Brand Name
Tembexa
Generic Name
Brincidofovir
View Brand Information FDA approval date: April 18, 2022
Form: Tablet, Suspension
What is Tembexa (Brincidofovir)?
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.
Approved To Treat
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Brand Information
Tembexa (Brincidofovir)
WARNING: INCREASED RISK FOR MORTALITY WHEN USED FOR LONGER DURATION
An increased incidence of mortality was seen in TEMBEXA-treated subjects compared to placebo-treated subjects in a 24-week clinical trial when TEMBEXA was evaluated in another disease
1DOSAGE FORMS AND STRENGTHS
Tablets
TEMBEXA tablets are blue, modified-oval shape, film-coated tablets debossed with BCV on one side and 100 on the other side. Each tablet contains 100 mg of brincidofovir.
Oral Suspension
TEMBEXA oral suspension is an aqueous based, preserved white to off-white opaque, lemon lime flavored suspension containing 10 mg/mL of brincidofovir.
2CONTRAINDICATIONS
None.
3ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Elevations in hepatic transaminases and bilirubin
- Diarrhea and other GI adverse events
3.1Clinical 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 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.
Common Adverse Reactions
The most common adverse reactions (adverse events assessed as causally related by the investigator) experienced in the first 2 weeks of dosing with TEMBEXA were diarrhea and nausea. Adverse reactions that occurred in at least 2% of subjects in the TEMBEXA treatment group are shown in
Adverse Reactions Leading to Discontinuation of TEMBEXA
Fifteen subjects (4%) had their treatment with TEMBEXA discontinued due to adverse reactions. One subject had two adverse reactions; the other subjects had one reaction each. These adverse reactions were:
- Diarrhea (n=9)
- Nausea (n=3)
- Vomiting (n=1)
- Enteritis (n=1)
- ALT increased (n=1)
- Dyspepsia (n=1)
These adverse reactions were mild (Grade 1, n=1), moderate (Grade 2, n=7) or severe (Grade 3, n=8) in severity and resolved upon discontinuation of TEMBEXA.
Less Common Adverse Reactions
Clinically significant adverse reactions that were reported in <2% of subjects (and also occurred in 2 or more subjects) exposed to TEMBEXA and at rates higher than in subjects who received placebo are listed below:
- General and administration site: peripheral edema
- Metabolism and nutrition: decreased appetite
- Musculoskeletal and connective tissue: muscular weakness
- Nervous system: dysgeusia
- Skin and subcutaneous tissue: rash (includes rash, maculo-papular rash, pruritic rash)
Selected treatment-emergent laboratory values occurring during the first 2 weeks of treatment with TEMBEXA are presented in
Adverse Reactions in Pediatric Subjects
In 23 pediatric subjects aged 7 months to 17 years who received TEMBEXA in a randomized, placebo-controlled clinical trial, the adverse reactions and laboratory abnormalities observed with TEMBEXA were similar to adults
4OVERDOSAGE
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.
5DESCRIPTION
TEMBEXA (brincidofovir) tablets, 100 mg, for oral use are immediate release film-coated tablets containing the following inactive ingredients: Colloidal Silicon Dioxide, Crospovidone, FD&C Blue #1/Brilliant Blue FCF Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake, Magnesium Stearate, Mannitol, Microcrystalline Cellulose, Polyethylene Glycol, Polyvinyl Alcohol, Purified Water, Silicified Microcrystalline Cellulose, Talc and Titanium Dioxide.
TEMBEXA (brincidofovir) oral suspension, 10 mg/mL, is an aqueous based, preserved, orally dosed suspension. The inactive ingredients are: Citric Acid Anhydrous, Lemon Lime Flavor, Microcrystalline Cellulose and Carboxymethyl Cellulose Sodium, Purified Water, Simethicone 30% Emulsion, Sodium Benzoate, Sucralose, Trisodium Citrate Anhydrous, and Xanthan Gum.
Brincidofovir is an orthopoxvirus nucleotide analog DNA polymerase inhibitor and a lipid conjugate of the nucleotide analog cidofovir and is indicated for the treatment of human smallpox disease.
The full chemical name is: Phosphonic acid,
The molecular formula of brincidofovir is C
The structure is shown below.
Brincidofovir is a white to off-white crystalline powder as a free acid and practically insoluble in water.
6CLINICAL STUDIES
Overview
The effectiveness of TEMBEXA 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 efficacy of the drug is not ethical. Therefore, the effectiveness of TEMBEXA for treatment of smallpox disease was established based on results of adequate and well-controlled animal efficacy studies of rabbits and mice infected with species specific non-variola orthopoxviruses. Survival rates observed in the animal studies may not be predictive of survival rates in clinical practice.
Study Design
Efficacy studies were conducted in the rabbitpox model (New Zealand White rabbits infected with rabbitpox virus) and the mousepox model (BALB/c mice infected with ectromelia virus).
The primary efficacy endpoint for these studies was survival. Survival was monitored for 4 to 5 times the mean time to death for untreated animals in each model.
In the rabbitpox study, rabbits were lethally challenged intradermally with 600 plaque-forming units of rabbitpox virus; brincidofovir was administered orally with a regimen of 20/5/5 mg/kg (administered every 48 hours for 3 doses) with brincidofovir treatment initiated on 3, 4, 5, or 6 days post-challenge. The timing of brincidofovir dosing was intended to assess efficacy when treatment is initiated after animals have developed clinical signs of disease, specifically fever in rabbits. Clinical signs of disease were evident in some animals at Day 3 post-challenge but were evident in all animals by Day 4 post-challenge.
In the mousepox study, mice were lethally challenged intranasally with 200 plaque-forming units of ectromelia virus; brincidofovir was administered orally with a regimen of 20/5/5 mg/kg or 10/5/5 mg/kg (administered every 48 hours for 3 doses) with brincidofovir treatment initiated on 4, 5, 6, or 7 days post-challenge. All animals had detectable viremia by 4 days post-challenge. In the mousepox model, a clinically evident sign of disease could not be identified to use as a trigger to initiate treatment.
Study Results
Treatment with brincidofovir resulted in statistically significant improvement in survival relative to placebo, except when the 10/5/5 mg/kg regimen was initiated at Day 6 post-challenge in the mousepox study (
7HOW SUPPLIED/STORAGE AND HANDLING
TEMBEXA Tablets:
Tablets are blue, modified-oval shape, film-coated tablets debossed with BCV on one side and 100 on the other side and packaged into blister cards. Each blister cavity contains one film-coated tablet containing 100 mg of brincidofovir. The blister card is placed in a child-resistant wallet. Each wallet (NDC 64678-010-01) contains one (1) blister card with a total of 4 film-coated tablets.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F)
Do not divide, break, or crush the tablets. Avoid direct contact with broken or crushed tablets. If contact with skin or mucous membranes occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with water
TEMBEXA Oral Suspension:
Aqueous based, preserved white to off-white opaque, lemon lime flavored suspension containing 10 mg/mL of brincidofovir packaged into a high density polyethylene bottle with a low density polyethylene press-in bottle adaptor (PIBA) inserted into the bottle. The bottle is capped by a child-resistant closure. Each bottle is filled to deliver 65 mL (NDC 64678-012-01) and 45 mL (NDC 64678-012-03) of brincidofovir.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F)
Avoid direct contact with oral suspension. If contact with skin or mucous membranes occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with water
8PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (
Efficacy Based on Animal Models Alone
Inform patients that the efficacy of TEMBEXA is based solely on efficacy studies demonstrating a survival benefit in animals and that the effectiveness of TEMBEXA has not been tested in humans with smallpox disease
Elevations of Hepatic Transaminases and Bilirubin
Inform patients of the need for liver monitoring before treatment with TEMBEXA and during treatment if signs or symptoms of liver injury occur. Advise patients to report symptoms that may indicate liver injury, including right upper abdominal discomfort, dark urine, or jaundice
Diarrhea and Other Gastrointestinal Adverse Events
Inform patients of the risk of diarrhea and other GI adverse events (nausea, vomiting, and abdominal pain) while taking TEMBEXA. Advise patients to inform their healthcare provider if they develop severe diarrhea or other severe GI symptoms
Important Drug Interactions
Inform patients that TEMBEXA may interact with some drugs. If concomitant use of OATP1B1 and 1B3 inhibitors with TEMBEXA is necessary, advise patients to postpone the dosing of these medicines for at least 3 hours after TEMBEXA administration
Embryo-fetal Toxicity
Advise pregnant individuals and individuals of childbearing potential of the risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy. Advise individuals of childbearing potential to use effective contraception during treatment with TEMBEXA and for at least 2 months after the last dose. Due to animal findings of testicular toxicity, advise individuals of reproductive potential with partners of childbearing potential to use condoms during treatment with TEMBEXA and for at least 4 months after the last dose
Infertility
Advise individuals of reproductive potential that treatment with TEMBEXA may deplete sperm, resulting in infertility
Lactation
Instruct individuals with smallpox not to breastfeed their infant because of the risk of passing variola virus to the breastfed infant
Important Administration Instructions for Oral Suspension
Instruct patients or caregivers to use an oral dosing syringe to correctly measure the prescribed amount of medication. Oral dosing syringes may be obtained from the pharmacy. Refer to instructions above for administration of TEMBEXA oral suspension through enteral tubes
Advise patients taking the oral suspension to discard unused portion after completion of the 2 prescribed doses.
Handling
Advise patients not to divide, break, or crush tablets. Advise patients to avoid direct contact with broken or crushed tablets and oral suspension. If contact with skin or mucous membranes occurs, inform patients to wash thoroughly with soap and water, and rinse eyes thoroughly with water
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9Patient Package Insert
This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 10/2022
10PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
For oral use
Rx Only
TEMBEXA
brincidofovir
Oral Suspension, 10 mg/mL
Contents: 65 mL
NDC 64678-012-01
For oral use
Rx Only
TEMBEXA
brincidofovir
Oral Suspension, 10 mg/mL
Contents: 65 mL
11PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
For oral use
Rx Only
TEMBEXA
brincidofovir
Oral Suspension, 10 mg/mL
Contents: 45 mL
See Full
NDC 64678-012-03
For oral use
Rx Only
TEMBEXA
brincidofovir
Oral Suspension, 10 mg/mL
Contents: 45 ml
12PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
For oral use
Rx Only
TEMBEXA
brincidofovir
Oral Suspension, 10 mg/mL
Contents: 45 mL
See Full
For Strategic National
NDC 64678-012-04
For oral use
Rx Only
TEMBEXA
brincidofovir
Oral Suspension, 10 mg/mL
Contents: 45 mL