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

From the Guidelines

The recommended treatment regimen for Paxlovid (nirmatrelvir/ritonavir) in adults with mild to moderate COVID-19 is nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one tablet), all taken together twice daily for 5 days, as supported by the American College of Physicians' living, rapid practice points 1.

Key Considerations for Treatment

• Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset to maximize efficacy.
• Dosage adjustments are necessary for patients with moderate renal impairment (eGFR 30-60 mL/min), who should receive nirmatrelvir 150 mg with ritonavir 100 mg twice daily.
• Paxlovid is not recommended for patients with severe renal impairment (eGFR <30 mL/min) or severe hepatic impairment due to the potential for increased toxicity.
• Important considerations include checking for potential drug interactions before starting treatment, as ritonavir is a strong CYP3A inhibitor that can affect metabolism of many medications.
• Patients should be advised to complete the full 5-day treatment course to prevent viral resistance.

Mechanism of Action and Efficacy

• Paxlovid works by inhibiting the SARS-CoV-2 main protease, preventing viral replication.
• The treatment has been shown to significantly reduce the risk of hospitalization and death in high-risk unvaccinated adults with COVID-19, as indicated by the practice points from the American College of Physicians 1.
• The use of nirmatrelvir–ritonavir combination therapy is supported for treating symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. Nirmatrelvir must be co-administered with ritonavir. • Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. • Administer orally with or without food. • Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days.

The recommended treatment regimen for Paxlovid (nirmatrelvir/ritonavir) in adults with mild to moderate COVID-19 is:

• Initiation: As soon as possible after diagnosis and within 5 days of symptom onset
• Administration: Orally with or without food
• Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days 2.
• Dose reduction for patients with moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir, taken together twice daily for 5 days 2.
• Contraindications: PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) or severe hepatic impairment (Child-Pugh Class C) 2.

From the Research

Treatment Regimen for Paxlovid

The recommended treatment regimen for Paxlovid (nirmatrelvir/ritonavir) in adults with mild to moderate COVID-19 is as follows:

• The treatment should be started within 5 days of symptoms onset and given for 5 days' duration 3
• The dosage is 300 mg of nirmatrelvir and 100 mg of ritonavir orally, twice daily for 5 days 4, 3

Efficacy of Paxlovid

The efficacy of Paxlovid in reducing the risk of hospitalization and mortality in adults with mild to moderate COVID-19 is supported by several studies:

• A systematic review and meta-analysis found that Paxlovid significantly reduced the risk of hospitalization, all-cause mortality, and intensive care unit admission compared to the control group 5
• A non-randomized controlled clinical trial found that Paxlovid significantly reduced nucleic acid shedding time, days until negative swab test, and days of first symptoms resolution, as well as improved nucleic acid test negative rate and post-COVID-19 condition 4
• A population-based real-world data study found that Paxlovid was associated with a significant decrease in the rate of severe COVID-19 or mortality, with an adjusted hazard ratio of 0.54 (95% CI, 0.39-0.75) 6

Patient Eligibility

Paxlovid is authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness 7

• Patients should be at high risk for severe COVID-19 and have no contraindications for Paxlovid use 6
• Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease 6