From the Guidelines
Paxlovid (nirmatrelvir/ritonavir) should be used in patients with mild to moderate COVID-19 who are at high risk for progression to severe disease, ideally within 5 days of symptom onset, as supported by the most recent evidence from the American College of Physicians 1. High-risk individuals include older adults (particularly those over 65), people with underlying medical conditions such as heart disease, diabetes, obesity, chronic lung disease, immunocompromised states, and cancer.
Key Considerations for Paxlovid Use
- The standard dosage is nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one tablet), taken together twice daily for 5 days.
- Dose adjustments are necessary for patients with moderate renal impairment (eGFR 30-60 mL/min), reducing to 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.
- Before prescribing, clinicians must carefully review the patient's medication list for potential drug interactions, as ritonavir is a strong CYP3A inhibitor that can significantly affect the metabolism of many medications, as noted in the guidelines from the American College of Physicians 1.
Mechanism and Benefits
- Paxlovid works by inhibiting the SARS-CoV-2 main protease, preventing viral replication.
- It has been shown to reduce the risk of hospitalization and death by approximately 89% when given early in the course of illness to high-risk patients, highlighting its effectiveness in improving morbidity, mortality, and quality of life outcomes 1.
- The use of Paxlovid is supported by practice points from the American College of Physicians, which recommend considering nirmatrelvir–ritonavir combination therapy for symptomatic patients with confirmed mild to moderate COVID-19 who are at high risk for progressing to severe disease 1.
From the FDA Drug Label
PAXLOVID which includes nirmatrelvir, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro: also referred to as 3CLpro or nsp5 protease) inhibitor, and ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor, is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.
• Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.
Paxlovid (nirmatrelvir/ritonavir) should be used in patients with COVID-19 who are at high risk for progression to severe COVID-19, including hospitalization or death.
- Treatment should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset 2.
- The patient should be an adult with mild-to-moderate COVID-19.
- Paxlovid is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
From the Research
Patient Eligibility for Paxlovid
Paxlovid (nirmatrelvir/ritonavir) should be used in patients with COVID-19 who are at risk for progression to severe disease, specifically those with mild to moderate symptoms 3. The treatment is recommended for patients aged 12 years and older, weighing at least 40 kg.
Timing of Paxlovid Administration
Paxlovid should be started within 5 days of symptom onset and given for a duration of 5 days 3. Early treatment is crucial to reduce the risk of hospitalization and death.
Efficacy of Paxlovid
Studies have shown that Paxlovid is effective in reducing the risk of hospitalization and death in patients with COVID-19. A meta-analysis found that Paxlovid significantly reduced the risk of hospitalization (RR = 0.53; 95% CI: 0.24-0.69, p < 0.001) and all-cause mortality (RR = 0.36; 95% CI: 0.27-0.50, p < 0.001) compared to the control group 4. Another study found that Paxlovid reduced the risk of severe COVID-19 or mortality by 46% (adjusted HR = 0.54; 95% CI: 0.39-0.75) 5.
Patient Characteristics
Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease 5. However, no significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status.
Key Points to Consider
- Paxlovid should be used in patients with mild to moderate COVID-19 who are at risk for progression to severe disease.
- Treatment should be started within 5 days of symptom onset and given for 5 days.
- Paxlovid has been shown to reduce the risk of hospitalization and death in patients with COVID-19.
- The treatment appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease.
- Paxlovid can be used in patients with or without COVID-19 vaccination. Some of the key findings are based on the following studies: 3, 6, 4, 5, 7