What is the recommended dose of Paxlovid (nirmatrelvir and ritonavir) for an adult patient with normal renal function or impaired renal function for the treatment of COVID-19?

Paxlovid Dosing for COVID-19

For adults with normal renal function (eGFR ≥60 mL/min), administer nirmatrelvir 300 mg with ritonavir 100 mg orally twice daily for 5 days, starting within 5 days of symptom onset. 1, 2

Standard Dosing Regimen

The standard dose consists of three tablets taken together twice daily: two 150 mg nirmatrelvir tablets plus one 100 mg ritonavir tablet, administered approximately every 12 hours for a total of 5 days. 1, 2

• Treatment must be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset for optimal effectiveness. 1, 3
• Administer with or without food at approximately the same time each day. 2
• Nirmatrelvir must always be co-administered with ritonavir; never give nirmatrelvir alone. 1, 2

Dose Adjustments for Renal Impairment

Moderate renal impairment (eGFR 30-59 mL/min): Reduce dose to nirmatrelvir 150 mg (one tablet) with ritonavir 100 mg (one tablet) twice daily for all 5 days. 1, 2, 4

Severe renal impairment (eGFR <30 mL/min), including hemodialysis patients:

• Day 1: nirmatrelvir 300 mg (two tablets) with ritonavir 100 mg (one tablet) as a single dose
• Days 2-5: nirmatrelvir 150 mg (one tablet) with ritonavir 100 mg (one tablet) once daily
• For hemodialysis patients, administer after dialysis on dialysis days. 2

Monitor renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury requiring reassessment of dosing. 3

Hepatic Impairment Considerations

Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). 2

• Use with caution in patients with severe liver impairment, as these patients were excluded from clinical trials. 1
• Monitor for hepatotoxicity, as hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred with ritonavir. 2

Critical Drug Interaction Management

Before prescribing Paxlovid, review all patient medications using the Liverpool COVID-19 Drug Interaction Tool, as ritonavir is a potent CYP3A inhibitor causing potentially life-threatening drug interactions. 1, 3, 2

• Ritonavir causes drug interactions during active treatment and for several days after completion. 1
• Certain medications are absolutely contraindicated with Paxlovid due to risk of serious or life-threatening events from elevated drug concentrations. 2
• Some concomitant medications require dose adjustment, temporary interruption, or additional monitoring. 2
• Do not co-administer with potent CYP3A inducers, as this may lead to loss of virologic response and possible resistance. 2

Common Adverse Effects

Dysgeusia (altered taste) and diarrhea are the most common adverse effects, occurring more frequently than placebo but rarely leading to treatment discontinuation. 1

• These adverse effects did not increase drug discontinuation rates in clinical trials. 3
• Hypersensitivity reactions including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome have been reported; discontinue immediately if these occur. 2

Special Population Considerations

Pregnant patients: Paxlovid may be used to reduce disease progression risk, though uncertainty exists regarding potential serious adverse reactions. No reports of serious adverse reactions in parent or child have been documented in WHO Vigibase to date. 1

HIV-positive patients: Use may lead to HIV-1 developing resistance to protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. 2

Pediatric patients (12 to <18 years) weighing ≥40 kg: Use the standard adult dose of nirmatrelvir/ritonavir 300/100 mg twice daily. 4