What are the dosing guidelines for Paxlovid (nirmatrelvir/ritonavir) in an adult COVID-19 patient with impaired renal function?

How to Write a Paxlovid Prescription

Standard Dosing Regimen

For patients with normal or mildly impaired renal function (eGFR ≥60 mL/min), prescribe nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one 100 mg tablet), all three tablets taken together twice daily for 5 days. 1

• Initiate treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
• Administer at approximately the same time each day, with or without food 1
• The total prescription requires 30 nirmatrelvir tablets (150 mg) and 10 ritonavir tablets (100 mg) 1

Dose Adjustments for Renal Impairment

Moderate Renal Impairment (eGFR 30-59 mL/min)

Reduce the dose to nirmatrelvir 150 mg (one 150 mg tablet) with ritonavir 100 mg (one 100 mg tablet) twice daily for all 5 days. 1, 2

• This requires 10 nirmatrelvir tablets (150 mg) and 10 ritonavir tablets (100 mg) total 1

Severe Renal Impairment (eGFR <30 mL/min, Including Hemodialysis)

Prescribe nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one 100 mg tablet) once on Day 1, then nirmatrelvir 150 mg (one 150 mg tablet) with ritonavir 100 mg (one 100 mg tablet) once daily on Days 2-5. 1

• On hemodialysis days, administer the dose after dialysis 1
• This requires 6 nirmatrelvir tablets (150 mg) and 5 ritonavir tablets (100 mg) total 1

Critical Pre-Prescribing Requirements

Absolute Contraindications - Do Not Prescribe If:

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir 1
• Patient is taking any contraindicated medication (see drug interaction section below) 1
• Severe hepatic impairment (Child-Pugh Class C) 1

Mandatory Drug Interaction Check

Before prescribing, use the Liverpool COVID-19 Drug Interaction Tool to systematically check all patient medications, as ritonavir is a strong CYP3A inhibitor that can cause severe, life-threatening, or fatal drug interactions. 2, 1

Common contraindicated medications include: 1

• Statins: lovastatin, simvastatin
• Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine
• Anticonvulsants: carbamazepine, phenobarbital, phenytoin
• Benzodiazepines: oral midazolam, triazolam
• Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
• PDE5 inhibitors: sildenafil (Revatio) for pulmonary arterial hypertension
• St. John's Wort and other potent CYP3A inducers (rifampin, rifapentine) 1

Required Laboratory Assessment

Check renal function (eGFR) and hepatic function (ALT/AST) before prescribing to determine appropriate dosing and identify contraindications. 2, 1

• Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury 2

Patient Selection Criteria

Prescribe Paxlovid for non-severe COVID-19 patients at high risk for hospitalization, including: 2

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

Prescription Writing Details

For Normal/Mild Renal Impairment (eGFR ≥60 mL/min):

• Nirmatrelvir 150 mg tablets: Dispense 30 tablets
• Ritonavir 100 mg tablets: Dispense 10 tablets
• Directions: Take 2 nirmatrelvir tablets with 1 ritonavir tablet by mouth twice daily for 5 days

For Moderate Renal Impairment (eGFR 30-59 mL/min):

• Nirmatrelvir 150 mg tablets: Dispense 10 tablets
• Ritonavir 100 mg tablets: Dispense 10 tablets
• Directions: Take 1 nirmatrelvir tablet with 1 ritonavir tablet by mouth twice daily for 5 days

For Severe Renal Impairment (eGFR <30 mL/min):

• Nirmatrelvir 150 mg tablets: Dispense 6 tablets
• Ritonavir 100 mg tablets: Dispense 5 tablets
• Directions: Take 2 nirmatrelvir tablets with 1 ritonavir tablet by mouth once on Day 1, then take 1 nirmatrelvir tablet with 1 ritonavir tablet by mouth once daily on Days 2-5. If on hemodialysis, take dose after dialysis.

Critical Patient Counseling Points

• Missed dose instructions: If missed within 8 hours of scheduled time, take as soon as possible; if more than 8 hours late, skip the missed dose and resume normal schedule—never double dose 1
• Common adverse effects: Dysgeusia (altered taste) and diarrhea occur more frequently but rarely lead to discontinuation 2
• Hypersensitivity warning: Immediately discontinue and seek medical attention if signs of allergic reaction develop (rash, hives, difficulty swallowing/breathing, angioedema) 1
• Complete the full course: Take all doses for 5 days even if feeling better 1

Special Monitoring Considerations

Patients older than 65 years have significantly higher plasma concentrations and increased risk of drug accumulation (odds ratio 11.2), warranting closer monitoring for adverse effects. 3

• Monitor for signs of drug toxicity, particularly in elderly patients with renally eliminated comedications 3
• Therapeutic drug monitoring may be considered in complex cases, though not routinely required 3