What is the recommended dosing regimen for Paxlovid (nirmatrelvir/ritonavir) in a patient with confirmed COVID-19, considering factors such as age, weight, renal function, and history of liver disease?

Paxlovid Dosing Recommendations

The standard dose of Paxlovid is nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one 100 mg tablet), taken together twice daily for 5 days, with dose reduction required for moderate-to-severe renal impairment. 1

Standard Dosing Regimen

• Initiate treatment within 5 days of COVID-19 symptom onset for maximum efficacy 1, 2
• Administer all three tablets together (two nirmatrelvir 150 mg + one ritonavir 100 mg) twice daily at approximately the same time each day 1
• Can be taken with or without food 1
• Complete the full 5-day course regardless of symptom improvement 1

Renal Function-Based Dose Adjustments

Normal renal function or mild impairment (eGFR ≥60 mL/min):

• Standard dose: 300 mg nirmatrelvir/100 mg ritonavir twice daily for 5 days 1

Moderate renal impairment (eGFR 30-59 mL/min):

• Reduced dose: 150 mg nirmatrelvir (one tablet)/100 mg ritonavir twice daily for 5 days 1, 3
• This reduction is critical as nirmatrelvir exposure increases by 187% in moderate renal impairment 3

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

• Day 1: 300 mg nirmatrelvir/100 mg ritonavir once daily 1
• Days 2-5: 150 mg nirmatrelvir/100 mg ritonavir once daily 1
• For hemodialysis patients, administer after dialysis on dialysis days 1
• Nirmatrelvir exposure increases by 304% in severe renal impairment, necessitating this substantial dose reduction 3

Hepatic Impairment Considerations

• No dose adjustment needed for mild-to-moderate hepatic impairment (Child-Pugh Class A or B) 1
• Paxlovid is NOT recommended in severe hepatic impairment (Child-Pugh Class C) as these patients were excluded from clinical trials 1

Age and Weight Considerations

• Adults and adolescents ≥12 years weighing ≥40 kg: Use standard adult dosing 1, 4
• Patients <40 kg: Paxlovid is not authorized for use 1
• Elderly patients (>65 years) achieve significantly higher plasma concentrations and require careful monitoring but no routine dose adjustment 5
• Body weight influences nirmatrelvir clearance through allometric scaling, but this is already accounted for in standard dosing 4

Critical Monitoring Parameters

Before initiating treatment:

• Calculate eGFR to determine appropriate dose 1, 3
• Review all concomitant medications for potential drug interactions, particularly CYP3A4 substrates 2
• Assess liver function if pre-existing liver disease is present 1

During treatment:

• Monitor for common adverse effects including dysgeusia (altered taste), diarrhea, and nausea—these are typically mild and do not require discontinuation 2
• In elderly patients or those with borderline renal function, consider monitoring renal function during treatment as COVID-19 itself can cause acute kidney injury 5
• Watch for signs of drug interactions, particularly with narrow therapeutic index medications 2

Common Pitfalls to Avoid

• Do not delay treatment while waiting for comprehensive drug interaction review—use the Liverpool COVID-19 Drug Interaction Tool for rapid assessment and initiate within 5 days of symptom onset 6, 1
• Do not use standard dosing in moderate renal impairment—the 187% increase in exposure necessitates dose reduction to prevent toxicity 3
• Do not prescribe for patients with severe hepatic impairment as safety data are lacking 1
• Do not assume age alone requires dose adjustment—while elderly patients achieve higher concentrations, dose modifications are based solely on renal function 5
• Do not discontinue for mild gastrointestinal symptoms (dysgeusia, diarrhea)—these are expected and self-limiting 2

Special Clinical Scenarios

Patients on anticoagulation (e.g., apixaban):

• Maintain anticoagulant dosing schedule but increase monitoring for bleeding due to ritonavir's CYP3A4 inhibition 6
• Do not delay Paxlovid initiation due to anticoagulation concerns—the interaction is manageable 6

Patients with multiple comorbidities:

• Renal function takes precedence over other factors in dose determination 1, 3
• Advanced age combined with renally eliminated comedications increases risk of excessive plasma concentrations 5