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 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:
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:
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.
The renal dose is for patients with moderate renal impairment. PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) is not recommended in patients with severe renal impairment (eGFR <30 mL/min) until more data are available.
PAXLOVID 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 sections 2, 3, 10, 16, and 17 of the Fact Sheet for Healthcare Providers here.
Before prescribing PAXLOVID, it is important to check for potential drug interactions, contraindications and impairments that may require a dose adjustment. Reference sections 4, 5, and 7 for this information in the Fact Sheet for Healthcare Providers here.
Reference the Dosing & Prescribing Reference Guide for more information here.
nirmatrelvir
tablet
(150 mg)
ritonavir
tablet
(100 mg)
Take 2 tablets at the same time.
nirmatrelvir
tablet
(150 mg)
ritonavir
tablet
(100 mg)
Take 2 tablets at the same time.
For 5 Consecutive Days
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. Alert the patient of the importance of completing the full 5-day treatment course and continued isolation in accordance with public health recommendations to maximize viral clearance and minimize transmission of SARS-CoV-2. If patients experience side effects while taking PAXLOVID, instruct them to speak with the prescribing healthcare provider before discontinuing treatment.
PAXLOVID consists of 2 medicines: nirmatrelvir and ritonavir. Nirmatrelvir must be coadministered with ritonavir. Failure to correctly coadminister nirmatrelvir with ritonavir may result in plasma levels of nirmatrelvir that are insufficient to achieve the desired therapeutic effect. Patients with moderate renal impairment should take 1 tablet of nirmatrelvir (150 mg) with 1 tablet of ritonavir (100 mg) by mouth twice daily (in the morning and in the evening) for 5 days. For each dose, the 2 tablets should be taken at the same time. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID.
NOTE: Providers should counsel patients about renal dosing instructions. Refer to the Important Prescribing & Dispensing Letter to Healthcare Professionals (Aug. 2022) and the Pharmacist Instruction Sheet for more information.
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:
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:
Important Dosing Information in 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 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) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined.
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 pharmacokinetics 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.
Important Drug Interactions with PAXLOVID
Refer to sections 4, 5, and 7 of the Fact Sheet for Healthcare Providers for important drug interactions with PAXLOVID. Interacting drugs listed in the Fact Sheet are a guide and not considered a comprehensive list of all possible drugs that may interact 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. Consider the potential for drug interactions prior to and during PAXLOVID therapy and review concomitant medications during PAXLOVID therapy [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7)].
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 the Dosing & Prescribing Reference Guide for more information.
Nirmatrelvir tablets and ritonavir tablets are supplied in separate cavities within the same child-resistant blister card.
Each carton contains 20 tablets divided in 5 daily-dose blister cards (NDC number: 0069‑1101‑20).
Each daily blister card (NDC number: 0069‑1101‑04) contains 2 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.
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 Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment and the Important Prescribing & Dispensing Letter to Healthcare Professionals (Aug. 2022).
Tablet |
Embossed Text |
---|---|
nirmatrelvir |
Front: 3CL | Back: PFE |
ritonavir, manufactured by AbbVie |
Front: |
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.
References:
PAXLOVID Fact Sheet for Healthcare Providers. Pfizer Inc.; February 2023.
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.
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 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:
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:
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
IMPORTANT SAFETY INFORMATION
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:
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:
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:
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.