Moderate Renal Impairment | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets)

Looking for information about the FDA approved indication for PAXLOVID^TM
(nirmatrelvir tablets; ritonavir tablets) ? Click here

AUTHORIZED USE

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of PAXLOVID^TM(nirmatrelvir tablets; ritonavir tablets) for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) 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 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 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.

How Do Patients with Moderate Renal Impairment Take PAXLOVID^TM (nirmatrelvir tablets; ritonavir tablets)?

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 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. 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.

Inform patients to take PAXLOVID with or without food
Advise patients to swallow all tablets for PAXLOVID whole and not to chew, break, or crush the tablets
Alert the patient of the importance of completing the full 5-day treatment course and of continuing isolation in accordance with public health recommendations to maximize viral clearance and minimize transmission of SARS-CoV-2
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 should instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose
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

NOTE: Providers should counsel patients about renal dosing instructions. Refer to the Pharmacist Instruction Sheet for Patients with Moderate Renal Impairment for more information.

Who Can Prescribe PAXLOVID?

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 FDA EUA. 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 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.

Prescription Details

In addition to specifying the numeric dose of each active ingredient within PAXLOVID, here are some suggestions on details to include*:

Images 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.

Additional prescribing information (also refer to Drug Interactions)

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, or in patients with severe (Child-Pugh Class C) hepatic impairment.
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

*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 put 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.

Tablet	Embossed Text
nirmatrelvir	Front: 3CL \| Back: PFE
ritonavir, manufactured by AbbVie	Front: NK \| Back: No text
ritonavir, manufactured by Hetero	Front: H \| Back: R9

AUTHORIZED USE

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 40 kg) 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 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

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.

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.

IMPORTANT SAFETY
INFORMATION

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IMPORTANT SAFETY INFORMATION

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WARNING: SIGNIFICANT DRUG INTERACTIONS WITH PAXLOVID

PAXLOVID includes ritonavir, a strong CYP3A inhibitor, which may lead to greater exposure of certainconcomitant 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 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:

Alpha₁-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
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. Caution should be exercised when administering PAXLOVID to patients withpre-existing liver diseases, liver enzyme abnormalities, or hepatitis.

Because nirmatrelvir is co-administered with ritonavir, there may be arisk 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 post-authorization use of PAXLOVID.

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

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:

Online: https://www.fda.gov/medwatch/report.htm
Complete and submit a postage-paid FDA Form 3500 and returning by mail/fax
Call 1-800-FDA-1088 to request a reporting form

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 an inhibitor of CYP2D6, P-gp, and OATP1B1. Co-administration 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. Co-administration 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: 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.

Renal impairment increases nirmatrelvir exposure, which may increase the risk of adverse reactions. No dosage adjustment is recommended in patients with mild renal impairment (eGFR ≥60 to <90 mL/min). Reduce the PAXLOVID dosage in patients with moderate renal impairment (eGFR ≥30 to <60 mL/min). PAXLOVID is not recommended 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. 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.

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