According to the U.S. Food and Drug Administration (FDA), an Emergency Use Authorization (EUA) is a mechanism to facilitate the availability and use of medical countermeasures during public health emergencies, such as the current COVID-19 pandemic. Under an EUA, the FDA may allow the use of unapproved medical products, or unapproved uses of approved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, including that there are no adequate, approved, and available alternatives. Taking into consideration input from the FDA, manufacturers decide whether and when to submit an EUA request to the FDA. Once submitted, the FDA will evaluate an emergency use authorization request and determine whether the relevant statutory criteria are met, taking into account the totality of the scientific evidence that is available to the FDA.
Click here to view the FDA letter granting EUA of PAXLOVID. For more information about the EUA of PAXLOVID, see Section 1: Emergency Use Authorization of the Fact Sheet for Healthcare Providers here.
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of PAXLOVID for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40kg) with 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 preexposure or postexposure prophylaxis for prevention of COVID‑19
- PAXLOVID is not authorized for use 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.
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.
For more information about who can be treated with PAXLOVID under EUA, see Section 1: Emergency Use Authorization of the Fact Sheet for Healthcare Providers here.
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 40kg) 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.
PAXLOVID is not authorized for use in pediatric patients younger than 12 years of age or weighing less than 40kg. 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.
About PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets)
PAXLOVID is nirmatrelvir tablets copackaged with ritonavir tablets. Nirmatrelvir is a SARS-CoV-2 main protease (Mpro) inhibitor, and ritonavir is an HIV-1 protease inhibitor and CYP3A inhibitor.
For more information on PAXLOVID, see Section 11: Description in the Fact Sheet for Healthcare Providers here.
Nirmatrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug.
Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 Mpro. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir.
For more information about how PAXLOVID works, see Section 12: Clinical Pharmacology in the Fact Sheet for Healthcare Providers here.
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, using FDA Form 3500 (for information on how to access this form, see below).
Serious adverse events are defined as:
- Death
- A life-threatening adverse event
- Inpatient hospitalization or prolongation of existing hospitalization
- A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
- A congenital anomaly/birth defect
- Other important medical event, which may require a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly
Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods:
- Complete and submit the report online: https://www.fda.gov/medwatch/report.htm
-
Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by:
- Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
- Fax to 1-800-FDA-0178
- Call 1-800-FDA-1088 to request a reporting form
In addition, please provide a copy of all FDA MedWatch forms to:
Website |
Fax number |
Telephone number |
|---|---|---|
For more information on what the FDA recommends to include in your FDA Form 3500 report, see Section 6.4: Required Reporting for Serious Adverse Events and Medication Errors in the Fact Sheet for Healthcare Providers here.
Upon oral administration of nirmatrelvir/ritonavir, the increase in systemic exposure appears to be less than dose proportional, up to 750 mg as a single dose and up to 500 mg twice daily as multiple doses. Twice daily dosing over 10 days achieved steady-state on Day 2 with approximately 2-fold accumulation.
For more information about the pharmacokinetics of PAXLOVID, see Section 12.3: Pharmacokinetics in the Fact Sheet for Healthcare Providers here.
As of January 18, 2023, the U.S. Food and Drug Administration (FDA) authorized an additional shelf-life extension for PAXLOVID from 18 months to 24 months. Please visit the PAXLOVID lot expiry site to confirm the most updated expiration date for any Pfizer PAXLOVID medication.
The product expiration date is stated on the product packaging, both on the carton and on the individual blister cards.
Under the Eleventh Amendment to the COVID PREP Act declaration, which preempts state law, pharmacists can continue to prescribe PAXLOVID, consistent with the terms of the FDA emergency use authorization (EUA) as specified in the EUA Fact Sheets and the conditions of the PREP Act declaration only while distribution of federally purchased supply continues.
Once the PREP Act coverage has sunset, pharmacists may prescribe PAXLOVID in accordance with the laws of the states in which they practice to eligible patients consistent with the final FDA-approved USPI.
This guidance is based on Pfizer’s interpretation of the PREP Act, FDA’s EUA of PAXLOVID, and state authorities. These points are for consideration only; each stakeholder should seek advice of counsel.
Yes, the end of the Public Health Emergency (PHE) on May 11th did not impact pharmacists’ authority to prescribe. The PHE’s end did not directly impact the FDA’s EUA authority nor the PREP ACT declaration authority, the two authorities from which pharmacist prescribing of PAXLOVID derives in this circumstance.
Once the PREP Act authorities have sunset, pharmacists may prescribe PAXLOVID in accordance with the laws in the states in which they are licensed. For states that have not granted pharmacists the ability to prescribe COVID-19 antivirals, patients will no longer be able to obtain prescriptions for PAXLOVID or any other COVID-19 antiviral from pharmacists. Changing the scope of practice for pharmacists to permit such prescribing in those states will require state legislation. Pfizer believes that enabling pharmacists to prescribe PAXLOVID and other COVID-19 antiviral treatments to appropriate patients will increase timely access to important treatments.
Samples/starters are not available. Please contact your state health authority to request COVID-19 treatment allocations and/or visit the U.S. Government’s Health Partner Ordering Portal (HPOP) for requesting and ordering COVID-19 treatment here.*
*This link will take you to a website that is owned and operated by the Department of Health and Human Services. Pfizer is not responsible for the content or services of this site.
The recommended dosage for PAXLOVID is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) with all 3 tablets taken together orally twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Completion of the full 5-day treatment course and continued isolation in accordance with public health recommendations are important to maximize viral clearance and minimize transmission of SARS-CoV-2.
Important Dosing Information for Patients with Renal Impairment
No dosage adjustment is needed in patients with mild renal impairment (eGFR ≥60 to <90 mL/min). In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of PAXLOVID is 150 mg nirmatrelvir (one 150 mg tablet) and 100 mg ritonavir (one 100 mg tablet) with both tablets taken together twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Healthcare providers should counsel patients about renal dosing instructions.
PAXLOVID is not recommended for use in patients with severe renal impairment (eGFR <30 mL/min) or patients with end-stage renal disease (eGFR <15 mL/min) receiving dialysis until more data are available.
For important PAXLOVID dispensing information for patients with moderate renal impairment, refer Fact Sheet for Healthcare Providers here. Also see the Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment.
Use in Patients with Hepatic Impairment
No dosage adjustment is needed in patients with 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 (Child-Pugh Class C) hepatic impairment; therefore, PAXLOVID is not recommended for use in patients with severe hepatic impairment.
Important Drug Interactions with PAXLOVID
No dosage adjustment is required when coadministered with other products containing ritonavir or cobicistat.
Patients on ritonavir- or cobicistat-containing HIV or HCV regimens should continue their treatment as indicated.
Refer to other sections of the Fact Sheet for important drug interactions with PAXLOVID. Consider the potential for drug interactions prior to and during PAXLOVID therapy and review concomitant medications during PAXLOVID therapy.
For more information about product dosage, see Section 2: Dosage and Administration in the Fact Sheet for Healthcare Providers here.
The 5-day treatment course of PAXLOVID should be initiated as soon as possible after a diagnosis of COVID‑19 has been made and within 5 days of symptom onset.
For more information about product dosage, see Section 2: Dosage and Administration in the Fact Sheet for Healthcare Providers here.
Patients can take any available FDA-authorized COVID-19 viral test (eg, RT-PCR, rapid antigen, etc) to determine if they may have COVID-19. Per the Centers for Disease Control and Prevention (CDC), a viral test checks specimens from a patient’s nose or mouth and can be performed in a laboratory, at a testing site, at home, or anywhere else.
For more information on COVID-19 testing, see the CDC's "COVID-19 Testing: What You Need to Know" web page.*
*This link will take you to a web page that is owned and operated by the CDC. Pfizer is not responsible for the content or services of this site.
Two important factors to consider are Age and Race & Ethnicity. Studies have shown that COVID-19 does not affect all populations equally. Age is the strongest risk factor for progressing to severe COVID-19. In addition, the COVID-19 pandemic has highlighted racial, ethnic, and socioeconomic disparities in COVID-19 illnesses, hospitalizations, and deaths due to multiple factors, including barriers to accessing health care.
Underlying medical conditions associated with high risk for severe COVID-19 include:
Higher risk (conclusive):
- Asthma
- Cancer
- Cerebrovascular disease
- Chronic kidney disease
- Chronic lung diseases limited to:
- Bronchiectasis
- COPD
- Interstitial lung disease
- Pulmonary embolism
- Pulmonary hypertension
- Chronic liver diseases limited to:
- Cirrhosis
- Non-alcoholic fatty liver disease
- Alcoholic liver disease
- Autoimmune hepatitis
- Cystic fibrosis
- Diabetes mellitus, type 1 and type 2
- Disabilities, including Down syndrome*
- Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
- HIV
- Mental health conditions limited to:
- Mood disorders, including depression
- Schizophrenia spectrum disorders
- Neurologic conditions limited to dementia
- Obesity (BMI ≥30 kg/m2 or ≥95th percentile in children)
- Physical inactivity
- Pregnancy and recent pregnancy
- Primary immunodeficiencies
- Smoking, current and former
- Solid organ or blood stem cell transplant
- Tuberculosis
- Use of corticosteroids or other immunosuppressive medications
Suggestive higher risk:
- Children with certain underlying conditions
- Overweight (BMI ≥25 kg/m2, but <30 kg/m2)
- Sickle cell disease
- Substance use disorders
Mixed evidence (inconclusive: no conclusions can be drawn from the evidence):
- Alpha-1 antitrypsin deficiency
- Bronchopulmonary dysplasia
- Hepatitis B and C
- Hypertension
- Thalassemia
Patients at high risk of severe COVID-19 may be appropriate for an authorized oral Rx COVID-19 treatment. Authorized oral Rx treatment must be started within 5 days from when symptoms begin—even when initial symptoms are mild.
Consult the CDC for the latest information on risk factors: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html.†
*Complete list of disabilities from CDC's systematic review process can be found here.†
†This link will take you to a website that is owned and operated by the CDC. Pfizer is not responsible for the content or services of this site.
In addition to specifying the numeric dose of each active ingredient within PAXLOVID, here are other common details to include*:
For patients with moderate renal impairment, the numeric dose will be 1 nirmatrelvir 150-mg tablet and 1 ritonavir 100-mg tablet together twice daily with or without food for 5 days.
Please fill prescription by [insert date].
[Additional notes to pharmacy for Standard Dose]
- Risk factor(s) for progression to severe COVID-19†
- Symptom onset ≤5 days, consistent with mild-to-moderate COVID-19, not requiring hospitalization
- No known/suspected renal impairment (eGFR ≥90 mL/min) OR patient has moderate renal impairment ((eGFR ≥60 mL/min to <90 mL/min)
- No known or suspected severe (Child-Pugh Class C) hepatic impairment
- No history of significant hypersensitivity reactions
- Concomitant medications (screen for drug interactions)
Notes above depict considerations for prescribing after the decision to prescribe has been made; examples shown are for illustrative purposes only as prescribing notes are subject to the healthcare professional’s discretion. COVID‑19=coronavirus disease 2019; eGFR=estimated glomerular filtration rate.
Providers should also specify that completion of the full 5-day treatment course and continued isolation in accordance with public health recommendations are important to maximize viral clearance and minimize transmission of SARS-CoV-2.
*For additional screening information, consult the FDA’s PAXLOVID Patient Eligibility Screening Checklist Tool for Prescribers‡ or a similar resource from your local public health authority.
†Consult the CDC‡ for the latest information on factors that puts patients at high risk for progression to severe COVID-19.
‡These links will take you to websites that are owned and operated by the FDA and CDC. Pfizer is not responsible for the content or services of these sites.
For important information related to drug interactions and dosing for patients with renal impairment, refer to the Dosing tab.
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.
For more information on the use of PAXLOVID during pregnancy, see Section 8.1: Pregnancy of the Fact Sheet for Healthcare Providers here.
To find COVID-19 treatments, please use the U.S. Dept. of Health and Human Services (HHS) COVID-19 Therapeutics Locator.* Alternatively, HHS has launched the Test-to-Treat initiative* to help appropriate patients access COVID-19 testing and treatment options in one location. Patients can find a location near them here* or call 1-800-232-0233.
*These links will take you to websites that are owned and operated by HHS. Pfizer is not responsible for the content or services of these sites.
Despite COVID-19 Public Health Emergency (PHE) ending, PAXLOVID remains available to patients at no charge. Other administrative fees may apply.
PAXLOVID is nirmatrelvir tablets copackaged with ritonavir tablets. It is supplied in 2 different Dose Packs (Standard Dose and Renal Dose).
Nirmatrelvir tablets and ritonavir tablets are supplied in separate cavities within the same child-resistant blister card.
The standard dose is for patients with normal renal function or mild renal impairment (eGFR ≥60 to <90 mL/min).
Each carton of PAXLOVID contains 30 tablets in 5 daily-dose blister cards.
Each daily blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each) and indicates which tablets need to be taken in the morning and evening.
The renal dose is for patients with moderate renal impairment. PAXLOVID is not recommended for use in patients with severe renal impairment (eGFR <30 mL/min) or patients with end-stage renal disease (eGFR <15 mL/min) receiving dialysis until more data are available. Each carton contains 20 tablets divided in 5 daily-dose blister cards. Each blister card contains 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each).
For more information about how PAXLOVID is supplied, see Section 16: How Supplied/Storage and Handling here or the Pharmacist Instruction Sheet.
Per the Fact Sheet for Healthcare Providers:
- No dosage adjustment is needed in patients with mild renal impairment (eGFR ≥60 to <90 mL/min).
- In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of PAXLOVID is 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 for use in patients with severe renal impairment (eGFR <30 mL/min) or patients with end-stage renal disease (eGFR <15 mL/min) receiving dialysis until more data are available. The appropriate dosage for patients with severe renal impairment has not been determined.
Pharmacists should refer to the Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment for information on how to adjust the dosage of PAXLOVID for patients with moderate renal impairment, as well as guidelines on how to dispose of unused nirmatrelvir and ritonavir tablets.
Healthcare providers can also refer to the Dosing tab for information about the treatment of renally impaired patients with PAXLOVID.
PAXLOVID consists of 2 medicines: nirmatrelvir and ritonavir. Nirmatrelvir must be coadministered with ritonavir. Failure to correctly coadminster nirmatrelvir with ritonavir may result in plasma levels of nirmatrelvir that are insufficient to achieve the desired therapeutic effect. Patients should take 2 tablets of nirmatrelvir (150 mg each) with 1 tablet of ritonavir (100 mg) by mouth twice daily (in the morning and in the evening) for 5 days. For each dose, all 3 tablets should be taken at the same time.
- Patient should swallow the tablets whole. They should not chew, break, or crush the tablets
- Patients can take PAXLOVID with or without food
- Even if patients feel better, they should not stop taking PAXLOVID without talking to the prescribing healthcare provider
- Alert the patient to the importance of completing the full 5-day treatment course and to continuing isolation in accordance with public health recommendations to maximize viral clearance and minimize transmission of SARS-CoV-2
To ensure appropriate dosing in patients with moderate renal impairment, reduce the dosage of PAXLOVID to 150 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days. Providers should counsel patients about renal dosing instructions. Refer to the Fact Sheet for Healthcare Providers.
For more information on how to take PAXLOVID, patients can refer to the Dosing tab.
Missed dose: If the patient misses a dose of PAXLOVID within 8 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 8 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.
Overdose: If patients overdose on PAXLOVID, they should call their prescribing healthcare provider or go to the nearest hospital emergency room right away. 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.
For more information on product dosage, see Section 2: Dosage and Administration and Section 10: Overdosage in the Fact Sheet for Healthcare Providers here.
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.
Pharmacists may also prescribe PAXLOVID in accordance with the laws of the states in which they practice to eligible patients consistent with the terms of the of the FDA Emergency Use Authorization (EUA).
PAXLOVID may 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 (eg, 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.
For medical questions related to PAXLOVID, you can visit pfizermedicalinformation.com or call Medical Information at 1-800-438-1985.
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, 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/with:
- 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 that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions
- 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.
For a list of clinically significant drug interactions, including contraindicated drugs, refer to Section 7, Table 1: Established and Other Potentially Significant Drug Interactions here.
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, 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 (nirmatrelvir copackaged with ritonavir) 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 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. Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 1.
Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect.
For a list of clinically significant drug interactions, including contraindicated drugs, refer to Section 7, Table 1: Established and Other Potentially Significant Drug Interactions here.
Authentic PAXLOVID from Pfizer Inc., will 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.
Nirmatrelvir tablets are supplied as oval, pink, immediate-release, film-coated tablets with “PFE” on one side and “3CL” on the other side. Each tablet contains 150 mg of nirmatrelvir. Ritonavir tablets are supplied as white, film-coated, ovaloid tablets with the "
" logo and the code NK, or white to off-white, capsule‑shaped, film‑coated tablets with H on the front and R9 on the back. Each tablet contains 100 mg of ritonavir.
Patients with moderate renal impairment will 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 here. Also see the Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment.
See more information about product authenticity here.
EPIC-HR and EPIC-SR were not designed to evaluate COVID-19 rebound; exploratory analyses were conducted to assess the relationship between PAXLOVID use and rebound in viral RNA shedding levels or self-reported COVID-19 symptoms.
Post-treatment increases in SARS-CoV-2 RNA shedding levels in nasopharyngeal samples were observed on Day 10 and/or Day 14 in a subset of PAXLOVID and placebo recipients in EPIC-HR and EPIC-SR, irrespective of COVID-19 symptoms. The frequency of detection of post-treatment viral RNA rebound varied according to analysis parameters, but was generally similar among PAXLOVID and placebo recipients. A similar or smaller percentage of placebo recipients compared to PAXLOVID recipients had nasopharyngeal viral RNA results < lower limit of quantitation (LLOQ) at all study timepoints in both the treatment and post-treatment periods.
In EPIC-HR, of 59 PAXLOVID-treated subjects identified with post-treatment viral RNA rebound and with available viral sequence data, treatment-emergent substitutions in Mpro potentially reducing nirmatrelvir activity were detected in 2 (3%) subjects, including E166V in 1 subject and T304I in 1 subject. Both subjects had viral RNA shedding levels <LLOQ by Day 14.
Post-treatment viral RNA rebound was not associated with the primary clinical outcome of COVID-19–related hospitalization or death from any cause through Day 28 following the single 5-day course of PAXLOVID treatment. The clinical relevance of post-treatment increases in viral RNA following PAXLOVID or placebo treatment is unknown.
The frequency of symptom rebound through Day 28, irrespective of viral RNA results, was similar among PAXLOVID and placebo recipients. The frequency of combined viral RNA rebound plus symptom rebound could not be fully assessed, as most episodes of symptom rebound occurred after Day 14 (the last day SARS‑CoV‑2 RNA levels were routinely assessed).