Tecovirimat

Tecovirimat is an antiviral drug against variola (smallpox) virus [see Microbiology ( 12.4 )] .

• TPOXX is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein and is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 3 kg. ( 1.1 ) Limitations of Use: The effectiveness of TPOXX for treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible, and inducing smallpox disease in humans to study the drug’s efficacy is not ethical.

• TPOXX Capsules: None. TPOXX Injection: The excipient hydroxypropyl-β-cyclodextrin is eliminated through glomerular filtration.contraindicated

Pediatric and Adult Patients weighing 40 kg or more ( 2.3 ) (Oral Dosing): 40 kg to less than 120 kg: 600 mg of TPOXX every 12 hours for 14 days 120 kg or more: 600 mg of TPOXX every 8 hours for 14 days Pediatrics and adult patients weighing 13 kg or more and those who cannot swallow capsules ( 2.3 ) (Oral Dosing): TPOXX Capsules can be administered by carefully opening the number of capsule noted below and mixing and administering the entire contents in 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., apple sauce, yogurt): 13 kg to less than 25 kg: 200 mg (1 Capsule) of TPOXX every 12 hours for 14 days 25 kg to less than 40 kg: 400 mg (2 Capsules) of TPOXX every 12 hours for 14 days 40 kg to less than 120 kg: 600 mg (3 Capsules) of TPOXX every 12 hours for 14 days 120 kg or more: 600 mg (3 capsules) every 8 hours for 14 days Patients weighing 3 kg and above ( 2.5 ) (Intravenous Dosing): 3 kg to less than 35 kg: 6 mg/kg every 12 hours by intravenous infusion over 6 hours for up to 14 days 35 kg to less than 120 kg: 200 mg every 12 hours by intravenous infusion over 6 hours for up to 14 days 120 kg and above: 300 mg every 12 hours by intravenous infusion over 6 hours for up to 14 days Pediatric patients weighing 13 kg or more should be switched to TPOXX Capsules to complete the 14-day treatment course as soon as oral therapy can be tolerated. Administration Instruction for TPOXX Capsules: Take within 30 minutes after a full meal containing moderate or high fat.

Hypoglycemia: Co-administration with repaglinide may cause hypoglycemia. Monitor blood glucose and monitor for hypoglycemic symptoms during co-administration. ( 5.1 ) 5.1 Hypoglycemia When Co-Administered with Repaglinide Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia. Monitor blood glucose and monitor for hypoglycemic symptoms when administering TPOXX with repaglinide [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . In a drug interaction study, 10 of 30 healthy subjects experienced mild (6 subjects) or moderate (4 subjects) hypoglycemia following co-administration of repaglinide (2 mg) and TPOXX. Symptoms resolved in all subjects after intake of food and/or oral glucose. 5.2 Risks of Hydroxypropyl-β-Cyclodextrin Excipient for Patients with Renal Insufficiency and Pediatric Patients < 2 Years of Age Patients with renal insufficiency TPOXX Injection: In healthy patients and in patients with mild to severe renal insufficiency, the majority of an 8 g dose of hydroxypropyl-β-cyclodextrin (per 200 mg tecovirimat/20 mL solution) is eliminated in the urine. It is known that clearance of hydroxypropyl-β-cyclodextrin is reduced in patients with mild, moderate, and severe renal impairment, resulting in higher exposure to hydroxypropyl-β-cyclodextrin; in these patients, half-life values are increased over normal values by approximately two-, four-, and six-fold, respectively. In these patients, successive infusions may result in accumulation of hydroxypropyl-β-cyclodextrin until steady state is reached.

The most common adverse reactions are: TPOXX Capsules (incidence ≥ 2%): headache, nausea, abdominal pain, and vomiting. ( 6.1 ) TPOXX Injection (incidence ≥ 4%): administration site reactions and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact SIGA Technologies Inc. at 1-888-899-3472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 safety of TPOXX has not been studied in patients with smallpox disease. TPOXX Clinical Trial (Oral Administration) The safety of TPOXX was evaluated in 359 healthy adult subjects ages 18-79 years in a Phase 3 clinical trial. Of the subjects who received at least one 600 mg dose of TPOXX, 59% were female, 69% were White, 28% were Black/African American, 1% were Asian, and 12% were Hispanic or Latino. Ten percent of the subjects who participated in the study were age 65 or older. Of these 359 subjects, 336 subjects received at least 23 of 28 doses of 600 mg TPOXX in a twice daily (every 12 hours) regimen for 14 days. Most Frequently Reported Adverse Reactions The most frequently reported adverse reactions were headache and nausea. Adverse reactions that occurred in at least 2% of subjects in the TPOXX treatment group are shown in Table 3 .

Lactation: Breastfeeding is not recommended in patients with smallpox. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no available data on the use of tecovirimat in pregnant individuals to evaluate for a drug-associated risk of major birth defects, miscarriage, and other adverse maternal and fetal outcomes. In animal reproduction studies, no embryofetal developmental toxicity was observed in mice during the period of organogenesis at tecovirimat exposures (area under the curve [AUC]) up to 23 times higher than human exposure at the recommended human dose (RHD). In rabbits, no embryofetal developmental toxicity was observed during organogenesis at tecovirimat exposures (AUC) less than human exposures at the RHD. In a mouse pre-/post-natal development study, no toxicities were observed at maternal tecovirimat exposures up to 24 times higher than human exposure at the RHD (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown, and the estimated background risk of miscarriage for the indicated population is higher than the general population. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Metabolism

At the recommended oral dosage of 600 mg every 12 hours administered in healthy adults weighing less than 120 kg, the mean steady-state values of tecovirimat AUC 0-24hr , C max , and C tau/trough are 29816 hr•ng/mL (n, CV: 43, 34%), 2159 ng/mL (n, CV: 46, 32%), and 845 ng/mL (n, CV: 45, 47%), respectively.

There is no clinical experience with overdosage of TPOXX. In case of overdosage, monitor patients for any signs or symptoms of adverse effects. Hemodialysis will not significantly remove TPOXX in overdosed patients.

• Jul 13, 2018NDANDA208627Siga Technologies
• May 18, 2022NDANDA214518Siga Technologies

1. 1Drug Resistance1918%
2. 2Headache1414%
3. 3Nausea1414%
4. 4Fatigue1212%
5. 5Diarrhoea109.7%
6. 6Acute Kidney Injury65.8%
7. 7Alanine Aminotransferase Increased65.8%
8. 8Decreased Appetite54.9%
9. 9Off Label Use54.9%
10. 10Abdominal Pain43.9%
11. 11Dizziness43.9%
12. 12Drug Ineffective43.9%
13. 13Skin Lesion43.9%
14. 14Vomiting43.9%
15. 15Abdominal Discomfort32.9%

The 10 most recently updated of 17 ClinicalTrials.gov registrations naming Tecovirimat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Assessment of the Efficacy and Safety of Tecovirimat in Patients With Monkeypox Virus Disease
  Active not recruiting · Phase 3 · Interventional · 480 enrolled · ANRS, Emerging Infectious Diseases
  NCT05597735updated 2026-05-26
• Study to Assess the Safety and Immunogenicity of TPOXX® When Administered Orally for 28 Days With JYNNEOS
  Active not recruiting · Phase 2 · Interventional · 100 enrolled · SIGA Technologies
  NCT04957485updated 2026-04-02
• Tecovirimat in Non-hospitalized Patients With Monkeypox
  Suspended · Phase 3 · Interventional · 120 enrolled · Marina Klein
  NCT05534165updated 2026-03-04
• Study of Tecovirimat for Human Mpox Virus
  Terminated · Phase 3 · Interventional · 719 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT05534984updated 2026-02-10
• Tecovirimat for Treatment of Monkeypox Virus
  Completed · Phase 2 · Interventional · 597 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT05559099updated 2025-10-09
• Tecovirimat for Treatment of Monkeypox Virus - Study Extension Providing Standard of Care Only
  Completed · Observational · 328 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT06721585updated 2025-09-04
• European Trial Into Mpox Infection
  Recruiting · Phase 4 · Interventional · 150 enrolled · Miquel Ekkelenkamp
  NCT06156566updated 2025-03-28
• Tecovirimat Intravenous Treatment for Orthopox Virus Exposure
  No longer available · Expanded access · U.S. Army Medical Research and Development Command
  NCT05380752updated 2025-03-10
• Tecovirimat (ST-246) Treatment for Orthopox Virus Exposure
  Available · Expanded access · U.S. Army Medical Research and Development Command
  NCT02080767updated 2025-03-06
• Drug-drug Interaction Study of TPOXX When Co-administered With Phosphate Binders
  Completed · Phase 4 · Interventional · 44 enrolled · SIGA Technologies
  NCT04485039updated 2024-12-27

Frequently asked questions

How does Tecovirimat work?

Tecovirimat is an antiviral drug against variola (smallpox) virus [see Microbiology ( 12.4 )] .

What is Tecovirimat used for?

According to FDA labeling, Tecovirimat carries indications including: TPOXX is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein and is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 3 kg. ( 1.1 ) Limitations of Use: The effectiveness of TPOXX for treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible, and inducing smallpox disease in humans to study the drug’s efficacy is not ethical.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tecovirimat?

Tecovirimat is classified as Other antivirals, Orthopoxvirus VP37 Envelope Wrapping Protein Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2C19 Inhibitors, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 3A Inducers, Viral Envelope Wrapping Protein Inhibitors.

What are the brand names for Tecovirimat?

Tecovirimat is marketed under brand names including Tpoxx.

What are the contraindications for Tecovirimat?

Tecovirimat labeling lists contraindications including: TPOXX Capsules: None. TPOXX Injection: The excipient hydroxypropyl-β-cyclodextrin is eliminated through glomerular filtration.. Always consult the full prescribing information and a clinician.