What is the recommended dose of Paxlovid (nirmatrelvir/ritonavir) for a 40-year-old female patient with normal kidney function and a confirmed diagnosis of COVID-19?

Paxlovid Dosing for a 40-Year-Old Female with COVID-19

For a 40-year-old female with normal kidney function and confirmed COVID-19, administer Paxlovid as 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days. 1

Standard Dosing Regimen

• Administer 300 mg nirmatrelvir plus 100 mg ritonavir twice daily for 5 days in patients with normal renal function (eGFR ≥60 mL/min). 1, 2
• All three tablets (two nirmatrelvir 150 mg tablets and one ritonavir 100 mg tablet) should be taken together at approximately the same time each day. 1
• Treatment can be taken with or without food. 1

Critical Timing Requirements

• Initiate treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset for optimal effectiveness. 1, 2, 3
• Treatment started beyond 5 days of symptom onset has not been studied and is not recommended. 3

Mandatory Pre-Treatment Assessment

Before prescribing Paxlovid, you must:

• Check renal function (eGFR) to determine if dose adjustment is needed. 1, 4
• Review ALL current medications using the Liverpool COVID-19 Drug Interaction Tool, as ritonavir is a potent CYP3A4 inhibitor causing potentially life-threatening drug interactions. 3, 1
• Assess hepatic function (ALT, AST) at baseline. 2, 3
• Confirm the patient is not pregnant, as safety data in pregnancy are limited. 3

Dose Modifications for Renal Impairment

If renal function is impaired, adjust dosing as follows:

• Moderate renal impairment (eGFR 30-59 mL/min): Reduce to 150 mg nirmatrelvir with 100 mg ritonavir twice daily for all 5 days. 1, 4
• Severe renal impairment (eGFR <30 mL/min): Give 300 mg nirmatrelvir with 100 mg ritonavir once on day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily on days 2-5. 1
• For patients on hemodialysis, administer the dose after dialysis on dialysis days. 1

The dose reduction in moderate renal impairment is necessary because nirmatrelvir exposure increases by 187% compared to normal renal function, and by 304% in severe renal impairment. 4

Absolute Contraindications

Do not prescribe Paxlovid if:

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir. 1
• Concomitant use of drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions (e.g., simvastatin, lovastatin, certain antiarrhythmics). 1, 3
• Concomitant use of potent CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) that would reduce nirmatrelvir levels and risk treatment failure. 1
• Severe hepatic impairment (Child-Pugh Class C). 1

Patient Selection Criteria

Paxlovid is indicated for:

• High-risk patients with mild-to-moderate COVID-19 who are at risk for progression to severe disease, hospitalization, or death. 1, 2
• High-risk factors include age ≥65 years, immunocompromised status, unvaccinated status, or significant comorbidities. 3

For a 40-year-old female, assess whether she has risk factors such as immunosuppression, diabetes, obesity, chronic lung disease, or other conditions that increase her risk of severe COVID-19. 3

Common Adverse Effects to Anticipate

• Dysgeusia (altered taste) and diarrhea are the most common adverse effects, occurring in >1% of patients. 1, 3
• These effects are generally mild and do not require treatment discontinuation. 3

Critical Drug Interaction Management

Ritonavir causes significant drug interactions that persist during treatment and for several days after completion:

• Statins: Temporarily discontinue simvastatin and lovastatin; reduce atorvastatin dose to maximum 20 mg daily. 3
• Antiarrhythmics: Many are contraindicated (amiodarone, flecainide, propafenone). 1
• Immunosuppressants: Tacrolimus, cyclosporine require dose reduction and monitoring. 3
• Anticoagulants: Rivaroxaban, apixaban may require dose adjustment. 3

Monitoring During Treatment

• Reassess renal function if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury. 3
• Monitor for signs of hepatotoxicity (elevated transaminases, jaundice), though this is uncommon. 1
• Watch for hypersensitivity reactions including anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis—discontinue immediately if these occur. 1

Special Considerations for This Patient

For a 40-year-old female specifically:

• Age alone does not place her at high risk, so confirm she has at least one additional risk factor before prescribing. 3
• If she is of childbearing potential, discuss pregnancy status, as Paxlovid may be used in pregnancy to reduce disease progression, though data are limited. 3
• Effectiveness does not vary by sex, so standard dosing applies. 2