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About PAXLOVIDAbout PAXLOVID

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When to TreatHigh-Risk FactorsMechanism of ActionDosingEfficacy & Real-World EvidenceEfficacy & Real-World Evidence

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EPIC-HR TrialEPIC-HR ResultsReal-World EvidenceSafetySafety

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Adverse ReactionsDrug InteractionsViral ReboundAccess & ResourcesAccess & Resources

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Access & ResourcesDownload Co-Pay CardResourcesRegister for PAXLOVID UpdatesFrequently Asked Questions
Full Prescribing Information and Patient InformationIndication HCP EUA WebsitePatient Website
Lewnard JA, et al. RWE Study Complements EPIC-HR1Lewnard JA, et al. RWE Study Complements EPIC-HR1

In contrast to EPIC-HR, the Lewnard JA, et al. study included:

  • Vaccinated patients
  • Data from the Omicron era
ExampleStudy design

Objective
To estimate the effectiveness of PAXLOVID in preventing severe outcomes of SARS-CoV-2 infection by retrospective analysis of real-world patients in an outpatient setting within a large, integrated US healthcare system.

Primary endpoint
Hospital admission or death from any cause within 30 days of a positive SARS-CoV-2 test in the subgroup that took PAXLOVID within 5 days of symptom onset.

Study design
  • Analysis was carried out within Kaiser Permanente Southern California (KPSC), a large, integrated US healthcare database
  • Data from patients who received a positive SARS-CoV-2 PCR test result between April 8, 2022, and October 7, 2022, were analyzed
  • The clinical outcomes associated with PAXLOVID treatment were analyzed by matching treated and untreated patients
  • Adjusted hazard ratios were calculated via the Cox proportional hazards model and used to determine the estimated effectiveness of PAXLOVID
 Patient demographics

Key inclusion criteria

  • Received a positive SARS-CoV-2 PCR test result, defined as their index test
  • No positive test result 90 days prior
  • Were ≥12 years old at the time of their index test
  • No hospitalization at the time of their index test or 7 days prior
  • Had ≥1 year of continuous enrollment in KPSC health plans before their index test
Parameters for matching
  • Age
  • Sex
  • Time from symptom onset to testing
  • Number of COVID-19 vaccine doses received
  • Charlson comorbidity index
  • Prior-year healthcare utilization
  • Body mass index
  • Week of SARS-CoV-2 testing
  • Patients lacking an unexposed eligible match were excluded from final analysis
Patient demographics

In the analytic sample (n=133,426), a subset of the eligible population that included patients prescribed PAXLOVID at any time (along with their matched nonrecipients), irrespective of the presence or timing of symptoms.Treated populationAge
  • 24.6% <50 years
  • 75.4% ≥50 years 
Sex
  • 42.3% Male
  • 57.7% Female
Race & ethnicity
  • 26.4% White
  • 16.8% Asian
  • 9.5% Black, non-Hispanic
  • 42.1% Hispanic
  • 1.0% Pacific Islander
  • 4.2% Other/unknown/mixed race
Untreated populationAge
  • 56.3% <50 years
  • 43.7% ≥50 years
Sex
  • 44.7% Male
  • 55.3% Female
Race & ethnicity
  • 21.3% White, non-Hispanic
  • 15.0% Asian
  • 7.9% Black, non-Hispanic
  • 47.8% Hispanic
  • 1.0% Pacific Islander
  • 7.1% Other/unknown/mixed race
Prior COVID-19 vaccinations
  • 13.3% 0 doses
  • 26.6% 1-2 doses
  • 60.1% 3+ doses
Lewnard JA, et al. study limitations
  1. Capture of several variables was incomplete within the data, and potential misclassification of immunity due to undiagnosed previous SARS-CoV-2 infections or those never reported to Kaiser Permanente Southern California (KPSC) remains a concern.
  2. Unmeasured confounding could have hindered causal inference. For example, other antivirals and monoclonal antibody therapies were rarely prescribed in the study sample but probably would have reduced the effectiveness of nirmatrelvir-ritonavir compared with not receiving nirmatrelvir-ritonavir, as these treatments were prioritized for patients who could not receive nirmatrelvir-ritonavir because of potential drug interactions.
  3. The investigators could not verify whether people who received nirmatrelvir-ritonavir adhered to treatment as recommended.
  4. Approach to variable selection via a directed acyclic graph, and use of matching to accommodate potential interactions among confounding variables, prioritized validity over precision of estimates, resulting in wide confidence intervals.
  5. Because of the low risk of severe disease within the highly vaccinated study population, the primary and secondary endpoints occurred rarely among both treatment recipients and nonrecipients, further limiting the precision of the estimates and the ability to explore effect modification.
  6. The endpoint of hospital admission or death due to any cause after a positive outpatient SARS-CoV-2 test might have captured admissions unrelated to COVID-19.
  7. Rapid progression to hospital admission among patients at the highest risk might have contributed to changes in the distribution of covariates among treated and untreated patients, possibly affecting the calculation of effectiveness.
79.6% estimated effectiveness against hospital admission or death
  • Patients treated within 5 days of symptom onset
  • 95% CI, 33.9-93.8, P=0.0080
  • The effectiveness of PAXLOVID in preventing the primary endpoint was calculated as (1-aHR) x 100%, estimating the aHR via Cox proportional hazards models and comparing the outcomes among patients who received or did not receive PAXLOVID
Effectiveness in vaccinated patientsIn a subgroup analysis of vaccinated patients treated with PAXLOVID within 5 days of symptom onset, patients who had received ≥2 and ≥3 COVID-19 vaccine doses, the effectiveness of PAXLOVID against the primary endpoint when dispensed within 5 days of symptom onset was 83.1% and 92.2%, respectively (95% Cl, 30.4-95.9; 52.0-98.7)Read the full article†Loading†This link will take you to a website that is owned and operated by The Lancet. Pfizer is not responsible for the content or services of this site. Next: Adverse ReactionsLoadingEfficacy & Real-World Evidence High-Risk Factors

3 out of 4 US adults are at high risk for progressing to severe COVID-192

 Learn who's at risk Loading Efficacy

See EPIC-HR trial results

 View data Loading*The analytic sample is a subset of the full eligible population (n=166,980) that fit the key inclusion criteria. This subset included PAXLOVID recipients and eligible nonrecipients who had at least one eligible match.aHR=adjusted hazard ratio; CI=confidence interval; EPIC-HR=Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients; PCR=polymerase chain reaction; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.References:Lewnard JA, McLaughlin JM, Malden D, et al. Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system. Lancet Infect Dis. 2023;23(7):806-815.Ajufo E, Rao S, Navar AM, et al. U.S. population at increased risk of severe illness from COVID-19. Am J Prev Cardiol. 2021;6:100156.

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Important Safety Information
 WARNING: SIGNIFICANT DRUG INTERACTIONS WITH PAXLOVID
  • PAXLOVID includes ritonavir, a strong CYP3A inhibitor, which may lead to greater exposure of certain concomitant medications, resulting in potentially severe, life-threatening, and/or fatal events
  • Prior to prescribing PAXLOVID: 1) Review all medications taken by the patient to assess for potential drug-drug interactions with a strong CYP3A inhibitor like PAXLOVID and 2) Determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring
  • Consider the benefit of PAXLOVID treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed
PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. 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. There are certain other drugs for which concomitant use with PAXLOVID should be avoided and/or dose adjustment, interruption, or therapeutic monitoring is recommended. Drugs listed here are a guide and not considered a comprehensive list of all drugs that may be contraindicated with PAXLOVID. The healthcare provider should consult other appropriate resources such as the prescribing information for the interacting drug for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor like PAXLOVID. Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions:
  • Alpha 1-adrenoreceptor antagonist: alfuzosin
  • Antianginal: ranolazine
  • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
  • Anti-gout: colchicine (in patients with renal and/or hepatic impairment)
  • Antipsychotics: lurasidone, pimozide
  • Benign prostatic hyperplasia agents: silodosin
  • Cardiovascular agents: eplerenone, ivabradine
  • Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
  • HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use)
  • Immunosuppressants: voclosporin
  • Microsomal triglyceride transfer protein inhibitor: lomitapide
  • Migraine medications: eletriptan, ubrogepant
  • Mineralocorticoid receptor antagonists: finerenone
  • Opioid antagonists: naloxegol
  • PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension
  • Sedative/hypnotics: triazolam, oral midazolam
  • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
  • Vasopressin receptor antagonists: tolvaptan

Drugs that are strong CYP3A inducers: PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer:

  • Anticancer drugs: apalutamide, enzalutamide
  • Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
  • Antimycobacterials: rifampin, rifapentine
  • Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
  • Herbal Products: St. John’s Wort (hypericum perforatum)
 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
  • Loss of therapeutic effect of PAXLOVID and possible development of viral resistance
Severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with PAXLOVID. The most commonly reported concomitant medications resulting in serious adverse reactions were calcineurin inhibitors (eg, tacrolimus, cyclosporine), followed by calcium channel blockers. Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering PAXLOVID to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. Because nirmatrelvir is coadministered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. The most common adverse reactions in the PAXLOVID group (≥1%) that occurred at a greater frequency than in the placebo group were dysgeusia (5% and <1%, respectively) and diarrhea (3% and 2%, respectively). The following adverse reactions have been identified during use of PAXLOVID under Emergency Use Authorization: Immune System Disorders: Anaphylaxis, hypersensitivity reactions Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome Nervous System Disorders: Headache Vascular Disorders: Hypertension Gastrointestinal Disorders: Abdominal pain, nausea, vomiting General Disorders and Administration Site Conditions: Malaise PAXLOVID is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp, and OATP1B1. Coadministration of PAXLOVID with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of such drugs and increase the risk of adverse events. Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring.Pregnancy: 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. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy.Lactation: Nirmatrelvir and ritonavir are present in human breast milk in small amounts (less than 2%). There are no available data on the effects of nirmatrelvir or ritonavir on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PAXLOVID and any potential adverse effects on the breastfed infant from PAXLOVID or from the underlying maternal condition.Contraception: Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. Advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception. Pediatrics: The optimal dose of PAXLOVID has not been established in pediatric patients. Renal impairment increases nirmatrelvir exposure. Reduce the PAXLOVID dosage in patients with moderate renal impairment (eGFR ≥30 to <60 mL/min). Reduce the dose and dose frequency in patients with severe renal impairment (eGFR <30 mL/min), including those requiring hemodialysis. On days when patients undergo hemodialysis, the PAXLOVID dose should be administered after hemodialysis. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions. PAXLOVID is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Please see Full Prescribing Information, including BOXED WARNING and Patient Information IndicationINDICATIONPAXLOVID 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.Limitations of UsePAXLOVID is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19.Please see Full Prescribing Information, including BOXED WARNING and Patient Information
Indication 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.

Limitations of Use

PAXLOVID is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19.

Please see Full Prescribing Information, including BOXED WARNING and Patient Information