Medical Editor: John P. Cunha, DO, FACOEP
What Is Paxlovid?
Paxlovid (nirmatrelvir tablets; ritonavir tablets) is an unapproved product that contains a SARS-CoV-2 main protease (Mpro: also referred to as 3CLpro or nsp5 protease) inhibitor and an HIV-1 protease inhibitor and CYP3A inhibitor issued under Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration 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 are at high risk for progression to severe COVID-19, including hospitalization or death.
What Are Side Effects of Paxlovid?
Side effects of Paxlovid include:
Seek medical care or call 911 at once if you have the following serious side effects:
- Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
- Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.
Dosage for Paxlovid
Paxlovid treatment should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. The dosage of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days administered orally without food.
Paxlovid In Children
Paxlovid is not authorized for use in pediatric patients younger than 12 years of age or weighing less than 40 kg. The safety and effectiveness of Paxlovid have not been established in pediatric patients. The authorized adult dosing regimen is expected to result in comparable serum exposures of nirmatrelvir and ritonavir in patients 12 years of age and older and weighing at least 40 kg as observed in adults, and adults with similar body weight were included in the trial EPIC-HR.
What Drugs, Substances, or Supplements Interact with Paxlovid?
Paxlovid may interact with other medicines such as:
- alpha 1-adrenoreceptor antagonists,
- anticancer drugs,
- anti-HIV protease inhibitors,
- anti-HIV medicines,
- calcium channel blockers,
- cardiac glycosides,
- endothelin receptor antagonists,
- ergot derivatives,
- hepatitis C direct acting antivirals,
- St. John's wort,
- HMG-CoA reductase inhibitors,
- hormonal contraceptives,
- long-acting beta-adrenoceptor agonists,
- narcotic analgesics,
- PDE5 inhibitors,
- sedative/hypnotics, and
- systemic corticosteroids
Tell your doctor all medications and supplements you use.
Paxlovid During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using Paxlovid; it is unknown how it might affect a fetus. COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. It is unknown if the medications in Paxlovid pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. Consult your doctor before breastfeeding.
Our Paxlovid (nirmatrelvir tablets; ritonavir tablets), Co-Packaged for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Adverse Reactions From Clinical Studies
The following adverse reactions have been observed in the clinical studies of PAXLOVID that supported the EUA. The adverse reaction rates observed in these clinical studies cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Additional adverse events associated with PAXLOVID may become apparent with more widespread use.
The safety of PAXLOVID is based on data from Study C4671005 (EPIC-HR), a Phase 2/3 randomized, placebo-controlled trial in nonhospitalized adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection [see Clinical Studies]. A total of 2,224 symptomatic adult subjects 18 years of age and older who are at high risk of developing severe COVID-19 illness received at least one dose of either PAXLOVID (n=1,109) or placebo (n=1,115). Adverse events were those reported while subjects were on study medication and through Day 34 after initiating study treatment. PAXLOVID [300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir] or matching placebo were to be taken twice daily for 5 days.
Adverse events (all grades regardless of causality) in the PAXLOVID group (≥1%) that occurred at a greater frequency (≥5 subject difference) than in the placebo group were dysgeusia (6% and <1%, respectively), diarrhea (3% and 2%), hypertension (1% and <1%), and myalgia (1% and <1%).
The proportions of subjects who discontinued treatment due to an adverse event were 2% in the PAXLOVID group and 4% in the placebo group.
Required Reporting For Serious Adverse Events And Medication Errors
The prescribing healthcare provider and/or the provider's designee are/is responsible for mandatory reporting of all serious adverse events3 and medication errors potentially related to PAXLOVID within 7 calendar days from the onset of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA recommends that such reports, using FDA Form 3500, include the following:
- Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race).
- A statement " PAXLOVID use for COVID-19 under Emergency Use Authorization (EUA)" under the "Describe Event, Problem, or Product Use/Medication Error" heading.
- Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes).
- Patient's pre-existing medical conditions and use of concomitant products.
- Information about the product (e.g., dosage, route of administration, NDC #).
Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods:
- Complete and submit the report online: https://www.fda.gov/medwatch/report.htm
- Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by:
- Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
- Fax to 1-800-FDA-0178, or
- Call 1-800-FDA-1088 to request a reporting form
In addition, please provide a copy of all FDA MedWatch forms to:
|Website||Fax number||Telephone number|
The prescribing healthcare provider and/or the provider's designee is/are to provide mandatory responses to requests from FDA for information about adverse events and medication errors associated with PAXLOVID.
3Serious adverse events are defined as:
- Death or a life-threatening adverse event;
- A medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly;
- Inpatient hospitalization or prolongation of existing hospitalization;
- A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or
- A congenital anomaly/birth defect.
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 [see CONTRAINDICATIONS and Table 1]. 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 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 [see CONTRAINDICATIONS].
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 [see CONTRAINDICATIONS].|
|Co-administration contraindicated due to potential for serious respiratory depression or hematologic abnormalities [see CONTRAINDICATIONS].|
|Antianginal||ranolazine||↑ ranolazine||Co-administration contraindicated due to potential for serious and/or life-threatening reactions [see CONTRAINDICATIONS].|
|↑ antiarrhythmic||Co-administration contraindicated due to potential for cardiac arrhythmias [see CONTRAINDICATIONS].|
|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 [see CONTRAINDICATIONS].|
|↑ 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.|
|Closely monitor INR if co-administration with warfarin is necessary.
Increased bleeding risk with rivaroxaban. Avoid concomitant use.
|Co-administration contraindicated due to potential loss of virologic response and possible resistance [see CONTRAINDICATIONS].|
|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.|
isavuconazonium sulfate itraconazole*
↑ isavuconazonium sulfate
|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 [see CONTRAINDICATIONS].|
|Anti-HIV protease inhibitors||amprenavir,
|↑ 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 [see DOSAGE AND ADMINISTRATION].|
zidovudine bictegravir/ emtricitabine/ tenofovir
|For further information, refer to the respective anti-HIV drugs prescribing information.|
|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 [see CONTRAINDICATIONS].|
|Refer to the bedaquiline product label for further information.
Refer to rifabutin product label for further information on rifabutin dose reduction.
|Co-administration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias [see CONTRAINDICATIONS].|
|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,
|↑ 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.|
|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 [see CONTRAINDICATIONS].|
|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 [see DOSAGE AND ADMINISTRATION].
ritonavir and dasabuvir
|Herbal products||St. John's Wort (hypericum perforatum)||↓ nirmatrelvir/ritonavir||Co-administration contraindicated due to potential loss of virologic response and possible resistance [see CONTRAINDICATIONS].|
|HMG-CoA reductase inhibitors||lovastatin,
|Co-administration contraindicated due to potential for myopathy including rhabdomyolysis [see CONTRAINDICATIONS]. Discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID.|
|HMG-CoA reductase inhibitors||atorvastatin,
|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.|
|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 [see CONTRAINDICATIONS].|
|Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see CONTRAINDICATIONS].|
|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.|
|↑ corticosteroid||Increased risk for Cushing's syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone and prednisolone should be considered.|
|* See CLINICAL PHARMACOLOGY.|
Read the entire FDA prescribing information for Paxlovid (Nirmatrelvir Tablets and Ritonavir Tablets)
© Paxlovid Patient Information is supplied by Cerner Multum, Inc. and Paxlovid Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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