Looking for information about the FDA approved indication for PAXLOVIDTM  
(nirmatrelvir tablets; ritonavir tablets) ?
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AUTHORIZED USE

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of PAXLOVIDTM  (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.

X

Important Update: Emergency Use Authorization labeled PAXLOVIDTM(nirmatrelvir tablets; ritonavir tablets) will no longer be authorized for emergency use after March 8, 2024. Please click here to learn more.

PAXCESS™ Patient Support Program is now available for patients prescribed PAXLOVID. Commercially insured patients may pay as little as $0* for their prescription by downloading a copay card here

Patients on Medicare, Medicaid, TRICARE, VA Community Care Network, and those who are uninsured, may enroll in the U.S. Government's Patient Assistance Program (USG PAP) operated by Pfizer to access PAXLOVID for free* through December 31, 2024, by clicking here.

Looking for information about the FDA approved indication for PAXLOVIDTM (nirmatrelvir tablets; ritonavir tablets) ? Click here.

*Eligible commercially insured patients can save up $1,500 per prescription.  Maximum annual savings up to $1,500.  Please click here for full terms and conditions for the PAXCESSTM  copay savings program. 
The USG PAP operated by Pfizer is an independent program with separate eligibility requirements offered by the United States Department of Health and Human Services and is not owned by Pfizer.  Please click here for the full terms and conditions of the USG PAP.

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Drug Interactions

PAXLOVIDTM (nirmatrelvir tablets; ritonavir tablets) has not been approved, but has been authorized for emergency use by FDA under an Emergency Use Authorization (EUA), for the treatment of mild-to-moderate COVID-19 in pediatric patients (12 years of age and older weighing at least 40 kg) 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 4, 5, and 7 of the Fact Sheet for Healthcare Providers 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​​​​​​​
Contraindications Due to Drug Interactions

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 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 (e.g., tacrolimus, cyclosporine), followed by calcium channel blockers.

Prior to prescribing PAXLOVID, review all medications taken by the patient to assess potential drug-drug interactions and determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring (e.g., calcineurin inhibitors). See Table 1 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 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.

Potential for PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) to Affect Other Drugs

PAXLOVID is a strong inhibitor of CYP3A and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A. 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.

Potential for Other Drugs to Affect PAXLOVID

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

Established and Other Potentially Significant Drug Interactions

Table 1 provides a listing of 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. 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. References contained in Table 1 are to the applicable section of the Fact Sheet for Healthcare Providers, which can be accessed here.

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Please see the full EUA Fact Sheet or contact Medical Information.

Table 1: Established and Other Potentially Significant Drug Interactions

Drug Class

Drugs within Class that are Contraindicated

Effect on Concentration

Clinical Comments

Alpha1-adrenoreceptor
antagonist

alfuzosin

↑ alfuzosin

Coadministration contraindicated due to potential hypotension [see Contraindications (4)].

Alpha1-adrenoreceptor
antagonist

tamsulosin

↑ tamsulosin

Avoid concomitant use with PAXLOVID.

Antianginal

ranolazine

↑ ranolazine

Coadministration contraindicated due to potential for serious and/or life-threatening reactions [see Contraindications (4)].

Antiarrhythmics

amiodarone, 
dronedarone, 
flecainide, 
propafenone, 
quinidine

↑ antiarrhythmic 

Coadministration contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)].

Antiarrhythmics

lidocaine (systemic),
disopyramide

↑ antiarrhythmic 

Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available. 

Anticancer drugs

apalutamide​​​​​​

↓ nirmatrelvir/ritonavir

​​​​​​Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].

Anticancer drugs

abemaciclib, 
ceritinib, 
dasatinib, 
encorafenib, 
ibrutinib, 
ivosidenib, 
neratinib, 
nilotinib, 
venetoclax, 
vinblastine, 
vincristine​​​​​​​

↑ anticancer drug​​s

​​​​​​​​​​​​Avoid coadministration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib.

Coadministration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects.
​​​​​​​
For further information, refer to individual product label for anticancer drug.

Anticoagulants

warfarin​​​​​​

rivaroxaban

dabigatrana

apixaban

↑↓ warfarin

​​​​​​​↑ rivaroxaban

↑ dabigatran

↑ apixaban

Closely monitor international normalized ratio (INR) if coadministration with warfarin is necessary.

Increased bleeding risk with rivaroxaban. Avoid concomitant use.

Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information.  

Combined P-gp and strong CYP3A inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for coadministration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information.

Anticonvulsants

carbamazepine,a
phenobarbital,
primidone,
phenytoin

↓ nirmatrelvir/ritonavir

Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].

Anticonvulsants

clonazepam

↑ anticonvulsant

A dose decrease may be needed for clonazepam when coadministered with PAXLOVID and clinical monitoring is recommended.

Antidepressants

bupropion

trazodone​​​​​​​

↓ bupropion and active metabolite
hydroxy-bupropion 

↑ trazodone

​​​​​​​Monitor for an adequate clinical response to bupropion. 


Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to trazadone product label for further information. 

Antifungals

voriconazole,


ketoconazole, 
isavuconazonium sulfate 
itraconazolea

↓ voriconazole


↑ ketoconazole
↑ isavuconazonium sulfate
↑ itraconazole


↑ nirmatrelvir/ritonavir

Avoid concomitant use of voriconazole.

Refer to ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information.

A nirmatrelvir/ritonavir dose reduction is not needed.

Anti-gout

colchicine

↑ colchicine

Coadministration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment [see Contraindications (4)].

Anti-HIV protease inhibitors

atazanavir,
darunavir,
tipranavir

↑ protease inhibitor

For further information, refer to the respective protease inhibitors’ prescribing information.

Patients on ritonavir- or 
cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or protease inhibitor adverse events.
​​​​​​​

Anti-HIV

efavirenz, 
maraviroc, 
nevirapine, 
zidovudine
bictegravir/
emtricitabine/
tenofovir

↑ efavirenz
↑ maraviroc
↑ nevirapine
↓ zidovudine
↑ bictegravir   
⟷emtricitabine 
↑ tenofovir

For further information, refer to the respective anti-HIV drugs prescribing information.

Anti-infective

clarithromycin,
​​​​​​​erythromycin

↑ clarithromycin
↑ erythromycin

Refer to the respective prescribing information for anti-infective dose adjustment.

Antimycobacterial

rifampin, 
rifapentine

↓ nirmatrelvir/ritonavir

Coadministration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered [see Contraindications (4)].

Antimycobacterial

bedaquiline

rifabutin

↑ bedaquiline

↑ rifabutin

Refer to the bedaquiline product label for further information.

Refer to rifabutin product label for further information on rifabutin dose reduction.

Antipsychotics

lurasidone, 
pimozide

↑ lurasidone
↑ pimozide

Coadministration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias [see Contraindications (4)].

Antipsychotics

quetiapine

clozapine

↑ quetiapine

↑ clozapine

If coadministration is necessary, reduce quetiapine dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations.

If coadministration is necessary, consider reducing the clozapine dose and monitor for adverse reactions.

Benign prostatic hyperplasia agents

silodosin

↑ silodosin

Coadministration contraindicated due to potential for postural hypotension [see Contraindications (4)].

Calcium channel blockers

amlodipine, 
diltiazem,
felodipine,
nicardipine,
nifedipine,
verapamil

↑ calcium channel blocker

Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when coadministered with PAXLOVID.

If coadministered, refer to individual product label for calcium channel blocker for further information.

Cardiac glycosides

digoxin

↑ digoxin

Caution should be exercised when coadministering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels.

Refer to the digoxin product label for further information.

Cardiovascular agents

eplerenone

ivabradine

↑ eplerenone

↑ ivabradine

Coadministration with eplerenone is contraindicated due to potential for hyperkalemia [see Contraindications (4)].

Coadministration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances [see Contraindications (4)].

Cardiovascular agents

aliskiren,
ticagrelor,
vorapaxar

clopidogrel


cilostazol

↑ aliskiren
↑ ticagrelor
↑ vorapaxar

↓ clopidogrel active metabolite


↑ cilostazol

Avoid concomitant use with PAXLOVID.

Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information.

Corticosteroids primarily metabolized by CYP3A

betamethasone,
budesonide,
ciclesonide,
dexamethasone,
fluticasone,
methylprednisolone,
mometasone,
triamcinolone

↑ corticosteroid

Coadministration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. However, the risk of Cushing’s syndrome and adrenal suppression associated with short-term use of a strong CYP3A inhibitor is low.

Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered.

Cystic fibrosis transmembrane conductance regulator potentiators

lumacaftor/ivacaftor

↓ nirmatrelvir/ritonavir

Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].

Cystic fibrosis transmembrane conductance regulator potentiators

ivacaftor

elexacaftor/tezacaftor/ivacaftor

tezacaftor/ivacaftor

↑ ivacaftor

↑elexacaftor/tezacaftor/ivacaftor

↑ tezacaftor/ivacaftor

Reduce dosage when coadministered with PAXLOVID. Refer to individual product labels for more information.

Dipeptidyl peptidase 4 (DPP4) inhibitors

saxagliptin

↑ saxagliptin

Dosage adjustment of saxagliptin is recommended. Refer to the saxagliptin product label for more information. 

Endothelin receptor antagonists

bosentan

↑ bosentan
↓ nirmatrelvir/ritonavir

Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID.

Refer to the bosentan product label for further information.

Ergot derivatives

dihydroergotamine,
ergotamine,
methylergonovine

↑ dihydroergotamine
​​​​​​​↑ ergotamine
↑ methylergonovine

Coadministration contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system [see Contraindications (4)].

Hepatitis C
direct-acting antivirals

elbasvir/grazoprevir, glecaprevir/pibrentasvir
 

ombitasvir/paritaprevir/
ritonavir and dasabuvir
 

sofosbuvir/velpatasvir/
voxilaprevir

↑ antiviral 

Increased grazoprevir concentrations can result in alanine transaminase (ALT) elevations.

Avoid concomitant use
of glecaprevir/pibrentasvir with PAXLOVID.

Refer to the ombitasvir/paritaprevir/ritonavir and dasabuvir label for further information.

Refer to the sofosbuvir/velpatasvir/voxilaprevir product label for further information.

Patients on ritonavir-containing HCV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use.

Herbal products

St John’s Wort
(hypericum perforatum)

↓ nirmatrelvir/ritonavir

Coadministration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)].

HMG-CoA reductase inhibitors

lovastatin,
simvastatin

↑ lovastatin
​​​​​​​↑ simvastatin

Coadministration contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4)].

If treatment with PAXLOVID is considered medically necessary, discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment and for 5 days after completing PAXLOVID.

HMG-CoA reductase inhibitors

atorvastatin,
rosuvastatin

↑ atorvastatin,
​​​​​​​↑ rosuvastatin

Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID. Atorvastatin and rosuvastatin do not need to be withheld prior to or after completing PAXLOVID.

Hormonal contraceptive

ethinyl estradiol

↓ ethinyl estradiol

An additional, nonhormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID.

Immunosuppressants

voclosporin

↑ voclosporin

Coadministration contraindicated due to potential for acute and/or chronic nephrotoxicity [see Contraindications (4)].

Immunosuppressants

calcineurin inhibitors:
cyclosporine,
tacrolimus
​​​​​​​
​​​​​​​



​​​​​​​


​​​​​​​ 

​​​​​​​mTOR inhibitors:
everolimus,
sirolimus

↑ cyclosporine
↑ tacrolimus

​​​​​​​



​​​​​​​

 
​​​​​​​↑ everolimus
↑ sirolimus

Avoid concomitant use of calcineurin inhibitors with PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible. If coadministered, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and adverse reactions are recommended during and after treatment with PAXLOVID. Obtain expert consultation to appropriately manage the complexity of this coadministration. [see Warnings and Precautions (5.1)]

Avoid concomitant use of everolimus and sirolimus and PAXLOVID.

Refer to the individual immunosuppressant product label and latest guidelines for further information.

Janus kinase (JAK) inhibitors 

tofacitinib,
upadacitinib

↑ tofacitinib



​​​​​​​
↑ upadacitinib

Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information.

Dosing recommendations for coadministration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib product label for more information.

Long-acting 
beta-adrenoceptor agonist

salmeterol

↑ salmeterol

Avoid concomitant use with PAXLOVID. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.

Microsomal triglyceride transfer protein (MTTP) inhibitor

lomitapide

↑ lomitapide

Coadministration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions [see Contraindications (4)].

Migraine medications

eletriptan

ubrogepant

↑ eletriptan

↑ ubrogepant

Coadministration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events [see Contraindications (4)].

Coadministration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions [see Contraindications (4)].

Migraine medications

rimegepant

↑ rimegepant

Avoid concomitant use with PAXLOVID.

Mineralocorticoid receptor antagonists

finerenone

↑ finerenone

Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia [see Contraindications (4)].

Muscarinic receptor antagonists

darifenacin

↑ darifenacin

The darifenacin daily dose should not exceed 7.5 mg when coadministered with PAXLOVID. Refer to the darifenacin product label for more information.

Narcotic analgesics

fentanyl,
hydrocodone,
oxycodone,
meperidine

methadone

↑ fentanyl
↑ hydrocodone
↑ oxycodone
↑ meperidine

↓ methadone

Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID. If concomitant use with PAXLOVID is necessary, consider a dosage reduction of the narcotic analgesic and monitor patients closely at frequent intervals. Refer to the individual product label for more information.  

Monitor methadone-maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly.

Neuropsychiatric
agents

suvorexant

aripiprazole,
brexpiprazole,
cariprazine,
iloperidone,
lumateperone,
pimavanserin

↑ suvorexant

↑ aripiprazole
↑ brexpiprazole
↑ cariprazine
↑ iloperidone
↑ lumateperone
↑ pimavanserin

Avoid concomitant use of suvorexant with PAXLOVID.

Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to individual product label for more information.

Opioid antagonists

naloxegol

↑ naloxegol

Coadministration contraindicated due to the potential for opioid withdrawal symptoms [see Contraindications (4)].

Pulmonary hypertension agents (PDE5 inhibitors)

sildenafil (Revatio®)

↑ sildenafil

Coadministration of sildenafil with PAXLOVID is contraindicated for use in pulmonary hypertension due to the potential for sildenafil associated adverse events, including visual abnormalities hypotension, prolonged erection, and syncope [see Contraindications (4)].

Pulmonary hypertension agents (PDE5 inhibitors)

Pulmonary hypertension agents (sGC stimulators)

tadalafil (Adcirca®)



riociguat

↑ tadalafil



↑ riociguat

Avoid concomitant use of tadalafil with PAXLOVID for pulmonary hypertension.

Dosage adjustment is recommended for riociguat when used for pulmonary hypertension. Refer to the riociguat product label for more information.

Erectile dysfunction agents (PDE5 inhibitors)

avanafil

sildenafil,
tadalafil,
vardenafil

↑ avanafil

↑ sildenafil
↑ tadalafil
↑ vardenafil

Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established.

Dosage adjustment is recommended for use of sildenafil, tadalafil, or vardenafil with PAXLOVID when used for erectile dysfunction. Refer to individual product label for more information.

Sedative/hypnotics

triazolam,
oral midazolama

↑ triazolam 
↑ midazolam

Coadministration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4)].

Sedative/hypnotics

buspirone, 
clorazepate,
diazepam,
estazolam,
flurazepam,
zolpidem 

midazolam 
(administered parenterally)

↑ sedative/hypnotic






↑ midazolam

A dose decrease may be needed for these drugs when coadministered with PAXLOVID and monitoring for adverse events.


Coadministration of midazolam
(parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. 

Refer to the midazolam product label for further information.

Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist

flibanserin

↑ flibanserin

Coadministration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4)].

Vasopressin receptor antagonists

tolvaptan

↑ tolvaptan

Coadministration contraindicated due to potential for dehydration, hypovolemia and hyperkalemia [see Contraindications (4)].

aSee Pharmacokinetics, Drug Interaction Studies Conducted with Nirmatrelvir and Ritonavir (12.3).
Related Pages Clinical Studies Safety
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.

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.; May 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-C1D-USA-0057

AUTHORIZED USE

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

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.

IMPORTANT SAFETY
INFORMATION

Expand

IMPORTANT SAFETY INFORMATION

Expand


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:


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.