What is the recommended Paxlovid (nirmatrelvir/ritonavir) dosing for an outpatient adult with mild‑to‑moderate COVID‑19 within five days of symptom onset, including adjustments for eGFR 30–60 mL/min and contraindications?

Paxlovid Dosing for COVID-19

Standard Dosing Regimen

For adults with mild-to-moderate COVID-19, prescribe nirmatrelvir 300 mg (two 150 mg tablets) plus ritonavir 100 mg (one 100 mg tablet) taken together orally twice daily for 5 consecutive days, initiated as soon as possible and within 5 days of symptom onset. 1

• Treatment must be started within the 5-day window from symptom onset to achieve clinical benefit in reducing hospitalization and death 2, 1
• All three tablets should be taken together at approximately the same time each day, with or without food 1
• Nirmatrelvir must always be co-administered with ritonavir; they cannot be used separately 1

Dose Adjustments for Renal Impairment

For patients with moderate renal impairment (eGFR 30–60 mL/min), reduce the dose to nirmatrelvir 150 mg (one 150 mg tablet) plus ritonavir 100 mg (one 100 mg tablet) twice daily for all 5 days. 2, 1

For patients with severe renal impairment (eGFR <30 mL/min), including those on hemodialysis:

• Day 1: nirmatrelvir 300 mg (two 150 mg tablets) plus ritonavir 100 mg (one 100 mg tablet) once daily 1
• Days 2–5: nirmatrelvir 150 mg (one 150 mg tablet) plus ritonavir 100 mg (one 100 mg tablet) once daily 1
• On hemodialysis days, administer Paxlovid after dialysis is completed 1

Important caveat: Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury and worsen renal function 2

Contraindications to Paxlovid

Do not prescribe Paxlovid in the following situations:

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir 1
• Severe hepatic impairment (Child-Pugh Class C), as safety and pharmacokinetic data are lacking 2, 1
• Concurrent use of drugs highly dependent on CYP3A4 for clearance where elevated concentrations cause serious or life-threatening reactions 1
• Concurrent use of potent CYP3A inducers that would significantly reduce nirmatrelvir/ritonavir levels and risk treatment failure 1

Critical Drug-Drug Interaction Management

Before prescribing Paxlovid, systematically check all concomitant medications using the Liverpool COVID-19 Drug Interaction Tool, as ritonavir is a potent CYP3A4 inhibitor that causes potentially life-threatening drug interactions. 2, 3, 1, 4

High-risk medications requiring specific management:

• Statins: Temporarily discontinue simvastatin and lovastatin during Paxlovid treatment due to myopathy risk; atorvastatin may be continued at reduced doses with close monitoring for muscle symptoms, or consider switching to pravastatin or fluvastatin 3, 4
• Antiarrhythmics: Avoid amiodarone, flecainide, and propafenone due to serious cardiac toxicity risk 3
• Anticoagulants: Rivaroxaban is contraindicated; other anticoagulants may require dose adjustment or temporary discontinuation 3, 4
• Ranolazine: Absolutely contraindicated due to QT prolongation and torsades de pointes risk when combined with CYP3A4 inhibition 2

The interaction risk extends several days beyond the 5-day treatment course due to ritonavir's prolonged effects on drug metabolism. 3, 5

Special Populations

Pregnancy: Paxlovid may be offered to pregnant persons to reduce disease progression, hospitalization, and death; no serious adverse reactions have been reported in WHO pharmacovigilance databases to date 2, 1

Age and weight restrictions:

• Not approved for patients younger than 12 years 2
• Not approved for patients weighing less than 40 kg 2

Immunosuppressed patients (transplant recipients): When prescribing Paxlovid, hold or reduce mycophenolate or azathioprine during the 5-day treatment course, particularly if pneumonia, lymphopenia, or persistent fever develops; continue maintenance corticosteroids to prevent adrenal insufficiency 2

Common Adverse Effects

Monitor patients for dysgeusia (altered taste) and diarrhea, which occur more frequently than placebo but rarely necessitate discontinuation 2, 1

Watch for potential hepatotoxicity, as hepatic transaminase elevations have been reported with ritonavir 1

Patient Selection Criteria

Paxlovid is indicated for adults at high risk for progression to severe COVID-19, including:

• Age ≥65 years 2
• Immunocompromised status (including hematological malignancies, transplant recipients) 2
• Unvaccinated or vaccine non-responders 2