Paxlovid (Nirmatrelvir/Ritonavir) Dosing Regimen
The standard recommended dosage for Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together orally twice daily for 5 days. 1
Standard Dosing Protocol
- Paxlovid should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
- The complete 5-day treatment course should be taken to maximize viral clearance and minimize transmission 1
- All three tablets (two nirmatrelvir 150 mg tablets plus one ritonavir 100 mg tablet) should be taken together twice daily, in the morning and at bedtime 1
- Paxlovid can be taken with or without food 1
- Tablets should be swallowed whole and not chewed, broken, or crushed 1
Dosage Adjustments for Special Populations
Renal Impairment
- No dosage adjustment needed for mild renal impairment (eGFR ≥60 to <90 mL/min) 1
- For moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) twice daily for 5 days 1, 2
- For severe renal impairment (eGFR <30 mL/min) including patients requiring hemodialysis 1:
- Day 1: 300 mg nirmatrelvir (two tablets) with 100 mg ritonavir (one tablet) once
- Days 2-5: 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) once daily
- For hemodialysis patients, administer dose after hemodialysis 1
Hepatic Impairment
- No dosage adjustment needed for mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment 1
- Not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C) 1
Important Clinical Considerations
- Ritonavir is a strong CYP3A inhibitor and can cause significant drug-drug interactions 3, 4
- Always check for drug interactions before prescribing Paxlovid using resources like the Liverpool COVID-19 Drug Interaction Tool 3, 4
- High-risk interactions to avoid include certain antiarrhythmics, anticoagulants, and statins 4
- The duration of interaction risk extends beyond the 5-day treatment period due to ritonavir's effects on metabolism and clearance 4
- Common adverse effects include dysgeusia (altered taste) and diarrhea 3, 1
Missed Dose Management
- If a dose is missed within 8 hours of the scheduled time: take it as soon as possible and resume normal schedule 1
- If a dose is missed by more than 8 hours: skip the missed dose and take the next dose at the regularly scheduled time 1
- Do not double the dose to make up for a missed dose 1
Pharmacokinetic Considerations
- Nirmatrelvir is primarily eliminated by the kidneys when co-administered with ritonavir 5, 2
- Ritonavir inhibits nirmatrelvir's CYP3A4-mediated metabolism, increasing its plasma concentration and extending its half-life 5
- When properly dosed with ritonavir, nirmatrelvir reaches concentrations well above the antiviral effective concentration (EC90) 5
Paxlovid has shown significant efficacy in reducing hospitalization and death in high-risk COVID-19 patients when administered within the recommended timeframe 3, 6. Careful attention to dosing adjustments based on renal function and potential drug interactions is essential for safe and effective treatment.