Changes to COVID-19 oral antiviral PBS eligibility criteria – July 2022

• On 11 July 2022, Pharmaceutical Benefits Scheme (PBS) eligibility criteria for oral COVID-19 antiviral medicines changed
  The changes expand access under the PBS and are the same for both molnupiravir and nirmatrelvir plus ritonavir listings.
• Vaccination status is no longer part of the criteria
  With many Australian adults having received more than one COVID-19 vaccination, the Pharmaceutical Benefits Advisory Committee (PBAC) recommended removing the requirement that a ‘patient has received less than 2 doses of SARS-CoV-2 vaccine’. Access to these medicines through the PBS for eligible patient groups is permitted irrespective of vaccination status.
• Eligible patient populations now include all people aged ≥ 70 years with a positive polymerase chain reaction (PCR) or verified rapid antigen test (RAT) result
  For this group, treatment with an oral COVID antiviral medicine must be initiated within 5 days of symptom onset or as soon as possible after a diagnosis is confirmed where the person is asymptomatic.
• Groups at high risk of developing severe disease from COVID-19 infection continue to include adults with additional risk factors, or who are moderately to severely immunocompromised
  Age criteria, definition of ‘high risk of progressing to severe disease’ and definition of ‘moderate to severe immunocompromise’ have been updated in these listings to provide greater clarity and/or expand patient eligibility.
• Prescribers and pharmacists are encouraged to discuss with eligible patients as soon as possible to support understanding of how to access health care and medicines if they are diagnosed with COVID-19
  Current guidance for both molnupiravir and nirmatrelvir plus ritonavir is to start treatment as soon as possible after a diagnosis of COVID-19 and within 5 days of symptom onset. Preparing patients may reduce delay in obtaining supply and optimise potential treatment benefits, without compromising requirements for patients to self-isolate if COVID-19 positive.

On 11 July 2022, the General Schedule (S85) Authority Required (Streamlined) listings for specific patient groups with mild-to-moderate COVID-19 at high risk of progressing to severe disease were changed for two oral antiviral medicines:^1,2

• molnupiravir (Lagevrio)
• nirmatrelvir plus ritonavir (Paxlovid)

The high-risk patient populations eligible for these oral antiviral medicines include people:^1-3

• 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.

Molnupiravir, and nirmatrelvir plus ritonavir are not PBS subsidised for pre-exposure or post-exposure prophylaxis for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.^1,2

May be prescribed by nurse practitioners 

Authorised nurse practitioners may prescribe these two medicines. See the PBS website for more information on nurse practitioner PBS prescribing.^1,2

Clinical criteria for all included patient populations

For all included patient populations, the clinical criteria for PBS-subsidised molnupiravir, and nirmatrelvir plus ritonavir are as follows.^1,2,4,5

COVID-19 diagnosis

This remains the same. Patients must have a:

• positive polymerase chain reaction (PCR) test result, or
• positive rapid antigen test (RAT) result verified by a medical practitioner or nurse practitioner^a.

The result, testing date, location and test provider (where relevant for the RAT) must be recorded on the patient record.

^a The medical practitioner or nurse practitioner does not have to administer or supervise the test; the onus is on them to ensure the test is valid.

Vaccination status

Vaccination status is no longer included in the listings for any of the patient populations.

Clinical criteria for people aged ≥ 70 years

Patients in this patient population are eligible for treatment:^1,2

• whether or not they have signs and symptoms ie, they can be asymptomatic
• whether or not they have risk factors for severe disease.

Patients must:

• have treatment initiated as soon as possible after diagnosis is confirmed when asymptomatic, or
• have the treatment initiated within 5 days of symptom onset, and
• not require hospitalisation at the time of prescribing.

Clinical criteria for all other patient populations

Specific clinical criteria for people:^1,2,4,5

• aged ≥ 50 years
• aged ≥ 30 years, who identify as Aboriginal or Torres Strait Islander
• aged ≥ 18 years, who are moderately to severely immunocompromised

are as follows.

COVID-19 signs and symptoms

These remain the same. Patients must have at least one sign or symptom from the following list that is attributable to COVID-19:

• fever > 38 ºC, chills
• cough, sore throat, shortness of breath or difficulty breathing with exertion
• fatigue
• nasal congestion, runny nose
• headache, muscle or body aches
• nausea, vomiting, diarrhoea
• loss of taste, loss of smell.

Details of the patient’s medical condition necessitating use of molnupiravir or nirmatrelvir plus ritonavir must be recorded in their medical records.

COVID-19 treatment

The treatment requirements remain the same. Patients must:

• have the treatment initiated within 5 days of symptom onset, and
• not require hospitalisation at the time of prescribing.

Defining ‘high risk of severe disease’

Each high-risk population has additional clinical criteria that define 'high risk of progressing to severe disease' and determine access to PBS-subsidised molnupiravir, and nirmatrelvir plus ritonavir. See Table 1 and Table 2.

These risk factors include a number of changes.

Table 1: Factors for high risk of progressing to severe disease by patient population group for molnupiravir, and nirmatrelvir plus ritonavir from 11 July 2022^1,2

Table 2: Definition of moderately to severely immunocompromised at high risk of severe disease for patients aged ≥ 18 years for molnupiravir, and nirmatrelvir plus ritonavir from 11 July 2022^1,2

See the PBS website for complete details.

Drug–drug interactions for nirmatrelvir plus ritonavir^2,4

Prescribers and dispensers should:

• be aware that nirmatrelvir plus ritonavir has significant drug–drug interactions
• refer to the Therapeutic Goods Administration (TGA)-approved Product Information
• carefully review a patient's concomitant medicines including over-the-counter medicines, herbal supplements and recreational drugs.

For more information about managing drug interactions when prescribing this antiviral see our NPS MedicineWise RADAR article Nirmatrelvir and ritonavir (Paxlovid) for mild-to-moderate COVID-19.

Authority Required (Streamlined) codes

Prior to 1 August 2022:³

• no change is being made to published restriction text or streamlined authority codes in the online version of the PBS schedule; and
• proprietary prescribing and dispensing software may not reflect the changed listings.

Prescribers and pharmacists are advised to use the existing streamlined codes to access molnupiravir, and nirmatrelvir plus ritonavir until PBS prescribing, dispensing and claiming software is updated on 1 August 2022. See Table 3.

Table 3. Authority Required (Streamlined) codes for molnupiravir, and nirmatrelvir plus ritonavir until 31 July 2022 and from 1 August 2022^3-5

Stock

Pharmacists are encouraged to stock these medicines on community pharmacy shelves. The government has a wholesaler guarantee and special stock return policies to ensure pharmacies will not be left holding nirmatrelvir plus ritonavir courses if they are ordered but not needed in that location. The sponsor of molnupiravir has commercial arrangements about terms of trade and return policies.³

Molnupiravir

Molnupiravir is an antiviral medicine taken orally in capsule form. It is a prodrug of N-hydroxycytidine, a ribonucleoside analogue that is incorporated into viral RNA, resulting in the inhibition of SARS-CoV-2 replication.⁶

It has been provisionally approved by the TGA for the treatment of Australian adults (≥ 18 years) with COVID-19 who:

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

The recommended dose is 800 mg (four 200 mg capsules) every 12 hours for 5 days.⁶ 

Molnupiravir was PBS listed on 1 March 2022 for the treatment of COVID-19.⁵ 

For more information about clinical trial data, dosing, oral solution, contraindications, drug interactions, pregnancy and breastfeeding and side effects, see our NPS MedicineWise RADAR article Molnupiravir (Lagevrio) for mild-to-moderate COVID-19.

Nirmatrelvir plus ritonavir

Nirmatrelvir plus ritonavir is a combination antiviral medicine taken orally in tablet form.⁷

Nirmatrelvir is a peptidomimetic inhibitor of the SARS‑CoV‑2 main protease (Mpro). Inhibition of SARS-CoV-2 Mpro makes the protein incapable of processing polyprotein precursors, which prevents viral replication.⁷

Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir. This boosts plasma concentrations of nirmatrelvir. Ritonavir itself is inactive against SARS-CoV-2.^7,8

Nirmatrelvir plus ritonavir has been provisionally approved by the TGA for the treatment of COVID-19 in Australian adults (≥ 18 years) who:⁷

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

Nirmatrelvir must be taken together with ritonavir. Failure to correctly take nirmatrelvir with ritonavir will result in plasma levels of nirmatrelvir that will be insufficient to achieve the desired therapeutic effect.⁷ 

The recommended dose is 300 mg nirmatrelvir (two 150 mg tablets) taken together with 100 mg ritonavir (one 100 mg tablet), every 12 hours for 5 days. A lower dose of 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) every 12 hours for 5 days can be given to patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min). This medicine is not recommended for patients with severe renal impairment (eGFR < 30 mL/min).⁷ 

Nirmatrelvir plus ritonavir was PBS- listed on 1 May 2022 for the treatment of COVID-19.⁴ 

The nirmatrelvir tablets are co-packaged with ritonavir tablets. The carton includes five blister cards, each marked with a ‘Morning Dose’ and ‘Evening Dose’ for tablets to be taken each morning and each evening. Each blister card contains four nirmatrelvir tablets and two ritonavir tablets.⁷

For more information about clinical data, dosing, contraindications, drug interactions, pregnancy and breastfeeding and side effects, see our NPS MedicineWise RADAR article Nirmatrelvir and ritonavir (Paxlovid) for mild-to-moderate COVID-19.

The listing changes expand PBS access to these oral antiviral medicines for Australians living in the community. It represents a pragmatic response to the current COVID-19 environment.

The Pharmaceutical Benefits Advisory Committee (PBAC) is continuing to monitor the conditions for PBS access for both medicines. This includes considering effectiveness and safety evidence, recent PBS utilisation patterns and the epidemiology of COVID-19.^3,9 The changes to eligibility have been made to help address the current urgent public health need for COVID-19 treatments and prevention of severe disease requiring hospitalisation.^3,10,11 The changes also reflect the current Australian situation where most adults have received more than one COVID-19 vaccination.^3,9 

Noting correspondence of several stakeholder groups representing Australians at increased risk of severe disease, the PBAC also recommended changes to the list of conditions that define high risk for developing severe disease and the definition of ‘moderate to severe immunocompromised’.^3,9

Prescribers and pharmacists are encouraged to discuss the likelihood of needing one of these medicines with patients (or their carers) who meet the eligibility criteria.

NPS MedicineWise has general information about the antivirals, as well as plain English summaries for each medicine (including culturally appropriate imagery for Aboriginal and Torres Strait Islander peoples) that may be useful to inform the discussion:

• Oral COVID-19 medicines
• Lagevrio for COVID-19
• Paxlovid for COVID-19.

Having a plan in place about which medicine best suits the patient’s needs, how to obtain a script and how to access the medicine from a pharmacy can improve the chances of successfully starting treatment within 5 days from diagnosis or start of symptoms.

Resources that can support these discussions include printed information or links about:

• signs and symptoms of COVID-19
• how to access telehealth to confirm COVID-19 diagnosis and obtain an antiviral script
• electronic prescriptions
• home delivery options from pharmacy providers

Medicine-specific information for patients about molnupiravir and about nirmatrelvir plus ritonavir can also be found in the NPS MedicineWise RADAR articles published for each medicine:

• Molnupiravir (Lagevrio) for mild-to-moderate COVID-19
• Nirmatrelvir and ritonavir (Paxlovid) for mild-to-moderate COVID-19

Other COVID-19 treatments for people with mild-to-moderate COVID-19 living in the community

For people with mild-to-moderate COVID-19 symptoms who do not require oxygen and are living in residential care facilities or at home, the National COVID-19 Clinical Evidence Taskforce Caring for people with COVID-19 Guidelines also recommends several other COVID-19 treatments:^12-14

• sotrovimab (Xevudy), a monoclonal antibody given as a single-dose intravenous treatment
• casirivimab and imdevimab (Ronapreve), a monoclonal antibody that may be given as a subcutaneous injection
• tixagevimab and cilgavimab (Evusheld), a combination of two monoclonal antibodies given as an intramuscular injection.

The National COVID-19 Clinical Evidence Taskforce Caring for people with COVID-19 Guidelines notes that its recommendation for tixagevimab and cilgavimab is not a TGA-approved indication.¹²

It recommends that molnupiravir be prescribed when other treatments such as nirmatrelvir and ritonavir or sotrovimab are not suitable or available. For sotrovimab only, where infection with Omicron BA.2 is confirmed or considered likely, use should only be considered where other treatments are not suitable or available. For casirivimab and imdevimab only, where Omicron is the dominant variant, this medicine should not be routinely used unless there is reason to believe the patient has another variant.¹²

For more information comparing the three treatments, molnupiravir, nirmatrelvir and ritonavir and sotrovimab, see NPS MedicineWise Oral antivirals and sotrovimab for adults with mild-to-moderate COVID-19 who do not require oxygen

• Department of Health Oral treatments for COVID-19
• National COVID-19 Clinical Evidence Taskforce Caring for people with COVID-19 Guidelines
• Royal Australian College of General Practitioners (RACGP) Oral antiviral treatments for COVID-19
• NPS MedicineWise Antiviral treatments for COVID-19
• TGA Product Information