New Oral Medicine to Help Prevent COVID-19 After Exposure

Xocova (ensitrelvir) is an oral SARS-CoV-2 main protease (Mpro / 3CLpro / nsp5) inhibitor. It blocks an enzyme the virus needs to copy itself. It is not a vaccine, not monoclonal-antibody prophylaxis, and — on the US label — not a treatment for people who already have COVID-19.

Brand names differ by region. Use the name on the carton your country’s regulator authorises:

• Xocova — United States and Japan (and the name used in sponsor US materials).
• Zokovea — proposed EU invented name on the EMA medicine page and CHMP positive opinion (ensitrelvir fumaric acid; applicant Shionogi B.V.).
• INN: ensitrelvir.

The FDA approved NDA 220442 on 29 May 2026 (Novel Drug Approvals for 2026 table row 19; approval letter signed Wendy Carter, DO, Director (Acting), Office of Infectious Diseases, CDER — electronic signature 05/29/2026 13:53:28). Manufactured for: Shionogi Inc., Florham Park, NJ. Parent company: Shionogi & Co., Ltd. (Osaka). The molecule came from joint research between Hokkaido University and Shionogi (sponsor materials). PDUFA target had been 16 June 2026; approval came early. The application was not referred to an FDA advisory committee.

Indication matrix by region (US / Japan / EU are different labelled uses):

Where this is taking place

Commercial labelled doors today

• United States — FDA-labelled Xocova for PEP (≥12). Primary care, urgent care, telehealth, infectious disease, or another clinician who can prescribe within the 72-hour window and check interactions. NDC blister 59630-711-07 (7 × 125 mg tablets). Company patient site describes US availability and a commercial co-pay offer — no dollar amounts in this article; prior authorization still applies. Authorized ≠ funded.
• Japan — PMDA/MHLW-labelled Xocova for treatment and for PEP. Local infectious-disease / clinic path under Japanese labelling. A Japan treatment carton is not a US treatment licence.

European Union — not a commercial door yet on sources used here

• Zokovea — CHMP positive opinion 23 July 2026 (EMA product EMEA/H/C/006063; applicant Shionogi B.V.). EMA meeting highlights list “Zokovea : pending EC decision.” SmPC publishes after the European Commission grants marketing authorisation. Until then: authorisation not confirmed.

SCORPIO-PEP — NCT05897541 (also Japan Registry jRCT2031230124) — Phase 3, global, randomized, double-blind, placebo-controlled. Lead sponsor on ClinicalTrials.gov: Shionogi. Status: COMPLETED. Enrollment 2,387. Start 9 Jun 2023; primary completion 30 Aug 2024; completion 18 Sep 2024. Site countries on the CT.gov record: United States, Japan, Argentina, South Africa, Vietnam. Completed — not an enrolment path. Trial geography ≠ a national licence.

Singapore — sponsor materials describe availability via a Special Access Route application from 2023 (historically framed around treatment access). That is not the same as a full HSA marketing authorisation asserted in this draft; ask a Singapore clinician what the current legal path is. Do not import on your own.

Canada / UK / Australia / Switzerland / China: authorisation not confirmed on sources used here.

The practical door in the US is a clinician who can see you fast after a known COVID-19 exposure, confirm you fit the PEP label, and run the drug-interaction check — not waiting for symptoms, not treating NCT05897541 as open enrolment, and not assuming a Japan treatment pack equals a US script.

Approval matrix

Access by country

• United States: Call a clinician as soon as you know you were exposed — primary care, urgent care, telehealth, ED follow-up, or infectious disease — so you can start within 72 hours. FDA-labelled 29 May 2026 for PEP in people ≥12. Dose: three 125 mg tablets (375 mg) on Day 1, then one 125 mg tablet daily on Days 2–5, with or without food, at about the same time each day. Missed dose: take the same day when remembered, then resume the next day’s schedule — do not take two doses to make up for a missed one. Verify pregnancy status before starting if you can become pregnant; use effective contraception during use and for 2 weeks after the last dose; do not breastfeed during use and for 2 weeks after. Bring a full medication list — many drugs are contraindicated (strong CYP3A / P-gp / BCRP story). Shionogi Inc. AE / information: 1-800-849-9707; MedWatch 1-800-FDA-1088; patient site www.xocova.com / www.shionogi.com. Company materials describe a commercial co-pay offer for some insured patients and an assistance programme “coming soon” for uninsured — no copay dollars here. Prior authorization still applies. Children under 12 not established on this label. Not for treating established COVID-19 in the US.

• Japan: In-country labelled Xocova for treatment and for PEP (PEP ≥12 from 23 Mar 2026). Ask a Japanese clinician which line fits. Pediatric treatment dosing for ages 6–<12 (≥20 kg) was added 19 Jun 2026 with a 25 mg tablet — that is a Japan treatment story, not the US PEP label. Do not import a Japan pack into the US as a care plan.

• European Union: Zokovea has a CHMP positive opinion (23 Jul 2026) for PEP ≥12. EC marketing authorisation not confirmed. Until an EC decision and SmPC land, there is no confirmed EU commercial labelled door from this draft. Do not import on your own.

• Canada: Authorisation not confirmed. Do not mail-order a US or Japan pack as the care plan. Ask the Canadian clinician what legal options exist (including whether any special-access pathway applies) while waiting for any future Canadian decision.

• United Kingdom / Australia / Switzerland / China: Authorisation not confirmed on sources used here.

• Singapore: Sponsor-described Special Access Route path from 2023 — confirm current status with a local clinician. Not a DIY order.

• If your regulator has not authorised it: do not import on your own.

Who is eligible (from the labels — they are not the same)

This is a post-exposure prophylaxis conversation when someone near you has COVID-19 and you are trying not to get sick. Timing matters.

United States (USPI, revised / issued May 2026) — PEP only:

• Age 12 years and older.
• Post-exposure prophylaxis of COVID-19 following contact with an individual who has COVID-19.
• Begin as soon as possible and within 72 hours following that contact.
• Dose: 375 mg (3 × 125 mg) Day 1; 125 mg daily Days 2–5; with or without food.
• Verify pregnancy status in females of reproductive potential before starting.
• Contraindications: clinically significant hypersensitivity to ensitrelvir or any component; co-administration with certain CYP3A substrates where higher levels can be serious/life-threatening; co-administration with strong CYP3A inducers that can wipe out ensitrelvir levels (examples on the Patient Information / USPI Table 1 include — not a complete list — apalutamide, carbamazepine, colchicine, dihydroergotamine, enzalutamide, eplerenone, ergotamine, finerenone, ivabradine, lomitapide, lumacaftor/ivacaftor, lurasidone, methylergonovine, phenytoin, pimozide, quinidine, rifampin, St. John’s wort, simvastatin, triazolam, voclosporin). The clinician must check the full interaction table.
• Renal: no dosage adjustment for mild/moderate/severe renal impairment on the label; not studied in kidney failure on dialysis.
• Hepatic: no adjustment for mild/moderate (Child-Pugh A/B); severe (Child-Pugh C) not studied.
• Geriatrics: SCORPIO-PEP included patients ≥65; no overall differences that change the labelled dose on the USPI narrative.
• Not labelled for: children under 12; treatment of COVID-19 in the US; starting after the 72-hour window as if the label still fits without clinician judgment.

Japan (Xocova — sponsor / MHLW communications):

• Treatment of COVID-19 (adults and, as of 19 Jun 2026, children 6–<12 years weighing ≥20 kg on a Japan-specific dose/tablet story).
• PEP of COVID-19 in ages ≥12 (approved 23 Mar 2026).
• Usual ≥12 oral regimen described as 375 mg Day 1 / 125 mg Days 2–5.
• A Japan treatment indication does not create a US treatment label.

European Union (CHMP opinion for Zokovea — pending EC):

• Proposed indication: PEP of COVID-19 in adults and adolescents aged 12 years and older, used in accordance with official recommendations.
• 125 mg tablets; benefit described as lower symptomatic COVID-19 risk in household contacts when given within 72 hours after index patient symptom onset.
• Not a granted MA until the Commission decides.

What the pivotal study showed (SCORPIO-PEP)

Use the USPI for a US prescription conversation. The NEJM paper (14 May 2026) is supportive reading — labelled numbers below follow the USPI.

SCORPIO-PEP — NCT05897541 / jRCT2031230124:

• Multinational, randomized 1:1, double-blind, placebo-controlled PEP trial in 5 countries.
• Household contacts ≥12, locally test-negative and asymptomatic at enrolment, living with an index patient who had symptomatic COVID-19; randomised within 72 hours of index symptom onset.
• XOCOVA 375 mg Day 1 + 125 mg Days 2–5 vs matching placebo.
• Randomised 2,387; mITT (central lab–negative at baseline) 2,041 (including 118 adolescents).
• Mean age ~42 (range 12–91); 59% female; 70% prior COVID-19 vaccination; >99% seropositive for SARS-CoV-2 antibody at screening; 37% had ≥1 risk factor for severe COVID-19.
• Primary: confirmed symptomatic SARS-CoV-2 infection (symptoms ≥48 hours + RT-PCR) through Day 10 in the mITT.

USPI Table 5:

Safety (SCORPIO-PEP): adverse events 15.1% Xocova (n=1,190) vs 15.5% placebo (n=1,187). Most common AEs more frequent than placebo: headache (2.9% vs 2.6%), diarrhea (1.7% vs 1.3%), cough (1.1% vs 0.6%). Discontinuations for AE <0.1% both arms. No dysgeusia attributed to Xocova in the trial narrative used by the sponsor. Asymptomatic hemoglobin drop >2 g/dL: 3% vs 1%. Postmarketing outside the US has reported anaphylaxis / angioedema / hypersensitivity.

How it is taken (US label — keep this exact)

• Strength: 125 mg film-coated tablets — white to light yellow-white, round; Shionogi mark + “711” / “125”.
• Day 1: three tablets (375 mg) at the same time.
• Days 2–5: one tablet (125 mg) each day.
• With or without food. Same time of day.
• Blister of 7 tablets — NDC 59630-711-07.
• Store in the original pack at 20–25 °C (excursions 15–30 °C).
• Tell the clinician about pregnancy/breastfeeding plans and every medicine and herbal product (including St. John’s wort and simvastatin).

Safety (USPI)

Contraindications: hypersensitivity to ensitrelvir / components; listed interacting drugs (CYP3A substrates with serious risk; strong CYP3A inducers) — see Table 1 / Patient Information list above.

Warnings and precautions:

• Embryofetal toxicity (animal data) — pregnancy test before start; contraception during + 2 weeks after; do not breastfeed during + 2 weeks after.
• Serious drug interactions — strong CYP3A inhibitor; also P-gp and BCRP inhibitor. Review all meds before prescribing.
• Hypersensitivity including anaphylaxis — stop and get emergency care for rash, swelling, breathing trouble, dizziness, vomiting, etc.

Most common adverse events (≥1% and greater than placebo in SCORPIO-PEP): headache, diarrhea, cough.

Report suspected adverse reactions to Shionogi Inc. 1-800-849-9707 or FDA MedWatch 1-800-FDA-1088.

No boxed warning on the USPI retrieved for this draft. That is not “no risk” — interactions, pregnancy, and allergy are the main labelled safety story for a five-day PEP course.

Research team (source-only)

Names and roles as they appear on primary sources — not a clinic directory.

• Shionogi Inc. — NDA 220442 applicant / manufactured for (Florham Park, NJ on USPI). US information / AE: 1-800-849-9707.
• Shionogi & Co., Ltd. (Osaka) — parent company; Japan marketing authorisation holder for Xocova.
• Shionogi B.V. — EMA CHMP applicant for Zokovea.
• Janet Ehlert, BSN, MBA, RAC-US — Executive Director, Regulatory Affairs, Global Development Projects, Shionogi Inc.; addressee on the NDA approval letter (corporate regulatory contact, not a treating clinic).
• Wendy Carter, DO — Director (Acting), Office of Infectious Diseases, CDER — signed the 29 May 2026 approval letter.
• Saebyeol Jang — FDA Regulatory Project Manager named on the approval letter (agency contact, not a patient hotline).
• Frederick Hayden, MD and co-authors (including Masaharu Shinkai and the SCORPIO-PEP Study Team) — NEJM 2026 efficacy publication authors; Hayden is also quoted in Shionogi’s US approval release (University of Virginia affiliation in that release) — publication credit, not a prescription desk.
• Hokkaido University — joint research origin of ensitrelvir with Shionogi (sponsor materials).

Site-level clinic phone numbers are not listed here — ask your own clinician after a known exposure.

How to talk to a doctor

Bring the brand for your country, the INN, the NCT number, and the label that will prescribe:

1. “I was exposed to someone with COVID-19 on [date/time]. The FDA labelled Xocova (ensitrelvir) on 29 May 2026 for post-exposure prophylaxis in people 12 and older. Can we start within 72 hours if I still qualify?”
2. “The labelled US dose is 375 mg (three tablets) on Day 1, then 125 mg daily for four more days. Is that right for me?”
3. “Here is my full medication and supplement list. Please check interactions — Xocova is a strong CYP3A inhibitor and some drugs are contraindicated.”
4. “SCORPIO-PEP (NCT05897541) showed about a 67% lower risk of symptomatic COVID-19 by Day 10 vs placebo (2.9% vs 9.0% in the mITT). Does that apply to my situation?”
5. “I do / do not need a pregnancy test first. I understand contraception / no breastfeeding for 2 weeks after the last dose if that applies to me.”
6. “I understand this is PEP, not a US treatment for COVID-19 I already have — and it is not a vaccine.”
7. If outside the US / Japan: “Has this country’s regulator authorised it yet? For the EU, is Zokovea past the EC decision? I will not import a foreign pack on my own.”
8. “Prior authorization — what does my plan need, and how fast can the pharmacy fill a 7-tablet blister?”

Canada zoom: not confirmed

There is no retrieved Health Canada Notice of Compliance or DIN for Xocova / ensitrelvir on the sources used for this draft. US FDA approval and Japan labelling do not create a Canadian Product Monograph. Do not treat cross-border mail-order as the care plan. Ask a Canadian clinician what legal options exist after a household COVID-19 exposure while waiting for any future Canadian decision.

Bottom line

Xocova (ensitrelvir) is an oral 3CL / main-protease antiviral. The FDA labelled it 29 May 2026 for COVID-19 post-exposure prophylaxis in people ≥12, started within 72 hours of contact — not for treating COVID-19 in the United States. Dose is 375 mg on Day 1 then 125 mg daily through Day 5. Japan labels Xocova for both treatment and PEP (PEP ≥12 from 23 Mar 2026). In the EU, the name is Zokovea: CHMP positive 23 Jul 2026, EC marketing authorisation not confirmed. SCORPIO-PEP (NCT05897541) showed a 67% relative reduction in symptomatic COVID-19 by Day 10 vs placebo. Main safety watch: drug interactions, pregnancy, and allergy. The practical door is a fast clinician visit after exposure and a labelled prescription where authorised — completed Phase 3 is not an enrolment path. Authorized is not funded.

---

Primary sources

1. FDA Prescribing Information PDF, NDA 220442, label 220442Orig1s000lbl.pdf, Revised 05/2026 — https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220442Orig1s000lbl.pdf
2. FDA NDA approval letter, NDA 220442, signed Wendy Carter, DO, 29 May 2026 — https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220442Orig1s000ltr.pdf
3. FDA Novel Drug Approvals for 2026 — Xocova / ensitrelvir / 5/29/2026 (row 19) — https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
4. ClinicalTrials.gov SCORPIO-PEP NCT05897541 — https://clinicaltrials.gov/study/NCT05897541
5. Hayden FG, Shinkai M, et al. Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts. N Engl J Med. 2026;394(19):1905-1915. doi:10.1056/NEJMoa2509306 (PMID 42127390) — journal; use USPI for US prescribing numbers
6. EMA — Zokovea medicine page (CHMP positive opinion; pending EC decision) — https://www.ema.europa.eu/en/medicines/human/EPAR/zokovea
7. EMA CHMP summary of positive opinion for Zokovea, 23 Jul 2026 — https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-zokovea_en.pdf
8. EMA — Meeting highlights from the CHMP 20–23 July 2026 (Zokovea : pending EC decision) — https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-20-23-july-2026
9. Shionogi — FDA approval of XOCOVA for PEP (company release, 1 Jun 2026; cites USPI) — https://www.shionogi.com/us/en/news/2026/06/shionogi-announces-fda-approval-of-xocova-ensitrelvir-the-first-and-only-oral-option-to-help-prevent-covid-19-following-exposure.html
10. Shionogi — Japan supplemental approval for PEP (23 Mar 2026) — https://www.shionogi.com/global/en/news/2026/03/20260323_1.html
11. Shionogi — Japan pediatric treatment dosage approval (19 Jun 2026) — https://www.shionogi.com/global/en/news/2026/06/20260619.html
12. Shionogi US patient site — How to get XOCOVA — https://www.xocova.com/how-to-get-xocova/