BRINCIDOFOVIR: 94 Adverse Event Reports & Safety Profile
Boost Your Natural Energy & Metabolism
Mitolyn — 6 exotic plants to unlock your body's fat-burning power. 90-day guarantee.
Route: ORAL · Manufacturer: Emergent BioDefense Operations Lansing LLC · FDA Application: 214460 · HUMAN PRESCRIPTION DRUG · FDA Label: Available
Patent Expires: Oct 10, 2034 · First Report: 20150614 · Latest Report: 20250831
What Are the Most Common BRINCIDOFOVIR Side Effects?
All BRINCIDOFOVIR Side Effects by Frequency
| Side Effect | Reports | % of Total | Deaths | Hosp. |
|---|---|---|---|---|
| Off label use | 27 | 28.7% | 8 | 0 |
| Acute kidney injury | 18 | 19.2% | 12 | 9 |
| Graft versus host disease in gastrointestinal tract | 10 | 10.6% | 9 | 1 |
| Hypotension | 9 | 9.6% | 7 | 5 |
| Pancytopenia | 9 | 9.6% | 6 | 0 |
| Adenovirus infection | 8 | 8.5% | 3 | 3 |
| Diarrhoea | 8 | 8.5% | 4 | 6 |
| Drug resistance | 8 | 8.5% | 7 | 2 |
| Multiple organ dysfunction syndrome | 8 | 8.5% | 8 | 4 |
| Blood bilirubin increased | 7 | 7.5% | 5 | 0 |
| Hepatic failure | 7 | 7.5% | 5 | 1 |
| Cardiac arrest | 6 | 6.4% | 6 | 1 |
| Condition aggravated | 6 | 6.4% | 3 | 1 |
| Drug ineffective | 6 | 6.4% | 3 | 2 |
| Scedosporium infection | 6 | 6.4% | 4 | 0 |
| Hyperbilirubinaemia | 5 | 5.3% | 4 | 5 |
| Immune reconstitution inflammatory syndrome | 5 | 5.3% | 2 | 5 |
| Nephropathy toxic | 5 | 5.3% | 5 | 0 |
| Renal impairment | 5 | 5.3% | 3 | 1 |
| Respiratory failure | 5 | 5.3% | 5 | 0 |
Who Reports BRINCIDOFOVIR Side Effects? Age & Gender Data
Gender: 36.2% female, 63.8% male. Average age: 31.5 years. Most reports from: US. View detailed demographics →
Is BRINCIDOFOVIR Getting Safer? Reports by Year
| Year | Reports | Deaths | Hosp. |
|---|---|---|---|
| 2015 | 1 | 0 | 1 |
| 2016 | 10 | 6 | 6 |
| 2017 | 11 | 5 | 5 |
| 2018 | 8 | 5 | 0 |
| 2019 | 8 | 3 | 0 |
| 2022 | 4 | 2 | 0 |
| 2023 | 2 | 2 | 1 |
| 2024 | 1 | 0 | 0 |
| 2025 | 3 | 0 | 2 |
What Is BRINCIDOFOVIR Used For?
| Indication | Reports |
|---|---|
| Adenovirus infection | 36 |
| Monkeypox | 21 |
| Acquired immunodeficiency syndrome | 5 |
Official FDA Label for BRINCIDOFOVIR
Official prescribing information from the FDA-approved drug label.
Drug Description
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, P -[[(1 S )-2-(4-amino-2-oxo-1(2 H )-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]-, mono[3-(hexadecyloxy)propyl] ester. The molecular formula of brincidofovir is C 27 H 52 N 3 O 7 P and the relative molecular mass is 561.70. The structure is shown below. Brincidofovir is a white to off-white crystalline powder as a free acid and practically insoluble in water. Brincidofovir structural formula
FDA Approved Uses (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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 , 5.2 )]</span> . 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 <span class="opacity-50 text-xs">[see Clinical Studies ( 14 )]</span> . TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals.
Dosage & Administration
AND ADMINISTRATION
- 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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.7 )]</span> . Perform pregnancy testing before initiation of TEMBEXA in individuals of childbearing potential to inform risk <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8.3 )]</span> .
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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.6 )]</span> .
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 )] . Swallow TEMBEXA tablets whole. Do not crush or divide TEMBEXA tablets.
Tembexa
Oral Suspension Take TEMBEXA oral suspension on an empty stomach [see Clinical Pharmacology ( 12.3 )] . Shake oral suspension before use. Use an appropriate oral dosing syringe to correctly measure the total prescribed dose [see Patient Counseling Information ( 17 )] . Discard unused portion after completion of 2 prescribed doses. For patients who cannot swallow, TEMBEXA oral suspension can be administered by enteral tube (naso-gastric or gastrostomy tubes) as follows:
- Draw up prescribed dose with a calibrated catheter-tip syringe, and utilize this syringe to administer the dose via the enteral tube.
- Refill the catheter-tip syringe with 3 mL of water, shake, and administer the contents via the enteral tube.
- Flush with water before and after enteral administration.
2.3 Recommended Dosage The recommended dosage of TEMBEXA in pediatric and adult patients is displayed in Table 1 <span class="opacity-50 text-xs">[see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )]</span> .
Table
1: Recommended Dosage in Pediatric and Adult Patients Patient’s Weight (kg)
Tembexa
Oral Suspension (10 mg/mL)
Tembexa
Tablet (100 mg) Less than 10 kg 6 mg/kg once weekly for 2 doses (on Days 1 and 8) N/A 10 kg to less than 48 kg 4 mg/kg once weekly for 2 doses (on Days 1 and 8) N/A 48 kg and above 200 mg (20 mL) once weekly for 2 doses (on Days 1 and 8) 200 mg (two 100 mg tablets) once weekly for 2 doses (on Days 1 and 8)
Contraindications
None. None. ( 4 )
Known Adverse Reactions
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 )] .
FDA Boxed Warning
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 [see Warnings and Precautions ( 5.1 )] . WARNING: INCREASED RISK FOR MORTALITY WHEN USED FOR LONGER DURATION See full prescribing information for complete boxed warning. 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 [see Warnings and Precautions ( 5.1 )] .
Warnings
AND PRECAUTIONS
- 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 <span class="opacity-50 text-xs">[see Indications and Usage ( 1.2 ) and Dosage and Administration ( 2.3 )]</span> .
Study
301 (CMX001-301) evaluated TEMBEXA versus placebo for the prevention of cytomegalovirus infection. A total of 303 subjects received TEMBEXA (100 mg twice weekly) and 149 subjects received matching placebo for up to 14 weeks. The primary endpoint was evaluated at Week 24. All-cause mortality at Week 24 was 16% in the TEMBEXA group compared to 10% in the placebo group. Safety and effectiveness of TEMBEXA have not been established for diseases other than human smallpox disease.
5.2 Elevations in Hepatic Transaminases and Bilirubin Elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin have been observed, including cases of concurrent increases in ALT and bilirubin. During the first 2 weeks of TEMBEXA therapy in 392 subjects, ALT elevations >3x the upper limit of normal were reported in 7% of subjects and bilirubin elevations >2x the upper limit of normal were reported in 2% of subjects; these elevations in hepatic laboratory tests were generally reversible and did not require discontinuation of TEMBEXA <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ) and Nonclinical Toxicology ( 13.2 )]</span> . Severe hepatobiliary adverse events including hyperbilirubinemia, acute hepatitis, hepatic steatosis, and venoocclusive liver disease have been reported in less than 1% of subjects. Perform hepatic laboratory testing in all patients before starting TEMBEXA and while receiving TEMBEXA, as clinically appropriate. Monitor patients who develop abnormal hepatic laboratory tests during TEMBEXA therapy for the development of more severe hepatic injury. Consider discontinuing TEMBEXA if ALT levels remain persistently >10x the upper limit of normal. Do not give the second and final dose of TEMBEXA on Day 8 if ALT elevation is accompanied by clinical signs and symptoms of liver inflammation or increasing direct bilirubin, alkaline phosphatase, or International Normalized Ratio (INR) <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ) and Drug Interactions ( 7.1 )]</span> .
5.3 Diarrhea and Other Gastrointestinal Adverse Events During the first 2 weeks of TEMBEXA therapy in 392 subjects, a composite term of diarrhea (all grade, all cause) occurred in 40% of TEMBEXA-treated subjects compared with 25% of subjects in the placebo control group. Treatment with TEMBEXA was discontinued in 5% of subjects for diarrhea (composite term) compared with 1% in the placebo control group. Additional gastrointestinal (GI) adverse events included nausea, vomiting, and abdominal pain; some of these adverse events required discontinuation of TEMBEXA <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ) and Drug Interactions ( 7.1 ) and Nonclinical Toxicology ( 13.2 )]</span> . Monitor patients for GI adverse events including diarrhea and dehydration, provide supportive care, and if necessary, do not give the second and final dose of TEMBEXA.
5.4 Coadministration with Related Products TEMBEXA should not be co-administered with intravenous cidofovir. Brincidofovir, a lipid-linked derivative of cidofovir, is intracellularly converted to cidofovir <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .
5.5 Embryo-fetal Toxicity Based on findings from animal reproduction studies, TEMBEXA may cause fetal harm when administered to pregnant individuals. TEMBEXA administration to pregnant rats and rabbits resulted in embryotoxicity, decreased embryo-fetal survival and/or structural malformations. These effects occurred in animals at systemic exposures less than the expected human exposure based on the recommended dose of TEMBEXA. Use an alternative therapy to treat smallpox during pregnancy, if feasible. Perform pregnancy testing in individuals of childbearing potential before initiation of TEMBEXA. Advise individuals of childbearing potential to avoid becoming pregnant and to use effective contraception during treatment with TEMBEXA and for at least 2 months after the last dose. 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 <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 , 8.3 )]</span> .
5.6 Carcinogenicity TEMBEXA is considered a potential human carcinogen. Mammary adenocarcinomas and squamous cell carcinomas occurred in rats at systemic exposures less than the expected human exposure based on the recommended dose of TEMBEXA <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . Do not crush or divide TEMBEXA tablets. 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 <span class="opacity-50 text-xs">[see How Supplied/Storage and Handling ( 16 )]</span> .
5.7 Male Infertility Based on testicular toxicity in animal studies, TEMBEXA may irreversibly impair fertility in individuals of reproductive potential <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.3 ) and Nonclinical Toxicology ( 13.1 )]</span> .
Drug Interactions
INTERACTIONS Concomitant use with OATP1B1 and 1B3 inhibitors increase TEMBEXA exposure which may increase TEMBEXA-associated adverse reactions. Consider alternative medication that are not OATP1B1 or 1B3 inhibitors. If concomitant use is necessary, increase monitoring for adverse reactions associated with TEMBEXA and postpone the dosing of OATP1B1 or 1B3 inhibitors at least 3 hours after TEMBEXA administration. ( 7.1 )