Tembexa
Generic: BRINCIDOFOVIR
Basic Information
Manufacturer
Emergent BioDefense Operations Lansing LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
0784838e-00bd-4b14-9b7e-653b7fbb7eea
Indications & Usage
1 INDICATIONS AND USAGE 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.
( 1.2 ) • 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 drug’s efficacy is not ethical.
( 1.2 ) • TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals.
( 1.2 ) 1.1 Treatment of Human Smallpox Disease TEMBEXA ® is indicated for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.
1.2 Limitations of Use TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease [see Warnings and Precautions ( 5.1 , 5.2 )] .
The effectiveness of TEMBEXA for the 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 [see Clinical Studies ( 14 )] .
TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals.
( 1.1 ) Limitations of Use: • TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease.
( 1.2 ) • 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 drug’s efficacy is not ethical.
( 1.2 ) • TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals.
( 1.2 ) 1.1 Treatment of Human Smallpox Disease TEMBEXA ® is indicated for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.
1.2 Limitations of Use TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease [see Warnings and Precautions ( 5.1 , 5.2 )] .
The effectiveness of TEMBEXA for the 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 [see Clinical Studies ( 14 )] .
TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals.
Adverse Reactions
6 ADVERSE REACTIONS 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.
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 Table 2 .
Table 2: Adverse Reactions (All Grades) Reported in ≥2% of Subjects Note: Only adverse reactions with onset in the first 2 weeks of treatment are presented.
a.
Composite term includes: bowel movement irregularity, defecation urgency, diarrhea, fecal incontinence, and frequent bowel movements.
b.
Composite term includes: vomiting and retching.
c.
Composite term includes: abdominal discomfort, abdominal distention, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, and gastrointestinal pain.
Adverse Reaction TEMBEXA 200 mg N=392 % Placebo N=208 % Diarrhea a 8 3 Nausea 5 1 Vomiting b 4 1 Abdominal pain c 3 2 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 Table 3 .
Table 3: Frequencies of Selected Laboratory Abnormalities ULN = upper limit of normal a.
Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 toxicity grading criteria.
b.
ALT >10x ULN occurred in one subject in the TEMBEXA group and no subjects in the placebo group.
c.
No subjects reported AST >10x ULN.
Laboratory Parameter Abnormality a TEMBEXA 200 mg N=392 Placebo N=208 Alanine aminotransferase (ALT) b n 382 203 Grade 2 (>3 to 5x ULN), (%) 3 2 Grade 3 (>5 to 20x ULN), (%) 2 1 Grade 4 (>20x ULN), (%) 0 0 Aspartate aminotransferase (AST) c n 380 201 Grade 2 (>3 to 5x ULN), (%) 2 1 Grade 3 (>5 to 20x ULN), (%) 1 0 Grade 4 (>20x ULN), (%) 0 0 Total bilirubin n 382 203 Grade 2 (>1.5 to 3x ULN), (%) 3 2 Grade 3 (>3 to 10x ULN), (%) 1 <1 Grade 4 (>10x ULN), (%) 0 0 Serum creatinine n 383 205 Grade 2 (>1.5 to 3x ULN), (%) 4 4 Grade 3 (>3 to 6x ULN), (%) <1 0 Grade 4 (>6x ULN), (%) 0 0 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 [see Use in Specific Populations ( 8.4 )] .
( 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.
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 Table 2 .
Table 2: Adverse Reactions (All Grades) Reported in ≥2% of Subjects Note: Only adverse reactions with onset in the first 2 weeks of treatment are presented.
a.
Composite term includes: bowel movement irregularity, defecation urgency, diarrhea, fecal incontinence, and frequent bowel movements.
b.
Composite term includes: vomiting and retching.
c.
Composite term includes: abdominal discomfort, abdominal distention, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, and gastrointestinal pain.
Adverse Reaction TEMBEXA 200 mg N=392 % Placebo N=208 % Diarrhea a 8 3 Nausea 5 1 Vomiting b 4 1 Abdominal pain c 3 2 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 Table 3 .
Table 3: Frequencies of Selected Laboratory Abnormalities ULN = upper limit of normal a.
Frequencies are based on treatment-emergent laboratory abnormalities.
Graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 toxicity grading criteria.
b.
ALT >10x ULN occurred in one subject in the TEMBEXA group and no subjects in the placebo group.
c.
No subjects reported AST >10x ULN.
Laboratory Parameter Abnormality a TEMBEXA 200 mg N=392 Placebo N=208 Alanine aminotransferase (ALT) b n 382 203 Grade 2 (>3 to 5x ULN), (%) 3 2 Grade 3 (>5 to 20x ULN), (%) 2 1 Grade 4 (>20x ULN), (%) 0 0 Aspartate aminotransferase (AST) c n 380 201 Grade 2 (>3 to 5x ULN), (%) 2 1 Grade 3 (>5 to 20x ULN), (%) 1 0 Grade 4 (>20x ULN), (%) 0 0 Total bilirubin n 382 203 Grade 2 (>1.5 to 3x ULN), (%) 3 2 Grade 3 (>3 to 10x ULN), (%) 1 <1 Grade 4 (>10x ULN), (%) 0 0 Serum creatinine n 383 205 Grade 2 (>1.5 to 3x ULN), (%) 4 4 Grade 3 (>3 to 6x ULN), (%) <1 0 Grade 4 (>6x ULN), (%) 0 0 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 [see Use in Specific Populations ( 8.4 )] .