What is the recommended treatment with Paxlovid (nirmatrelvir/ritonavir) for a high-risk patient with confirmed COVID-19 and potentially impaired renal function?

Paxlovid Treatment for High-Risk COVID-19 Patients with Renal Impairment

Consider nirmatrelvir/ritonavir (Paxlovid) for high-risk patients with confirmed mild-to-moderate COVID-19 within 5 days of symptom onset, with mandatory dose reduction for moderate renal impairment (eGFR 30-59 mL/min) to 150 mg nirmatrelvir with 100 mg ritonavir twice daily, and further reduction for severe renal impairment (eGFR <30 mL/min) to a single daily dose after day 1. 1, 2

Patient Selection Criteria

High-risk patients who should receive Paxlovid include: 3, 4

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

The American College of Physicians supports use of nirmatrelvir/ritonavir combination therapy for symptomatic patients with confirmed mild-to-moderate COVID-19 who are within 5 days of symptom onset and at high risk for progression to severe disease. 1 Evidence demonstrates a 39% reduction in hospitalization risk and 61% reduction in mortality risk, with particularly strong benefits in patients aged 65+ years. 5

Critical Timing Requirements

Initiate treatment as soon as possible after COVID-19 diagnosis, ideally within 5 days of symptom onset. 6, 4, 2 Real-world effectiveness data demonstrates significant reduction in hospitalization and death when treatment starts within this timeframe. 4

Renal Dosing Adjustments (Mandatory)

The FDA label provides specific dosing based on renal function: 2

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

• 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for all 5 days

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

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

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

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 2

Monitoring During Treatment

Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury. 3 Real-world data in chronic kidney disease patients undergoing hemodialysis showed no significant worsening of renal function with Paxlovid treatment. 7

Mandatory Pre-Treatment Drug Interaction Assessment

Before prescribing, systematically review ALL patient medications using the Liverpool COVID-19 Drug Interaction Tool. 3, 6, 4 This is explicitly recommended in guidelines because ritonavir is a potent CYP3A4 inhibitor causing potentially life-threatening drug interactions. 2, 8

The FDA boxed warning emphasizes that ritonavir may lead to greater exposure of concomitant medications, resulting in potentially severe, life-threatening, or fatal events. 2 Determine if medications require:

• Dose adjustment
• Temporary interruption
• Additional monitoring
• Complete contraindication 2

Drug interactions persist during active treatment and possibly for several days after completion. 3

Contraindications

Do not prescribe Paxlovid in patients with: 2

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir
• Medications highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions
• Concurrent use of potent CYP3A inducers (may cause loss of virologic response)
• Severe hepatic impairment (Child-Pugh Class C) 2

Administration Details

• Administer orally with or without food 2
• Take at approximately the same time each day 2
• Complete the full 5-day course 2

Common Adverse Effects

Monitor for dysgeusia (altered taste) and diarrhea, which occur more frequently than placebo but rarely lead to discontinuation. 3, 4 Watch for signs of hepatotoxicity, as hepatic transaminase elevations have been reported with ritonavir. 4, 2

Special Considerations

Pregnancy: Paxlovid may be an option to reduce disease progression in pregnant patients, with no reports of serious adverse reactions in parent or child documented in WHO Vigibase to date. 3, 4

Vaccinated patients: Paxlovid remains effective in vaccinated populations with similar absolute risk reduction for hospitalization. 4

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

Clinical Pitfalls to Avoid

• Do not delay treatment while waiting for complete drug interaction review—use the Liverpool tool immediately 3, 6
• Do not use standard dosing in renal impairment—dose reduction is mandatory, not optional 2
• Do not dismiss treatment concerns about viral rebound—rebound occurs with and without treatment, and when it occurs, symptoms remain mild with no hospitalizations or deaths reported 9
• Do not prescribe for low-risk patients—benefits are trivial with high certainty 6