XOCOVA Ensitrelvir 125 mg Tablet, 7-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Protease inhibitors class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Patient education
Supplement & herbal interactions
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Xocova 125 mgthis 59630-0711-07 | Shionogi | 7 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 12559474 ↗ | Drug substance | U-4553 | May 1, 2042 |
| US 11814368 ↗ | Drug substance | U-4553 | May 1, 2042 |
| US 9150546 ↗ | Drug substance | — | Dec 12, 2030 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | May 29, 2031 |
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 59630-0711-07 You're viewing this | 1 BLISTER PACK in 1 CARTON (59630-711-07) / 7 TABLET in 1 BLISTER PACK | 2026-07-02 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE XOCOVA is indicated for post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19. XOCOVA, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M pro : also referred to as 3CL pro or nsp5 protease) inhibitor, is indicated for post-exposure prophylaxis of coronavirus disease 2019 (COVID‑19) in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Verify pregnancy status of females of reproductive potential prior to initiating XOCOVA. ( 2.1 ) Begin XOCOVA as soon as possible and within 72 hours following contact with an individual who has COVID-19. ( 2.2 ) Dosage: 375 mg (three 125-mg tablets taken at the same time) orally on Day 1 and 125 mg (one 125-mg tablet) orally on Days 2 to 5 taken with or without food. ( 2.2 )
2.1Pregnancy Evaluation Prior to Initiating XOCOVA Verify pregnancy status of females of reproductive potential prior to initiating XOCOVA [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1 , 8.3) ] .
2.2Recommended Dosage The recommended dosage of XOCOVA in adults and adolescents 12 years of age and older is 375 mg (three 125-mg tablets taken together) orally on Day 1 and 125 mg (one 125-mg tablet) orally on Days 2 to 5 with or without food [see Clinical Pharmacology (12.3) ] . Begin XOCOVA as soon as possible and within 72 hours following contact with an individual who has COVID-19. The tablets should be taken at approximately the same time each day.
If a dose of XOCOVA is missed, take the missed dose as soon as possible on the same day, and then take the next dose as scheduled the following day.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: white to light yellow-white, round tablets containing 125 mg of ensitrelvir, debossed with the Shionogi trademark ( ) above the identifier code "711" on one side and with a "125" on the other side. Tablets: 125 mg of ensitrelvir ( 3 ) Image
⛔ Contraindications ▾
4 CONTRAINDICATIONS XOCOVA is contraindicated in patients with a history of clinically significant hypersensitivity reactions to ensitrelvir or any other components of the product. XOCOVA is contraindicated in patients taking drugs that are: Primarily metabolized by CYP3A for which elevated concentrations may be associated with serious and/or life-threatening reactions [see Drug Interactions (7.3) ] and Strong CYP3A inducers because they may significantly reduce ensitrelvir plasma concentrations, leading to the potential loss of virologic response [see Drug Interactions (7.3) ] .
History of clinically significant hypersensitivity reactions to ensitrelvir or any other components of the product. ( 4 ) Co-administration with drugs primarily metabolized by CYP3A for which elevated concentrations may be associated with serious and/or life-threatening reactions. ( 4 , 7.3 ) Co-administration with strong CYP3A inducers considered to significantly reduce ensitrelvir plasma concentrations and may be associated with the potential for loss of virologic response.
( 4 , 7.3 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Embryofetal toxicity: Based on animal data, XOCOVA may cause fetal harm. Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. Advise females of reproductive potential to use effective contraception during XOCOVA use and for 2 weeks after the final dose.
( 5.1 , 8.1 , 8.3 ) The concomitant use of XOCOVA and certain other drugs may result in potentially significant drug interactions. Consult the Full Prescribing Information prior to and during treatment for potential drug interactions. ( 5.2 , 7 ) Hypersensitivity reactions, including anaphylaxis, anaphylactic shock, and angioedema, have been reported with XOCOVA.
If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue XOCOVA and initiate appropriate treatment. ( 5.3 )
5.1Embryofetal Toxicity Based on animal reproduction studies, XOCOVA may cause fetal harm when administered to a pregnant woman. In rabbits, embryofetal toxicity (including skeletal malformations and embryofetal lethality) was observed in rabbit offspring following exposure of pregnant rabbits to ensitrelvir at 7 times the human exposures at the recommended human dose (RHD). Likewise in rats, fetal growth retardation, low fetal body weight, skeletal variations, offspring lethality, low body weight in offspring, and retardation of morphological development were observed following exposure during gestation and lactation at exposures 9 times the human exposures at the RHD [see Use in Specific Populations (8.1) ] .
Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. Verify pregnancy status of females of reproductive potential prior to initiating XOCOVA. Advise females of reproductive potential to use effective contraception during XOCOVA use and for 2 weeks after the final dose [see Use in Specific Populations (8.1 , 8.3) ] .
5.2Risk of Serious Adverse Reactions Due to Drug Interactions XOCOVA is a strong CYP3A inhibitor and an inhibitor of P-gp and BCRP. In patients receiving or initiating medications metabolized by CYP3A or transported by P-gp or BCRP, XOCOVA may increase plasma concentrations of those medications and may potentially lead to severe, life-threatening, or fatal events from increased exposure of concomitant medications. In addition, medications that induce CYP3A may decrease concentrations of ensitrelvir, leading to loss of therapeutic effect of XOCOVA.
Prior to prescribing XOCOVA, review all medications taken by the patient to assess potential drug-drug interactions and determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring (e.g., calcineurin inhibitors) [see Contraindications (4) and Drug Interactions (7) ] . Consider the benefit of XOCOVA and whether the risk of potential drug-drug interactions can be appropriately managed [see Drug Interactions (7) ] .
5.3Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions, including anaphylaxis, anaphylactic shock, and angioedema, have been reported with XOCOVA [see Adverse Reactions (6.2) ] . If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue XOCOVA and initiate appropriate treatment.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.3) ] The most common adverse events (regardless of causality) occurring in ≥1% of the XOCOVA group and at a greater frequency compared to placebo were headache, diarrhea, and cough. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc. at 1-800-849-9707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The overall safety profile of XOCOVA is based on data from 2,831 adults and adolescents exposed to the recommended dosage and duration of XOCOVA in controlled clinical trials. Trial SCORPIO-PEP was a randomized, double-blind, placebo-controlled trial in which 1,190 subjects received oral XOCOVA (375 mg [Day 1]/125 mg [Days 2-5]) and 1,187 subjects received oral placebo (Days 1-5).
The most common adverse events (regardless of causality) occurring in ≥1% of the XOCOVA group and at a greater frequency compared to placebo were headache (2.9% and 2.6%, respectively), diarrhea (1.7% and 1.3%, respectively), and cough (1.1% and 0.6%, respectively). The proportion of subjects who discontinued study intervention due to an adverse event was <0.1% in both the XOCOVA and placebo groups. Laboratory Abnormalities: Asymptomatic hemoglobin declines from baseline of >2 g/dL occurred in 3% of XOCOVA recipients versus 1% of placebo recipients.
6.2Postmarketing Experience The following adverse reactions have been identified during post approval use of XOCOVA outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders: Anaphylaxis (including anaphylactic shock), angioedema, hypersensitivity, urticaria
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Co-administration of XOCOVA can alter the plasma concentrations of other drugs, and other drugs may alter the plasma concentrations of XOCOVA. Consider the potential for drug interactions prior to and during XOCOVA use and review concomitant medications during XOCOVA use. ( 4 , 5.2 , 7 , 12.3 )
7.1Potential 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.
7.2Potential 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.
7.3Established 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) ] 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 carbamazepine See Clinical Pharmacology (12.3) , 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. Ergot derivatives dihydroergotamine, ergotamine, methylergonovine ↑ dihydroergotamine, ergotamine, methylergonovine Co-administ…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed during XOCOVA use and for 2 weeks after the final dose. ( 8.2 )
8.1Pregnancy Risk Summary Based on animal reproduction studies, XOCOVA may cause fetal harm when administered to a pregnant woman. Embryofetal toxicity (including skeletal malformations and embryofetal lethality) was observed in rabbits during the period of organogenesis at ensitrelvir exposures 7 times the human exposures at the recommended human dose (RHD). In rats, fetal growth retardation, low fetal body weight, and skeletal variations were observed during the period of organogenesis at ensitrelvir exposures 9 times the RHD.
In addition, lethality, low body weight, and retardation of morphological development were observed in pre-weaning pups during gestation and lactation at ensitrelvir exposures 9 times the RHD (see Data ) . Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. The available clinical data on the use of XOCOVA during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defects, loss, and other adverse outcomes. In the general population in the United States, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In an embryofetal development study in pregnant rabbits, ensitrelvir was administered at oral doses of 30, 100, or 300 mg/kg/day on gestation days (GD) 6-19. Embryofetal lethality, skeletal malformations and variations, abortion, and post-implantation loss were observed with maternal toxicity (decreased food consumption and body weight and body weight gain) at doses ≥100 mg/kg/day. Malformations of the axial skeleton included fused sternebra, branched rib, fused cervical centrum, supernumerary thoracic vertebra, fused thoracic arch, and fused caudal centrum.
Skeletal variations included splitting of the thoracic centrum and increased frequencies of full supernumerary rib and/or supernumerary lumbar vertebra. No effects were observed at 30 mg/kg/day, which is estimated to be 3 times the human exposure at the RHD based on the area under the curve (AUC). In a second embryofetal development study in pregnant rabbits, ensitrelvir was administered at 300 mg/kg/day on GD 6-9, 10-12, 13-15, and 16-19.
Similar malformations of the axial skeleton were observed, with most of the abnormalities present in animals dosed on GD 6-9; maternal toxicity (presenting as low food consumption) was also present during each segmented dosing period. In an embryofetal development study in pregnant rats, ensitrelvir was administered at oral doses of 20, 60, or 1000 mg/kg/day on GD 6-17. A delay in fetal development (as measured by decreased bone ossification and fetal body weight), as well as an increased incidence of short supernumerary rib, were observed at 1000 mg/kg/day.
Decreased food consumption and body weight were also observed at this dose. No effects were observed at 60 mg/kg/day, which is estimated to be 5 times the human exposure at the RHD based on AUC. In a pre- and postnatal development study, ensitrelvir was administered to pregnant rats at oral doses of 20, 60, or 1000 mg/kg/day from GD 6 to postnatal day (PND) 20.
Lethality, low body weight, and retardation of morphological development (delayed eyelid opening and sexual maturation) were observed at the highest dose of 1000 mg/kg/day, accompanied by maternal toxicity (total litter loss, decreased body weight and body weight gain, and decreased food consumption). No effects were observed at 60 mg/kg/day, which is estimated to be 5 times the human exposure at the RHD based on AUC.
8.2 Lactation Risk Summary There are no data on the presence of ensitrelvir in hu…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on animal reproduction studies, XOCOVA may cause fetal harm when administered to a pregnant woman. Embryofetal toxicity (including skeletal malformations and embryofetal lethality) was observed in rabbits during the period of organogenesis at ensitrelvir exposures 7 times the human exposures at the recommended human dose (RHD). In rats, fetal growth retardation, low fetal body weight, and skeletal variations were observed during the period of organogenesis at ensitrelvir exposures 9 times the RHD.
In addition, lethality, low body weight, and retardation of morphological development were observed in pre-weaning pups during gestation and lactation at ensitrelvir exposures 9 times the RHD (see Data ) . Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. The available clinical data on the use of XOCOVA during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defects, loss, and other adverse outcomes. In the general population in the United States, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In an embryofetal development study in pregnant rabbits, ensitrelvir was administered at oral doses of 30, 100, or 300 mg/kg/day on gestation days (GD) 6-19. Embryofetal lethality, skeletal malformations and variations, abortion, and post-implantation loss were observed with maternal toxicity (decreased food consumption and body weight and body weight gain) at doses ≥100 mg/kg/day. Malformations of the axial skeleton included fused sternebra, branched rib, fused cervical centrum, supernumerary thoracic vertebra, fused thoracic arch, and fused caudal centrum.
Skeletal variations included splitting of the thoracic centrum and increased frequencies of full supernumerary rib and/or supernumerary lumbar vertebra. No effects were observed at 30 mg/kg/day, which is estimated to be 3 times the human exposure at the RHD based on the area under the curve (AUC). In a second embryofetal development study in pregnant rabbits, ensitrelvir was administered at 300 mg/kg/day on GD 6-9, 10-12, 13-15, and 16-19.
Similar malformations of the axial skeleton were observed, with most of the abnormalities present in animals dosed on GD 6-9; maternal toxicity (presenting as low food consumption) was also present during each segmented dosing period. In an embryofetal development study in pregnant rats, ensitrelvir was administered at oral doses of 20, 60, or 1000 mg/kg/day on GD 6-17. A delay in fetal development (as measured by decreased bone ossification and fetal body weight), as well as an increased incidence of short supernumerary rib, were observed at 1000 mg/kg/day.
Decreased food consumption and body weight were also observed at this dose. No effects were observed at 60 mg/kg/day, which is estimated to be 5 times the human exposure at the RHD based on AUC. In a pre- and postnatal development study, ensitrelvir was administered to pregnant rats at oral doses of 20, 60, or 1000 mg/kg/day from GD 6 to postnatal day (PND) 20.
Lethality, low body weight, and retardation of morphological development (delayed eyelid opening and sexual maturation) were observed at the highest dose of 1000 mg/kg/day, accompanied by maternal toxicity (total litter loss, decreased body weight and body weight gain, and decreased food consumption). No effects were observed at 60 mg/kg/day, which is estimated to be 5 times the human exposure at the RHD based on AUC.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of XOCOVA for the post-exposure prophylaxis of COVID-19 in adolescents is supported by results of SCORPIO-PEP, an adequate and well-controlled trial that enrolled adults and adolescents ≥12 years of age. Of the 139 adolescents enrolled in this trial, 72 received XOCOVA. The safety of XOCOVA in adolescents is further supported by data from 16 adolescents who received XOCOVA in another clinical trial.
No overall differences in safety, pharmacokinetics, or efficacy of XOCOVA were observed between adolescents and adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ] . The safety and effectiveness of XOCOVA have not been established in pediatric patients less than 12 years of age. Juvenile Animal Toxicity Data In a juvenile toxicology study in rats, ensitrelvir was administered orally at 0, 10, 30 or 90 mg/kg for 8 or 9 days, from PND 4-11 or PND 12-20, respectively (PND 4-20 in rats is equivalent to approximately 0 to 2 years in humans).
Femur bone shortening (accompanied by decreased body weight) was observed in rats dosed from PND 4-11 at 90 mg/kg, which is estimated to be 14 times the human exposure at the recommended human dose (RHD) in adults based on AUC. These effects were not observed in animals dosed from PND 4-11 with 90 mg/kg followed by a 41-day dose-free period. No effects were observed at 30 mg/kg for animals dosed from PND 4-11, which is estimated to be 8 times the human exposure at the RHD in adults.
No effects were observed at 90 mg/kg for animals dosed from PND 12-20, which is estimated to be 12 times the human exposure at the RHD in adults. In another juvenile toxicology study in rats, ensitrelvir was administered orally at 0, 30, 90 or 1000 mg/kg for 8 days from PND 21-28 or PND 29-36, or 9 days from PND 37-45 (PND 21-45 in rats is equivalent to approximately 2 to 12 years in humans). Femur bone shortening (accompanied by decreased body weight and food consumption) was observed in rats dosed from PND 21-28 at 1000 mg/kg which is estimated to be 11 times the human exposure at the RHD in adults based on AUC.
These effects were not observed in animals dosed from PND 21-28 with 1000 mg/kg followed by a 22-day dose-free period. No effects were observed at 90 mg/kg, which is estimated to be 6 times the human exposure at the RHD in adults. No effects were observed at 1000 mg/kg for animals dosed from PND 29-36 or PND 37-45, which is estimated to be approximately 10 times the human exposure at the RHD in adults.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of XOCOVA included subjects 65 years of age and older and their data contributes to the overall assessment of safety and efficacy [see Adverse Reactions (6.1) and Clinical Studies (14.1) ] . Among XOCOVA recipients in Trial SCORPIO-PEP, 114 (10%) were 65 years of age or older, and 41 (3%) were 75 years of age and older. No overall differences in efficacy and safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in safety between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE Treatment of overdose with XOCOVA 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 XOCOVA.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Ensitrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug [see Microbiology (12.4) ].
12.2Pharmacodynamics Exposure-Response Within the ensitrelvir arm of SCORPIO-PEP, there was no association between plasma ensitrelvir concentration and the primary endpoint (COVID-19 symptoms and RT-PCR-positive), consistent with the determination that dose adjustments are not needed based on age, sex, race/ethnicity, or body weight. Cardiac Electrophysiology No QT prolongation was observed based on concentration-QTc analysis after a single dose of ensitrelvir ranging from 20 mg to 2000 mg. A single dose of ensitrelvir 2,000 mg resulted in C max that was approximately 3.4-fold higher than the mean C max observed on Day 5 at the recommended dose.
12.3Pharmacokinetics Table 2 Pharmacokinetic Properties of Ensitrelvir Parameter Ensitrelvir General Information N/A, not applicable. Exposure Represents data at the recommended clinical dose in Trial SCORPIO-PEP predicted by population PK analysis. Data represents geometric mean (coefficient of variation, CV%).
Day 1 Day 5 Day 10 The primary endpoint was assessed at Day 10. C max (mcg/mL) 18.1 (22.6) 18.2 (40.5) N/A C min (mcg/mL) 13.2 (31.3) 13.0 (59.4) N/A AUC 0-tau (mcg*hr/mL) 345.9 (28.4) 380.8 (47.0) N/A C day10 (mcg/mL) N/A N/A 1.48 (374.8) Dose Proportionality C max and AUC 0-inf exposures increase in an almost dose-proportional manner across the single dose range of 20 to 2000 mg in healthy adult individuals. Absorption Median T max (hours) (range) Ensitrelvir 375 mg on Day 1 followed by 125 mg on Days 2 to 5; tau is dosing interval of 24 hours.
Day 1: 2.50 (1.50, 8.00) hours Day 5: 2.00 (1.00, 8.00) hours Effect of Food High-fat, high-calorie meal. Total calories were 863 kcal (27.2% carbohydrates, 17.3% proteins, and 55.4% fat). No clinically significant differences in ensitrelvir pharmacokinetics were observed following administration of a high-fat, high-calorie meal.
Distribution Apparent (Oral) Volume of Distribution in Central Compartment Data from population pharmacokinetic analysis. 16.7 (22.9) L Human Serum Protein Binding 97.7% to 98.7% (in vitro) Blood to Plasma Ratio 0.538 Elimination Major Route of Elimination Primarily eliminated via the biliary route Terminal Half-Life (hours) 42.2 to 48.1 hours Following a single-dose administration of ensitrelvir 20 to 2000 mg. Apparent (Oral) Clearance 0.316 (52.6) L/hour Metabolism Unchanged ensitrelvir (≥90%) was the primary drug component detected in plasma.
Primary Responsible Metabolic Enzyme CYP3A Excretion Feces 64.8% of dose (50.7% unchanged) Urine 25.8% of dose (19.0% unchanged) Specific Populations There were no clinically significant differences in the pharmacokinetics of ensitrelvir based on age (12-91 years), sex, body weight (32-190 kg), race/ethnicity (77% Asian, 20% White, 2% Black, 1% Other). No clinically significant differences in the pharmacokinetics of ensitrelvir was observed in mild (estimated glomerular filtration rate [eGFR] 60 to <90 mL/min as determined by MDRD equation), moderate (eGFR 30-<60 mL/min), or severe (eGFR 15-<30 mL/min) renal impairment, or mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.
The pharmacokinetics and safety of ensitrelvir have not been studied in patients with severe hepatic impairment (Child-Pugh Class C) or patients with kidney failure receiving dialysis. Pediatric Patients The pharmacokinetics of ensitrelvir in children under 12 years of age has not been established. Drug Interaction Studies Clinical Drug Interaction Studies Effect of CYP3A4 Inducers on the Pharmacokinetics of Ensitrelvir Strong CYP3A4 Inducers: Coadministration with the strong CYP3A inducer carbamazepine (titrated from 100 mg twice daily to 300 mg twice daily over 1 week and then maintained at 300 mg twice daily dose for 11 days with some subjects requiring dose reduction) decreased the AUC of ensitrelvir b…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Ensitrelvir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral drug [see Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING XOCOVA (ensitrelvir) tablets 125 mg are white to light yellow-white, round, debossed with the Shionogi trademark ( ) above the identifier code "711" on one side and "125" on the other side and are supplied in a blister pack containing 7 tablets - NDC 59630-711-07. Image Store XOCOVA in the original package at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
📦 Storage and Handling ▾
Store XOCOVA in the original package at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION XOCOVA tablets contain ensitrelvir, a SARS-CoV-2 main protease (M pro ) inhibitor. Ensitrelvir is present as a 1:1 co-crystal with fumaric acid and has the following chemical name: (6 E )-6-[(6-Chloro-2-methyl-2 H -indazol-5-yl)imino]-3-[(1-methyl-1 H -1,2,4-triazol-3-yl)methyl]-1-[(2,4,5-trifluorophenyl)methyl]-1,3,5-triazinane-2,4-dione monofumaric acid The molecular formula is C 22 H 17 ClF 3 N 9 O 2 ∙C 4 H 4 O 4 and the molecular weight is 647.96. The structural formula is: Ensitrelvir fumaric acid is a white powder that is freely soluble in dimethyl sulfoxide; slightly soluble in acetone, ethanol, and methanol; and practically insoluble in water.
XOCOVA is provided as tablets for oral use containing 125 mg of ensitrelvir. Inactive ingredients are colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, and magnesium stearate. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryofetal Toxicity Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. Advise females of reproductive potential to inform their healthcare providers of a known or suspected pregnancy.
Advise females of reproductive potential to use effective contraception during use of XOCOVA and for 2 weeks after the final dose [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1 , 8.3) ] . Verify Pregnancy Status Before Initiating XOCOVA Inform patients that they need to verify pregnancy status prior to initiating XOCOVA [see Dosage and Administration (2.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , 8.3) ]. Drug Interactions Advise patients that XOCOVA can interact with certain drugs and is contraindicated for use with certain drugs; therefore, advise patients to report to their healthcare provider the use of any prescription or non-prescription medication or herbal products [see Contraindications (4) , Warnings and Precautions (5.2) , and Drug Interactions (7) ] .
Hypersensitivity Reactions Including Anaphylaxis Advise patients that hypersensitivity reactions, including anaphylaxis, anaphylactic shock, and angioedema, have been reported with XOCOVA and to immediately discontinue XOCOVA and alert the healthcare provider if signs and symptoms of a clinically significant hypersensitivity reaction occur [see Warnings and Precautions (5.3) and Adverse Reactions (6.2) ]. Administration Instructions Advise to begin XOCOVA as soon as possible and within 72 hours following contact with an individual who has COVID-19.
Advise patients to take three 125-mg tablets together orally on Day 1 and one 125-mg tablet on Days 2 to 5. Inform patients to take XOCOVA with or without food at approximately the same time each day as instructed [see Dosage and Administration (2.2) ] . Lactation Advise women not to breastfeed while on XOCOVA and for 2 weeks after the final dose [see Use in Specific Populations (8.2) ] .