PAXLOVID

What it is

PAXLOVID contains nirmatrelvir tablets co-packaged with ritonavir tablets. Each nirmatrelvir film-coated tablet contains 150 mg of nirmatrelvir. Each ritonavir film-coated tablet contains 100 mg ritonavir. Nirmatrelvir tablets are oval, pink immediate-release, film-coated tablets debossed with "PFE" on one side and "3CL" on the other side. 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.

Approved indications

— Treatment of coronavirus disease 2019 (COVID-19) in adults 18 years of age and older, who do not require initiation of supplemental oxygen due to COVID-19 and are at increased risk of progression to hospitalisation or death.

Dosing overview

The recommended dosage is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together orally every 12 hours for 5 days. PAXLOVID should be taken as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptoms onset even if baseline COVID-19 symptoms are mild. PAXLOVID (both nirmatrelvir and ritonavir tablets) can be taken with or without food. In patients with moderate renal impairment, the dose of PAXLOVID should be reduced to nirmatrelvir/ritonavir 150 mg/100 mg every 12 hours for 5 days to avoid increased toxicity due to over-exposure (this dose adjustment has not been clinically tested). PAXLOVID is contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73m²) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined.

Key safety warnings

Initiation of PAXLOVID, a CYP3A inhibitor, in patients receiving medicinal products metabolised by CYP3A or initiation of medicinal products metabolised by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medicinal products metabolised by CYP3A. Initiation of medicinal products that inhibit or induce CYP3A may increase or decrease concentrations of PAXLOVID, respectively. These interactions may lead to clinically significant adverse reactions, potentially leading to severe, life-threatening or fatal events from greater exposures of concomitant medications, clinically significant adverse reactions from greater exposures of PAXLOVID, or loss of therapeutic effect of PAXLOVID and possible development of viral resistance. Severe, life-threatening, and fatal adverse reactions due to drug interactions have been reported in patients treated with PAXLOVID. Anaphylaxis, hypersensitivity reactions, and serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported with PAXLOVID. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. Hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering PAXLOVID to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. As nirmatrelvir is co-administered with low dose ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.

Contraindications

PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions to its active ingredients (nirmatrelvir/ritonavir) or any other components of the product. PAXLOVID is contraindicated in patients with severe renal impairment. PAXLOVID is contraindicated in patients with severe hepatic impairment. PAXLOVID is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. PAXLOVID is contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.

PBS listing

In November 2023, PBAC provided advice regarding nirmatrelvir and ritonavir for high-risk patients with mild to moderate COVID-19. PBAC maintained previous advice of greater efficacy over molnupiravir and recommended change to restriction for patients aged 50–69 years and price reduction due to declined cost-effectiveness.

Regulatory history

PAXLOVID nirmatrelvir 150 mg tablet and ritonavir 100 mg tablet blister composite pack was first listed on the ARTG on 2022-01-20. An AusPAR was approved on 2024-08-26. The TGA approved Paxlovid for the treatment of COVID-19 in adults 18 years of age and older who do not require supplemental oxygen and are at increased risk of progression to hospitalisation or death. PAXLOVID is subject to additional monitoring in Australia. This will allow quick identification of new safety information.