Paxlovid

Paxlovid is a prescription medicine used to treat the symptoms of COVID-19. Paxlovid may be used alone or with other medications.

Paxlovid belongs to a class of drugs called Antivirals, SARS-CoV-2. 

It is not known if Paxlovid is safe and effective in children younger than 12 years of age or weighing less than 88 pounds (40 kg).  

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product Paxlovid for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who is at high risk for progression to severe COVID-19, including hospitalization or death.

For information on medical conditions and factors associated with increased risk for progression to severe COVID-19, see the Centers for Disease Control and Prevention (CDC) website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

Limitations Of Authorized Use

• Paxlovid is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19.
• Paxlovid is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
• Paxlovid is not authorized for use for longer than 5 consecutive days.

Paxlovid may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which Paxlovid belongs (i.e., antiinfectives).

Paxlovid is not approved for any use, including for use for the treatment of COVID-19.

Paxlovid is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of Paxlovid under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

Patients requiring hospitalization due to severe or critical COVID-19 after starting treatment with Paxlovid may complete the full 5-day treatment course per the healthcare provider's discretion.

Justification For Emergency Use Of Drugs During The COVID-19 Pandemic

There is currently an outbreak of COVID-19 caused by SARS-CoV-2, a novel coronavirus. The Secretary of Health and Human Services (HHS) has declared that:

• A public health emergency related to COVID-19 has existed since January 27, 2020.
• Circumstances exist justifying the authorization of emergency use of drugs and biological products during the COVID-19 pandemic (March 27, 2020 declaration).

An EUA is a U.S. Food and Drug Administration authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that there is a public health emergency that affects the national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include:

• The biological agent(s) can cause a serious or life-threatening disease or condition;
• Based on the totality of the available scientific evidence (including data from adequate and well-controlled clinical trials, if available), it is reasonable to believe that
  • the product may be effective in diagnosing, treating, or preventing the serious or life-threatening disease or condition; and
  • the known and potential benefits of the product—when used to diagnose, prevent, or treat such disease or condition—outweigh the known and potential risks of the product, taking into consideration the material threat posed by the biological agent(s);
• There is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating the serious or life-threatening disease or condition.

Information Regarding Available Alternatives for The EUA Authorized Use

• There are no approved alternatives to Paxlovid for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
• Other therapeutics are currently authorized for the same use as Paxlovid. For additional information on all products authorized for treatment or prevention of COVID-19, please see https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy- framework/emergency-use-authorization.
• For information on clinical studies that are testing the use of Paxlovid in COVID-19, please see https:www.clinicaltrials.gov.

There are limited clinical data available for Paxlovid. Serious and unexpected adverse events may occur that have not been previously reported with Paxlovid use.

Paxlovid may cause serious side effects including:

• hives, 
• difficulty breathing, 
• swelling of your face, lips, tongue, or throat, 
• severe dizziness, and
• abnormal lab test results 

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Paxlovid include:

• diarrhea, 
• myalgia, 
• altered sense of taste, and 
• high blood pressure 

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Paxlovid. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dosage for Emergency Use of Paxlovid

• Paxlovid is nirmatrelvir tablets co-packaged with ritonavir tablets.
• 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.
• The dosage for Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) with all three 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.
• 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. 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. The tablets should be swallowed whole and not chewed, broken, or crushed.

Important Dosing Information 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. 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 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 hepatic impairment (Child-Pugh Class C); therefore, Paxlovid is not recommended for use in patients with severe hepatic impairment.

Important Drug Interactions with Paxlovid

• No dosage adjustment is required when co-administered with other products containing ritonavir or cobicistat.
• Patients on ritonavir- or cobicistat-containing HIV or HCV regimens should continue their treatment as indicated.
• Refer to other sections of the Fact Sheet for important drug interactions with Paxlovid. Consider the potential for drug interactions prior to and during Paxlovid therapy and review concomitant medications during Paxlovid therapy.

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.

Potential for Paxlovid To Affect Other Drugs

• Paxlovid (nirmatrelvir co-packaged with ritonavir) is an inhibitor of CYP3A and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A.
• 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. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 1.

Potential for Other Drugs to Affect Paxlovid

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

Established and Other Potentially Significant Drug Interactions

• Table 1 provides a listing of clinically significant drug interactions, including contraindicated drugs. Drugs listed in Table 1 are a guide and not considered a comprehensive list of all possible drugs that may interact with Paxlovid. The healthcare provider should consult appropriate references for comprehensive information.

Table 1: Established and Other Potentially Significant Drug Interactions

• There are no available human data on the use of nirmatrelvir during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Published studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy.
• There are no available data on the presence of nirmatrelvir in human or animal milk, the effects on the breastfed infant, or the effects on milk production. There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug on milk production.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Paxlovid and any potential adverse effects on the breastfed infant from Paxlovid or from the underlying maternal condition.
• Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

Tell your healthcare provider if you:

• Have any allergies
• Have liver or kidney disease
• Are pregnant or plan to become pregnant
• Are breastfeeding a child
• Have any serious illnesses

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Some medicines may interact with Paxlovid and may cause serious side effects. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.

You can ask your healthcare provider or pharmacist for a list of medicines that interact with Paxlovid. Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take Paxlovid with other medicines.

Tell your healthcare provider if you are taking combined hormonal contraceptive. Paxlovid may affect how your birth control pills work. Females who are able to become pregnant should use another effective alternative form of contraception or an additional barrier method of contraception. Talk to your healthcare provider if you have any questions about contraceptive methods that might be right for you.

Do not take Paxlovid if:

• You are allergic to nirmatrelvir, ritonavir, or any of the ingredients in Paxlovid.
• You are taking any of the following medicines:
  • Alfuzosin
  • Pethidine, piroxicam, propoxyphene
  • Ranolazine
  • Amiodarone, dronedarone, flecainide, propafenone, quinidine
  • Colchicine
  • Lurasidone, pimozide, clozapine
  • Dihydroergotamine, ergotamine, methylergonovine
  • Lovastatin, simvastatin
  • Sildenafil (Revatio^®) for pulmonary arterial hypertension (PAH)
  • Triazolam, oral midazolam
  • Apalutamide
  • Carbamazepine, phenobarbital, phenytoin
  • Rifampin
  • St. John's Wort (hypericum perforatum)

Taking Paxlovid with these medicines may cause serious or life-threatening side effects or affect how Paxlovid works.

These are not the only medicines that may cause serious side effects if taken with Paxlovid. Paxlovid may increase or decrease the levels of multiple other medicines. It is very important to tell your healthcare provider about all of the medicines you are taking because additional laboratory tests or changes in the dose of your other medicines may be necessary while you are taking Paxlovid.

Your healthcare provider may also tell you about specific symptoms to watch out for that may indicate that you need to stop or decrease the dose of some of your other medicines.