Therapeutic indications

Paxlovid is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19 

Posology and method of administration

For oral use

Nirmatrelvir must be coadministered with ritonavir. Failure to correctly coadminister nirmatrelvir with ritonavir will result in plasma levels of this active substance that will be insufficient to achieve the desired therapeutic effect. Paxlovid can be taken with or without food. The tablets should be swallowed whole and not chewed, broken or crushed, as no data is currently available.  

Posology 

The recommended dosage is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) all taken together orally every 12 hours for 5 days. Paxlovid should be administered as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset. Completion of the full 5-day treatment course is recommended even if the patient requires hospitalisation due to severe or critical COVID-19 after starting treatment with Paxlovid. If the patient misses a dose of Paxlovid within 8 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more 3 than 8 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.  

Special populations  

Renal impairment

No dose adjustment is needed in patients with mild renal impairment (eGFR ≥ 60 to < 90 mL/min). In patients with moderate renal impairment (eGFR ≥ 30 to < 60 mL/min), the dose of Paxlovid should be reduced to nirmatrelvir/ritonavir 150 mg/100 mg every 12 hours for 5 days to avoid over-exposure (this dose adjustment has not been clinically tested). Paxlovid should not be used in patients with severe renal impairment [eGFR < 30 mL/min, including patients with End Stage Renal Disease (ESRD) under haemodialysis] 

Hepatic impairment 

No dose adjustment of Paxlovid is needed for patients with either mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Paxlovid should not be used in patients with severe hepatic impairment

Concomitant therapy with ritonavir- or cobicistat-containing regimen No dose adjustment of Paxlovid is needed. Patients diagnosed with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection who are receiving ritonavir- or cobicistat-containing regimen should continue their treatment as indicated.  

Paediatric population

The safety and efficacy of Paxlovid in patients below 18 years of age have not been established. No data are available.  

Special warnings and precautions for use 

Risk of serious adverse reactions due to interactions with other medicinal products  

Management of drug-drug interactions (DDIs) in high-risk COVID-19 patients receiving multiple concomitant medications can be complex and require a thorough understanding of the nature and magnitude of interaction with all concomitant medications. In certain patients, a multi-disciplinary approach (e.g., involving physicians and specialists in clinical pharmacology) should be considered for management of DDIs especially if concomitant medications are withheld, their dosage is reduced, or if monitoring of side effects is necessary.  

Effects of Paxlovid on other medicinal products

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

Effects of other medicinal products on Paxlovid

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 medicinal products.

 Clinically significant adverse reactions from greater exposures of Paxlovid.

 Loss of therapeutic effect of Paxlovid and possible development of viral resistance.  

Hypersensitivity reactions 

Anaphylaxis and other hypersensitivity reactions have been reported with Paxlovid. Cases of Toxic Epidermal Necrolysis and Stevens-Johnson syndrome have been reported withritonavir, a component of Paxlovid (refer to Norvir Summary of Product Characteristics). If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue Paxlovid and initiate appropriate medications and/or supportive care.  

Severe renal impairment 

No clinical data are available in patients with severe renal impairment (including patients with ESRD). Based on pharmacokinetic data,the use of Paxlovid in patients with severe renalimpairment could lead to over-exposure with potential toxicity. No recommendation in terms of dose adjustment could be elaborated at this stage pending dedicated investigation. Therefore, Paxlovid should not be used in patients with severe renal impairment (eGFR < 30 mL/min, including patients with ESRD under haemodialysis).  

Severe hepatic impairment 

No pharmacokinetic and clinical data are available in patients with severe hepatic impairment. Therefore, Paxlovid should not be used in patients with severe hepatic impairment. 

Hepatotoxicity  

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.  

Risk of HIV-1 resistance development  

Because nirmatrelvir is coadministered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. 

Excipients 

Nirmatrelvir tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Nirmatrelvir and ritonavir tablets each contain less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. 

Paxlovidinformation

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