FAQs about the use of COVID-19 oral antiviral medicines in residential aged care

Therapeutic Goods Administration (TGA) provisional approval

Molnupiravir (Lagevrio) has been provisionally approved by the TGA for the treatment of Australian adults (≥ 18 years) with COVID-19 who:^1,2

• do not require initiation of oxygen due to COVID-19, and
• are at increased risk for hospitalisation or death.

The dosing guidance is to administer molnupiravir:

• as soon as possible after a diagnosis of COVID-19, and
• within 5 days of symptom onset (safety and efficacy after 5 days has not been established),
• 800 mg (four 200 mg capsules) orally every 12 hours for 5 days, with or without food.

See the molnupiravir product information (PI) for more information.

Molnupiravir was added to the Pharmaceutical Benefits Scheme (PBS) on 1 March 2022 for use in treating patients with mild–moderate COVID-19 at risk of developing severe disease requiring hospitalisation. Medical practitioners and nurse prescribers can prescribe molnupiravir through the PBS.

Molnupiravir is listed in the General Schedule (S85) as Authority Required (Streamlined) for the treatment of specific patient groups with mild–moderate COVID-19, not requiring supplemental oxygen and at high risk of progressing to severe disease. Nirmatrelvir plus ritonavir is also listed on the PBS for treatment of the same specific patient groups.

This list includes people:

• aged ≥ 70 years, with or without COVID-19 symptoms
• aged ≥ 50 years, who have one or more COVID-19 symptoms, and two or more risk factors ^ for severe disease
• aged ≥ 30 years, who identify as Aboriginal or Torres Strait Islander, have one or more COVID-19 symptoms, and two or more risk factors ^ for severe disease
• aged ≥ 18 years who are moderately to severely immunocompromised*, have one or more COVID-19 symptoms, and are at risk of progressing to severe disease due to their immunocompromised status

^{BMI = body mass index, COPD = chronic obstructive pulmonary disease, eGFR = estimated glomerular filtration rate, NYHA = New York Heart Association Classification of Heart Failure}

^{BTK = Bruton's tyrosine kinase, HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome, JAK = Janus kinase}

Clinical Guidelines

For people with mild–moderate COVID-19 who do not meet PBS criteria, access to molnupiravir may be possible through state and territory health departments.

The National COVID-19 Clinical Evidence Taskforce recommends that prescribers consider using molnupiravir:

• within 5 days of symptom onset for adults with mild or moderate COVID-19 who do not require oxygen due to COVID-19 and:

i) are unvaccinated and have one or more risk factors (based on the MOVe-OUT trial inclusion criteria)³ for disease progression, or

ii) are immunosuppressed or not immunocompetent, regardless of vaccination status, or

iii) have received one or two doses of a COVID-19 vaccine and are at high risk of severe disease on the basis of age and multiple risk factors

• AND where other treatments such as nirmatrelvir plus ritonavir (Paxlovid) or sotrovimab (Xevudy) are not suitable or available.

See Disease-modifying treatments for adults with COVID-19 Flowchart for the place in therapy for molnupiravir and other treatments.

The National COVID-19 Clinical Evidence Taskforce Living Guidelines also state that decisions about the appropriateness of treatment should also be based on the patient’s time since vaccination. The guidelines also include details about what constitutes immunocompromised in this context.

Molnupiravir is a prescription only (S4) medicine in all jurisdictions. 

In February 2022, initial distribution of molnupiravir was directed through state and territory health departments via the National Medical Stockpile (NMS) to people most at risk, including those in RACFs across Australia. This included pre-placement in all RACFs across Australia and requires prescription by a general practitioner (GP), medical specialist or nurse practitioners (according to their state or territory regulations, and local RACF policies). Following prescription, the RACF can dispense molnupiravir that it holds in storage as it does any other medicine held onsite by the facility, in line with the regulations of the RACF’s state or territory.

On 1 March 2022 molnupiravir also became available through the PBS General Schedule (Authority Required Streamlined) for prescription by GPs and other authorised prescribers and for dispensing by community pharmacists across Australia. Molnupiravir will also continue to be available through state and territory-directed supplies. 

When a person living in a RACF is diagnosed with COVID-19, the decision to prescribe molnupiravir should be guided by the TGA provisionally approved indication, PBS clinical criteria and National COVID-19 Clinical Evidence Taskforce Living Guidelines. 

NPS MedicineWise have prepared RADAR articles following the PBS listing of molnupiravir and nirmatrelvir plus ritonavir.

See COVID-19 oral treatments update for aged care 7 February 2022 for more information.

How is access to this medicine possible for people living in RACFs?

Nirmatrelvir plus ritonavir (Paxlovid) has not been pre-placed in RACFs. It can be accessed through the PBS (listed 1 May 2022) and through state and territory health departments. If prescribing through the latter option, the states and territories will determine access to people who may be most at risk of progress to severe COVID-19 infection.^6,7

Nirmatrelvir plus ritonavir has a large number of contraindications and drug-drug interactions, including with a wide range of commonly prescribed medicines.⁸ These can impact the suitability of this treatment for many people living in a RACF.

See the nirmatrelvir plus ritonavir PI for more information. 

Current guidance for both nirmatrelvir plus ritonavir and molnupiravir is to start treatment as soon as possible after a diagnosis of COVID-19 and within 5 days of symptom onset.^1,8 The impact of delay while waiting for supply should be considered when making treatment decisions.

Read more about how medical professionals can access COVID-19 treatments through the NMS.

Why hasn’t nirmatrelvir plus ritonavir been pre-placed from the National Medical Stockpile to RACFs, when it has been demonstrated to be more clinically effective?

Nirmatrelvir plus ritonavir has a large number of contraindications and drug-drug interactions. It has not been pre-placed in RACFs because it is not a suitable treatment option for many frail, older people living in these settings.⁵

The contraindications and drug-drug interactions for nirmatrelvir plus ritonavir include:^8,9

• people with severe renal impairment (<30 ml/min)
• people with severe hepatic impairment (Child-Pugh Class C)
• people taking medicines that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. See Table 1 of the nirmatrelvir plus ritonavir PI for more information.
• people taking medicines that are potent CYP3A inducers where reduced nirmatrelvir plus ritonavir plasma concentrations may lead to loss of virologic response and possible resistance. See Table 2 of the nirmatrelvir plus ritonavir PI for more information

Further, dose adjustment is required for nirmatrelvir plus ritonavir in patients with moderate renal impairment.⁸

No contraindications (except for hypersensitivity to active substance and excipients), no drug-drug interactions and no situations requiring dose adjustment have been identified for molnupiravir.¹ See the molnupiravir PI for more information.

There is no available head-to-head clinical trial evidence allowing direct comparison of the efficacy (or safety) of the two medicines. The TGA has found the efficacy and safety of both medicines sufficient in their indicated patient populations to allow provisional registration. Individual prescribers will be best placed to determine whether a particular medicine is suitable for a patient’s own clinical circumstances.

Distribution of oral antiviral medicines was consistent with the National COVID-19 Clinical Evidence Taskforce Living Guidelines at the time, which recommended prescribers consider molnupiravir ‘where other treatments such as sotrovimab (Xevudy) or nirmatrelvir plus ritonavir (Paxlovid) are not suitable or available.’ 

Clinicians should note that where infection with Omicron BA.2 is confirmed or considered likely, use of sotrovimab should only be considered where other treatments are not suitable or available. Currently, there is no clinical evidence to evaluate its effectiveness against the Omicron variant or BA.1 or BA.2 sub-variants.

Read more about how medical professionals can access COVID-19 treatments through the National Medical Stockpile.

Will nirmatrelvir plus ritonavir be pre-placed in the future?

Initial distribution of nirmatrelvir plus ritonavir was through the state and territory health departments via the National Medical Stockpile. State and territory governments are responsible for providing access to stockpile medicines within their jurisdictions to people most at risk.

The Australian Government Department of Health did not pre-place nirmatrelvir with ritonavir for people living in RACFs because molnupiravir was considered more likely to be suitable for them as it has no contraindications (except for hypersensitivity to active substance and excipients) and no identified drug-drug interactions.

On 1 May 2022, nirmatrelvir plus ritonavir became available through the PBS General Schedule (Authority Required Streamlined) for prescription by GPs and other prescribers, and for dispensing by community pharmacists across Australia.⁷

Medicines are made available through the PBS following a number of steps. First an application is made to the PBAC, generally by the sponsor (manufacturer). The PBAC then makes a recommendation that the medicine can be subsidised under the PBS. Lastly the medicine is listed (included) on the PBS Schedule, which includes the restrictions such as patient population and clinical criteria.

Read our RADAR article for more information.

What are the potential side effects of molnupiravir (Lagevrio)?

Pivotal safety data are limited to results from a single trial.³ In this trial, the most frequently reported side effects occurring ≥ 1% of subjects receiving molnupiravir were diarrhoea (2% of participants); nausea (1%); and dizziness (1%). All these reactions were classified as either mild or moderate in severity. Prescribers are reminded that these side effects can lead to significant morbidity such as dehydration, delirium and falls in frail, elderly people. Older people receiving molnupiravir should be closely monitored for side effects.

The TGA closely assesses safety data prior to approval, and continues to monitor the safety of treatments after they are registered in Australia so that any safety concerns can be detected and responded to. The TGA encourages reporting of adverse events for molnupiravir as follows:

This medicine is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

It is recommended that the PI be reviewed for a full description of molnupiravir’s safety profile.

What are the drug interactions for molnupiravir (Lagevrio)?

No drug interactions have been identified, based on limited data.^1-3 

Am I required to report a potential adverse drug reaction? How should an adverse drug reaction for molnupiravir (Lagevrio) be reported? Does this differ depending on jurisdiction?

Molnupiravir is included in the Black Triangle Scheme. All possible adverse reactions for molnupiravir should be reported using existing processes. This requirement and the type of information to provide does not differ between jurisdictions.

• Report online: Complete the online form to report a possible medicine or vaccine adverse reaction.
• Report by email: Email the TGA to report a possible medicine or vaccine adverse reaction. The email should include:
  • contact details
  • a description of the adverse reaction (what happened, when it happened and how long it lasted)
  • a description of the medicine or vaccine thought to have caused the adverse reaction (including any other medicines or medical devices being taken or used by the person experiencing the adverse event).

In addition, medical practices using the Best Practice or Medical Director software can download and install templates to their software to create Adverse Drug Reaction reports. Completed reports can be emailed, faxed or posted to the TGA.

Does molnupiravir (Lagevrio) need to be dispensed and labelled for use by residents in RACFs?

Molnupiravir is a prescription only (S4) medicine.¹ For patients who may be eligible through the National Medical Stockpile, RACFs will need to reach out to their GPs, Medical specialist or nurse practitioners (according to their state or territory regulations, and local RACF policies) to talk about the possible prescribing of this medicine. Once a prescription has been issued, the medicine can be provided in the same way as other medicines held onsite by the facility, in line with the relevant state or territory regulations.⁵

For patients eligible to receive PBS-listed molnupiravir, once a prescription has been issued, the medicine can be supplied in the same way as other PBS-prescribed medicines would be supplied. 

More details (including any requirements for S4 substances such as an 'imprest' medication system) are available through the health departments or Chief Pharmacist for each state or territory.

Can the same pack of molnupiravir (Lagevrio) be used to supply doses for multiple residents?

This is not a recommended way to manage multiple patients.

Each bottle of molnupiravir contains 40 capsules, sufficient for one patient to complete a 5-day course.¹ This is the required duration of treatment to optimise benefit for all patients prescribed this medicine. Splitting a single pack among multiple patients increases the risk of missing doses or not completing a full course.

Once a person living in residential aged care is prescribed molnupiravir, supply of the medicine can be used in a manner consistent with relevant state or territory medicine regulations.⁴

Can a RACF order more stock of molnupiravir (Lagevrio) if all the initial supply is used? If so, what is the process for this?

Pre-placement is being conducted for all RACFs in Australia, with outbreak sites prioritised first. The amount allocated is based on the number of residents on site as reported through My Aged Care. Consideration is given to the number of residents who may be impacted by COVID-19 if an outbreak occurs.⁵

Additional supplies of molnupiravir are available through the PBS for specific patient populations. See the PBS listing for more details.

Can molnupiravir (Lagevrio) supplied from the National Medicines Stockpile be transferred to other RACFs?

Do not transfer pre-placed treatments between facilities. RACFs that require additional supply of molnupiravir should contact their Commonwealth case management team.

If a resident needs to be transferred to hospital or another care facility while receiving a course of molnupiravir, send the already started pack of medicine with them (if appropriate). This should be reviewed on a case-by-case basis.⁴

An open pack should not be used by another person. The receiving hospital or other facility will decide whether to use that pack or whether to dispense from their own supplies.

How will prescribing of molnupiravir (Lagevrio) appear on a patient’s medication profile?

Molnupiravir is a prescription only (S4) medicine.

During February 2022, to support timely access to at-risk patients, the Australian Government supplied this medicine directly to RACFs.

If a resident is eligible for this treatment, and is experiencing mild-moderate COVID-19, the facility should contact the regular treating clinician or health professional to arrange a clinical assessment as soon as possible .

An order to dispense molnupiravir should be documented/charted (on a paper record or in electronic files) following consultation and direction from the authorised prescriber.⁴

Many residents will now be able to access molnupiravir via the PBS.

Where a prescriber considers treatment is clinically indicated but the patient is not eligible under the PBS, the medication can then be taken from storage according to the specific processes for that RACF, and in line with state or territory regulations.

Does a RACF need to inform a community pharmacy, which regularly supplies dose-administration aids, that a patient has been prescribed molnupiravir (Lagevrio)?

During February 2022 supplies of molnupiravir were pre-placed at each RACF across Australia. Once an aged care resident is prescribed the medicine, the facility’s medicines supply can be used in a manner consistent with medicine regulation in their jurisdiction.⁴

If the facility determines that molnupiravir should be included within a resident’s pre-prepared dose administration aids (DAA) pack, the facility will need to inform the community pharmacy and co-ordinate access to the medicine for inclusion.

When deciding if molnupiravir should be packed, it may be useful to consider the risk of possible non-adherence if not included in a DAA.¹⁰

Please note: it has been reported that molnupiravir appears stable when kept under manufacturer defined storage conditions.¹¹ It is unknown if potency or physical integrity of the product is impacted if packed in a DAA.

Can molnupiravir (Lagevrio) be administered to residents by a carer, or does it need to be administered by a registered nurse?

Once an aged care resident is prescribed the relevant medicine, the facility’s supply of the medicines can be used in a manner consistent with medicine regulation in that jurisdiction.

Depending on the state or territory where the facility is located, a registered nurse or a carer supervised by a nurse may be able to administer the treatment.⁴

Are there any special instructions for administration of molnupiravir (Lagevrio)?

(General information) Where possible, facilities are encouraged to pre-assess any residents who may potentially be eligible for molnupiravir should the need arise. This pre-assessment will support timely access to treatment.^4,5

Pre-assessment actions should include:

• discussing consent options for potential treatment with the aged care resident and relevant decision-maker
• identifying eligible aged care residents in RACF clinical management systems
• discussing potential medicine administration with the aged care resident’s GP, nurse practitioner or facility clinical care staff.

(Medicine specific) Treatment with molnupiravir should be commenced as soon as possible after a diagnosis of COVID-19, and within 5 days of symptom onset.^1,2 A course of molnupiravir is 800 mg (four 200 mg capsules) twice a day (every 12 hours) for 5 days. It can be taken with or without food. Molnupiravir is supplied as a bottle of 40 capsules; it should be stored below 30°C.

Can molnupiravir (Lagevrio) be modified for patients with swallowing difficulties?

Molnupiravir is generally administered as whole capsules as outlined in the TGA PI.¹

While the recommendation is to swallow the capsules, if this is not possible, and if alternative treatments are not available or not suitable, the manufacturer has advised (instructions provided below) that the procedure set out below allows preparation of an oral solution. Please note that this advice is based on preliminary data and should be limited to those circumstances where there is no other option. This is regarded as an 'off label' use – it is recommended that this decision be documented in the patient record and consent should be obtained from the patient or their designated decision-maker for use of the treatment in this way.

For more information about alternative treatment options please see the consensus recommendations and flowchart for disease-modifying treatment of adults with COVID-19 prepared by the National COVID-19 Clinical Evidence Taskforce.

How urgently should the first dose of molnupiravir (Lagevrio) be administered? What should happen if a registered nurse is not available on-site at the time of prescribing?

Treatment with molnupiravir must begin as soon as possible after a diagnosis of COVID-19, and within 5 days of symptom onset. While timely access to these medicines is important to ensure best possible outcomes, delaying the first dose due to absence of a registered nurse may be appropriate if it can still occur within this 5-day window.

To minimise disruption to initiation of molnupiravir, each RACF is encouraged to develop medicine management policies and procedures, similar to those for administering other medicines in an emergency or acute situation (eg, acute urinary tract infection) that specify circumstances where a registered nurse can delegate medicine administration to other appropriately trained and competent staff (where this is permitted by relevant state or territory legislation and regulation).¹²

How will consent be managed for molnupiravir (Lagevrio) in RACFs, particularly for residents with mental incapacity or cognitive impairment?

Consider arranging consent in advance of people becoming infected or of outbreaks occurring. This allows discussions to take place between facility staff and the resident or their family members (or other decision-makers) about the agreed approach to management if the resident should be diagnosed with COVID-19. This is the same as arranging advanced consent for residents to receive COVID-19 vaccinations.

How should unused molnupiravir (Lagevrio) tablets be safely disposed of?

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.¹

Anyone handling the medicine should consider the risks of exposure (refer to the molnupiravir PI for more information; Section 4.6 Fertility, Pregnancy and Lactation).

Can molnupiravir (Lagevrio) be prescribed for staff at the RACF?

Pre-placement of molnupiravir in RACFs is for the treatment of residents only.

Molnupiravir for eligible people is now available through PBS prescription, staff diagnosed with COVID-19 who meet the clinical criteria may be able to access the medicine.

Can quality use of medicine (QUM) education be provided to RACFs on the use of molnupiravir (Lagevrio) and ritonavir-boosted nirmatrelvir (Paxlovid) by pharmacists? Is this allowed under the program rules?

Under the program rules for QUM services, education activities that may be provided include:¹³

• in-service for nursing staff and carers or residents taking medicines, disease state management or prescribing trend issues
• drug information for medical practitioners and facility staff, including provision of newsletters.

The type and frequency of QUM services are to be documented within the service agreement between the service provider and the facility.

Learn more about available programs and program rules for QUM.

Contact details for local state and territory health departments

Flow chart: disease-modifying treatments for adults with COVID-19

National COVID-19 Clinical Evidence Taskforce guidelines:

• Molnupiravir (Lagevrio)
• Nirmatrelvir plus ritonavir (Paxlovid)

COVID-19 information from the Australian Government 

COVID-19 Oral treatments: Information for residents, & their families, in residential aged care facilities

NPS MedicineWise COVID-19 information hub

Australian Prescriber:

• Molnupiravir for COVID-19
• Nirmatrelvir and ritonavir for COVID-19

RACGP - What do GPs need to know about the new COVID antivirals?