WARNINGS
Do not take XOCOVA if you:
• are allergic to ensitrelvir or any of the ingredients in XOCOVA. See the end of this leaflet for a complete list of ingredients in XOCOVA. See “What are the possible side effects of XOCOVA?” for signs and symptoms of allergic reactions.
• take any of the following medicines, as these medicines may interact with XOCOVA and may cause severe or life-threatening side effects or death:
o apalutamide
o carbamazepine
o colchicine
o dihydroergotamine
o enzalutamide
o eplerenone
o ergotamine
o finerenone
o ivabradine
o lomitapide
o lumacaftor/ivacaftor
o lurasidone
o methylergonovine
o phenytoin
o pimozide
o quinidine
o rifampin o St. John’s wort
o simvastatin
o triazolam
o voclosporin
These are not the only medicines that may cause serious or life-threatening side effects if taken with XOCOVA. XOCOVA may increase or decrease the levels of many medicines in your body. It is very important to tell your healthcare provider about all of the medicines you take because additional laboratory tests or changes in the dose of your other medicines may be necessary during treatment with XOCOVA. Your healthcare provider may tell you about specific symptoms to watch for that may indicate that you need to stop or decrease the dose of some of your other medicines.
Before taking XOCOVA, tell your healthcare provider about all of your medical conditions, including if you:
• are pregnant or plan to become pregnant. XOCOVA may harm your unborn baby. Females who are able to become pregnant:
o Your healthcare provider will check with you to see if you are pregnant before you start XOCOVA.
o Use effective birth control (contraception) during treatment with XOCOVA and for 2 weeks after the final dose of XOCOVA.
o Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with XOCOVA.
• are breastfeeding or plan to breastfeed. It is not known if XOCOVA passes into your breastmilk. Do not breastfeed during treatment with XOCOVA and for 2 weeks after the final dose of XOCOVA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. See “Do not take XOCOVA if you:” for a list of medicines that interact with XOCOVA.
• Your healthcare provider can tell you if it is safe to take XOCOVA with other medicines.
• You can ask your healthcare provider or pharmacist for a list of medicines that interact with XOCOVA.
• Do not start taking a new medicine without telling your healthcare provider.
USES
What is XOCOVA? XOCOVA is a prescription medicine that is used to help prevent coronavirus disease 2019 (COVID-19) in adults and children 12 years of age and older following contact with a person who has COVID-19 (post-exposure prophylaxis). It is not known if XOCOVA is safe and effective in children less than 12 years of age.
HOW TO USE
How should I take XOCOVA?
• Take XOCOVA exactly as your healthcare provider tells you to take it.
• Take XOCOVA for 5 days. Do not stop taking XOCOVA without talking to your healthcare provider.
• XOCOVA comes in a blister pack containing 7 tablets.
• Do not remove XOCOVA tablets from the blister pack until you are ready to take your dose.
• Take XOCOVA with or without food.
• Take XOCOVA at about the same time each day.
• If you miss a dose of XOCOVA, take the missed dose as soon as possible on that same day. Then return to the normal dosing schedule the next day.
• If you take too much XOCOVA, call your healthcare provider or go to the nearest hospital emergency room right away.
What are the possible side effects of XOCOVA? XOCOVA may cause serious side effects, including:
• Allergic reactions, including severe allergic reactions (anaphylaxis). Stop taking XOCOVA and get medical help right away if you get any of the following symptoms of an allergic reaction:
o skin rash, hives
o itching
o swelling of the mouth, lips, tongue, or face
o trouble swallowing or breathing
o throat tightness o dizziness or feeling lightheaded o stomach-area (abdomen) pain
o vomiting The most common side effects of XOCOVA include:
• headache
• diarrhea
• cough These are not all of the possible side effects of XOCOVA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of XOCOVA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use XOCOVA for a condition for which it was not prescribed. Do not give XOCOVA to other people. It may harm them. You can ask your pharmacist or healthcare provider for information about XOCOVA that is written for healthcare professionals.
What are the ingredients in XOCOVA?
Active ingredient: ensitrelvir
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, and magnesium stearate.
OVERDOSE
If you take too much XOCOVA, call your healthcare provider or go to the nearest hospital emergency room right away.
MISSED DOSE
If you miss a dose of XOCOVA, take the missed dose as soon as possible on that same day. Then return to the normal dosing schedule the next day.
STORAGE
How should I store XOCOVA?
• Store XOCOVA at room temperature between 68-degrees F to 77-degrees F (20-degrees C to 25-degrees C).
• Store XOCOVA in the original package. Keep XOCOVA and all medicines out of the reach of children.
NOTES
Medication Guide: revision date 05/2026
Prescribing Information: revision date 05/2026
DRUG INTERACTIONS
1. Potential for XOCOVA to Affect Other Drugs Ensitrelvir is a strong inhibitor of CYP3A and an inhibitor of P-gp and BCRP. Co-administration of XOCOVA with drugs that are primarily metabolized by CYP3A or are transported by P-gp or BCRP may result in increased plasma concentrations of such drugs and increase the risk of adverse events [see Contraindications (4), Warnings and Precautions (5.2), Drug Interactions (7.3), and Clinical Pharmacology (12.3)]. For drugs that are CYP3A substrates and contraindicated with XOCOVA, initiation of XOCOVA should be considered only after careful evaluation of relevant clinical and pharmacokinetic factors related to the concomitant medication. In addition, re-initiation of contraindicated CYP3A substrates should be considered based on an assessment of the duration of CYP3A inhibition and patient‑specific considerations. Refer to individual drug prescribing information for additional information.
2. Potential for Other Drugs to Affect XOCOVA
Ensitrelvir is a CYP3A substrate; therefore, drugs that induce CYP3A may decrease ensitrelvir plasma concentrations and reduce XOCOVA therapeutic effect [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)]. Therefore, use of XOCOVA with strong CYP3A4 inducers is contraindicated [see Contraindications (4)]. No dose adjustment is recommended when XOCOVA is used concomitantly with moderate or weak CYP3A inducers [see Warnings and Precautions (5.2)]. Refer to individual drug prescribing information for additional information.
3. Established and Other Potentially Significant Drug Interactions Table 1 provides examples of drugs that are contraindicated with XOCOVA [see Contraindications (4) and Warnings and Precautions (5.2)]. Table 1 is provided as a guide and is not a comprehensive list of all possible drugs that may interact with XOCOVA. The healthcare provider should consult other appropriate resources, such as the prescribing information for the interacting drug, for comprehensive information on dosing and monitoring with concomitant use of a strong CYP3A inhibitor, like XOCOVA [see Drug Interactions (7.1)]. Table 1 Drugs Contraindicated with XOCOVA due to Risk of Potentially Serious or Fatal Interaction [see Contraindications (4)]
Table 1 Drugs Contraindicated with XOCOVA due to Risk of Potentially Serious or Fatal Interaction [see Contraindications (4)] Drug Class Drug(s) within Class Effect on Drug Concentration Clinical Comment Antiarrhythmics quinidine ↑ antiarrhythmic Co-administration is contraindicated due to potential for cardiac arrhythmias. Anticancer drugs apalutamide, enzalutamide ↓ ensitrelvir Co-administration is contraindicated due to potential loss of virologic response. Anticonvulsants carbamazepinea , phenytoin ↓ ensitrelvir Co-administration is contraindicated due to potential loss of virologic response. Antigout agents colchicine ↑ colchicine Co-administration is contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment.
Antimycobacterials rifampin ↓ ensitrelvir Co-administration is contraindicated due to potential loss of virologic response. Antipsychotics lurasidone, pimozide ↑ lurasidone, pimozide Co-administration is contraindicated due to serious and/or life-threatening reactions, such as cardiac arrhythmias. Cardiovascular drugs eplerenone, ivabradine ↑ eplerenone, ivabradine Co-administration is contraindicated.
Cystic fibrosis transmembrane conductance regulator potentiators lumacaftor/ivacaftor ↓ ensitrelvir Co-administration is contraindicated due to potential loss of virologic response.
Drug Class Drug(s) within Class Effect on Drug Concentration Clinical Comment Ergot derivatives dihydroergotamine, ergotamine, methylergonovine ↑ dihydroergotamine, ergotamine, methylergonovine Co-administration is contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues, including the central nervous system.
Herbal products (for depression) St. John's wort ↓ ensitrelvir Co-administration is contraindicated due to potential loss of virologic response. HMG-CoA reductase inhibitors (statins) simvastatin ↑ simvastatin Co-administration is contraindicated. Discontinue use of simvastatin at least 12 hours prior to initiation of XOCOVA. Immunosuppressants voclosporin ↑ voclosporin Co-administration is contraindicated due to potential for acute and/or chronic nephrotoxicity.
Microsomal triglyceride transfer protein (MTTP) inhibitors lomitapide ↑ lomitapide Co-administration is contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions. Mineralocorticoid receptor antagonists finerenone ↑ finerenone Co-administration is contraindicated due to potential for serious adverse reactions, including hyperkalemia, hypotension, and hyponatremia. Sedatives triazolam ↑ triazolam Co-administration is contraindicated.
See the section WARNINGS above.
