These Highlights Do Not Include All The Information Needed To Use Paxlovid Safely And Effectively. See Full Prescribing Information For Paxlovid.

Limitations of Use

PAXLOVID is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19 [see Clinical Studies (14.3)].

This Patient Information has been approved by the U.S. Food and Drug Administration.      Revised: 02/2026

Storage and Handling

Store at USP controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

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.

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. Nirmatrelvir is a SARS-CoV-2 main protease (M^pro) inhibitor, and ritonavir is an HIV-1 protease inhibitor and CYP3A inhibitor.

Mechanism of Action

Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (M^pro), also referred to as 3C-like protease (3CL^pro) or nonstructural protein 5 (nsp5) protease. Inhibition of SARS-CoV-2 M^pro renders it incapable of processing the viral polyproteins pp1a and pp1ab, preventing viral replication. Nirmatrelvir inhibited the activity of recombinant SARS-CoV-2 M^pro in a biochemical assay with a K_i value of 3.1 nM and an IC₅₀ value of 19.2 nM. Nirmatrelvir was found to bind directly to the SARS-CoV-2 M^pro active site by X-ray crystallography.

The optimal dose of PAXLOVID has not been established in pediatric patients.

Clinical studies of PAXLOVID include subjects 65 years of age and older and their data contributes to the overall assessment of safety and efficacy [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. Of the total number of subjects in the integrated dataset consisting of EPIC-HR and EPIC-SR who were randomized to and received PAXLOVID (N=1,578), 165 (10%) were 65 years of age and older and 39 (2%) were 75 years of age and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in safety between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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.

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

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 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 like PAXLOVID [see Drug Interactions (7.3)]:

• ➢
  Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7.3)]:
  • •
    Alpha 1-adrenoreceptor antagonist: alfuzosin
  • •
    Antianginal: ranolazine
  • •
    Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
  • •
    Anti-gout: colchicine (in patients with renal and/or hepatic impairment [see Table 2 , Drug Interactions (7.3)] )
  • •
    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 [see Table 2 , Drug Interactions (7.3)])
  • •
    Immunosuppressants: voclosporin
  • •
    Microsomal triglyceride transfer protein inhibitor: lomitapide
  • •
    Migraine medications: eletriptan, ubrogepant
  • •
    Mineralocorticoid receptor antagonists: finerenone
  • •
    Non-opioid analgesic (selective blocker of Na_v1.8 sodium channels): suzetrigine
  • •
    Opioid antagonists: naloxegol
  • •
    PDE5 inhibitor: sildenafil (Revatio^®) when used for pulmonary arterial hypertension (PAH)
  • •
    Sedative/hypnotics: triazolam, oral midazolam
  • •
    Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
  • •
    Vasopressin receptor antagonists: tolvaptan
• ➢
  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. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer [see Drug Interactions (7.3)]:
  • •
    Anticancer drugs: apalutamide, enzalutamide
  • •
    Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
  • •
    Antimycobacterials: rifampin, rifapentine
  • •
    Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
  • •
    Herbal products: St. John's Wort (hypericum perforatum)

The following clinically significant adverse reactions are described elsewhere in the labeling:

• •
  Hypersensitivity reactions [see Warnings and Precautions (5.2)]

Co-administration of PAXLOVID can alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PAXLOVID. Consider the potential for drug interactions prior to and during PAXLOVID therapy and review concomitant medications during PAXLOVID therapy. (4, 5.1, 7, 12.3)

Renal impairment increases nirmatrelvir exposure, which may increase the risk of PAXLOVID 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). Reduce the PAXLOVID dose and dose frequency in patients with severe renal impairment (eGFR <30 mL/min), including those requiring hemodialysis. On days when patients undergo hemodialysis, the PAXLOVID dose should be administered after hemodialysis [see Dosage and Administration (2.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.3)]. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions [see Patient Counseling Information (17)].

Cardiac Electrophysiology

At 3 times the steady state peak plasma concentration (C_max) at the recommended dose, nirmatrelvir does not prolong the QTc interval to any clinically relevant extent.

The pharmacokinetics of nirmatrelvir/ritonavir were similar in healthy subjects and in subjects with mild-to-moderate COVID-19.

Nirmatrelvir AUC increased in a less than dose proportional manner over a single dose range from 250 mg to 750 mg (0.83 to 2.5 times the approved recommended dose) and multiple dose range from 75 mg to 500 mg (0.25 to 1.67 times the approved recommended dose), when administered in combination with 100 mg ritonavir. Nirmatrelvir steady state was achieved on Day 2 following administration of the approved recommended dosage and the mean accumulation ratio was approximately 2-fold.

The pharmacokinetic properties of nirmatrelvir/ritonavir are displayed in Table 3.

The predicted Day 5 nirmatrelvir exposure parameters in adult subjects with mild-to-moderate COVID-19 who were treated with PAXLOVID in EPIC-HR are presented in Table 4.

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 in the morning and at bedtime for 5 days.

No dosage adjustment of PAXLOVID is recommended for 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 (Child-Pugh Class C) hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

PAXLOVID is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.

Nirmatrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug [see Microbiology (12.4)].

Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 M^pro. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir.

• •
  The concomitant use of PAXLOVID and certain other drugs may result in potentially significant drug interactions. Consult the Full Prescribing Information prior to and during treatment for potential drug interactions. (5.1, 7)
• •
  Hypersensitivity Reactions: Anaphylaxis, serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome), and other hypersensitivity reactions have been reported with PAXLOVID. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. (5.2)
• •
  Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. (5.3)
• •
  HIV-1 Drug Resistance: PAXLOVID use may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. (5.4)

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. (2.1)

Nirmatrelvir must be co-administered with ritonavir. (2.1)

• •
  Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. (2.1)
• •
  Administer orally with or without food. (2.1)
• •
  Administer at approximately the same time each day. (2.2, 2.3)
• •
  Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days. (2.2)
• •
  Dose Reduction for Renal Impairment (2.3, 8.6, 12.3)

• •
  PAXLOVID is not recommend in patients with severe hepatic impairment (Child-Pugh Class C). (2.4, 8.7)

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets [see How Supplied/Storage and Handling (16)].

• •
  Nirmatrelvir is supplied as oval, pink immediate-release, film-coated tablets debossed with "PFE" on one side and "3CL" on the other side. Each tablet contains 150 mg of nirmatrelvir.
• •
  Ritonavir is supplied as white or white to off-white film-coated tablets uniquely identified by the color, shape, and debossing. Each tablet contains 100 mg of ritonavir.

Anaphylaxis, serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome), and other hypersensitivity reactions have been reported with PAXLOVID [see Adverse Reactions (6.1)]. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of PAXLOVID is based on two Phase 2/3 randomized, placebo-controlled trials in symptomatic adult subjects 18 years of age and older with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Subjects in both studies received PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo every 12 hours for 5 days for the treatment of mild-to-moderate COVID-19 within 5 days of symptom onset [see Clinical Studies (14)]:

• •
  Trial C4671005 (EPIC-HR) enrolled subjects who were at high risk for progression to severe disease.
• •
  Trial C4671002 (EPIC-SR) enrolled subjects who were at standard risk for progression to severe disease (previously unvaccinated subjects at standard risk or fully vaccinated subjects with at least 1 risk factor for progression to severe disease).

Adverse reactions were those reported while subjects were on study medication and through 28 days after the last dose of study treatment.

In Trial C4671005 (EPIC-HR), 1,038 subjects received PAXLOVID and 1,053 subjects received placebo. The most common adverse reactions (≥1% incidence in the PAXLOVID group and occurring at a greater frequency than in the placebo group) were dysgeusia (5% and <1%, respectively) and diarrhea (3% and 2%, respectively).

Among vaccinated or unvaccinated subjects at standard risk or fully vaccinated subjects with at least 1 risk factor for progression to severe disease in Trial C4671002 (EPIC-SR), 540 subjects received PAXLOVID and 528 subjects received placebo. The adverse reactions observed were consistent with those observed in EPIC-HR.

Trial C4671028 (EPIC-SRI) was a Phase 1, open-label trial that evaluated the effects of severe renal impairment on the pharmacokinetics, safety, and tolerability of PAXLOVID in non-hospitalized adult participants with COVID-19 and severe renal impairment. A total of 15 subjects with severe renal impairment were enrolled in this trial, with 12 subjects receiving intermittent hemodialysis and 3 subjects not on hemodialysis. Subjects received nirmatrelvir/ritonavir 300 mg/100 mg once on Day 1 followed by nirmatrelvir/ritonavir 150 mg/100 mg once daily from Days 2-5. The safety profile of PAXLOVID in subjects with severe renal impairment, including those requiring hemodialysis, was consistent with the safety profile observed in the Phase 2/3 randomized, placebo-controlled trials.

Emergency Use Authorization Experience in Subjects with COVID-19

The following adverse reactions have been identified during use of PAXLOVID under Emergency Use Authorization.

Immune System Disorders: Anaphylaxis, hypersensitivity reactions [see Warnings and Precautions (5.2)]

Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome [see Warnings and Precautions (5.2)]

Nervous System Disorders: Headache

Vascular Disorders: Hypertension

Gastrointestinal Disorders: Abdominal pain, nausea, vomiting

General Disorders and Administration Site Conditions: Malaise

Advise the patient to read the FDA-approved patient labeling (Patient Information).

PAXLOVID is not indicated for the post-exposure prophylaxis of COVID-19.

In a double-blind, double-dummy, placebo-controlled trial, the efficacy of PAXLOVID when administered for 5 or 10 days as post-exposure prophylaxis of COVID-19 was evaluated. Eligible subjects were asymptomatic adults 18 years of age and older who were SARS-CoV-2 negative at baseline and who lived in the same household with symptomatic individuals with a recent diagnosis of SARS-CoV-2. A total of 2,736 subjects were randomized (1:1:1) to receive PAXLOVID orally every 12 hours for 5 days, PAXLOVID orally every 12 hours for 10 days, or placebo.

The primary endpoint for this trial was not met. The primary endpoint was the risk reduction between the 5-day and 10-day PAXLOVID regimens versus placebo in the proportion of subjects who developed RT-PCR or RAT-confirmed symptomatic SARS-CoV-2 infection through Day 14 who had a negative SARS-CoV-2 RT-PCR result at baseline. The proportion of subjects who had events through Day 14 was 2.6% for the 5-day PAXLOVID regimen, 2.4% for the 10-day PAXLOVID regimen, and 3.9% for placebo. There was not a statistically significant risk reduction versus placebo for either the 5-day or 10-day PAXLOVID regimen.

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 [see Contraindications (4) and Drug Interactions (7)].

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 [see Use in Specific Populations (8.7)].

Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions [see Patient Counseling Information (17)].

No dosage adjustment is recommended in patients with mild renal impairment [estimated glomerular filtration rate (eGFR) ≥60 to <90 mL/min].

In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min) or with severe renal impairment (eGFR <30 mL/min) including those requiring hemodialysis, the dosage of PAXLOVID should be reduced as shown in Table 1. PAXLOVID should be administered at approximately the same time each day for 5 days. On days patients with severe renal impairment undergo hemodialysis, the PAXLOVID dose should be administered after hemodialysis [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3), and How Supplied/Storage and Handling (16)].

Table 1: Recommended Dose and Regimen for Patients with Renal Impairment

PAXLOVID (nirmatrelvir co-packaged with ritonavir) 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 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 [see Contraindications (4) and Drug Interactions (7.3)  Table 2 ]. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 2.

Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect [see Contraindications (4) and Drug Interactions (7.3)  Table 2 ].

Pfizer

NDC 0069-5045-30

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg Dose Pack

Take all 3 tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 30 tablets in 10 blister cards

Each blister card contains 3 tablets:

• •
  2 nirmatrelvir tablets (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5317-20

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg Dose Pack

Take both tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 20 tablets in 10 blister cards

Each blister card contains 2 tablets:

• •
  1 nirmatrelvir tablet (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5321-30

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg Dose Pack

Take all 3 tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 30 tablets in 10 blister cards

Each blister card contains 3 tablets:

• •
  2 nirmatrelvir tablets (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5434-20

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg Dose Pack

Take both tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 20 tablets in 10 blister cards

Each blister card contains 2 tablets:

• •
  1 nirmatrelvir tablet (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-0521-11

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg (Day 1)

150 mg; 100 mg (Days 2 – 5)

Day 1:

Take 2 nirmatrelvir tablets and

1 ritonavir tablet together

Days 2 - 5:

Take 1 nirmatrelvir tablet and

1 ritonavir tablet together

Carton contains 1 blister card with 11 tablets:

• •
  6 nirmatrelvir tablets (150 mg each)
• •
  5 ritonavir tablets (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5450-11

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg (Day 1)

150 mg; 100 mg (Days 2 – 5)

Day 1:

Take 2 nirmatrelvir tablets and

1 ritonavir tablet together

Days 2 - 5:

Take 1 nirmatrelvir tablet and

1 ritonavir tablet together

Carton contains 1 blister card with 11 tablets:

• •
  6 nirmatrelvir tablets (150 mg each)
• •
  5 ritonavir tablets (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. There are three different dose packs available:

• •
  PAXLOVID (nirmatrelvir; ritonavir) co-packaged for oral use 300 mg;100 mg [see Dosage and Administration (2.2)].
• •
  PAXLOVID (nirmatrelvir; ritonavir) co-packaged for oral use 150 mg;100 mg for patients with moderate renal impairment [see Dosage and Administration (2.3)].
• •
  PAXLOVID (nirmatrelvir; ritonavir) co-packaged for oral use 300 mg;100 mg (Day 1) and 150 mg;100 mg (Days 2-5) for patients with severe renal impairment [see Dosage and Administration (2.3)].

Nirmatrelvir must be co-administered with ritonavir. Failure to correctly co-administer nirmatrelvir with ritonavir may result in plasma levels of nirmatrelvir that are insufficient to achieve the desired therapeutic effect.

Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID [see Dosage and Administration (2.2, 2.3)]. 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.

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 even if baseline COVID-19 symptoms are mild. Should a patient require hospitalization due to severe or critical COVID-19 after starting treatment with PAXLOVID, the patient should complete the full 5-day treatment course per the healthcare provider's discretion.

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.

PAXLOVID (both nirmatrelvir and ritonavir tablets) can be taken with or without food [see Clinical Pharmacology (12.3)]. The tablets should be swallowed whole and not chewed, broken, or crushed.

• •
  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 [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7)].
• •
  Prior to prescribing PAXLOVID: 1) Review all medications taken by the patient to assess 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 [see Drug Interactions (7)].
• •
  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 [see Warnings and Precautions (5.1), Drug Interactions (7), and Clinical Studies (14)].

NDC 0069-5317-02

Rx only

nirmatrelvir

tablet

(150 mg)

This cavity

intentionally

left empty

Take these

2 tablets

together

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg

This cavity

intentionally

left empty

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

PAA206982

NDC 0069-5434-02

Rx only

nirmatrelvir

tablet

(150 mg)

This cavity

intentionally

left empty

Take these

2 tablets

together

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg

This cavity

intentionally

left empty

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

PAA232045

NDC 0069-5045-06

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg

nirmatrelvir

tablet

(150 mg)

Take these

3 tablets

together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Rx only

PAA232044

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

NDC 0069-5321-03

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg

nirmatrelvir

tablet

(150 mg)

Take these

3 tablets

together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Rx only

PAA206981

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

Day 1 (300 mg; 100 mg)

Your first day’s dose. Take these 3 tablets together

nirmatrelvir

tablet

(150 mg)

nirmatrelvir

tablet

(150 mg)

ritonavir

tablet

(100 mg)

NDC 0069-0521-11

Rx only

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets), co-packaged for oral use

nirmatrelvir

tablet

(150 mg)

Day 2 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

PAA228321

nirmatrelvir

tablet

(150 mg)

Day 3 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 4 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 5 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs, Div. of Pfizer Inc., NY, NY 10001

Day 1 (300 mg; 100 mg)

Your first day’s dose. Take these 3 tablets together

nirmatrelvir

tablet

(150 mg)

nirmatrelvir

tablet

(150 mg)

ritonavir

tablet

(100 mg)

NDC 0069-5450-11

Rx only

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets), co-packaged for oral use

nirmatrelvir

tablet

(150 mg)

Day 2 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

PAA228417

nirmatrelvir

tablet

(150 mg)

Day 3 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 4 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 5 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs, Div. of Pfizer Inc., NY, NY 10001

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 (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 Contraindications (4) and Drug Interactions (7)]. See Table 2 for clinically significant drug interactions, including contraindicated drugs. Drugs listed in Table 2 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 [see Drug Interactions (7) and Clinical Studies (14)].

Table 2 provides a listing of clinically significant drug interactions, including contraindicated drugs [see Contraindications (4) and Warnings and Precautions (5.1)]. Drugs listed in Table 2 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.

EPIC-HR (NCT04960202) was a Phase 2/3, randomized, double-blind, placebo-controlled trial in non-hospitalized symptomatic adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Eligible subjects were 18 years of age and older with at least 1 of the following risk factors for progression to severe disease: diabetes, overweight (BMI >25), chronic lung disease (including asthma), chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or were 60 years of age and older regardless of comorbidities. Subjects with COVID-19 symptom onset of ≤5 days were included in the study. Subjects were randomized (1:1) to receive PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo orally every 12 hours for 5 days. The trial excluded individuals with a history of prior COVID-19 infection or vaccination and excluded individuals taking any medications with clinically significant drug interactions with PAXLOVID. The primary efficacy endpoint was the proportion of subjects with COVID-19 related hospitalization or death from any cause through Day 28. The analysis was conducted in the modified intent-to-treat (mITT) analysis set [all treated subjects with onset of symptoms ≤3 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic monoclonal antibody (mAb) treatment], the mITT1 analysis set (all treated subjects with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), and the mITT2 analysis set (all treated subjects with onset of symptoms ≤5 days).

A total of 2,113 subjects were randomized to receive either PAXLOVID or placebo. At baseline, mean age was 45 years; 51% were male; 71% were White, 15% were Asian, 9% were American Indian or Alaska Native, 4% were Black or African American, and 1% was missing or unknown; 41% were Hispanic or Latino; 67% of subjects had onset of symptoms ≤3 days before initiation of study treatment; 49% of subjects were serological negative at baseline; the mean (SD) baseline viral RNA in nasopharyngeal samples was 4.71 log₁₀ copies/mL (2.89); 27% of subjects had a baseline viral RNA of ≥10^7 (log₁₀ copies/mL); 6% of subjects either received or were expected to receive COVID-19 therapeutic monoclonal antibody treatment at the time of randomization and were excluded from the mITT and mITT1 analyses.

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

The proportions of subjects who discontinued treatment due to an adverse event were 2.0% in the PAXLOVID group and 4.2% in the placebo group.

Table 9 provides results of the primary endpoint in mITT1 analysis population. For the primary endpoint, the relative risk reduction in the mITT1 analysis population for PAXLOVID compared to placebo was 86% (95% CI: 72%, 93%).

Consistent results were observed in the mITT and mITT2 analysis populations.

Similar trends have been observed across subgroups of subjects (see Figure 1).

Figure 1: Subgroup Analysis of Adults with COVID-19 Dosed within 5 Days of Symptom Onset with COVID-19 Related Hospitalization or Death from Any Cause Through Day 28: EPIC-HR

Among subjects who were SARS-CoV-2 seropositive at baseline, 1/490 (0.2%) PAXLOVID recipients versus 8/479 (1.7%) placebo recipients met the primary endpoint of COVID-19 related hospitalization or death from any cause through Day 28 [reduction relative to placebo -1.47% (-2.70%, -0.25%)].

PAXLOVID is not indicated for the treatment of COVID-19 in patients without a risk factor for progression to severe COVID-19.

EPIC-SR (NCT05011513) was a Phase 2/3, randomized, double-blind, placebo-controlled trial in non-hospitalized symptomatic adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Eligible subjects were 18 years of age or older with COVID-19 symptom onset of ≤5 days who were at standard risk for progression to severe disease. The trial included previously unvaccinated subjects with no risk factors for progression to severe disease or subjects fully vaccinated against COVID-19 (i.e., completed a primary vaccination series) with at least 1 of the risk factors for progression to severe disease as defined in EPIC-HR. Through the December 19, 2021, data cutoff, a total of 1,075 subjects were randomized (1:1) to receive PAXLOVID or placebo orally every 12 hours for 5 days; of these, 59% were fully vaccinated high-risk subjects.

The primary endpoint in this trial, the difference in time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28 among PAXLOVID versus placebo recipients, was not met.

In an exploratory analysis of the subgroup of fully vaccinated subjects with at least 1 risk factor for progression to severe disease, a non-statistically significant numerical reduction relative to placebo for the secondary endpoint of COVID-19 related hospitalization or death from any cause through Day 28 was observed.

Limitations of Use

PAXLOVID is not approved for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19 [see Clinical Studies (14.3)].

This Patient Information has been approved by the U.S. Food and Drug Administration.      Revised: 02/2026

Storage and Handling

Store at USP controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

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.

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. Nirmatrelvir is a SARS-CoV-2 main protease (M^pro) inhibitor, and ritonavir is an HIV-1 protease inhibitor and CYP3A inhibitor.

Mechanism of Action

Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (M^pro), also referred to as 3C-like protease (3CL^pro) or nonstructural protein 5 (nsp5) protease. Inhibition of SARS-CoV-2 M^pro renders it incapable of processing the viral polyproteins pp1a and pp1ab, preventing viral replication. Nirmatrelvir inhibited the activity of recombinant SARS-CoV-2 M^pro in a biochemical assay with a K_i value of 3.1 nM and an IC₅₀ value of 19.2 nM. Nirmatrelvir was found to bind directly to the SARS-CoV-2 M^pro active site by X-ray crystallography.

The optimal dose of PAXLOVID has not been established in pediatric patients.

Clinical studies of PAXLOVID include subjects 65 years of age and older and their data contributes to the overall assessment of safety and efficacy [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. Of the total number of subjects in the integrated dataset consisting of EPIC-HR and EPIC-SR who were randomized to and received PAXLOVID (N=1,578), 165 (10%) were 65 years of age and older and 39 (2%) were 75 years of age and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in safety between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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.

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

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 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 like PAXLOVID [see Drug Interactions (7.3)]:

• ➢
  Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7.3)]:
  • •
    Alpha 1-adrenoreceptor antagonist: alfuzosin
  • •
    Antianginal: ranolazine
  • •
    Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
  • •
    Anti-gout: colchicine (in patients with renal and/or hepatic impairment [see Table 2 , Drug Interactions (7.3)] )
  • •
    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 [see Table 2 , Drug Interactions (7.3)])
  • •
    Immunosuppressants: voclosporin
  • •
    Microsomal triglyceride transfer protein inhibitor: lomitapide
  • •
    Migraine medications: eletriptan, ubrogepant
  • •
    Mineralocorticoid receptor antagonists: finerenone
  • •
    Non-opioid analgesic (selective blocker of Na_v1.8 sodium channels): suzetrigine
  • •
    Opioid antagonists: naloxegol
  • •
    PDE5 inhibitor: sildenafil (Revatio^®) when used for pulmonary arterial hypertension (PAH)
  • •
    Sedative/hypnotics: triazolam, oral midazolam
  • •
    Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
  • •
    Vasopressin receptor antagonists: tolvaptan
• ➢
  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. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer [see Drug Interactions (7.3)]:
  • •
    Anticancer drugs: apalutamide, enzalutamide
  • •
    Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
  • •
    Antimycobacterials: rifampin, rifapentine
  • •
    Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
  • •
    Herbal products: St. John's Wort (hypericum perforatum)

The following clinically significant adverse reactions are described elsewhere in the labeling:

• •
  Hypersensitivity reactions [see Warnings and Precautions (5.2)]

Co-administration of PAXLOVID can alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PAXLOVID. Consider the potential for drug interactions prior to and during PAXLOVID therapy and review concomitant medications during PAXLOVID therapy. (4, 5.1, 7, 12.3)

Renal impairment increases nirmatrelvir exposure, which may increase the risk of PAXLOVID 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). Reduce the PAXLOVID dose and dose frequency in patients with severe renal impairment (eGFR <30 mL/min), including those requiring hemodialysis. On days when patients undergo hemodialysis, the PAXLOVID dose should be administered after hemodialysis [see Dosage and Administration (2.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.3)]. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions [see Patient Counseling Information (17)].

Cardiac Electrophysiology

At 3 times the steady state peak plasma concentration (C_max) at the recommended dose, nirmatrelvir does not prolong the QTc interval to any clinically relevant extent.

The pharmacokinetics of nirmatrelvir/ritonavir were similar in healthy subjects and in subjects with mild-to-moderate COVID-19.

Nirmatrelvir AUC increased in a less than dose proportional manner over a single dose range from 250 mg to 750 mg (0.83 to 2.5 times the approved recommended dose) and multiple dose range from 75 mg to 500 mg (0.25 to 1.67 times the approved recommended dose), when administered in combination with 100 mg ritonavir. Nirmatrelvir steady state was achieved on Day 2 following administration of the approved recommended dosage and the mean accumulation ratio was approximately 2-fold.

The pharmacokinetic properties of nirmatrelvir/ritonavir are displayed in Table 3.

The predicted Day 5 nirmatrelvir exposure parameters in adult subjects with mild-to-moderate COVID-19 who were treated with PAXLOVID in EPIC-HR are presented in Table 4.

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 in the morning and at bedtime for 5 days.

No dosage adjustment of PAXLOVID is recommended for 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 (Child-Pugh Class C) hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

PAXLOVID is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.

Nirmatrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug [see Microbiology (12.4)].

Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 M^pro. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir.

• •
  The concomitant use of PAXLOVID and certain other drugs may result in potentially significant drug interactions. Consult the Full Prescribing Information prior to and during treatment for potential drug interactions. (5.1, 7)
• •
  Hypersensitivity Reactions: Anaphylaxis, serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome), and other hypersensitivity reactions have been reported with PAXLOVID. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care. (5.2)
• •
  Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. (5.3)
• •
  HIV-1 Drug Resistance: PAXLOVID use may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. (5.4)

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. (2.1)

Nirmatrelvir must be co-administered with ritonavir. (2.1)

• •
  Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. (2.1)
• •
  Administer orally with or without food. (2.1)
• •
  Administer at approximately the same time each day. (2.2, 2.3)
• •
  Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days. (2.2)
• •
  Dose Reduction for Renal Impairment (2.3, 8.6, 12.3)

• •
  PAXLOVID is not recommend in patients with severe hepatic impairment (Child-Pugh Class C). (2.4, 8.7)

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets [see How Supplied/Storage and Handling (16)].

• •
  Nirmatrelvir is supplied as oval, pink immediate-release, film-coated tablets debossed with "PFE" on one side and "3CL" on the other side. Each tablet contains 150 mg of nirmatrelvir.
• •
  Ritonavir is supplied as white or white to off-white film-coated tablets uniquely identified by the color, shape, and debossing. Each tablet contains 100 mg of ritonavir.

Anaphylaxis, serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome), and other hypersensitivity reactions have been reported with PAXLOVID [see Adverse Reactions (6.1)]. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of PAXLOVID is based on two Phase 2/3 randomized, placebo-controlled trials in symptomatic adult subjects 18 years of age and older with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Subjects in both studies received PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo every 12 hours for 5 days for the treatment of mild-to-moderate COVID-19 within 5 days of symptom onset [see Clinical Studies (14)]:

• •
  Trial C4671005 (EPIC-HR) enrolled subjects who were at high risk for progression to severe disease.
• •
  Trial C4671002 (EPIC-SR) enrolled subjects who were at standard risk for progression to severe disease (previously unvaccinated subjects at standard risk or fully vaccinated subjects with at least 1 risk factor for progression to severe disease).

Adverse reactions were those reported while subjects were on study medication and through 28 days after the last dose of study treatment.

In Trial C4671005 (EPIC-HR), 1,038 subjects received PAXLOVID and 1,053 subjects received placebo. The most common adverse reactions (≥1% incidence in the PAXLOVID group and occurring at a greater frequency than in the placebo group) were dysgeusia (5% and <1%, respectively) and diarrhea (3% and 2%, respectively).

Among vaccinated or unvaccinated subjects at standard risk or fully vaccinated subjects with at least 1 risk factor for progression to severe disease in Trial C4671002 (EPIC-SR), 540 subjects received PAXLOVID and 528 subjects received placebo. The adverse reactions observed were consistent with those observed in EPIC-HR.

Trial C4671028 (EPIC-SRI) was a Phase 1, open-label trial that evaluated the effects of severe renal impairment on the pharmacokinetics, safety, and tolerability of PAXLOVID in non-hospitalized adult participants with COVID-19 and severe renal impairment. A total of 15 subjects with severe renal impairment were enrolled in this trial, with 12 subjects receiving intermittent hemodialysis and 3 subjects not on hemodialysis. Subjects received nirmatrelvir/ritonavir 300 mg/100 mg once on Day 1 followed by nirmatrelvir/ritonavir 150 mg/100 mg once daily from Days 2-5. The safety profile of PAXLOVID in subjects with severe renal impairment, including those requiring hemodialysis, was consistent with the safety profile observed in the Phase 2/3 randomized, placebo-controlled trials.

Emergency Use Authorization Experience in Subjects with COVID-19

The following adverse reactions have been identified during use of PAXLOVID under Emergency Use Authorization.

Immune System Disorders: Anaphylaxis, hypersensitivity reactions [see Warnings and Precautions (5.2)]

Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome [see Warnings and Precautions (5.2)]

Nervous System Disorders: Headache

Vascular Disorders: Hypertension

Gastrointestinal Disorders: Abdominal pain, nausea, vomiting

General Disorders and Administration Site Conditions: Malaise

Advise the patient to read the FDA-approved patient labeling (Patient Information).

PAXLOVID is not indicated for the post-exposure prophylaxis of COVID-19.

In a double-blind, double-dummy, placebo-controlled trial, the efficacy of PAXLOVID when administered for 5 or 10 days as post-exposure prophylaxis of COVID-19 was evaluated. Eligible subjects were asymptomatic adults 18 years of age and older who were SARS-CoV-2 negative at baseline and who lived in the same household with symptomatic individuals with a recent diagnosis of SARS-CoV-2. A total of 2,736 subjects were randomized (1:1:1) to receive PAXLOVID orally every 12 hours for 5 days, PAXLOVID orally every 12 hours for 10 days, or placebo.

The primary endpoint for this trial was not met. The primary endpoint was the risk reduction between the 5-day and 10-day PAXLOVID regimens versus placebo in the proportion of subjects who developed RT-PCR or RAT-confirmed symptomatic SARS-CoV-2 infection through Day 14 who had a negative SARS-CoV-2 RT-PCR result at baseline. The proportion of subjects who had events through Day 14 was 2.6% for the 5-day PAXLOVID regimen, 2.4% for the 10-day PAXLOVID regimen, and 3.9% for placebo. There was not a statistically significant risk reduction versus placebo for either the 5-day or 10-day PAXLOVID regimen.

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 [see Contraindications (4) and Drug Interactions (7)].

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 [see Use in Specific Populations (8.7)].

Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions [see Patient Counseling Information (17)].

No dosage adjustment is recommended in patients with mild renal impairment [estimated glomerular filtration rate (eGFR) ≥60 to <90 mL/min].

In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min) or with severe renal impairment (eGFR <30 mL/min) including those requiring hemodialysis, the dosage of PAXLOVID should be reduced as shown in Table 1. PAXLOVID should be administered at approximately the same time each day for 5 days. On days patients with severe renal impairment undergo hemodialysis, the PAXLOVID dose should be administered after hemodialysis [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3), and How Supplied/Storage and Handling (16)].

Table 1: Recommended Dose and Regimen for Patients with Renal Impairment

PAXLOVID (nirmatrelvir co-packaged with ritonavir) 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 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 [see Contraindications (4) and Drug Interactions (7.3)  Table 2 ]. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 2.

Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect [see Contraindications (4) and Drug Interactions (7.3)  Table 2 ].

Pfizer

NDC 0069-5045-30

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg Dose Pack

Take all 3 tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 30 tablets in 10 blister cards

Each blister card contains 3 tablets:

• •
  2 nirmatrelvir tablets (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5317-20

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg Dose Pack

Take both tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 20 tablets in 10 blister cards

Each blister card contains 2 tablets:

• •
  1 nirmatrelvir tablet (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5321-30

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg Dose Pack

Take all 3 tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 30 tablets in 10 blister cards

Each blister card contains 3 tablets:

• •
  2 nirmatrelvir tablets (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5434-20

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg Dose Pack

Take both tablets from one blister

card together, twice daily (in morning

and at bedtime) for 5 days.

Each carton contains 20 tablets in 10 blister cards

Each blister card contains 2 tablets:

• •
  1 nirmatrelvir tablet (150 mg each)
• •
  1 ritonavir tablet (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-0521-11

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg (Day 1)

150 mg; 100 mg (Days 2 – 5)

Day 1:

Take 2 nirmatrelvir tablets and

1 ritonavir tablet together

Days 2 - 5:

Take 1 nirmatrelvir tablet and

1 ritonavir tablet together

Carton contains 1 blister card with 11 tablets:

• •
  6 nirmatrelvir tablets (150 mg each)
• •
  5 ritonavir tablets (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

Pfizer

NDC 0069-5450-11

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg (Day 1)

150 mg; 100 mg (Days 2 – 5)

Day 1:

Take 2 nirmatrelvir tablets and

1 ritonavir tablet together

Days 2 - 5:

Take 1 nirmatrelvir tablet and

1 ritonavir tablet together

Carton contains 1 blister card with 11 tablets:

• •
  6 nirmatrelvir tablets (150 mg each)
• •
  5 ritonavir tablets (100 mg each)

Note to pharmacist:

Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that

should NOT be taken with Paxlovid

Rx only

PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. There are three different dose packs available:

• •
  PAXLOVID (nirmatrelvir; ritonavir) co-packaged for oral use 300 mg;100 mg [see Dosage and Administration (2.2)].
• •
  PAXLOVID (nirmatrelvir; ritonavir) co-packaged for oral use 150 mg;100 mg for patients with moderate renal impairment [see Dosage and Administration (2.3)].
• •
  PAXLOVID (nirmatrelvir; ritonavir) co-packaged for oral use 300 mg;100 mg (Day 1) and 150 mg;100 mg (Days 2-5) for patients with severe renal impairment [see Dosage and Administration (2.3)].

Nirmatrelvir must be co-administered with ritonavir. Failure to correctly co-administer nirmatrelvir with ritonavir may result in plasma levels of nirmatrelvir that are insufficient to achieve the desired therapeutic effect.

Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID [see Dosage and Administration (2.2, 2.3)]. 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.

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 even if baseline COVID-19 symptoms are mild. Should a patient require hospitalization due to severe or critical COVID-19 after starting treatment with PAXLOVID, the patient should complete the full 5-day treatment course per the healthcare provider's discretion.

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.

PAXLOVID (both nirmatrelvir and ritonavir tablets) can be taken with or without food [see Clinical Pharmacology (12.3)]. The tablets should be swallowed whole and not chewed, broken, or crushed.

• •
  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 [see Contraindications (4), Warnings and Precautions (5.1), and Drug Interactions (7)].
• •
  Prior to prescribing PAXLOVID: 1) Review all medications taken by the patient to assess 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 [see Drug Interactions (7)].
• •
  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 [see Warnings and Precautions (5.1), Drug Interactions (7), and Clinical Studies (14)].

NDC 0069-5317-02

Rx only

nirmatrelvir

tablet

(150 mg)

This cavity

intentionally

left empty

Take these

2 tablets

together

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg

This cavity

intentionally

left empty

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

PAA206982

NDC 0069-5434-02

Rx only

nirmatrelvir

tablet

(150 mg)

This cavity

intentionally

left empty

Take these

2 tablets

together

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

150 mg; 100 mg

This cavity

intentionally

left empty

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

PAA232045

NDC 0069-5045-06

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg

nirmatrelvir

tablet

(150 mg)

Take these

3 tablets

together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Rx only

PAA232044

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

NDC 0069-5321-03

PAXLOVID™

(nirmatrelvir tablets;

ritonavir tablets),

co-packaged for oral use

300 mg; 100 mg

nirmatrelvir

tablet

(150 mg)

Take these

3 tablets

together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Rx only

PAA206981

Dist. by Pfizer Labs

Div. of Pfizer Inc., NY, NY 10001

LOT:

EXP:

Day 1 (300 mg; 100 mg)

Your first day’s dose. Take these 3 tablets together

nirmatrelvir

tablet

(150 mg)

nirmatrelvir

tablet

(150 mg)

ritonavir

tablet

(100 mg)

NDC 0069-0521-11

Rx only

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets), co-packaged for oral use

nirmatrelvir

tablet

(150 mg)

Day 2 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

PAA228321

nirmatrelvir

tablet

(150 mg)

Day 3 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 4 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 5 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs, Div. of Pfizer Inc., NY, NY 10001

Day 1 (300 mg; 100 mg)

Your first day’s dose. Take these 3 tablets together

nirmatrelvir

tablet

(150 mg)

nirmatrelvir

tablet

(150 mg)

ritonavir

tablet

(100 mg)

NDC 0069-5450-11

Rx only

PAXLOVID™

(nirmatrelvir tablets; ritonavir tablets), co-packaged for oral use

nirmatrelvir

tablet

(150 mg)

Day 2 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

PAA228417

nirmatrelvir

tablet

(150 mg)

Day 3 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 4 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

nirmatrelvir

tablet

(150 mg)

Day 5 (150 mg; 100 mg)

Take these

2 tablets together

ritonavir

tablet

(100 mg)

Dist. by Pfizer Labs, Div. of Pfizer Inc., NY, NY 10001

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 (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 Contraindications (4) and Drug Interactions (7)]. See Table 2 for clinically significant drug interactions, including contraindicated drugs. Drugs listed in Table 2 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 [see Drug Interactions (7) and Clinical Studies (14)].

Table 2 provides a listing of clinically significant drug interactions, including contraindicated drugs [see Contraindications (4) and Warnings and Precautions (5.1)]. Drugs listed in Table 2 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.

EPIC-HR (NCT04960202) was a Phase 2/3, randomized, double-blind, placebo-controlled trial in non-hospitalized symptomatic adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Eligible subjects were 18 years of age and older with at least 1 of the following risk factors for progression to severe disease: diabetes, overweight (BMI >25), chronic lung disease (including asthma), chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or were 60 years of age and older regardless of comorbidities. Subjects with COVID-19 symptom onset of ≤5 days were included in the study. Subjects were randomized (1:1) to receive PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo orally every 12 hours for 5 days. The trial excluded individuals with a history of prior COVID-19 infection or vaccination and excluded individuals taking any medications with clinically significant drug interactions with PAXLOVID. The primary efficacy endpoint was the proportion of subjects with COVID-19 related hospitalization or death from any cause through Day 28. The analysis was conducted in the modified intent-to-treat (mITT) analysis set [all treated subjects with onset of symptoms ≤3 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic monoclonal antibody (mAb) treatment], the mITT1 analysis set (all treated subjects with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), and the mITT2 analysis set (all treated subjects with onset of symptoms ≤5 days).

A total of 2,113 subjects were randomized to receive either PAXLOVID or placebo. At baseline, mean age was 45 years; 51% were male; 71% were White, 15% were Asian, 9% were American Indian or Alaska Native, 4% were Black or African American, and 1% was missing or unknown; 41% were Hispanic or Latino; 67% of subjects had onset of symptoms ≤3 days before initiation of study treatment; 49% of subjects were serological negative at baseline; the mean (SD) baseline viral RNA in nasopharyngeal samples was 4.71 log₁₀ copies/mL (2.89); 27% of subjects had a baseline viral RNA of ≥10^7 (log₁₀ copies/mL); 6% of subjects either received or were expected to receive COVID-19 therapeutic monoclonal antibody treatment at the time of randomization and were excluded from the mITT and mITT1 analyses.

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

The proportions of subjects who discontinued treatment due to an adverse event were 2.0% in the PAXLOVID group and 4.2% in the placebo group.

Table 9 provides results of the primary endpoint in mITT1 analysis population. For the primary endpoint, the relative risk reduction in the mITT1 analysis population for PAXLOVID compared to placebo was 86% (95% CI: 72%, 93%).

Consistent results were observed in the mITT and mITT2 analysis populations.

Similar trends have been observed across subgroups of subjects (see Figure 1).

Figure 1: Subgroup Analysis of Adults with COVID-19 Dosed within 5 Days of Symptom Onset with COVID-19 Related Hospitalization or Death from Any Cause Through Day 28: EPIC-HR

Among subjects who were SARS-CoV-2 seropositive at baseline, 1/490 (0.2%) PAXLOVID recipients versus 8/479 (1.7%) placebo recipients met the primary endpoint of COVID-19 related hospitalization or death from any cause through Day 28 [reduction relative to placebo -1.47% (-2.70%, -0.25%)].

PAXLOVID is not indicated for the treatment of COVID-19 in patients without a risk factor for progression to severe COVID-19.

EPIC-SR (NCT05011513) was a Phase 2/3, randomized, double-blind, placebo-controlled trial in non-hospitalized symptomatic adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Eligible subjects were 18 years of age or older with COVID-19 symptom onset of ≤5 days who were at standard risk for progression to severe disease. The trial included previously unvaccinated subjects with no risk factors for progression to severe disease or subjects fully vaccinated against COVID-19 (i.e., completed a primary vaccination series) with at least 1 of the risk factors for progression to severe disease as defined in EPIC-HR. Through the December 19, 2021, data cutoff, a total of 1,075 subjects were randomized (1:1) to receive PAXLOVID or placebo orally every 12 hours for 5 days; of these, 59% were fully vaccinated high-risk subjects.

The primary endpoint in this trial, the difference in time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28 among PAXLOVID versus placebo recipients, was not met.

In an exploratory analysis of the subgroup of fully vaccinated subjects with at least 1 risk factor for progression to severe disease, a non-statistically significant numerical reduction relative to placebo for the secondary endpoint of COVID-19 related hospitalization or death from any cause through Day 28 was observed.