell disease
* Chronic lung disease (COPD, ILD)
One interpretation of the Matrix is that there are no plans at this point in time to prioritise antivirals access for fully vaccinated patients, irrespective of whether they have one or more high or moderate risk co-morbidities.
This will be cold comfort for that cohort of risk-adverse patients over 50 with generally poor health that have taken all necessary steps to keep their vaccinations up to date and are more reluctant to join in the ‘opening up’ of society.
It is hoped that these antivirals will become widely available as quickly as possible – so doctors can, within parameters set by government regulators – make proper assessments about which patients should access the medications based on their deep understanding of each patient and their susceptibility to serious infection.
Whether we are 4 weeks, 4 months, or even longer away from the antivirals being available through a visit to a doctor or specialist is not currently known.
Australian guidelines for the clinical care of people with COVID-19, National COVID-19 Clinical Evidence Taskforce: https://app.magicapp.org/#/guideline/L4Q5An/section/jboz6G
What GPs need to know about the new COVID antivirals, NewsGP: https://www1.racgp.org.au/newsgp/clinical/what-gps-need-to-know-about-the-new-covid-antivira
TGA provisionally approves two oral COVID-19 treatments, molnupiravir (LAGEVRIO) and nirmatrelvir + ritonavir (PAXLOVID), Therapeutic Goods Administration, 20 January 2022: https://www.tga.gov.au/media-release/tga-provisionally-approves-two-oral-covid-19-treatments-molnupiravir-lagevrio-and-nirmatrelvir-ritonavir-paxlovid
Prioritisation of COVID-19 medications, Department of Health (Victoria), 15 February 2022: https://www.health.vic.gov.au/prioritisation-of-covid-19-medications-word
Australian Product Information Paxlovid: https://www.tga.gov.au/sites/default/files/paxlovid-pi.pdf
Australian Product Information Lagevrio: https://www.tga.gov.au/sites/default/files/lagevrio-pi.pdf
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