Usual Adult Dose for COVID-19

Nirmatrelvir: 300 mg orally twice a day
Ritonavir: 100 mg orally twice a day

Duration of therapy: 5 days

Comments:

• Limitations of Use: This product is not approved for use as preexposure or postexposure prophylaxis for prevention of coronavirus disease 2019 (COVID-19).
• Nirmatrelvir must be coadministered with ritonavir; the dosage consists of 3 tablets (2 nirmatrelvir 150-mg tablets and 1 ritonavir 100-mg tablet), and all 3 tablets should be administered together.
• Prescriptions should specify the numeric dose of each active component within this product.
• The 5-day treatment course of this product should be started as soon as possible after COVID-19 has been diagnosed and within 5 days of symptom onset, even if baseline COVID-19 symptoms are mild.
• If hospitalization is required due to severe/critical COVID-19 after starting treatment with this product, the patient should complete the full 5-day treatment course per health care provider's discretion.
• The US FDA issued an Emergency Use Authorization (EUA) to allow the emergency use of nirmatrelvir co-packaged with ritonavir for the treatment of patients with mild to moderate COVID-19 and who are at high risk for progression to severe COVID-19, including hospitalization or death.
• For additional information: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs

Use: For the treatment of mild to moderate COVID-19 in patients who are at high risk for progression to severe COVID-19, including hospitalization or death

Usual Pediatric Dose for COVID-19

For investigational use only

12 years and older, weighing at least 40 kg:

• Nirmatrelvir: 300 mg orally twice a day
• Ritonavir: 100 mg orally twice a day

Duration of therapy: 5 days

Comments:

• The US FDA issued an EUA to allow the emergency use of nirmatrelvir co-packaged with ritonavir for the treatment of patients with mild to moderate COVID-19 and who are at high risk for progression to severe COVID-19, including hospitalization or death.
• Nirmatrelvir must be coadministered with ritonavir; the dosage consists of 3 tablets (2 nirmatrelvir 150-mg tablets and 1 ritonavir 100-mg tablet), and all 3 tablets should be administered together.
• Prescriptions should specify the numeric dose of each active component within this product.
• The 5-day treatment course of this product should be started as soon as possible after COVID-19 has been diagnosed and within 5 days of symptom onset, even if baseline COVID-19 symptoms are mild.
• If hospitalization is required due to severe/critical COVID-19 after starting treatment with this product, the patient should complete the full 5-day treatment course per health care provider's discretion.
• For additional information: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs

Use: For the treatment of patients with mild to moderate COVID-19 and who are at high risk for progression to severe COVID-19, including hospitalization or death

Renal Dose Adjustments

Mild renal dysfunction (estimated GFR [eGFR] 60 to less than 90 mL/min): No adjustment recommended

Moderate renal dysfunction (eGFR 30 to less than 60 mL/min):

• Nirmatrelvir: 150 mg orally twice a day
• Ritonavir: 100 mg orally twice a day

Duration of therapy: 5 days

Severe renal dysfunction (eGFR less than 30 mL/min): Not recommended.

Comments:

• Prescriptions should specify the numeric dose of each active component within this product.
• Patients with moderate renal dysfunction should be advised about renal dosing instructions; the adjusted dosage consists of 2 tablets (1 nirmatrelvir 150-mg tablet and 1 ritonavir 100-mg tablet), and both tablets should be administered together.
• EUA: If the 150 mg nirmatrelvir-100 mg ritonavir dose pack is unavailable, the pharmacist should refer to "IMPORTANT PAXLOVID EUA DISPENSING INFORMATION FOR PATIENTS WITH MODERATE RENAL IMPAIRMENT" for dispensing of this product to patients with moderate renal dysfunction; patients should be advised that their daily blister card has been altered to ensure they receive the correct dose.
• The appropriate dosage for patients with severe renal dysfunction has not been established.

Liver Dose Adjustments

Mild or moderate liver dysfunction (Child-Pugh A or B): No adjustment recommended
Severe liver dysfunction (Child-Pugh C): Not recommended.

Comments:

• No pharmacokinetic or safety data are available regarding the use of either component in patients with severe liver dysfunction.

Precautions

US BOXED WARNING:

• SIGNIFICANT DRUG INTERACTIONS WITH THIS PRODUCT: This product includes ritonavir (a strong CYP450 3A inhibitor) which may lead to greater exposure of certain concomitant drugs, resulting in potentially severe, life-threatening, or fatal events. Before prescribing this product, all drugs taken by the patient should be reviewed to assess potential drug-drug interactions with a strong CYP450 3A inhibitor like this product and it should be determined if concomitant drugs require dose adjustment, interruption, and/or additional monitoring. The benefit of this product in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed should be considered.

CONTRAINDICATIONS:

• History of clinically significant hypersensitivity reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) to either active component or to any of the ingredients
• Coadministration with drugs primarily metabolized by CYP450 3A and for which elevated levels are associated with serious and/or life-threatening reactions, including alfuzosin, ranolazine, amiodarone, dronedarone, flecainide, propafenone, quinidine, colchicine (in patients with renal and/or liver dysfunction), lurasidone, pimozide, silodosin, eplerenone, ivabradine, dihydroergotamine, ergotamine, methylergonovine, lovastatin, simvastatin, voclosporin, lomitapide, eletriptan, ubrogepant, finerenone, naloxegol, oral midazolam, triazolam, flibanserin, tolvaptan, sildenafil (when used for pulmonary arterial hypertension)
• Coadministration with strong CYP450 3A inducers where significantly reduced nirmatrelvir or ritonavir plasma levels may be associated with the potential for loss of virologic response and possible resistance, including apalutamide, carbamazepine, phenobarbital, primidone, phenytoin, rifampin, rifapentine, ivacaftor-lumacaftor, St. John's wort

Safety and efficacy have not been established in patients younger than 18 years; this product is not authorized for use in pediatric patients weighing less than 40 kg or younger than 12 years.

Consult WARNINGS section for additional precautions.

Dialysis

ESRD (eGFR less than 15 mL/min) receiving dialysis: Not recommended.

Other Comments

Administration advice:

• Nirmatrelvir must be coadministered with ritonavir; failure to correctly coadminister nirmatrelvir with ritonavir may result in nirmatrelvir plasma levels insufficient to achieve desired therapeutic effect.
• Administer with or without food.
• Swallow the tablets whole; do not chew, break, or crush the tablets.
• Completion of the full 5-day treatment course and continued isolation (according to public health recommendations) are important to maximize viral clearance and minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Do not start this product immediately after discontinuation of any of the following drugs (due to delayed offset of the recently discontinued CYP450 3A inducer): apalutamide, carbamazepine, phenobarbital, primidone, phenytoin, rifampin, rifapentine, ivacaftor-lumacaftor, St. John's wort.
• Lovastatin and simvastatin can be temporarily discontinued to allow the use of this product.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).

General:

• This product is nirmatrelvir tablets co-packaged with ritonavir tablets; there are 2 different dose packs available: 300 mg nirmatrelvir co-packaged with 100 mg ritonavir and 150 mg nirmatrelvir co-packaged with 100 mg ritonavir for patients with moderate renal dysfunction.
• Drugs listed in CONTRAINDICATIONS are a guide and not considered a comprehensive list of all drugs that may be contraindicated with this product; other appropriate resources (e.g., the manufacturer product information for the interacting drug) should be consulted for comprehensive information on dosing or monitoring with concomitant use of a strong CYP450 3A inhibitor like this product.
• There are certain other drugs for which concomitant use of this product should be avoided and/or dose adjustment, interruption, or therapeutic monitoring is recommended.
• EUA: Limitations of Authorized Use:
• This product is not authorized for initiation of therapy in patients requiring hospitalization due to severe or critical COVID-19.
• This product is not authorized for use as preexposure or postexposure prophylaxis for prevention of COVID-19.
• This product is not authorized for use longer than 5 consecutive days.
• EUA: Determining whether a patient is at high risk for progression to severe COVID-19 (including hospitalization or death) is based on the provider's assessment of the individual patient being considered for COVID-19 treatment and that patient's medical history; the US CDC website (https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html) should be consulted for information on medical conditions and factors associated with increased risk for progression to severe COVID-19.
• EUA: This product may be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants licensed/authorized under state law to prescribe drugs.
• This product may also be prescribed for an individual patient by a state-licensed pharmacist under certain conditions; however, 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/authorized under state law to prescribe drugs under certain circumstances. The Fact Sheet for Health Care Providers should be consulted for further guidance.
• EUA: The Fact Sheet for Health Care Providers should be consulted for information regarding approved alternatives for the EUA authorized use.
• EUA: ClinicalTrials.gov should be consulted for information on clinical trials testing the use of this product in COVID-19.

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• For EUA: Read the Fact Sheet for Patients, Parents, and Caregivers.
• Avoid missing doses and complete the entire course of therapy.
• If a dose is missed within 8 hours of the usual time taken, administer the missed dose as soon as possible and resume the normal dosing schedule; if a dose is missed by more than 8 hours, do not administer the missed dose and instead administer the next dose at the regularly scheduled time. Do not double the dose to make up for a missed dose.
• Continue to self-isolate according to public health recommendations.
• Immediately discontinue this product and inform health care provider at the first sign of skin rash, hives/other skin reactions, difficulty in swallowing/breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.

Frequently asked questions

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