News

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What GPs need to know about the new COVID antivirals

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UPDATED, December 2022: This article was first published in February 2022. It was updated in May to reflect that the oral antiviral treatments are now available on the Pharmaceutical Benefits Scheme (PBS) and also includes the specific PBS eligibility criteria for both. The article was subsequently updated in July to reflect expanded eligibility. In December, the article was updated to reflect further eligiblity expansion, as well as to incorporate new advice that molnupiravir should no longer be routinely used to treat COVID-19.

Nirmatrelvir in combination with ritanovir (sold as Paxlovid) and molnupiravir (sold as Lagevrio) are now available on the PBS in Australia for the treatment of COVID-19. They were provisionally approved for use in Australia by the Therapeutic Goods Administration (TGA) in January 2022.

There have been a number of webinars held by the Department of Health (DoH) discussing the treatments and their presciption in primary care. See the 2 May webinar for the most recent information. 

The eligibility criteria for PBS prescription of the two treatments, as well as their contraindications, are outlined below.

Lagevrio
See the PBS listing here. 
  
Indications
Access to PBS subsidised prescriptions is available for adults who have mild-to-moderate COVID-19 confirmed by a PCR or medically verified rapid antigen test and who can start treatment within five days of symptom onset or as soon as possible after diagnosis is confirmed where asymptomatic, if they:

• are aged 70 or older
• are aged 50 or older with two additional risk factors for severe disease
• are aged 30 or older and identify as Aboriginal or Torres Strait Islander, with one additional risk factor for severe disease
• are aged over 18 and moderately to severely immunocompromised.

Dosage
Four capsules every 12 hours (for example, at 8 am and at 8 pm), for five days. Lagevrio can be taken with or without food, but patients should not open, break, or crush the capsules.
 
Contraindications
While not considered a high risk in residential aged care facilities (RACFs), it is especially important to note that Lagevrio is not recommended in pregnancy. 
 
Patients must use effective birth control while taking Lagevrio and for four days after stopping if there is a possibility of them getting pregnant.
 
Male patients who are sexually active with a partner who could become pregnant should use a reliable method of contraception during treatment and for three months after their last dose.
 
Likewise, breastfeeding is not recommended during treatment and for four days after the last dose of Lagevrio.
 
If there are contraindications to Lagevrio then Paxlovid may be considered, however; there are also many significant drug interactions to note with Paxlovid and GPs must make a special application to state and territory authorities to gain access.
 
There are no known drug interactions identified with Lagevrio based on the limited data that is currently available. The most common side effects are diarrhoea, nausea and dizziness.

However, the National COVID-19 Clinical Evidence Taskforce recently updated its listing for Lagevrio to ‘do not routinely use’ after determining that that there is now ‘high certainty evidence’ that it does not impact hospitalisation and/or mortality rates in multiply-vaccinated adults with one or more risk factors for disease progression.
 
Paxlovid
See the PBS listing here. 
 
Paxlovid is a medicine that has two different tablets; one containing the active ingredient, nirmatrelvir (pink oval tablet) and the other containing the active ingredient, ritonavir, (white oval tablet). They must be taken as instructed in order to be effective against COVID-19.
 
As with molnupiravir, access to PBS subsidised prescriptions is available for adults who have mild-to-moderate COVID-19 confirmed by a PCR or medically verified rapid antigen test and who can start treatment within five days of symptom onset, if they:
 

• are aged 70 or older
• are aged 50 or older with two additional risk factors for severe disease
• are aged 30 or older and identify as Aboriginal or Torres Strait Islander, with one further risk factor for severe disease
• are aged over 18 and moderately to severely immunocompromised.

Contraindications
There are a number of potential complex and serious drug–drug interactions that can result in severe or life-threatening side effects, or reduce the drugs’ effectiveness against COVID-19.
 
Paxlovid is contraindicated with the following drugs:
 

• Alfuzosin, medicine to treat an enlarged prostate
• Ranolazine, medicine to treat chronic chest pain (angina)
• Pethidine, and Piroxicam, medicine to relieve pain
• Amiodarone, and Flecainide, medicine to correct or change heart rhythm or lower blood pressure
• Neratinib, Apalutamide, and Venetoclax, medicine to treat certain types of cancers
• Colchicine, medicine to treat gout
• Lurasidone, and Clozapine medicine to treat certain mental and emotional health conditions
• Ergometrine, medicine to stop excessive bleeding that may occur following childbirth, miscarriage or termination of pregnancy
• Simvastatin, medicine to lower blood cholesterol
• Sildenafil, Avanafil, Vardenafil, and Tadalafil medicines for erectile dysfunction;
  • Sildenafil, medicine to treat high blood pressure in the lungs;
  • Tadalafil, medicine for urinary difficulties due to an enlarged prostate
• Diazepam, medicine to assist anxiety, agitation or muscle spasms, spasticity
• Carbamazepine, Phenobarbital, Phenytoin medicine to treat epilepsy to prevent convulsions, fits
• Rifampicin, medicine to treat tuberculosis
• St. John’s Wort (hypericum perforatum), a herbal remedy used for depression and anxiety

In addition, the following drugs have the potential for complex and serious drug–drug interactions that can result in severe or life-threatening side effects, or reduce the drugs’ effectiveness against COVID-19:
 

• Fentanyl, and Methadone, medicine to treat pain
• Digoxin, medicine to treat certain heart conditions 
• Lidocaine, medicine to correct or change heart rhythm
• Atinib, Abemaciclib, Ceritinib, Dasatinib, Nilotinib, Encorafenib, Ibrutinib, Vinblastine, and Vincristine, medicine to treat certain types of cancer 
• Haloperidol, Risperidone, and Quetiapine, medicine to treat certain mental and emotional conditions
• Rivaroxaban, and Warfarin, medicine to treat or prevent blood clots
• Lamotrigine, medicine to prevent or treat convulsions, fits
• Amitriptyline, Fluoxetine, Imipramine, Nortriptyline, Paroxetine, and Sertraline, medicine to treat depression
• Loratadine, medicine to treat allergies 
• Atovaquone, Clarithromycin, Erythromycin, Rifabutin, Ketoconazole, Isavuconazonium Sulfate, Voriconazole, and Itraconazole, medicine to treat infections
• Atazanavir, Darunavir, Efavirenz, Fosamprenavir, Maraviroc, Nevirapine, Saquinavir, Tipranavir, Raltegravir, Zidovudine, Bictegravir/Emtricitabine/Tenofovir, medicine to treat HIV
• Glecaprevir/Pibrentasviror, Sofosbuvir/Velpatasvir/Voxilaprevir, medicine to treat hepatitis C 
• Salmeterol, medicine to treat severe lung conditions, including asthma and chronic obstructive pulmonary disease (COPD)
• Amlodipine, Diltiazem, Felodipine, and Nifedipine, medicine to treat angina or lower blood pressure
• Bosentan, and Riociguat, medicine to treat high blood pressure in the lungs 
• Ethinylestradiol, medicine to treat hormone deficiency or for contraception 
• Ciclosporin, Everolimus, Tacrolimus, and Sirolimus, medicine to suppress the immune system 
• Atorvastatin, and Rosuvastatin, medicine to lower cholesterol
• Alprazolam, Midazolam, and Zolpidem, medicine to help you sleep 
• Bupropion, a medicine to assist in giving up smoking 
• Betamethasone, Budesonide, Dexamethasone, Prednisone, Methylprednisolone, and Triamcinolone, medicine to treat various inflammatory conditions

The combination treatment should also not be prescribed to patients who are allergic to nirmatrelvir and/or ritonavir, nor any of the ingredients listed in the CMI.
 
There is no available clinical data on Paxlovid in pregnancy or with breast feeding. In animal studies, reduced fetal body weights were seen at around 10 times the nirmatrelvir exposure seen in humans with the authorised dose; no other adverse developmental effects were seen.
 
Paxlovid is not recommended for patients with severe liver or kidney disease, but can be prescribed at a lower dose for patients with moderate kidney disease.
 
Dosage
The standard dose of Paxlovid is two 150 mg tablets of nirmatrelvir, together with one 100 mg tablet of ritonavir. Patients with reduced kidney function can be prescribed a lower dose of one 150 mg tablet of nirmatrelvir with one 100 mg tablet of ritonavir.
 
Both tablets must be taken together with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed.
 

eGFR*	Paxlovid dose
Greater than 60 mL/min (normal renal function or mild renal impairment)	300 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for five days
≥30 to ≥60 mL/min (moderate renal impairment)	150 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for five days
<30mL/min (severe renal impairment)	Paxlovid is not recommended (the appropriate dose has not been determined)

 
*eGFR = estimated glomerular filtration rate based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula
 
Pronunciation
Mol-nu-pir-a-veer or La-gev-rio
Nirma-trel-vir and rit-on-a-vir or Pax-Lovid
 
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Aboriginal and Torres Strait Islander health aged care antivirals COVID-19 Lagevrio molnupiravir nirmatrelvir and ritonavir Paxlovid

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