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COVID-19 Oral Antiviral Medicine Information

June 2022

Plan now for when your DVA patient gets COVID-19

Covid-19-rapid-response-2022_Insert
December 2022 Update

Nirmatrelvir-ritonavir remains first line for treatment of COVID-19 in adults that have one or more risk factors and do not require supplemental oxygen.

Use the covid interaction checker veteransmates.net.au/covid-checker to assess the safety of nirmatrelvir-ritonavir in your veteran patient. If this combination cannot be used follow the decision tree at covid19evidence.net.au/wp-content/uploads/DECISION-TOOL-DT-FOR-ADULTS.pdf

Molnupiravir should not be used routinely for the treatment of COVID-19. It should be considered for use only if nirmatrelvir and ritonavir is contraindicated or otherwise unsuitable. Nirmatrelvir Plus Ritonavir Interaction Checker

As the COVID-19 pandemic evolves, the role of GPs is becoming even more important for managing at-risk patients in the community.

An estimated 35,000 DVA patients are considered at risk of progressing to severe illness and needing hospitalisation if they develop COVID-19 infection.

Vaccination continues to be the most important and beneficial intervention to prevent severe illness.1

Two oral antiviral medicines may help prevent hospitalisation in such patients. Nirmatrelvir and ritonavir (Paxlovid®) and molnupiravir (Lagevrio®) have been listed on the PBS for use in non-pregnant patients 18 years and older who have at least one symptom and have tested positive by polymerase chain reaction (PCR) or rapid antigen test (RAT) for COVID-19 and meet eligibility criteria.1, 2, 3

PBS criteria

Nirmatrelvir and ritonavir www.pbs.gov.au/medicine/item/12996B

Molnupiravir www.pbs.gov.au/medicine/item/12910L

Covid antivirals are effective in reducing mortality.2, 4, 5, 6, 7 Nirmatrelvir and ritonavir (Paxlovid®) was significantly more effective in clinical trials than molnupiravir (Lagevrio®) at reducing hospitalisation (84% compared to 43%).1, 6 Both medicines must be started within 5 days of diagnosis and should be taken twice a day for 5 days.1, 3, 5, 8

Nirmatrelvir and ritonavir (Paxlovid®)

Is the first choice in high-risk patients, but it has potential for significant drug interactions.3, 5, 6, 9, 10, 11

Potential interactions can be assessed using the COVID-19 medicine interaction checker www.veteransmates.net.au/covid-checker

Covid checker tool

Paxlovid® should not be used in severe hepatic and renal (eGFR < 30 mL/min) impairment and dosage must be reduced in moderate impairment (eGFR > 30 to 59 mL/min).3

Molnupiravir (Lagevrio®)

Although molnupiravir is not known to cause significant drug interactions and does not need dose adjustment in renal or liver impairment, it is significantly less effective than nirmatrelvir and ritonavir at reducing hospitalisation. Because it is potentially teratogenic, male partners of women of reproductive age should use barrier contraception for 3 months after finishing their treatment course.8, 11, 12, 13, 14

These medicines have been provisionally approved based on trials in unvaccinated adults with mild to moderate COVID-19. Evidence for their clinical efficacy and adverse effects continues to accumulate.15 For updated evidence see the COVID Living Guidelines at www.covid19evidence.net.au

Take a structured approach when considering these medicines:

Identify – Identify which of your patients may be at risk of progressing to severe illness.

Prepare – Talk to your patient via TeleMed or face to face (at their next scheduled appointment or organise a recall) about what they should do if they test positive for COVID-19, explaining the need for urgent review if they develop the illness. Check on their vaccination status.

Ask about over the counter medicines like St Johns Wort and recreational drugs.

Use the COVID-19 medicine interaction checker to assess if Paxlovid® can be used www.veteransmates.net.au/covid-checker

If an interaction is identified, the tool will provide one of six suggested actions:

  1. Consider alternative COVID-19 treatment
  2. temporarily cease medicine (this will usually be for 8 days but for some patients it may be longer)
  3. temporarily reduce the dose
  4. continue medicine but monitor for adverse effects
  5. Seek specialist advice (therapeutic efficacy may be affected, seek specialist advice about possibility of withholding current treatment)
  6. Switch medicine (there is a small potential for interaction and there are alternative medicines that can be prescribed for similar indications).

If patient is on a combination product seek pharmacy advice about how to split the components. If the patient uses a Dose Administration Aid (DAA) e.g. Webster-pak®, liaise with the patient’s pharmacist to organise an alternative dose administration system while using nirmatrelvir and ritonavir.

Seek specialist advice if your patient is taking:10

  • chemotherapy or immunotherapy for cancer
  • immunotherapy for rheumatologic and dermatologic conditions
  • opioid substitution
  • disease modifying treatment for multiple sclerosis
  • antiviral medicine for hepatitis or human immunodeficiency virus (HIV)
  • >20 mg prednisolone equivalent daily
  • anti-rejection medicine for organ transplantation.

Support – Offer subsequent visits to answer any concerns and create a plan should your patient become unwell outside of consulting hours. Advise them about using conservative measures to treat mild COVID-19 symptoms at home16 www.racgp.org.au/clinical-resources/covid-19-resources/clinical-care/covid-19-home-care-guidelines

Assess – If your patient tests positive, make sure they are safe to receive treatment at home. If their symptoms suggest that they are deteriorating, organise transfer to an emergency department.

Prescribe – If the patient consents to treatment, meets PBS criteria, is stable and safe to be treated at home, and does not have absolute contraindications, use nirmatrelvir and ritonavir (Paxlovid®) as first line.1, 2, 3, 5, 6, 10, 11 Organise medicine changes as planned (stop and restart potentially interacting medicines as per the interaction checker www.veteransmates.net.au/covid-checker).

Use molnupiravir (Lagevrio®) only if there are absolute contraindications to nirmatrelvir and ritonavir (Paxlovid®).

Although vaccinations have been shown to reduce the risk of long COVID, not enough evidence has been gathered to say whether COVID treatments also reduce the incidence of long COVID.17

Living guidelines at www.covid19evidence.net.au are constantly updated and contain clear and invaluable decision-making tools for GPs.

Practice points

    • Vaccination remains essential. Check your patient’s status and encourage them to have a booster if appropriate.
    • All things COVID change – get advice if you are unsure. All states and territories have specialised COVID-19 clinics and online advice.
    • Refer patients who do not meet PBS criteria but may benefit from oral antivirals or other treatment to state and territory services.
    • Liaise with residential aged care facility (RACF) nursing staff about RACF patients at very high risk of deteriorating and needing hospital admission.16
    • Ritonavir has been used for many years in the treatment of HIV – this may appear as a warning in prescribing software.
    • Side effects are usually mild and well tolerated, nirmatrelvir and ritonavir (Paxlovid®): altered taste, headache, diarrhoea, vomiting; molnupiravir (Lagevrio®): diarrhoea, nausea, dizziness. During trials, no patients ceased treatment because of adverse effects.2, 3, 5, 6, 8, 11
    • The most complete advice on interactions can be found at the Liverpool interaction checker www.covid-druginteractions.org
    • Inhaled budesonide or ciclesonide may increase rate of symptom resolution and prevent hospitalisation and death in patients with mild to moderate disease.1, 18
    • The National Coronavirus Helpline provides clinical and non-clinical advice on COVID-19 and vaccines, 24 hours a day, 7 days a week: 1800 020 080.

References

  1. National COVID-19 Clinical Evidence Taskforce. Caring for people with COVID-19. Available at: www.covid19evidence.net.au/ [Accessed May 2022].
  2. Australian Government Department of Health. Oral treatments for COVID-19. Available at: www.health.gov.au/health-alerts/covid-19/treatments/oral#:~:text=The%20first%20oral%20treatments%20for,on%2018%20January%202022 [Accessed May 2022].
  3. NPS MedicineWise. Antiviral treatments for COVID-19. Available at: www.nps.org.au/coronavirus/antiviral-treatments-for-covid-19 [Accessed May 2022].
  4. Drug and Therapeutics Bulletin. Two new oral antivirals for covid-19: molnupiravir and nirmatrelvir plus ritonavir. BJM. 2022; 60(5): 73-77.
  5. NPS MedicineWise. Nirmatrelvir and ritonavir for COVID-19. Available at: www.nps.org.au/australian-prescriber/articles/nirmatrelvir-and-ritonavir-for-covid-19 [Accessed May 2022].
  6. World Health Organization. Therapeutics and COVID-19: living guidline. Available at: https://app.magicapp.org/#/guideline/nBkO1E/rec/LwrMyv [Accessed May 2022].
  7. Australian Government Department of Health. Therapeutic Goods Administration. TGA provisionally approves two oral COVID-19 treatments, molnupiravir (LAGEVRIO) and nirmatrelvir + ritonavir (PAXLOVID). Available at: www.tga.gov.au/media-release/tga-provisionally-approves-two-oral-covid-19-treatments-molnupiravir-lagevrio-and-nirmatrelvir-ritonavir-paxlovid [Accessed May 2022].
  8. NPS MedicineWise. Molnupiravir for COVID-19. Aust Prescr. 2022; 45(2): 60-60.
  9. Australian Government Department of Health. Therapeutic Goods Administration. Australian product information - Paxlovid (nirmatrelvir/ritonavir tablets). Available at: www.tga.gov.au/sites/default/files/paxlovid-pi.pdf [Accessed May 2022].
  10. Government of South Australia. SA Health. COVID-19: Medication management of mild illness in the outpatient setting clinical guidelines. Available at: www.sahealth.sa.gov.au/wptick s/wcm/connect/public+content/sa+health+internet/conditions/infectious+diseases/covid-19/health+professionals/monoclonal+antibody+infusion+application+for+covid-19+positive+patients [Accessed May 2022].
  11. Cohen P, Gebo K. COVID-19: Outpatient evaluation and management of acute illness in adults. Available at: www.uptodate.com/contents/covid-19-outpatient-evaluation-and-management-of-acute-illness-in-adults [Accessed May 2022].
  12. Australian Government Department of Health. Therapeutic Goods Administration. Australian product information - Lagevrio (molnupiravir) capsules. Available at: https://www.tga.gov.au/sites/default/files/lagevrio-pi.pdf [Accessed May 2022].
  13. Kabinger F, Stiller C, Schmitzová J, Dienemann C, Kokic G, Hillen H et al. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021; 28(9): 740-746.
  14. Extance A. Covid-19: What is the evidence for the antiviral molnupiravir? BMJ. 2022; 377: o926.
  15. Combes I, Legg A, Patterson T, Kelly T, Henderson A, Roberts J. Oral antivirals for mild–moderate COVID‑19: a panacea or a logistical and clinical conundrum? Aust Prescr. 2022; 45: 67-68.
  16. RACGP Home-care guidelines for patients with COVID-19. Available at: www.racgp.org.au/clinical-resources/covid-19-resources/clinical-care/covid-19-home-care-guidelines [Accessed May 2022].
  17. Nature. Can drugs reduce the risk of ling COVID? What scientists know so far. Available at: www.nature.com/articles/d41586-022-00823-y [Accessed May 2022].
  18. Griesel M, Wagner C, Mikolajewska A, Stegemann M, Fichtner F, Metzendorf M et al. Inhaled corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2022; 3: CD015125.