What is the recommended dosage of PAXLOVID (nirmatrelvir and ritonavir) for COVID-19 treatment?

PAXLOVID Dosage for COVID-19

Standard Dosing Regimen

The recommended dosage of PAXLOVID for COVID-19 treatment is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days. 1

• Treatment must be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
• All three tablets should be taken together at approximately the same time each day 1
• PAXLOVID can be administered with or without food 1
• Nirmatrelvir must always be co-administered with ritonavir; nirmatrelvir should never be given alone 1

Dose Adjustments for Renal Impairment

Renal function is the primary determinant requiring dose modification, as nirmatrelvir is primarily eliminated renally when co-administered with ritonavir. 1, 2

Moderate Renal Impairment (eGFR ≥30 to <60 mL/min)

• Reduce dose to 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for all 5 days 1, 3

Severe Renal Impairment (eGFR <30 mL/min, including hemodialysis)

• Day 1: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) once daily 1
• Days 2-5: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) once daily 1
• On hemodialysis days, administer PAXLOVID after hemodialysis 1
• Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury 4

Normal Renal Function or Mild Impairment

• No dose adjustment necessary; use standard dosing 1, 3

Hepatic Impairment Considerations

• PAXLOVID is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1
• No dose adjustment is required for mild to moderate hepatic impairment 1
• Monitor for hepatotoxicity, as hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred with ritonavir 1

Critical Drug Interaction Management

Before prescribing PAXLOVID, always check for drug-drug interactions using the Liverpool COVID-19 Drug Interaction Tool, as ritonavir is a strong CYP3A inhibitor that can cause potentially life-threatening interactions. 5, 4, 1

High-Risk Contraindicated Medications

• Drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious or life-threatening reactions are contraindicated 1
• Potent CYP3A inducers are contraindicated as they may reduce nirmatrelvir/ritonavir concentrations and lead to loss of virologic response 1
• Specific high-risk interactions include certain antiarrhythmics, anticoagulants, and some statins 5

Duration of Interaction Risk

• The risk of drug interactions extends beyond the 5-day treatment period due to ritonavir's prolonged effects on drug metabolism and clearance 5
• Medications may require dose adjustment, temporary interruption, or additional monitoring 1

Special Populations

Pediatric Patients (12 to <18 years)

• Adolescents weighing ≥40 kg should receive the standard adult dose of 300 mg nirmatrelvir with 100 mg ritonavir twice daily 3

Pregnancy

• PAXLOVID may be an option for pregnant individuals to reduce disease progression, though uncertainty exists regarding potential serious adverse reactions 4
• No reports of serious adverse reactions in parent or child have been documented in WHO Vigibase to date 4

Elderly Patients

• Patients older than 65 years have significantly higher plasma trough concentrations and increased risk of excessive drug levels compared to younger patients 6
• Standard dosing applies unless renal impairment is present, but closer monitoring for adverse effects is warranted 6

Common Adverse Effects

• Dysgeusia (altered taste) and diarrhea are the most common adverse reactions, occurring in 5.8% and 2.1% of patients respectively 1, 7
• These adverse effects did not lead to increased drug discontinuation rates in clinical trials 4
• Monitor for signs of drug accumulation, particularly in patients with renal impairment 4

Patient Selection Criteria

• PAXLOVID is indicated for adults with mild-to-moderate COVID-19 who are at high risk for progression to severe disease, including hospitalization or death 1
• The medication is not approved for pre-exposure or post-exposure prophylaxis 1
• In standard-risk or fully vaccinated patients with only one risk factor, efficacy data are limited and the benefit may be less clear 7