A range of anti‑SARS‑CoV‑2 monoclonal antibodies and antiviral medications have been provisionally approved by the Therapeutic Goods Administration.

These medications are for prophylaxis or for the treatment of patients in the early phase of infection with COVID‑19 who are at risk of progression to severe disease. This guidance outlines the use of these medications in NSW.

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Methodology

The National Clinical Evidence Taskforce (NCET) Guidelines specify recommendations for the use of anti‑SARS‑CoV‑2 monoclonal antibodies and antivirals in adults, and children and adolescents (aged over 12 years) in Australia based on available evidence.1 This guidance is based on these recommendations and the evidence checks undertaken by the NSW Critical Intelligence Unit (CIU).2-7

The available evidence was considered by an expert group of NSW clinicians to inform the development of this guidance. Emerging medications are also being monitored by the CIU and will be included in this document, as required. This document should be read in conjunction with drug guidance developed by the Clinical Excellence Commission (CEC).8

Updates - November 2022

Inclusion of advice around the off label use of tixagevimab and cilgavimab (Evusheld) for treatment of COVID-19.

Who can be treated

Clinical criteria and risk factors

The medications covered in this model of care are:

The drug guidelines for these medications are available on the CEC website.

Generally, these drugs are for use early in the course of the disease before significant symptoms or severe disease have developed, and within a window of 5 to 7 days from the onset of infection (preferably as early as possible). These agents prevent the replication and spread of the virus and are likely to work best soon after infection has occurred. This limits the spread of the virus beyond the respiratory tract and before a severe systemic immune response has been initiated. The guidance outlined in this document is for the use of a single medication for this indication.

Note: Tixagevimab plus cilgavimab can be used for pre-exposure prophylaxis and casirivimab plus imdevimab for post‑exposure prophylaxis.

Currently only some of these medications are approved for children and adolescents aged 12 to 17 years who weigh >40kg.

Only specific patient groups are expected to benefit from, and hence be eligible for, these medicines. They are not an alternative to COVID‑19 vaccination, which remains the best way to protect vulnerable populations from severe outcomes of COVID‑19 infection.

Although the indications for these medications are similar, they are not identical. As such, NCET eligibility criteria recommendations and individual drug guidelines should be reviewed, particularly with respect to the COVID‑19 variants likely to be present.

Considerations for all medications are outlined in Table 1. Overview of Medications for details.

Vaccination

Routine use of these medications is not encouraged in patients who are up to date with their COVID‑19 vaccinations, unless a suboptimal response is predicted (e.g. severe immunosuppression from a medical condition or medication) or if the patient has multiple co‑morbidities that increase their risk of disease progression.9

The Australian Technical Advisory Group on Immunisation (ATAGI) specifies the interval for vaccination. Vaccination can take up to 14 days to be effective.9

ATAGI does not recommend a minimum time frame to defer vaccination due to monoclonal antibody medicine or antiviral administration. However, it is recommended to follow guidance to defer vaccination for 3 months following infection.10

Adverse events

All adverse events should be reported to the Therapeutic Goods Administration (TGA) at www.tga. gov.au/reporting-problems. NSW Health staff must also report adverse events via the local incident management system (IIMS+).

Criteria for prescription in NSW

The criteria for prescribing monoclonal antibody treatments and antiviral medicines in NSW align to the NCET recommendations (for TGA‑approved indications) or PBS criteria, with some additions, as summarised in Table 1. Overview of Medications for details.

Where Aboriginal or Torres Strait Islander status appears as a risk factor, an age of 30 years or older should be applied.

Wherever possible, prescribing of the oral antivirals (molnupiravir and nirmatrelvir plus ritonavir) must occur via the Pharmaceutical Benefits Scheme. However, in the following circumstances dispensing by a NSW Health Pharmacy Department may continue to occur:

  • where the patient is an inpatient in an NSW health facility
  • for patients presenting to emergency departments
  • for patients prescribed tixagevimab plus cilgavimab for pre-exposure prophylaxis by their community- based GP or medical specialist (only if the patient does not have an existing link to a NSW Health facility or private hospital)
  • for virtual care or COVID Care in the Community patients
  • for patients identified by general practitioners or community-based medical specialists who meet the criteria outlined by the NCET but are ineligible for PBS supply.

Evidence indicates that there is reduced efficacy of monoclonal antibodies plus imdevimab against Omicron (including all subvariants).11,12

To support ongoing use of this document all medications within scope have been retained. However, clinicians and services should note:

  • the information provided regarding efficacy against current variants
  • the most current decision advice in Figure 1
  • the considerations outlined in Table 1. Overview of Medications
  • updated recommendations from the NCET.

The NCET has also developed a risk classification tool for adults with mild COVID‑19 that assists clinicians to select the medication likely to be the most effective.13

Use of available medications for off‑label indications or in combination

The NCET has made:

  • a conditional recommendation regarding the use of tixagevimab plus cilgavimab as treatment for non‑hospitalised patients with mild to moderate disease14
  • a consensus recommendation regarding the use of nirmatrelvir plus ritonavir in children and adolescents aged 12 years and over and weighing at least 40 kg who do not require oxygen and who are at high risk of deterioration.15

Consider use of tixagevimab plus cilgavimab for treatment only in patients with persisting active infection despite using other available treatments (dose 300mg tixagevimab plus 300mg cilgavimab).

These medicines are not currently approved by the TGA for these indications and therefore, use is off-label

There is no supporting evidence for combination therapy (antivirals plus monoclonal antibodies). The NCET recommends that the use of two or more monoclonal antibodies should be avoided except where co-formulated.14

Where a clinician believes that a patient may benefit from the use of an available medication for an off‑label indication or combination therapy (antivirals plus monoclonal antibodies), approval must be sought from the local Drug and Therapeutics Committee (via the Individual Patient Use process, see PD2016_033) prior to commencing therapy. An independent peer‑review process is also encouraged. Primary care practitioners should flag the patient through their local LHD escalation pathways.

Table 1. Overview of medications

MedicationUsage NSW criteria for administration
Variant Route of administration
Nirmatrelvir plus ritonavir (Paxlovid)
Treatment
​As per PBS criteriaand NCET recommendationsfor adults (with the Aboriginal and Torres Strait Islander age threshold of 30 years)*19,20

For expanded eligibility criteria as at 11 July 2022, see Paxlovid - Pharmaceuticals Benefits Scheme Factsheet.

Oral

Molnupiravir

(Lagevrio)

Treatment

As per PBS criteriaand NCET recommendationsfor adults (with the Aboriginal and Torres Strait Islander age threshold of 30 years) *17,18

For expanded eligibility criteria as at 11 July 2022, see Lagevrio - Pharmaceuticals Benefits Scheme Factsheet.

Oral
Remdesivir (Veklury)
Treatment (early treatment only, within 7 days of symptom onset)

As per NCCET recommendations (with the Aboriginal and Torres Strait Islander age threshold of 30 years)§ for:


Intravenous infusion

Tixagevimab plus cilgavimab (Evusheld)

Pre‑exposure prophylaxisAs per TGA approved product information for adults, pregnant women, and children and adolescents 12 years or older and weighing at least 40 kg (pre‑exposure prophylaxis). 21Intramuscular injection
Sotrovimab (Xevudy)
Treatment

As per NCET recommendations (with the Aboriginal and Torres Strait Islander age threshold of 30 years) for:

Reduced effectiveness against Omicron BA.2, BA.4 and BA.5
Intravenous infusion
Casirivimab plus imdevimab (Ronapreve)
Treatment Post‑exposure prophylaxis

As per NCET recommendations (with the Aboriginal and Torres Strait Islander age threshold of 30 years) for:


Reduced effectiveness against Omicron BA.1, BA.2, BA.4 and BA.5
Intravenous infusion or subcutaneous injection

* Wherever possible, prescribing of the oral antivirals (molnupiravir and nirmatrelvir plus ritonavir) must occur via the PBS. However, in the following circumstances dispensing by a NSW Health Pharmacy Department may continue to occur:

  • where the patient is an inpatient in an NSW health facility
  • for patients presenting to Emergency Departments
  • for patients prescribed tixagevimab plus cilgavimab for pre-exposure prophylaxis by their community-based GP or medical specialist (only if the patient does not have an existing link to a NSW Health facility or private hospital)
  • for virtual care or COVID Care in the Community patients
  • for patients identified by general practitioners or community-based medical specialists that meet the criteria outlined by the NCET but are ineligible for PBS supply. (NCET requires only one risk factor to trigger treatment and has a lower age threshold than the PBS.)

† Where uncertainty exists regarding vaccine response in an individual, anti‑SARS‑CoV‑2 spike antibody testing may be useful. Repeat dosing is usually not recom- mended for individuals who have received tixagevimab plus cilgavimab for prophylaxis. This may be reconsidered at clinician discretion where the dose was given more than six months ago and there is a high level of clinical concern.

§ Between days 5 to 7 following symptom onset remdesivir may be suitable for high‑risk patients. Where GPs believe this is indicated, this should be escalated to the local LHD lead via the HealthPathways escalation line as prescription cannot occur through the PBS.

Figure 1: Decision pathway: suitability for sotrovimab, casirivimab plus imdevimab, molnupiravir, nirmatrelvir plus ritonavir and remdesivir

Decision pathway. Text alternative follows image.

Text alternative

  • Branch A1: Patient meets eligibility criteria.
    • Branch A2: Is the patient a child or adolescent aged >12 years and weighing >40kg. If no, proceed to branch A3.
      • Branch B1: If yes, consider remdesivir OR monoclonal antibody administration (noting reduced efficacy against Omicron).
    • Branch A3: Is the patient pregnant? If no, proceed to branch A4.
      • Branch B2: If yes, consider remdesivir OR monoclonal antibody administration (noting reduced efficacy against Omicron).
    • Branch A4: Is the patient of childbearing potential or sexually active with a partner of childbearing potential and unable to effectively use suitable contraception? If no, proceed to branch A5.
      • Branch B3: If yes, neither oral antiviral agent is recommended in pregnancy and malnupiravir has potential teratogenic effects. Oral antivirals must only be used in patients of childbearing potential or sexually active with a partner of childbearing potential in conjunction with suitable contraception.
    • Branch A5: Does the patient have pre-existing severe liver disease (Child Pugh class C)? If no, proceed to branch A6.
      • Branch B4: If yes, consider molnupirovir. Nirmatrelvir plus ritonavir causes hepatotoxicity and should not be administered to patients with these pre-existing conditions.
    • Branch A6: Does the patient have pre-existing renal disease? If no, proceed to branch A7.
      • Branch B5: If yes, eGFR <30mL/min. Consider molnupirovir. eGFR 30- 60mL/min. Consider a dose reduction of nimatrelvir plus nitonavir OR molnupiravir.
    • Branch A7: Will the patient have difficulty accessing an infusion clinic? For example, due to poor mobility and/or frailty, geographical location or residential aged care facility (RACF) residents. If no, proceed to branch A8.
      • Branch B6: If yes, consider nirmatrelvir plus ritonovir (unless drug interactions or renal disease (eGFR <30mL/min) preclude its use) OR Molnupirovir (noting nimatrelvir plus ritonavir is preferred where suitable).
    • Branch A8: Patient is suitable for either monoclonal antibody infusion or antiviral agents. Efficacy of monoclonal antibodies against Omicron should inform decision.

References

  1. National Clinical Evidence Taskforce Living Guidelines
  2. NSW Agency for Clinical Innovation. COVID‑19 Critical Intelligence Unit: Monoclonal antibodies - in brief.
  3. NSW Agency for Clinical Innovation. COVID‑19 Critical Intelligence Unit: Omicron (B.1.1.529)
  4. NSW Agency for Clinical Innovation. COVID-19 Critical Intelligence Unit: Paxlovid - in brief 
  5. NSW Agency for Clinical Innovation. COVID-19 Critical Intelligence Unit: Disease modifying treatments for COVID-19 in children – in brief 
  6. NSW Agency for Clinical Innovation. COVID-19 Critical Intelligence Unit: Sotrovimab – in brief 
  7. NSW Agency for Clinical Innovation. COVID-19 Critical Intelligence Unit: Molnupiravir – in brief 
  8. Clinical Excellence Commission. Medication safety updates
  9. Australian Government Department of Health. ATAGI statement on defining ‘up-to-date’ status for COVID‑19 vaccination
  10. Australian Government Department of Health. Clinical recommendations for COVID‑19 vaccines
  11. National Clinical Evidence Taskforce. Living guidelines 6.1.8.1 Sotrovimab for adults
  12. National Clinical Evidence Taskforce. Living guidelines 6.1.1.1 Casirivimab plus imdevimab (Ronapreve) for adults
  13. National Clinical Evidence Taskforce. Risk classification tool for adults with mild COVID-19
  14. National Clinical Evidence Taskforce. Living guidelines 6.1.9.1 Tixagevimab plus cilgavimab (Evusheld) for adults
  15. National Clinical Evidence Taskforce. Living guidelines 6.1.5.3 Nirmatrelvir plus ritonavir (Paxlovid) for children and adolescents
  16. National Clinical Evidence Taskforce. Living guidelines 7.1 Casirivimab plus imdevimab (Ronapreve) for post-exposure prophylaxis
  17. Australian Government Department of Health. The Pharmaceutical Benefits Scheme, Molnupiravir
  18. National Clinical Evidence Taskforce. Living guidelines 6.1.4.1 Molnupiravir (Lagevrio) for adults
  19. Australian Government Department of Health. The Pharmaceutical Benefits Scheme, Nirmatrelvir (&) Ritonavir
  20. National Clinical Evidence Taskforce. Living guidelines 6.1.5.1 Nirmatrelvir plus ritonavir (Paxlovid) for adults
  21. Australian Government Department of Health, Therapeutic Good Administration. Australian Product Information, EvusheldTM (tixagevimab and cilgavimab)
  22. National Clinical Evidence Taskforce. Living guidelines 6.1.7.1 Remdesivir for adults
  23. National Clinical Evidence Taskforce. Living guidelines 6.1.8.2 Sotrovimab for pregnant women
  24. National Clinical Evidence Taskforce. Living guidelines 6.1.8.3 Sotrovimab for children and adolescents
  25. National Clinical Evidence Taskforce. Living guidelines 6.1.1.2 Casirivimab plus imdevimab (Ronapreve) for pregnant or breastfeeding women
  26. National Clinical Evidence Taskforce. Living guidelines 6.1.1.3 Casirivimab plus imdevimab (Ronapreve) for children and adolescents
  27. National Clinical Evidence Taskforce. Living guidelines 6.1.7.2 Remdesivir for pregnant or breastfeeding women
  28. National Clinical Evidence Taskforce. Living guidelines 6.1.7.3 Remdesivir for children and adolescents

Document information

Developed by

Working Group comprising representatives of the Infectious Diseases CoP, Aged Care CoP, Cancer Care CoP, Respiratory CoP, Care in the Community CoP, Drug and Therapeutics CoP, Emergency Department CoP, General Practice, Intensive Care CoP, Agency for Clinical Innovation, Clinical Excellence Commission, Ministry of Health.

Consultation

  • Ministry of Health
  • Clinical Excellence Commission.

This document has been informed by the National Clinical Evidence Taskforce guidance.

Endorsed by

Deb Willcox, Deputy Secretary, Health System Strategy and Planning

For use by

Health services and clinicians assessing patients suitable for sotrovimab infusion and its administration:

  • COVID‑19 response teams
  • Community services and Hospital in the Home
  • Respiratory, Infectious Diseases, Immunology
  • Drug and Therapeutics Committees
  • Cancer care and blood and marrow transplant services.


Current as at: Monday 21 November 2022
Contact page owner: Health Protection NSW