Paxlovid Dosing for COVID-19
The standard dose of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) plus 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days, initiated within 5 days of symptom onset. 1
Standard Dosing Regimen
- Administer 300 mg nirmatrelvir with 100 mg ritonavir orally twice daily for 5 consecutive days 1
- Treatment must begin as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
- All three tablets should be taken together at approximately the same time each day 1
- Can be administered with or without food 1
Dose Adjustments for Renal Impairment
Moderate renal impairment (eGFR 30-59 mL/min):
- Reduce to 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir twice daily for all 5 days 1
Severe renal impairment (eGFR <30 mL/min), including hemodialysis:
- Day 1: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir once daily 1
- Days 2-5: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir once daily 1
- On hemodialysis days, administer after dialysis 1
Hepatic Impairment
- Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1
- No dose adjustment needed for mild to moderate hepatic impairment 1
Critical Drug Interaction Considerations
Ritonavir is a potent CYP3A4 inhibitor, creating significant drug-drug interaction risks 2, 3:
- Approximately 60% of available medications undergo at least partial CYP3A4 metabolism 3
- For patients on tacrolimus, reduce dose to 2-5% of baseline (or 1/20 to 1/50 of usual dose) when using lopinavir/ritonavir 2
- Similar dramatic dose reductions required for cyclosporine, sirolimus, and everolimus 2
- Review all concomitant medications for CYP3A4 interactions before prescribing 1, 3
Monitoring Requirements
The FDA recommends baseline and during-treatment monitoring 2:
- Do not use if eGFR <30 mL/min without dose adjustment 1
- Assess kidney function at baseline and during treatment 2
- Monitor hepatic function (ALT, AST, bilirubin, alkaline phosphatase, INR) 2
- Discontinue if ALT increases ≥5 times upper limit of normal or if any ALT elevation accompanies signs of liver inflammation 2
Efficacy Evidence
For high-risk, unvaccinated outpatients with mild COVID-19:
- Low-certainty evidence suggests Paxlovid reduces all-cause mortality at 28 days (RR 0.04,95% CI 0.00-0.68) 4
- Reduces hospital admission or death within 28 days (RR 0.13,95% CI 0.07-0.27) 4
- Meta-analysis confirms reduced hospitalization (RR 0.53), all-cause mortality (RR 0.36), and ICU admission (RR 0.45) 5
For standard-risk or vaccinated patients:
- A 2024 trial found no significant difference in time to symptom resolution between Paxlovid and placebo (12 vs 13 days, p=0.60) 6
- Hospitalization rates were low in both groups (0.8% vs 1.6%) 6
Safety Profile
- Probably has little or no effect on treatment-emergent adverse events overall (RR 0.95) 4
- Probably increases treatment-related adverse events, particularly dysgeusia (altered taste) and diarrhea (RR 2.06) 4, 6
- Dysgeusia reported in 5.8% and diarrhea in 2.1% of participants 6
- May reduce serious adverse events (RR 0.24) 4
- Hypersensitivity reactions including anaphylaxis have been observed 2
Special Populations
Elderly patients (>65 years):
- Significantly higher risk of excessive plasma trough concentrations (OR 11.2,95% CI 1.04-120.4) 7
- Plasma levels often exceed reference values, particularly with renally eliminated comedications 7
- Consider more intensive monitoring in this population 7
Pregnant women:
- Evidence does not apply as pregnant women were excluded from trials 2
Common Pitfalls to Avoid
- Do not prescribe without checking renal function and adjusting dose accordingly 1
- Do not overlook drug-drug interactions, especially with immunosuppressants 2, 3
- Do not initiate beyond 5 days of symptom onset 1
- Do not use in severe hepatic impairment 1
- Ensure nirmatrelvir and ritonavir are always co-administered—nirmatrelvir alone is ineffective 1