Is Paxlovid (nirmatrelvir/ritonavir) effective for COVID-19 (Coronavirus disease 2019)?

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Last updated: May 8, 2025View editorial policy

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From the Guidelines

Paxlovid is a recommended treatment for COVID-19 in certain high-risk populations, as it has been shown to reduce the risk of hospitalization and death. The American College of Physicians suggests considering nirmatrelvir–ritonavir combination therapy, the active ingredients in Paxlovid, for symptomatic patients with confirmed mild to moderate COVID-19 who are at high risk for progressing to severe disease and are within 5 days of symptom onset 1. This recommendation is based on the latest evidence, which indicates that nirmatrelvir–ritonavir combination therapy can reduce the risk of hospitalization and death in high-risk patients 1.

Key Considerations

  • The standard regimen for Paxlovid consists of nirmatrelvir (300 mg) with ritonavir (100 mg) taken together twice daily for 5 days.
  • Paxlovid is recommended for adults and children (12 years and older, weighing at least 40 kg) who have mild-to-moderate COVID-19 and are at high risk for progression to severe disease.
  • Patients with severe kidney or liver disease may need dose adjustments or alternative treatments due to the ritonavir component.
  • Common side effects include altered taste, diarrhea, muscle aches, and high blood pressure.

Benefits and Risks

  • The benefits of Paxlovid generally outweigh the risks for those in high-risk categories, with a significant reduction in hospitalization and death.
  • "Rebound" symptoms may occur after completing treatment, but the overall benefits of Paxlovid make it a recommended treatment option for eligible patients 1.

Clinical Decision-Making

  • Clinicians should consider the individual patient's risk factors and medical history when deciding whether to prescribe Paxlovid.
  • The latest evidence and guidelines should be consulted to ensure that patients receive the most effective and safe treatment for COVID-19 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. PAXLOVID 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 effective for COVID-19 treatment in adults with mild-to-moderate disease who are at high risk for progression to severe COVID-19, including hospitalization or death 2, 2, 2.

  • Key points:
    • Indicated for treatment of mild-to-moderate COVID-19
    • For adults at high risk for progression to severe COVID-19
    • Not approved for pre-exposure or post-exposure prophylaxis

From the Research

Effectiveness of Paxlovid in Treating COVID-19

  • Paxlovid has been shown to be effective in reducing the risk of severe COVID-19 or mortality in high-risk patients 3.
  • A 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) 3.
  • Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease 3.

Comparison with Other Antiviral Drugs

  • Paxlovid (nirmatrelvir-ritonavir) has been compared to other antiviral drugs, such as molnupiravir, in terms of efficacy and safety 4, 5, 6.
  • A systematic review and meta-analysis found that Paxlovid was effective in reducing hospitalization and mortality in COVID-19 patients, with a risk ratio of 0.53 (95% CI, 0.24-0.69) for hospitalization and 0.36 (95% CI, 0.27-0.50) for all-cause mortality 7.
  • Another study found that Paxlovid was associated with a lower risk of death or hospitalization compared to remdesivir, but not compared to molnupiravir 6.

Safety and Adverse Events

  • Paxlovid has been shown to have a good safety profile, with no significant difference in serious and non-serious adverse events compared to other antiviral drugs 5, 6.
  • However, one study found that adverse events occurred more frequently in patients treated with Paxlovid (49.2%) compared to other antiviral drugs 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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

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

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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