Recommended Treatment Regimen for Paxlovid in Adults with Mild to Moderate COVID-19
Paxlovid (nirmatrelvir/ritonavir) should be administered as 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days in adults with mild to moderate COVID-19 who are at high risk for disease progression and within 5 days of symptom onset. 1, 2
Patient Selection and Timing
- Paxlovid is indicated for adults with mild to moderate COVID-19 who are at high risk for progression to severe disease
- Treatment must be initiated within 5 days of symptom onset
- Patients should have confirmed COVID-19 (positive test result)
- High-risk factors include:
- Advanced age (especially ≥65 years)
- Underlying medical conditions
- Immunocompromised status
- Unvaccinated status
Standard Dosing Regimen
- Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
- Frequency: Twice daily
- Duration: 5 days
- Administration: Orally with or without food
- Timing: At approximately the same time each day 2
Dose Adjustments for Special Populations
Renal Impairment 2
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
Severe renal impairment (eGFR <30 mL/min) including hemodialysis:
- 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
Hepatic Impairment 2
- Mild to moderate hepatic impairment: No dose adjustment needed
- Severe hepatic impairment (Child-Pugh Class C): Not recommended
Critical Considerations Before Prescribing
Drug-Drug Interactions
Paxlovid includes ritonavir, a strong CYP3A inhibitor, which can cause significant drug interactions 2, 3:
Prior to prescribing:
- Review all medications the patient is taking
- Assess potential drug-drug interactions
- Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
Contraindicated medications:
- Drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions
- Potent CYP3A inducers that may reduce nirmatrelvir/ritonavir effectiveness
Common problematic drug classes:
- Antiarrhythmics
- Anticoagulants
- Immunosuppressants
- Statins
- Sedatives/hypnotics
- Certain antipsychotics
Adverse Effects Monitoring
- Most common adverse reactions (≥1%): dysgeusia and diarrhea 2
- Monitor for potential hepatotoxicity (hepatic transaminase elevations, clinical hepatitis)
- Watch for hypersensitivity reactions including anaphylaxis and serious skin reactions
Evidence for Effectiveness
Paxlovid has demonstrated significant benefits in reducing:
- All-cause mortality 1, 4
- COVID-19 mortality 1
- Hospitalization rates 1, 5, 4
- Time to recovery 1, 6
- Viral clearance time 6
Recent evidence shows a 39% reduction in hospitalization risk and 61% reduction in death risk, with greatest absolute benefit in patients aged 65+ years 4.
Pitfalls and Caveats
COVID-19 rebound: Symptoms or positive test results may recur 2-8 days after recovery or negative test results in some patients treated with Paxlovid 5
Drug interactions: Potentially severe or life-threatening interactions can occur; thorough medication review is essential 2, 3, 7
Timing is critical: Efficacy is significantly reduced if not started within 5 days of symptom onset
Treatment disparities: Lower treatment rates have been observed among Black and Hispanic/Latino patients and within socially vulnerable communities 4
Encephalopathy risk: Acute encephalopathy has been reported due to interactions with benzodiazepines and narcotics 7
By following this treatment regimen and carefully screening for contraindications and drug interactions, Paxlovid can effectively reduce the risk of hospitalization and death in high-risk adults with mild to moderate COVID-19.