What is the recommended dosage and administration of Paxlovid (nirmatrelvir/ritonavir) for the treatment of COVID-19?

Paxlovid Dosing and Administration for COVID-19 Treatment

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, starting within 5 days of symptom onset in high-risk patients with mild-to-moderate COVID-19. 1

Standard Dosing Regimen

• Initiate treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
• Take all three tablets together (two nirmatrelvir 150 mg + one ritonavir 100 mg) twice daily 1
• Administer at approximately the same time each day for optimal therapeutic effect 1
• Can be taken with or without food 1
• Complete the full 5-day course regardless of symptom improvement 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 (one 100 mg tablet) 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 (one 100 mg tablet) once daily 1
• Days 2-5: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) once daily 1
• On hemodialysis days, administer after dialysis 1
• Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury 2

Critical Drug Interaction Management

Before prescribing, you must check for drug interactions using the Liverpool COVID-19 Drug Interaction Tool 3, 2—this is not optional, as ritonavir is a strong CYP3A inhibitor that can cause potentially severe, life-threatening, or fatal drug interactions 1.

Contraindicated medications (do not co-administer):

• Drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions 1
• Potent CYP3A inducers that may reduce nirmatrelvir/ritonavir to subtherapeutic levels 1
• High-risk categories include certain antiarrhythmics, anticoagulants, and statins 3

Key interaction considerations:

• Ritonavir inhibits CYP3A4, CYP2D6, and P-glycoprotein 4
• Drug interaction risk extends beyond the 5-day treatment period due to ritonavir's prolonged metabolic effects 3
• Many concomitant medications require dose adjustment, temporary interruption, or additional monitoring 1

Hepatic Impairment

• Not recommended in severe hepatic impairment (Child-Pugh Class C) 1
• Use with caution in severe liver impairment as clinical trials excluded these patients 2

Patient Selection Criteria

• Indicated for adults with mild-to-moderate COVID-19 at high risk for progression to severe disease, hospitalization, or death 1
• Not approved for pre-exposure or post-exposure prophylaxis 1
• The American College of Physicians strongly recommends Paxlovid for high-risk patients with non-severe COVID-19 2

Common Adverse Effects to Monitor

• Dysgeusia (altered taste) and diarrhea occur more frequently than placebo but rarely lead to discontinuation 3, 2
• Monitor for potential hepatotoxicity with liver enzyme elevations 3
• Watch for hypersensitivity reactions including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome—discontinue immediately if these occur 1

Special Populations

Pediatric patients (12 to <18 years):

• Same adult dosing (300 mg/100 mg twice daily) if weight ≥40 kg 5

Pregnancy:

• May be considered to reduce disease progression, though data are limited 2
• No serious adverse reactions reported in WHO Vigibase to date 2

Elderly patients (>65 years):

• Higher plasma concentrations observed; monitor for drug accumulation signs 6
• Significantly increased risk of excessive plasma levels compared to younger patients 6

Critical Timing Pitfall

The 5-day window from symptom onset is absolute—efficacy data support treatment only when initiated within this timeframe 2, 1. Do not prescribe outside this window as there is no evidence of benefit.