What is the recommended treatment regimen for Paclovid (nirmatrelvir/ritonavir) in adults with mild to moderate COVID-19?

Paxlovid (Nirmatrelvir/Ritonavir) Treatment Regimen

For adults with mild to moderate COVID-19 at high risk for progression to severe disease, administer nirmatrelvir 300 mg (two 150 mg tablets) plus ritonavir 100 mg (one 100 mg tablet) orally twice daily for 5 days, initiated within 5 days of symptom onset. 1, 2, 3

Dosing Regimen

Standard Dosing (Normal Renal Function)

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days 3
• Administer orally with or without food 3
• Take at approximately the same time each day 3
• Nirmatrelvir must be co-administered with ritonavir 3

Timing of Initiation

• Initiate treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1, 2, 3
• Earlier initiation is associated with better outcomes 4, 5

Dose Adjustments for Renal Impairment

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

• 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 3

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 3
• Days 2-5: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) once daily 3
• On hemodialysis days, administer after dialysis 3

Hepatic Impairment

• Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 3

Patient Selection Criteria

High-Risk Patients Who Should Receive Treatment

• Age ≥65 years 2, 5
• Immunocompromised status, including hematological malignancies 2
• Multiple comorbidities 2
• Unvaccinated or vaccine non-responders 2
• Treatment benefit demonstrated across all age groups (18-49 years, 50-64 years, ≥65 years) and vaccination statuses (including those with ≥3 mRNA vaccine doses) 5

Critical Drug Interaction Management

Before Prescribing - Mandatory Steps

• Review ALL patient medications to assess potential drug-drug interactions with ritonavir, a potent CYP3A4 inhibitor 3, 6
• Determine if concomitant medications require dose adjustment, temporary interruption, or additional monitoring 3, 6
• Ritonavir causes numerous serious, potentially life-threatening drug interactions 3, 6

Contraindicated Medications

• Do not co-administer with drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions 3
• Do not co-administer with potent CYP3A inducers that may reduce nirmatrelvir/ritonavir concentrations and cause treatment failure 3

Practical DDI Management Options

• Preemptive or symptom-driven pausing of the comedication during the 5-day treatment course 6
• Patient counseling on managing additional risk 6
• Clinical monitoring or dosage adjustment of comedications is difficult to implement given the short treatment window 6

Common Pitfalls to Avoid

Drug Interaction Oversights

• Failure to check drug interactions before prescribing is the most critical error 2, 6
• The 5-day treatment course still poses significant DDI risk despite short duration 6
• Options for mitigating DDI risk are limited due to the short intervention window 6

Hypersensitivity Reactions

• Immediately discontinue Paxlovid if signs/symptoms of clinically significant hypersensitivity reaction or anaphylaxis occur 3
• Anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome, and other serious reactions have been reported 3

Hepatotoxicity Monitoring

• Be aware that hepatic transaminase elevations, clinical hepatitis, and jaundice can occur with ritonavir 3

Expected Clinical Outcomes

Efficacy Data

• Significantly reduces hospitalization risk (adjusted hazard ratio 0.49 overall; 0.50 in those with ≥3 mRNA vaccines) 5
• Reduces nucleic acid shedding time (3.26 vs 7.75 days compared to standard treatment) 4
• Shortens time to symptom resolution (4.86 vs 7.45 days) 4
• Reduces post-COVID-19 condition incidence (18.60% vs 31.57%) 4
• Hospitalization or ED encounters during days 5-15 after treatment occur in <1% of patients 7

Limitations of Use

• Paxlovid is not approved for pre-exposure or post-exposure prophylaxis for prevention of COVID-19 3