AUTHORIZED USE

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product PAXLOVID for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including hospitalization or death.

LIMITATIONS OF AUTHORIZED USE
 

  • PAXLOVID is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19
  • PAXLOVID is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19
  • PAXLOVID is not authorized for use for longer than 5 consecutive days

PAXLOVID may be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs.

PAXLOVID may also be prescribed for an individual patient by a state-licensed pharmacist under the following conditions:

  • Sufficient information is available, such as through access to health records less than 12 months old or consultation with a health care provider in an established provider‑patient relationship with the individual patient, to assess renal and hepatic function; and
  • Sufficient information is available, such as through access to health records, patient reporting of medical history, or consultation with a health care provider in an established provider‑patient relationship with the individual patient, to obtain a comprehensive list of medications (prescribed and non-prescribed) that the patient is taking to assess for potential drug interaction.
     

The state-licensed pharmacist should refer an individual patient for clinical evaluation (e.g., telehealth, in-person visit) with a physician, advanced practice registered nurse, or physician assistant licensed or authorized under state law to prescribe drugs, if any of the following apply:

  • Sufficient information is not available to assess renal and hepatic function.
  • Sufficient information is not available to assess for a potential drug interaction.
  • Modification of other medications is needed due to a potential drug interaction.
  • PAXLOVID is not an appropriate therapeutic option based on the authorized Fact Sheet for Healthcare Providers or due to potential drug interactions for which recommended monitoring would not be feasible.


PAXLOVID is not approved for any use, including for use for the treatment of COVID-19.

PAXLOVID is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of PAXLOVID under 564(b)(1) of the Food Drug and Cosmetic Act unless the authorization is terminated or revoked sooner.

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Clinical Studies

PAXLOVIDTM (nirmatrelvir tablets; ritonavir tablets) has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including hospitalization or death.

The emergency use of PAXLOVID is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner.
 

 

Information contained in this section can be found in section 14 of the Fact Sheet for Healthcare Providers here

Efficacy in Subjects at High Risk of Progressing to Severe COVID-19 Illness

The data supporting this EUA are based on the analysis of EPIC-HR (NCT04960202), a phase 2/3, randomized, double-blind, placebo-controlled study in nonhospitalized, symptomatic adult subjects with a laboratory-confirmed diagnosis of SARS-CoV-2 infection.

Eligible participants were 18 years of age and older with at least one of the following risk factors for progression to severe disease:  
​​​​​​​​​​​​​​

  • diabetes 
  • overweight (BMI >25) 
  • chronic lung disease (including asthma) 
  • chronic kidney disease
  • current smoker 
  • immunosuppressive disease or immunosuppressive treatment 
  • cardiovascular disease 
  • hypertension
  • sickle cell disease
  • neurodevelopmental disorders 
  • active cancer
  • medically related technological dependence 
  • 60 years of age and older regardless of comorbidities 

Subjects with COVID-19 symptom onset of ≤5 days were included in the study. Subjects were randomized (1:1) to receive PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo orally every 12 hours for 5 days. The study excluded individuals with a history of prior COVID-19 infection or vaccination.

The primary efficacy endpoint was the proportion of subjects with COVID-19–related hospitalization or death from any cause through Day 28. The analysis was conducted in the modified intent-to-treat (mITT) analysis set (all treated subjects with onset of symptoms ≤3 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic monoclonal antibody [mAb] treatment), the mITT1 analysis set (all treated subjects with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), and the mITT2 analysis set (all treated subjects with onset of symptoms ≤5 days).

A total of 2246 subjects were randomized to receive either PAXLOVID or placebo. At baseline, mean age was 46 years; 51% were male; 72% were White, 5% were Black, and 14% were Asian; 45% were Hispanic or Latino; 66% of subjects had onset of symptoms ≤3 days from initiation of study treatment; 47% of subjects were serological negative at baseline; the mean (SD) baseline viral RNA shedding in nasopharyngeal samples was 4.63 log10 copies/mL (2.87); 26% of subjects had a baseline viral RNA shedding of >7 log10 copies/mL; 6% of subjects either received or were expected to receive COVID-19 therapeutic monoclonal antibody treatment at the time of randomization and were excluded from the mITT and mITT1 analyses. 

The baseline demographic and disease characteristics were balanced between the PAXLOVID and placebo groups.

Table 9 provides results of the primary endpoint in mITT1 analysis population. For the primary endpoint, the relative risk reduction in the mITT1 analysis population for PAXLOVID compared with placebo was 88% (95% CI: 75%, 94%).

Table 9: Efficacy Results in Nonhospitalized Adults With COVID-19 Dosed Within 5 Days of Symptom Onset Who Did Not Receive COVID-19 Monoclonal Antibody Treatment at Baseline (mITT1 Analysis Set)

PAXLOVID
​​​​​​​N=1039

Placebo
​​​​​​​​​​​​​​N=1046

COVID-19–related hospitalization or death from any cause through Day 28



n (%)

8 (0.8%)

66 (6.3%)

Reduction relative to placeboa [95% CI], %

-5.62 (-7.21, -4.03)


All-cause mortality through Day 28, %

0

12 (1.1%)


Abbreviations: CI=confidence interval.
The determination of primary efficacy was based on a planned interim analysis of 780 subjects in the mITT population. The estimated risk reduction was -6.3% with a 95% CI of (-9.0%, -3.6%) and 2-sided P<0.0001.
a. The estimated cumulative proportion of participants hospitalized or death by Day 28 was calculated for each treatment group using the Kaplan–Meier method, where subjects without hospitalization and death status through Day 28 were censored at the time of study discontinuation.

 

Consistent results were observed in the mITT and mITT2 analysis populations. A total of 1379 subjects were included in the mITT analysis population. The event rates were 5/697 (0.72%) in the PAXLOVID group and 44/682 (6.45%) in the placebo group. The primary SARS-CoV-2 variant across both treatment arms was Delta (98%), including clades 21J, 21A, and 21I.
 

Related Pages    Safety     Frequently Asked Questions
Verifying Product Authenticity

PAXLOVID must be prescribed by a licensed healthcare provider and supplied by a government-approved pharmacy or medical facility.

Authentic PAXLOVID, from Pfizer Inc., may include the Pfizer name on the label and will be packaged in 5 aluminum push-through blister cards. Individual doses are not for sale. PAXLOVID will be packaged in a rectangular carton. The carton has a colorless, glossy coating that contains a repeated pattern of the Pfizer name and logo all over, and these repeating features are seen in a contrasting matte finish.

PAXLOVID consists of tablets for a 5-day oral treatment regimen, with morning and evening doses.

Patients with moderate renal impairment may receive a carton that has been opened and modified by the pharmacist to indicate a dose adjustment. To view PAXLOVID dispensing information for patients with moderate renal impairment, see the Fact Sheet for Healthcare Providers. Also see the Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment and the Important Prescribing & Dispensing Letter to Healthcare Professionals (Aug. 2022).

To help determine whether the tablets are authentic, look for specific text on each side of the tablets

Tablet

Embossed Text

nirmatrelvir

Front: 3CL | Back: PFE

ritonavir, manufactured by AbbVie

Front: iconNK | Back: No text

ritonavir, manufactured by Hetero

Front: H | Back: R9

Pfizer is committed to patient safety and ensuring that people have accurate information about the investigational drug PAXLOVID, including how it is accessed and administered. We are actively monitoring for fraudulent offers of illegitimate PAXLOVID to protect patients from products that might be dangerous and lead to serious and life-threatening harm.

If you suspect the product you have received may be counterfeit, contact us at 1-800-438-1985 or visit www.pfizersafetyreporting.com.


Reference: PAXLOVID Fact Sheet for Healthcare Providers. Pfizer Inc.; September 26, 2022.

References:
 

  • PAXLOVID Fact Sheet for Healthcare Providers. Pfizer Inc.; February 2023.

For more  information

Contact One of the Following Groups

For Medical Information visit www.pfizermedicalinformation.com or call 1‑800‑438‑1985

For General Product Inquiries call 1‑877‑C19PACK (1‑877‑219‑7225)

This site is intended only for U.S. healthcare professionals. The products discussed in this site may have different product labeling in different countries. The information provided is for educational purposes only.

Copyright © 2023 Pfizer Inc. All rights reserved. PP-PAX-USA-0562

AUTHORIZED USE

AUTHORIZED USE


The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product PAXLOVID for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including hospitalization or death.


LIMITATIONS OF AUTHORIZED USE​​​​​​​

  • PAXLOVID is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19
  • PAXLOVID is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of
    COVID-19

  • PAXLOVID is not authorized for use for longer than 5 consecutive days
     

PAXLOVID may be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs.

PAXLOVID may also be prescribed for an individual patient by a state-licensed pharmacist under the following conditions:

  • Sufficient information is available, such as through access to health records less than 12 months old or consultation with a health care provider in an established provider-patient relationship with the individual patient, to assess renal and hepatic function; and
  • Sufficient information is available, such as through access to health records, patient reporting of medical history, or consultation with a health care provider in an established provider-patient relationship with the individual patient, to obtain a comprehensive list of medications (prescribed and non-prescribed) that the patient is taking to assess for potential drug interaction.


The state-licensed pharmacist should refer an individual patient for clinical evaluation (e.g., telehealth, in-person visit) with a physician, advanced practice registered nurse, or physician assistant licensed or authorized under state law to prescribe drugs, if any of the following apply:

  • Sufficient information is not available to assess renal and hepatic function.
  • Sufficient information is not available to assess for a potential drug interaction.
  • Modification of other medications is needed due to a potential drug interaction.
  • PAXLOVID is not an appropriate therapeutic option based on the authorized Fact Sheet for Healthcare Providers or due to potential drug interactions for which recommended monitoring would not be feasible.

PAXLOVID is not approved for any use, including for use for the treatment of COVID-19.

PAXLOVID is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of PAXLOVID under 564(b)(1) of the Food Drug and Cosmetic Act unless the authorization is terminated or revoked sooner.

​​​​​​

IMPORTANT SAFETY
INFORMATION

Expand

IMPORTANT SAFETY INFORMATION

Expand


PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis [TEN] or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product.

Drugs listed in this section 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 such as ritonavir.


PAXLOVID is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions:

  • Alpha1-adrenoreceptor antagonist: alfuzosin
  • Antianginal: ranolazine
  • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
  • Anti-gout: colchicine
  • Antipsychotics: lurasidone, pimozide
  • Benign prostatic hyperplasia agents: silodosin
  • Cardiovascular agents: eplerenone, ivabradine
  • Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
  • HMG-CoA reductase inhibitors: lovastatin, simvastatin
  • 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


PAXLOVID is contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. 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
  • Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
  • Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
  • Antimycobacterials: rifampin
  • Herbal Products: St. John’s Wort (hypericum perforatum)


There are limited clinical data available for PAXLOVID. Serious and unexpected adverse events may occur that have not been previously reported with PAXLOVID use.

Risk of Serious Adverse Reactions Due to Drug Interactions: Initiation of PAXLOVID, a 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. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of PAXLOVID, respectively. ​​​​​These interactions may lead to:

  • Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications
  • Clinically significant adverse reactions from greater exposures of PAXLOVID
  • Loss of therapeutic effect of PAXLOVID and possible development of viral resistance


Consult Table 1 of the Fact Sheet for Healthcare Providers for clinically significant drug interactions, including contraindicated drugs. Drugs listed in Table 1 are a guide and not considered a comprehensive list of all possible drugs that may interact with PAXLOVID. Consider the potential for drug interactions prior to and during PAXLOVID therapy; review concomitant medications during PAXLOVID therapy and monitor for the adverse reactions associated with the concomitant medications.

Anaphylaxis and other hypersensitivity reactions have been reported with PAXLOVID. Cases of Toxic Epidermal Necrolysis and Stevens-Johnson syndrome have been reported with ritonavir, a component of PAXLOVID (refer to NORVIR prescribing information). If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.

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 co-administered 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.

Adverse events in the PAXLOVID group (≥1%) that occurred at a greater frequency (≥5 subject difference) than in the placebo group were dysgeusia (6% and <1%, respectively), diarrhea (3% and 2%), hypertension (1% and <1%), and myalgia (1% and <1%). The proportions of subjects who discontinued treatment due to an adverse event were 2% in the PAXLOVID group and 4% in the placebo group.

The following adverse reactions have been identified during post-authorization use of PAXLOVID. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Anaphylaxis, hypersensitivity reactions
Gastrointestinal Disorders: Abdominal pain, nausea
General Disorders and Administration Site Conditions: Malaise


Required Reporting for Serious Adverse Events and Medication Errors: The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events and medication errors potentially related to PAXLOVID within 7 calendar days from the healthcare provider's awareness of the event.

Submit adverse event and medication error reports to FDA MedWatch using one of the following methods:


In addition, please provide a copy of all FDA MedWatch forms to: www.pfizersafetyreporting.com, or by fax (1‑866‑635‑8337) or phone (1‑800‑438‑1985).

PAXLOVID is a strong inhibitor of CYP3A and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A. Co-administration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring.

Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect.

Pregnancy: There are no available human data on the use of nirmatrelvir during pregnancy 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: There are no available data on the presence of nirmatrelvir in human or animal milk, the effects on the breastfed infant, or the effects on milk production. A transient decrease in body weight was observed in the nursing offspring of rats administered nirmatrelvir. Limited published data reports that ritonavir is present in human milk. There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug 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. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. 

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: PAXLOVID is not authorized for use in pediatric patients younger than 12 years of age or weighing less than 40 kg. The safety and effectiveness of PAXLOVID have not been established in pediatric patients. The authorized adult dosing regimen is expected to result in comparable serum exposures of nirmatrelvir and ritonavir in patients 12 years of age and older and weighing at least 40 kg as observed in adults, and adults with similar body weight were included in the trial EPIC-HR.

Systemic exposure of nirmatrelvir increases in renally impaired patients with increase in the severity of renal impairment. No dosage adjustment is needed in patients with mild renal impairment. In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), reduce the dose of PAXLOVID to 150 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions. PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min based on CKD-EPI formula) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined. 

No dosage adjustment of PAXLOVID is needed for patients with either mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. No pharmacokinetic or safety data are available regarding the use of nirmatrelvir or ritonavir in subjects with severe hepatic impairment (Child-Pugh Class C); therefore,
PAXLOVID is not recommended for use in patients with severe hepatic impairment.

Please see Fact Sheet for Healthcare Providers and Fact Sheet for Patients, Parents, and Caregivers.