Is Paxlovid (nirmatrelvir and ritonavir) safe in patients with Chronic Kidney Disease (CKD)?

Is Paxlovid Safe in CKD?

Paxlovid can be safely used in patients with CKD, but requires dose adjustment based on renal function: no adjustment for mild CKD (eGFR ≥60 mL/min), reduced dose for moderate CKD (eGFR 30-59 mL/min), and further reduction for severe CKD (eGFR <30 mL/min) including dialysis patients. 1

Dosing Algorithm by CKD Stage

Mild Renal Impairment (eGFR ≥60 to <90 mL/min)

• Standard dosing: 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1
• No dose adjustment required 1

Moderate Renal Impairment (eGFR 30 to <60 mL/min)

• Reduced dosing: 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1, 2
• This represents a 50% dose reduction based on pharmacokinetic data showing 187% increased nirmatrelvir exposure in moderate renal impairment 2

Severe Renal Impairment (eGFR <30 mL/min)

• Modified regimen: 300 mg nirmatrelvir with 100 mg ritonavir on Day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily on Days 2-5 1
• For patients on hemodialysis, administer after dialysis on dialysis days 1
• Nirmatrelvir exposure increases by 304% in severe renal impairment, necessitating both dose and frequency reduction 2

Safety Evidence in Advanced CKD

Recent clinical trial data demonstrates favorable safety in advanced CKD. A prospective interventional trial of 85 patients with eGFR <30 mL/min/1.73 m² (69.4% on dialysis) showed that 94.1% completed the full treatment course with modified dosing 3. Adverse events occurred in only 9.4% and serious adverse events in 5.9%, with rates comparable between those with eGFR < or >30 mL/min/1.73 m² 3.

The pharmacokinetic study supporting dose adjustments found that nirmatrelvir/ritonavir exhibited an acceptable safety profile across all renal function groups, with treatment-related adverse events being mild in severity and no significant laboratory, vital sign, or ECG abnormalities 2.

Critical Drug Interaction Considerations

The ritonavir component is a potent CYP3A4 inhibitor, creating significant drug interaction risks that are particularly important in CKD patients who typically take multiple medications. 1, 4

High-Risk Interactions in CKD Patients

• Colchicine: Contraindicated when used concomitantly with Paxlovid in patients with renal impairment due to increased colchicine toxicity risk 5
• Immunosuppressants: Require careful monitoring in kidney transplant recipients, though Paxlovid can be used safely with dose adjustments of immunosuppressive agents 6
• Statins: Some statins require temporary discontinuation during Paxlovid treatment 1

A retrospective analysis found that 81.4% of patients prescribed Paxlovid had drug-drug interactions, with 17% classified as severe 4. Pharmacist intervention was required in 63.6% of cases to prevent drug-related problems 4.

Clinical Efficacy in CKD

Virological efficacy is maintained in CKD patients with appropriate dose adjustment. The viral load significantly decreased on days 5,15, and 30 (P < .001 for all), with consistent reduction in the subgroup with eGFR <30 mL/min/1.73 m² 3. Virological rebound occurred in 10 patients but was transient, asymptomatic, and associated with low infectivity 3.

Common Pitfalls and How to Avoid Them

Prescribing Errors

• Contraindication in severe renal impairment: A study found 3 patients (2.1%) were prescribed Paxlovid despite severe renal impairment being a relative contraindication without dose adjustment 4
• Solution: Always calculate eGFR before prescribing and specify the numeric dose of each active ingredient (nirmatrelvir and ritonavir separately) on the prescription 1

Medication Reconciliation Failure

• Problem: 24.3% of patients had both renal impairment and significant drug-drug interactions that required intervention 4
• Solution: Review all concomitant medications before prescribing, particularly focusing on CYP3A4 substrates, and determine if dose adjustment, interruption, or additional monitoring is needed 1

Timing of Administration in Dialysis

• Critical detail: On hemodialysis days, administer Paxlovid after dialysis to avoid removing the drug during the dialysis session 1

Monitoring Requirements

• Calculate baseline eGFR to determine appropriate dosing regimen 1
• Review complete medication list for drug-drug interactions before prescribing 1, 4
• Monitor for adverse events, particularly in patients with eGFR <30 mL/min/1.73 m² 3
• Ensure completion of full 5-day course even if symptoms improve 1
• For dialysis patients, coordinate dosing schedule with dialysis sessions 1

Contraindications Specific to CKD

Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C), regardless of renal function. 1 While not absolutely contraindicated in severe renal impairment, earlier prescribing information suggested avoiding use in eGFR <30 mL/min/1.73 m², but recent evidence supports modified dosing in this population 7, 3.