Brand Name: Paxlovid
Generic Name: nirmatrelvir; ritonavir
Drug Class: Antivirals
What is Paxlovid, and what is it used for?
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).
Warnings
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.
What are the side effects of Paxlovid?
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.
What are the dosages of Paxlovid?
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.
Addiction/overdose
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.
What drugs interact 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
Drug Class
Drugs within Class
Effect on Concentration
Clinical Comments
Alpha 1-adrenoreceptor antagonist
alfuzosin
↑ alfuzosin
Co-administration contraindicated due to potential hypotension.
Analgesics
pethidine,
piroxicam,
propoxyphene
↑ pethidine
↑ piroxicam
↑ propoxyphene
Co-administration contraindicated due to potential for serious respiratory depression or hematologic abnormalities.
Antianginal
ranolazine
↑ ranolazine
Co-administration contraindicated due to potential for serious and/or life-threatening reactions.
Antiarrhythmics
amiodarone,
dronedarone,
flecainide,
propafenone, quinidine
↑ antiarrhythmic
Co-administration contraindicated due to potential for cardiac arrhythmias.
Antiarrhythmics
bepridil, lidocaine (systemic)
↑ antiarrhythmic
Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.
Anticancer drugs
apalutamide
↓ nirmatrelvir/ritonavir
Co-administration contraindicated due to potential loss of virologic response and possible resistance.
Anticancer drugs
abemaciclib,
ceritinib,
dasatinib,
encorafenib,
ibrutinib,
ivosidenib,
neratinib,
nilotinib,
venetoclax,
vinblastine,
vincristine
↑ anticancer drug
Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib. Co-administration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects. For further information, refer to individual product label for anticancer drug.
Anticoagulants
warfarin
rivaroxaban
↑↓ warfarin
↑ rivaroxaban
Closely monitor INR if co-administration with warfarin is necessary.
Increased bleeding risk with rivaroxaban. Avoid concomitant use.
Anticonvulsants
carbamazepine* ,
phenobarbital,
phenytoin
↓ nirmatrelvir/ritonavir
↑ carbamazepine
↓ phenobarbital
↓ phenytoin
Co-administration contraindicated due to potential loss of virologic response and possible resistance.
Antidepressants
bupropion
↓ bupropion and active metabolite hydroxybupropion
Monitor for an adequate clinical response to bupropion.
trazodone
↑ trazodone
Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following co-administration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to trazadone product label for further information.
Antifungals
voriconazole,
ketoconazole,
isavuconazonium sulfate itraconazole*
↓ voriconazole
↑ ketoconazole
↑ isavuconazonium sulfate
↑ itraconazole
↑ nirmatrelvir/ritonavir
Avoid concomitant use of voriconazole. Refer to ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information.
Anti-gout
colchicine
↑ colchicine
Co-administration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment.
Anti-HIV protease inhibitors
amprenavir,
atazanavir,
darunavir,
fosamprenavir,
indinavir,
nelfinavir,
saquinavir,
tipranavir
↑ protease Inhibitor
For further information, refer to the respective protease inhibitors' prescribing information. Patients on ritonavir- or cobicistatcontaining HIV regimens should continue their treatment as indicated. Monitor for increased Paxlovid or protease inhibitor adverse events with concomitant use of these protease inhibitors.
Anti-HIV
didanosine,
delavirdine,
efavirenz,
maraviroc,
nevirapine,
raltegravir,
zidovudine bictegravir/ emtricitabine/ tenofovir
↑ didanosine
↑ efavirenz
↑ maraviroc
↓ raltegravir
↓ zidovudine
↑ bictegravir
↔ emtricitabine
↑ tenofovir
For further information, refer to the respective anti-HIV drugs prescribing information.
Anti-infective
clarithromycin,
erythromycin
↑ clarithromycin
↑ erythromycin
Refer to the respective prescribing information for anti-infective dose adjustment.
Antimycobacterial
rifampin
↓ nirmatrelvir/ritonavir
Co-administration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered.
Antimycobacterial
bedaquiline
rifabutin
↑ bedaquiline
↑ rifabutin
Refer to the bedaquiline product label for further information.
Refer to rifabutin product label for further information on rifabutin dose reduction.
Antipsychotics
lurasidone,
pimozide,
clozapine
↑ lurasidone
↑ pimozide
↑ clozapine
Co-administration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias.
Antipsychotics
quetiapine
↑ quetiapine
If co-administration is necessary, reduce quetiapine dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations.
Calcium channel blockers
amlodipine,
diltiazem,
felodipine,
nicardipine,
nifedipine
↑ calcium channel blocker
Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with Paxlovid.
If co-administered, refer to individual product label for calcium channel blocker for further information.
Cardiac glycosides
digoxin
↑ digoxin
Caution should be exercised when coadministering Paxlovid with digoxin, with appropriate monitoring of serum digoxin levels. Refer to the digoxin product label for further information.
Endothelin receptor Antagonists
bosentan
↑ bosentan
Discontinue use of bosentan at least 36 hours prior to initiation of Paxlovid. Refer to the bosentan product label for further information.
Ergot derivatives
dihydroergotamine,
ergotamine,
methylergonovine
↑ dihydroergotamine
↑ ergotamine
↑ methylergonovine
Co-administration contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system.
Hepatitis C direct acting antivirals
elbasvir/grazoprevir, glecaprevir/pibrentasvir
↑ antiviral
Increased grazoprevir concentrations can result in ALT elevations. It is not recommended to co-administer ritonavir with glecaprevir/pibrentasvir.
Refer to the ombitasvir/paritaprevir/ritonavir and dasabuvir label for further information.
Refer to the sofosbuvir/velpatasvir/voxilaprevir product label for further information.
Patients on ritonavir-containing HCV regimens should continue their treatment as indicated. Monitor for increased Paxlovid or HCV drug adverse events with concomitant use.
ombitasvir/paritaprevir/
ritonavir and dasabuvir
sofosbuvir/velpatasvir/
voxilaprevir
Herbal products
St. John's Wort (hypericum perforatum)
↓ nirmatrelvir/ritonavir
Co-administration contraindicated due to potential loss of virologic response and possible resistance.
HMG-CoA reductase inhibitors
lovastatin,
simvastatin
↑ lovastatin
↑ simvastatin
Co-administration contraindicated due to potential for myopathy including rhabdomyolysis. Discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of Paxlovid.
HMG-CoA reductase inhibitors
atorvastatin,
rosuvastatin
↑ atorvastatin
↑ rosuvastatin
Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with Paxlovid.
Hormonal contraceptive
ethinyl estradiol
↓ ethinyl estradiol
An additional, non-hormonal method of contraception should be considered.
Immunosuppressants
cyclosporine,
tacrolimus,
sirolimus
↑ cyclosporine
↑ tacrolimus
↑ sirolimus
Therapeutic concentration monitoring is recommended for immunosuppressants. Avoid use of Paxlovid when close monitoring of immunosuppressant serum concentrations is not feasible.
Avoid concomitant use of sirolimus and Paxlovid.
If co-administered, refer to individual product label for immunosuppressant for further information.
Long-acting betaadrenoceptor agonist
salmeterol
↑ salmeterol
Co-administration is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.
Narcotic analgesics
fentanyl
↑ fentanyl
Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl is concomitantly administered with Paxlovid.
methadone
↓ methadone
Monitor methadone-maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly.
PDE5 inhibitor
sildenafil (Revatio®) when used for pulmonary arterial hypertension
↑ sildenafil
Co-administration contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities hypotension, prolonged erection, and syncope.
Sedative/hypnotics
triazolam,
oral midazolam
↑ triazolam
↑ midazolam
Co-administration contraindicated due to potential for extreme sedation and respiratory depression.
Sedative/hypnotics
midazolam (administered parenterally)
↑ midazolam
Co-administration of midazolam (parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. Refer to the midazolam product label for further information.
Systemic corticosteroids
betamethasone,
budesonide,
ciclesonide,
dexamethasone,
fluticasone,
methylprednisolone,
mometasone,
prednisone,
triamcinolone
↑ corticosteroid
Increased risk for Cushing's syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone and prednisolone should be considered.
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Pregnancy and breastfeeding
- 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.
What else should I know about Paxlovid?
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.
