Nirmatrelvir

Nirmatrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug [see Microbiology (12.4) ]. Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 M pro .

• 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 which includes nirmatrelvir, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M pro : also referred to as 3CL pro 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.ICD-10: B20

• PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions [e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome] to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product. PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.contraindicated

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. ( 2.1 ) Nirmatrelvir must be co-administered with ritonavir. ( 2.1 ) • Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. ( 2.1 ) • Administer orally with or without food. ( 2.1 ) • Administer at approximately the same time each day. ( 2.2 , 2.3 ) • 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. ( 2.2 ) • Dose Reduction for Renal Impairment ( 2.3 , 8.6 , 12.3 ) Abbreviation: eGFR=estimated glomerular filtration rate. Renal Function Days of Treatment Dose and Dose Frequency PAXLOVID should be administered at approximately the same time each day for 5 days. Moderate renal impairment (eGFR ≥30 to <60 mL/min) Days 1-5 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily Severe renal impairment (eGFR <30 mL/min) including those requiring hemodialysis On days of hemodialysis, the PAXLOVID dose should be administered after hemodialysis. Day 1 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) once Days 2-5 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) once daily • PAXLOVID is not recommend in patients with severe hepatic impairment (Child-Pugh Class C). ( 2.4 , 8.7 ) 2.1 Important Dosage and Administration Information PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets.

• The concomitant use of PAXLOVID and certain other drugs may result in potentially significant drug interactions. Consult the Full Prescribing Information prior to and during treatment for potential drug interactions. ( 5.1 , 7 ) • Hypersensitivity Reactions: Anaphylaxis, serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome), and other hypersensitivity reactions have been reported with PAXLOVID. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. ( 5.2 ) • Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. ( 5.3 ) • HIV-1 Drug Resistance: PAXLOVID use may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. ( 5.4 ) 5.1 Risk of Serious Adverse Reactions Due to Drug Interactions Initiation of PAXLOVID, which contains ritonavir, a strong CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medications metabolized by CYP3A. Medications that induce CYP3A may decrease concentrations of PAXLOVID. These interactions may lead to: • Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥1% and greater incidence than in the placebo group) are dysgeusia and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PAXLOVID is based on two Phase 2/3 randomized, placebo-controlled trials in symptomatic adult subjects 18 years of age and older with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Subjects in both studies received PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo every 12 hours for 5 days for the treatment of mild-to-moderate COVID-19 within 5 days of symptom onset [see Clinical Studies (14) ] : • Trial C4671005 (EPIC-HR) enrolled subjects who were at high risk for progression to severe disease. • Trial C4671002 (EPIC-SR) enrolled subjects who were at standard risk for progression to severe disease (previously unvaccinated subjects at standard risk or fully vaccinated subjects with at least 1 risk factor for progression to severe disease).

8.1 Pregnancy Risk Summary Available data on the use of nirmatrelvir during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Published studies with ritonavir are insufficient to identify a drug associated risk of miscarriage (see Data ). There are maternal and fetal risks associated with untreated COVID-19 in pregnancy (see Clinical Considerations ). In an embryo-fetal development study with nirmatrelvir, reduced fetal body weights following oral administration of nirmatrelvir to pregnant rabbits were observed at systemic exposures (AUC) approximately 11 times higher than clinical exposure at the approved human dose of PAXLOVID. No other adverse developmental outcomes were observed in animal reproduction studies with nirmatrelvir at systemic exposures (AUC) greater than or equal to 3 times higher than clinical exposure at the approved human dose of PAXLOVID (see Data ) .

Metabolism

The pharmacokinetics of nirmatrelvir/ritonavir were similar in healthy subjects and in subjects with mild-to-moderate COVID-19. Nirmatrelvir AUC increased in a less than dose proportional manner over a single dose range from 250 mg to 750 mg (0.83 to 2.5 times the approved recommended dose) and multiple dose range from 75 mg to 500 mg (0.25 to 1.67 times the approved recommended dose), when administered in combination with 100 mg ritonavir.

Treatment of overdose with PAXLOVID should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with PAXLOVID.

• May 25, 2023NDANDA217188Pfizer

1. 1Covid-1922,79843%
2. 2Disease Recurrence20,09838%
3. 3Dysgeusia7,33914%
4. 4Diarrhoea4,0227.5%
5. 5Nausea2,6314.9%
6. 6Headache2,1704.1%
7. 7Cough2,0443.8%
8. 8Fatigue2,0113.8%
9. 9Incorrect Dose Administered1,7003.2%
10. 10Vomiting1,4012.6%
11. 11Malaise1,3712.6%
12. 12Nasal Congestion1,3672.6%
13. 13Off Label Use1,3202.5%
14. 14Drug Interaction1,2772.4%
15. 15Pyrexia1,2512.3%

The 10 most recently updated of 74 ClinicalTrials.gov registrations naming Nirmatrelvir as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• AGILE (Early Phase Platform Trial for COVID-19)
  Recruiting · Phase 1 · Phase 2 · Interventional · 600 enrolled · University of Liverpool
  NCT04746183updated 2026-06-01
• SARS-CoV-2 and Herpesvirus Inhibition for Ending Long COVID Dysfunction
  Not yet recruiting · Phase 2 · Interventional · 150 enrolled · Icahn School of Medicine at Mount Sinai
  NCT07597902updated 2026-05-19
• A Study to Learn About the Medicine (PF-07321332 or Nirmatrelvir/Ritonavir) in Healthy Lactating Women
  Completed · Phase 1 · Interventional · 8 enrolled · Pfizer
  NCT05441215updated 2026-05-01
• Randomised Evaluation of COVID-19 Therapy
  Recruiting · Phase 3 · Interventional · 70,000 enrolled · University of Oxford
  NCT04381936updated 2026-04-21
• RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms
  Completed · Phase 2 · Interventional · 964 enrolled · Kanecia Obie Zimmerman
  NCT05965726updated 2026-03-27
• OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial
  Recruiting · Phase 2 · Interventional · 256 enrolled · ANRS, Emerging Infectious Diseases
  NCT05587894updated 2026-02-23
• Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
  Recruiting · Phase 2 · Interventional · 3,800 enrolled · University of Oxford
  NCT05041907updated 2026-02-19
• OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients
  Recruiting · Phase 2 · Interventional · 256 enrolled · Calmy Alexandra
  NCT07406217updated 2026-02-18
• Clinical Outcomes and Pharmacotherapy Effectiveness in the VA Health Care System (COPE-VA)
  Recruiting · Observational · 400,000 enrolled · VA Office of Research and Development
  NCT06160128updated 2026-02-10
• A US Study to Look at Loss of Work and Healthcare Costs for People Affected With Mild-to-moderate COVID 19 Who Have High Chances of the Disease Becoming Severe
  Completed · Observational · 131,005 enrolled · Pfizer
  NCT07072793updated 2026-02-09

Frequently asked questions

How does Nirmatrelvir work?

Nirmatrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug [see Microbiology (12.4) ]. Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 M pro .

What is Nirmatrelvir used for?

According to FDA labeling, Nirmatrelvir carries indications including: 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 which includes nirmatrelvir, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M pro : also referred to as 3CL pro 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Nirmatrelvir?

Nirmatrelvir is classified as Protease Inhibitors.

What are the contraindications for Nirmatrelvir?

Nirmatrelvir labeling lists contraindications including: PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions [e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome] to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product. PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.. Always consult the full prescribing information and a clinician.