Brincidofovir

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

• TEMBEXA is an orthopoxvirus nucleotide analog DNA polymerase inhibitor and is indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates. ( 1.1 ) Limitations of Use: • TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease.

• None. None.contraindicated

• Testing: Before initiation and during treatment with TEMBEXA perform hepatic laboratory testing and pregnancy testing. ( 2.1 ) • See full prescribing information for details on important administration instructions. ( 2.2 ) • Adult and pediatric patients weighing 48 kg or above: 200 mg (two 100 mg tablets or 20 mL oral suspension for patients who cannot swallow tablets) once weekly for 2 doses. ( 2.3 ) • Adult and pediatric patients weighing 10 kg to less than 48 kg: 4 mg/kg oral suspension once weekly for 2 doses. ( 2.3 ) • Pediatric patients weighing less than 10 kg: 6 mg/kg oral suspension once weekly for 2 doses. ( 2.3 ) 2.1 Testing Before Initiating and During Treatment with TEMBEXA Perform hepatic laboratory testing in all patients before starting TEMBEXA and while receiving TEMBEXA, as clinically appropriate [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.7 )] . Perform pregnancy testing before initiation of TEMBEXA in individuals of childbearing potential to inform risk [see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8.3 )] . 2.2 Important Administration Instructions Avoid direct contact with broken or crushed tablets or oral suspension. If contact with skin or mucous membranes occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with water [see Warnings and Precautions ( 5.6 )] . TEMBEXA Tablets TEMBEXA tablets can be taken on an empty stomach or with a low-fat meal (approximately 400 calories, with approximately 25% of calories from fat) [see Clinical Pharmacology ( 12.3 )] .

• Elevations in Hepatic Transaminases and Bilirubin: May cause increases in serum transaminases (ALT or AST) and serum bilirubin. Monitor liver laboratory parameters before and during treatment. ( 5.2 ) • Diarrhea and Other Gastrointestinal Adverse Events: Diarrhea and additional gastrointestinal adverse events including nausea, vomiting, and abdominal pain may occur. Monitor patients, provide supportive care, and if necessary, do not give the second and final dose of TEMBEXA. ( 5.3 ) • Coadministration with Related Products: TEMBEXA should not be coadministered with intravenous cidofovir. ( 5.4 ) • Embryo-fetal Toxicity: May cause fetal harm. Advise individuals of childbearing potential of the potential risk to the fetus and to use effective contraception. ( 5.5 , 8.1 , 8.3 ) • Carcinogenicity: TEMBEXA should be considered a potential human carcinogen. Do not crush or divide TEMBEXA tablets. ( 5.6 , 13.1 ) • Male Infertility: Based on testicular toxicity in animal studies, TEMBEXA may irreversibly impair fertility in individuals of reproductive potential. ( 5.7 , 8.3 ) 5.1 Increased Risk for Mortality When Used for Longer Duration TEMBEXA is not indicated for use in diseases other than human smallpox. An increase in mortality was observed in a randomized, placebo-controlled Phase 3 trial when TEMBEXA was evaluated in another disease. An increased risk in mortality is possible if TEMBEXA is used for a duration longer than at the recommended dosage on Days 1 and 8 [see Indications and Usage ( 1.2 ) and Dosage and Administration ( 2.3 )] .

The following clinically significant adverse reactions are described elsewhere in the labeling: • Elevations in hepatic transaminases and bilirubin [see Warnings and Precautions ( 5.2 )] • Diarrhea and other GI adverse events [see Warnings and Precautions ( 5.3 )] Common adverse reactions (occurring in at least 2% of TEMBEXA-treated subjects) were diarrhea, nausea, vomiting, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Emergent BioDefense Operations Lansing LLC at 1-877-246-8472 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 TEMBEXA has not been studied in patients with smallpox disease. The safety of TEMBEXA was evaluated in 392 adult subjects aged 18 to 77 years in Phase 2 and 3 randomized, placebo-controlled clinical trials. Of the subjects who received a 200 mg total weekly dose of TEMBEXA, 54% were male, 85% were White, 7% were Black/African American, 6% were Asian, and 10% were Hispanic or Latino. Twenty-one percent of subjects in the studies were age 65 or older. Of these 392 subjects, 85% received a 200 mg total weekly dose of TEMBEXA for at least 2 weeks.

• Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, TEMBEXA may cause fetal harm when administered to pregnant individuals. Use an alternative therapy to treat smallpox during pregnancy, if feasible. There are no available data on the use of brincidofovir 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, oral administration of brincidofovir to pregnant rats and rabbits during the period of organogenesis resulted in embryotoxicity and structural malformations. These effects occurred in animals at systemic exposures less than the expected human exposure based on the recommended dose of TEMBEXA ( see Data ). The estimated background risk of major birth defects 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% to 4% and 15% to 20%, respectively.

Metabolism

Brincidofovir is a prodrug that is converted intracellularly to cidofovir, which is subsequently phosphorylated to cidofovir diphosphate, the active antiviral moiety, following oral administration. Brincidofovir plasma exposures do not accumulate after repeat doses.

There is no clinical experience with overdosage of TEMBEXA. In the event of an overdose, monitor patients for adverse effects and provide appropriate supportive care.

• Jun 4, 2021NDANDA214460Emergent Biodefense
• Jun 4, 2021NDANDA214461Emergent Biodefense

1. 1Off Label Use3929%
2. 2Acute Kidney Injury2720%
3. 3Adenovirus Infection1511%
4. 4Drug Ineffective1410%
5. 5Drug Resistance128.8%
6. 6Graft Versus Host Disease In Gastrointestinal Tract118.1%
7. 7Hypotension118.1%
8. 8Immune Reconstitution Inflammatory Syndrome118.1%
9. 9Multiple Organ Dysfunction Syndrome118.1%
10. 10Condition Aggravated96.6%
11. 11Cytomegalovirus Infection96.6%
12. 12Pancytopenia96.6%
13. 13Respiratory Failure96.6%
14. 14Acute Graft Versus Host Disease In Skin85.9%
15. 15Diarrhoea85.9%

The 10 most recently updated of 24 ClinicalTrials.gov registrations naming Brincidofovir as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study
  Recruiting · Phase 2 · Interventional · 24 enrolled · National Institute of Neurological Disorders and Stroke (NINDS)
  NCT07511049updated 2026-06-11
• A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT
  Recruiting · Phase 3 · Interventional · 180 enrolled · SymBio Pharmaceuticals
  NCT07387367updated 2026-04-27
• A Phase 1b/2 Study of Intravenous Brincidofovir in Patients With Relapsed or Refractory Lymphoma and Relapsed or Refractory Extranodal Natural Killer/T-cell Lymphoma
  Suspended · Phase 1 · Phase 2 · Interventional · 43 enrolled · SymBio Pharmaceuticals
  NCT06761677updated 2026-02-05
• Study Evaluating the Bioequivalence of Brincidofovir Form H and Form II Tablets in Healthy Adults
  Completed · Phase 1 · Interventional · 44 enrolled · Emergent BioSolutions
  NCT05935917updated 2025-01-15
• Study to Confirm of the Safety and Tolerability of Brincidofovir in Subjects With BK Virus Infection (Viremia) After Kidney Transplantation
  Terminated · Phase 2 · Interventional · 1 enrolled · SymBio Pharmaceuticals
  NCT05511779updated 2024-12-04
• A Phase 2a Study of IV BCV in Subjects With Adenovirus Infection
  Recruiting · Phase 2 · Interventional · 52 enrolled · SymBio Pharmaceuticals
  NCT04706923updated 2024-06-21
• Safety and Pharmacokinetics of CMX001 in Impaired Hepatic Function and Healthy Subjects
  Completed · Phase 1 · Interventional · 25 enrolled · Jazz Pharmaceuticals
  NCT05391724updated 2022-05-26
• Expanded Access Protocol to Provide Brincidofovir for the Treatment of Serious Adenovirus Infection or Disease
  No longer available · Expanded access · Jazz Pharmaceuticals
  NCT02596997updated 2022-03-14
• CMX001 in Post-transplant Patients With BK Virus Viruria
  Completed · Phase 1 · Phase 2 · Interventional · 29 enrolled · Jazz Pharmaceuticals
  NCT00793598updated 2021-08-16
• Study to Assess the Safety and Efficacy of Brincidofovir in Treatment of Early Versus Late Adenovirus Infection
  Completed · Phase 3 · Interventional · 201 enrolled · Jazz Pharmaceuticals
  NCT02087306updated 2021-08-13

Frequently asked questions

How does Brincidofovir work?

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

What is Brincidofovir used for?

According to FDA labeling, Brincidofovir carries indications including: TEMBEXA is an orthopoxvirus nucleotide analog DNA polymerase inhibitor and is indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates. ( 1.1 ) Limitations of Use: • TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Brincidofovir?

Brincidofovir is classified as Nucleosides and nucleotides excl. reverse transcriptase inhibitors, DNA Polymerase Inhibitors.

What are the brand names for Brincidofovir?

Brincidofovir is marketed under brand names including Tembexa.

What are the contraindications for Brincidofovir?

Brincidofovir labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.