How does PAXLOVID work?1Nirmatrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro, also referred to as 3CLpro or nsp5 protease) inhibitor.
Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 Mpro. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir.
For more information about how PAXLOVID works, see Section 12: Clinical Pharmacology in the Prescribing Information
here.
The pharmacokinetics of nirmatrelvir/ritonavir have been studied in healthy subjects and in subjects with mild-to-moderate COVID-19.
Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 Mpro. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvir.
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.
For more information about the pharmacokinetics of PAXLOVID, see Section 12.3: Pharmacokinetics in the Prescribing Information
here.
The expiration date can be found on the PAXLOVID carton.
On January 18, 2023, the FDA authorized a shelf life extension to 24 months for certain lots of PAXLOVID. For more information and to look up adjusted product expiration dates by original printed expiry date or batch number, please refer to the
following update.*
*This link will take you to a website that is owned and operated by the FDA. Pfizer is not responsible for the content or services of this site.
What is the recommended dosage and important dosing information?1
Standard Dosage
The Standard Dosage for PAXLOVID is 300 mg nirmatrelvir (two 150-mg tablets) with 100 mg ritonavir (one 100-mg tablet) with all 3 tablets taken together orally twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Completion of the full 5-day treatment course and continued isolation in accordance with public health recommendations are important to maximize viral clearance and minimize transmission of SARS-CoV-2.
Dosage in patients with renal impairment
No dosage adjustment is needed in patients with mild renal impairment (eGFR ≥60 to <90 mL/min).
In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of PAXLOVID is 150 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Healthcare providers should counsel patients about renal dosing instructions.
PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined.
Use in Patients with Hepatic Impairment
No dosage adjustment is recommended 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 hepatic impairment (Child-Pugh Class C); therefore, PAXLOVID is not recommended for use in patients with severe hepatic impairment.
For more information about product dosage, see Section 2: Dosage and Administration in the Prescribing Information
here.
The 5-day treatment course of PAXLOVID should be initiated as soon as possible after a diagnosis of COVID‑19 has been made and within 5 days of symptom onset even if baseline COVID-19 symptoms are mild.
For more information about product dosage, see Section 2: Dosage and Administration in the Full Prescribing Information
here.
You may diagnose patients based on clinical presentation and/or COVID-19 test status. A COVID-19 diagnosis is required to prescribe PAXLOVID.
Patients can take any available FDA-authorized COVID-19 viral test (eg, RT-PCR, rapid antigen, etc) to determine if they may have COVID-19. Per the Centers for Disease Control and Prevention (CDC), a viral test checks specimens from a patient’s nose or mouth and can be performed in a laboratory, at a testing site, at home, or anywhere else.
*This link will take you to a website that is owned and operated by the CDC. Pfizer is not responsible for the content or services of this site.
What risk factors put my patients at high risk for severe COVID-19?2Studies have shown that COVID-19 does not affect all populations equally. Age remains the strongest risk factor for progressing to severe COVID-19 (age 50+). In addition, the COVID-19 pandemic has highlighted racial, ethnic, and socioeconomic disparities in COVID-19 illnesses, hospitalizations, and deaths due to multiple factors, including barriers to accessing health care.
Additionally, being unvaccinated or not being up to date on COVID-19 vaccinations also increases the risk of severe COVID-19 outcomes.
Providers should consider the patient’s age, presence of underlying medical conditions and other risk factors, and vaccination status in determining the risk of severe COVID-19–associated outcomes for any patient.
Underlying medical conditions and factors associated with high risk for severe COVID-19 include:
Higher risk (conclusive evidence):
- Asthma
- Cancer
- Hematologic malignancies
- Cerebrovascular disease
- Chronic kidney disease*
- -People receiving dialysis†
- Chronic lung diseases limited to:
- -Bronchiectasis
- -COPD (chronic obstructive pulmonary disease)
- -Interstitial lung disease
- -Pulmonary embolism
- -Pulmonary hypertension
- Chronic liver diseases limited to:
- -Cirrhosis
- -Nonalcoholic fatty liver disease
- -Alcoholic liver disease
- -Autoimmune hepatitis
- Cystic fibrosis
- Dementia
- Diabetes mellitus type 1
- Diabetes mellitus type 2*
- Disabilities, including Down syndrome
- Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
- HIV
- Mental health conditions limited to:
- Neurologic conditions limited to dementia
- Obesity (BMI ≥30 kg/m2 or ≥95th percentile in children)
- Physical inactivity
- Pregnancy and recent pregnancy
- Primary immunodeficiencies
- Smoking, current and former
- Solid organ or blood stem cell transplantation
- Tuberculosis
- Use of corticosteroids or other immunosuppressive medications
Suggestive higher risk‡:
- Overweight (BMI ≥25 kg/m2, but <30 kg/m2)
- Sickle cell disease
- Substance use disorders
Mixed evidence (inconclusive: no conclusions can be drawn from the evidence):
- Alpha-1 antitrypsin deficiency
- Bronchopulmonary dysplasia
- Hepatitis B and C
- Hypertension*
- Thalassemia
*Indicates presence of evidence for pregnant and non-pregnant people.
†Risk may be further increased for people receiving dialysis.
‡The language expressed on this page is consistent with CDC guidance, with the exception of risk factors regarding pediatric patients, which were removed from this list. PAXLOVID is not approved for use in pediatric patients.
§This link will take you to a website that is owned and operated by the CDC. Pfizer is not responsible for the content or services of this site.
How much will my patients pay for PAXLOVID? With the PAXCESS™ Co-Pay Savings Program, eligible prescribed patients with commercial insurance may pay as little as $0* for their PAXLOVID prescription.
*Eligible commercially insured patients can save up to $1,500 per prescription. Maximum annual savings up to $1,500. Full terms and conditions apply. Please click
here for full terms and conditions.
Patients enrolled in federal programs
† such as Medicare, Medicaid,
‡ and VA are not eligible for the Co-Pay Savings Program but may qualify for other financial assistance resources for PAXLOVID.
†The USG PAP operated by Pfizer will continue to provide patients on Medicare, Medicaid, TRICARE, Veteran Affairs Community Care Network, and those who are uninsured access to PAXLOVID for free through December 31, 2024. PAXLOVID, through the USG PAP, is not available to patients who have commercial prescription drug health insurance. The USG PAP operated by Pfizer is an independent program with separate eligibility requirements offered by the U.S. Department of Health and Human Services and is not owned by Pfizer.
‡Medicaid patients eligible through December 31, 2024.
Please visit
the access page to learn more.
Per the Prescribing Information:
-
No dosage adjustment is needed in patients with mild renal impairment (eGFR ≥60 to <90 mL/min)
- In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of PAXLOVID is 150 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days. Prescriptions should specify the numeric dose of each active ingredient within PAXLOVID. Providers should counsel patients about renal dosing instructions
- PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined
For more information on dosing adjustments, see Section 2.3: Dosage in Patients with Renal Impairment in the Full Prescribing Information
here.
PAXLOVID consists of 2 medicines: nirmatrelvir and ritonavir. Nirmatrelvir must be coadministered with ritonavir. Failure to correctly coadminster nirmatrelvir with ritonavir may result in plasma levels of nirmatrelvir that are insufficient to achieve the desired therapeutic effect.
Patients should take 2 tablets of nirmatrelvir (150 mg each) with 1 tablet of ritonavir (100 mg) by mouth twice daily (in the morning and in the evening) for 5 days. For each dose, all 3 tablets should be taken at the same time.
- Patient should swallow the tablets whole. They should not chew, break, or crush the tablets
- Patients can take PAXLOVID with or without food
- Even if patients feel better, they should not stop taking PAXLOVID without talking to the prescribing healthcare provider
- Alert the patient to the importance of completing the full 5-day treatment course and to continuing isolation in accordance with public health recommendations to maximize viral clearance and minimize transmission of SARS-CoV-2
To ensure appropriate dosing in patients with moderate renal impairment, reduce the dosage of PAXLOVID to 150 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days. Providers should counsel patients about renal dosing instructions.
For more information on how to take PAXLOVID, patients can refer to Patient Information
here.
Missed dose: If the patient misses a dose of PAXLOVID within 8 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 8 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.
Overdose: If patients overdose on PAXLOVID, they should call their prescribing healthcare provider or go to the nearest hospital emergency room right away. Treatment of overdose with PAXLOVID should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with PAXLOVID.
For more information on product dosage, see Section 2: Dosage and Administration and Section 10: Overdosage in the Prescribing Information
here.
PAXLOVID is contraindicated in/with:
- Patients with a history of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product
- Drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions
- Alpha 1-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 (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 the any of the medications in the linked table 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)
What are the potential drug interactions with PAXLOVID?1See a list of established and other potentially significant drug interactions here.
PAXLOVID (nirmatrelvir copackaged with ritonavir) is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp and OATP1B1. Coadministration of PAXLOVID with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of such drugs and increase the risk of adverse events. Coadministration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life‑threatening events is contraindicated. Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in
Table 1.
Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect.
For a list of clinically significant drug interactions, including contraindicated drugs, refer to Section 7, Table 1: Established and Other Potentially Significant Drug Interactions
here.
Per the U.S. Prescribing Information, EPIC-HR and EPIC-SR were not designed to evaluate COVID-19 rebound; exploratory analyses were conducted to assess the relationship between PAXLOVID use and rebound in viral RNA shedding levels or self-reported COVID-19 symptoms.
Post-treatment increases in SARS-CoV-2 RNA shedding levels (ie, viral RNA rebound) in nasopharyngeal samples were observed on Day 10 and/or Day 14 in a subset of PAXLOVID and placebo recipients in the EPIC-HR trial, irrespective of COVID-19 symptoms. The frequency of detection of post-treatment viral RNA rebound varied according to analysis parameters but was generally similar among PAXLOVID and placebo recipients, regardless of the rebound definition used. A similar or smaller percentage of placebo recipients compared to PAXLOVID recipients had nasopharyngeal viral RNA results < lower limit of quantitation (LLOQ) at all study time points in both the treatment and post-treatment periods.
In EPIC-HR, of 59 PAXLOVID-treated subjects identified with post-treatment viral RNA rebound and with available viral sequence data, treatment-emergent substitutions in Mpro potentially reducing nirmatrelvir activity were detected in 2 (3%) subjects, including E166V in 1 subject and T304I in 1 subject. Both subjects had viral RNA shedding levels <LLOQ by Day 14.
Post-treatment viral RNA rebound was not associated with the primary clinical outcome of COVID-19–related hospitalization or death from any cause through Day 28 following the single 5-day course of PAXLOVID treatment. The clinical relevance of post-treatment increases in viral RNA following PAXLOVID or placebo treatment is unknown.
The frequency of symptom rebound through Day 28, irrespective of viral RNA results, was similar among PAXLOVID and placebo recipients. The frequency of combined viral RNA rebound plus symptom rebound could not be fully assessed as most episodes of symptom rebound occurred after Day 14 (the last day SARS‑CoV‑2 RNA levels were routinely assessed).