For what patients is Paxlovid (nirmatrelvir/ritonavir) indicated for the treatment of Coronavirus disease 2019 (COVID-19)?

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Last updated: April 21, 2025View editorial policy

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From the Guidelines

Paxlovid is indicated for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) who test positive for SARS-CoV-2 and are at high risk for progression to severe COVID-19, including hospitalization or death, as supported by the American College of Physicians in their living, rapid practice points from 2024 1.

Key Considerations

  • Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset.
  • The standard regimen consists of nirmatrelvir (300 mg) with ritonavir (100 mg) taken together twice daily for 5 days.
  • High-risk factors include older age (especially over 65), obesity, diabetes, chronic kidney disease, immunosuppression, cardiovascular disease, chronic lung disease, and cancer.
  • Paxlovid works by inhibiting the SARS-CoV-2 main protease, preventing viral replication.
  • Dose adjustments are necessary for patients with moderate renal impairment (eGFR 30-60 mL/min), reducing nirmatrelvir to 150 mg while maintaining ritonavir at 100 mg twice daily.
  • Paxlovid has significant drug interactions due to the ritonavir component, so a thorough medication review is essential before prescribing.

Practice Points

  • Consider molnupiravir to treat 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.
  • Consider nirmatrelvir–ritonavir combination therapy to treat 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.
  • Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.
  • Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

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 is indicated for the treatment of mild-to-moderate COVID-19 in adults at high risk for progression to severe COVID-19. Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 2. Key points include:

  • Indication: Treatment of mild-to-moderate COVID-19
  • Patient population: Adults at high risk for progression to severe COVID-19
  • Timing of treatment: As soon as possible after diagnosis and within 5 days of symptom onset

From the Research

Indications for Paxlovid Treatment

Paxlovid, an oral antiviral treatment, is indicated for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness 3. The treatment should be started within 5 days of symptom onset and given for 5 days' duration 4.

Patient Eligibility

Paxlovid is authorized for adults with mild-to-moderate COVID-19 who are at high risk for progression to severe illness, including those who are unvaccinated or have underlying health conditions 5, 6. The treatment is suitable for outpatient settings with asymptomatic or mild disease 6.

Benefits of Paxlovid Treatment

The benefits of Paxlovid treatment include:

  • Reduced risk of hospitalization and death 3, 5, 6
  • Lower viral load 5
  • Reduced risk of severe COVID-19 5, 6
  • Good safety profile with minimal adverse events 6, 7

Key Considerations

Key considerations for Paxlovid treatment include:

  • The treatment should be started within 5 days of symptom onset 4
  • The treatment is given for 5 days' duration 4
  • Drug interactions are a major concern for nirmatrelvir-ritonavir, and prohibited prior or concomitant therapies include medications highly dependent on CYP3A4 for clearance and CYP3A4 inducers 5, 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

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

The New England journal of medicine, 2022

Research

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.

The Cochrane database of systematic reviews, 2022

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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