What is the severity of COVID-19 for which Paxlovid (nirmatrelvir/ritonavir) is indicated?

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Last updated: May 30, 2025View editorial policy

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From the Guidelines

Paxlovid is primarily indicated for mild to moderate COVID-19 in adults and children (12 years and older weighing at least 40 kg) who are at high risk for progression to severe disease, including hospitalization or death. According to the most recent evidence from the Annals of Internal Medicine 1, Paxlovid, which consists of nirmatrelvir tablets and ritonavir tablets, should be started as soon as possible after diagnosis and within 5 days of symptom onset for maximum effectiveness. The key benefits of Paxlovid include:

  • Reduction in the risk of hospitalization or death due to COVID-19
  • Inhibition of a viral enzyme called the main protease, which prevents the virus from replicating
  • Suitable for high-risk individuals, including older adults and those with underlying medical conditions like heart disease, diabetes, obesity, chronic lung disease, immunocompromised states, and cancer However, it's essential to note that Paxlovid has significant drug interactions due to the ritonavir component, so patients should discuss all medications they're taking with their healthcare provider before starting treatment, as highlighted in the study 1. Additionally, the evidence suggests that Paxlovid is not typically used for patients who already have severe COVID-19 requiring hospitalization, as stated in the practice points from the American College of Physicians 1. Overall, the current evidence supports the use of Paxlovid for mild to moderate COVID-19 in high-risk individuals, and healthcare providers should consider this treatment option when managing patients with COVID-19.

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. PAXLOVID is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19, and it is not recommended in patients with severe renal impairment (eGFR <30 mL/min) or severe hepatic impairment (Child-Pugh Class C).

Paxlovid is for mild-to-moderate COVID-19 2.

From the Research

Paxlovid Treatment for COVID-19

  • Paxlovid is authorized for the treatment of mild to moderate COVID-19 in patients who are at risk for progression to severe illness 3, 4, 5, 6, 7.
  • The treatment is typically administered for 5 days and should be started within 5 days of symptom onset 3, 6.
  • Studies have shown that Paxlovid is effective in reducing the risk of hospitalization and death in patients with mild to moderate COVID-19 4, 6, 7.

Patient Eligibility

  • Paxlovid is recommended for patients aged 12 years and older who weigh at least 40 kg 3.
  • Patients with certain underlying health conditions, such as immunosuppression, neurological or cardiovascular disease, may benefit more from Paxlovid treatment 7.
  • Paxlovid can be prescribed to eligible adults, regardless of their COVID-19 vaccination status 4, 7.

Efficacy of Paxlovid

  • Paxlovid has been shown to reduce the risk of hospitalization and death in patients with mild to moderate COVID-19 by approximately 50% 4, 6, 7.
  • The treatment has also been found to shorten the duration of nucleic acid shedding and improve symptoms resolution 5, 6.
  • A systematic review and meta-analysis found that Paxlovid was associated with a significant reduction in hospitalization, all-cause mortality, and intensive care unit admission 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023

Research

Paxlovid for the treatment of COVID-19: a systematic review and meta-analysis.

Journal of infection in developing countries, 2024

Research

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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