Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

BRIVIACT (NDA-205836)

(BRIVARACETAM)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

08/28/2025 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Serious Dermatologic Reactions

Newly added subsection:

Serious dermatologic reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with BRIVIACT. Time to onset of the serious dermatologic reaction ranged from 3 to 45 days after BRIVIACT initiation in reported cases. BRIVIACT should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest a serious dermatologic reaction, use of BRIVIACT should not be resumed and alternative therapy should be considered.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Serious Dermatologic Reactions [see Warnings and Precautions (5.5)]

6.2 Postmarketing Experience

Newly added subsection:

The following adverse reactions have been identified during post approval use of BRIVIACT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and Subcutaneous Tissue Disorders: Serious dermatologic reactions (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis) [see Warnings and Precautions (5.5)]

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What are the possible side effects of BRIVIACT?

BRIVIACT may cause serious side effects, including:

…

Serious allergic reactions. Stop taking BRIVIACT and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:
- swelling of your face, mouth, lips, gums, tongue, throat, or neck
- trouble breathing
Serious skin rashes. BRIVIACT may cause a severe rash with blisters and peeling skin. This may occur around the mouth, nose, eyes, and genitals or over much of the body. A mild rash may become a serious reaction and may cause death. Call your healthcare provider right away if you have a rash, skin blisters, sores in the mouth, or hives. Do not stop taking BRIVIACT without first talking to your healthcare provider.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Serious Dermatologic Reactions

Advise patients of the early signs and symptoms of serious dermatologic adverse reactions and to report any occurrence immediately to a healthcare provider [see Warnings and Precautions (5.5)].

…

05/17/2023 (SUPPL-14)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions underlined)

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as BRIVIACT, during pregnancy. Encourage patients who are taking BRIVIACT during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.

Risk Summary

Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series are insufficient to identify a risk of major birth defects, miscarriage or other maternal or fetal outcomes associated with BRIVIACT use during pregnancy. In animal studies, brivaracetam produced evidence of developmental toxicity (increased embryofetal mortality and decreased fetal body weights in rabbits; decreased growth, delayed sexual maturation, and long-term neurobehavioral changes in rat offspring) at maternal plasma exposures greater than clinical exposures [see Data].

The background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

8.2 Lactation

(Additions and/or revisions underlined)

Risk Summary

Data from published literature indicate that brivaracetam is present in human milk. There is insufficient information on the effects of brivaracetam on the breastfed infant or on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BRIVIACT and any potential adverse effects on the breastfed infant from BRIVIACT or from the underlying maternal condition.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Lactation

Counsel patients that brivaracetam, the active ingredient in BRIVIACT, is present in breast milk. Instruct patients to discuss with their healthcare provider if they are breastfeeding or intend to breastfeed [see Use in Specific Populations (8.2)].

08/27/2021 (SUPPL-9)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

Table 4: Adverse Reactions in Pooled Placebo-Controlled Adjunctive Therapy Studies in Adult Patients with Partial- Onset Seizures (BRIVIACT 50 mg/day, 100 mg/day, and 200 mg/day)

Pediatric Patients

Safety of BRIVIACT was evaluated in two open-label, safety and pharmacokinetic trials in pediatric patients 2 months to less than 16 years of age. Across studies of pediatric patients with partial onset seizures, 186 patients received BRIVIACT oral solution or tablet, of whom 123 received BRIVIACT for at least 12 months. Adverse reactions reported in clinical studies of pediatric patients were generally similar to those seen in adult patients. Decreased appetite was also observed in these pediatric trials.

Adverse Reactions with BRIVIACT Injection

Adverse reactions with BRIVIACT injection administered to adults and pediatric patients 2 months to 16 years of age were generally similar to those observed with BRIVIACT tablets. Other adverse events that occurred in at least 3% of adult patients who received BRIVIACT injection included dysgeusia, euphoric mood, feeling drunk, and infusion site pain.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

Safety and effectiveness of BRIVIACT have been established in pediatric patients 1 month to less than 16 years of age. Use of BRIVIACT in these age groups is supported by evidence from adequate and well-controlled studies of BRIVIACT in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in pediatric patients 2 months to less than 16 years of age [see Dosage and Administration (2.1), Warnings and Precautions (5.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)].

Safety and effectiveness in pediatric patients below the age of 1 month have not been established …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is BRIVIACT?

BRIVIACT is a prescription medicine used to treat partial-onset seizures in people 1 month of age and older.

It is not known if BRIVIACT is safe and effective in children younger than 1 month of age.

What are the possible side effects of BRIVIACT?

BRIVIACT may cause serious side effects, including:

Side effects of BRIVIACT in children 1 month to less than 16 years of age are similar to those seen in adults.

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide). The Medication Guide accompanies the product and can also be accessed on www.briviact.com or by calling 1-844-599-2273.

05/10/2018 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Psychiatric Adverse Reactions

Addition of the following:

… Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

Table 3 lists adverse reactions for BRIVIACT …

Table 3: Adverse Reactions in Pooled Placebo-Controlled Adjunctive Therapy Studies in Adult Patients with Partial- Onset Seizures (BRIVIACT 50 mg/day, 100 mg/day, and 200 mg/day)

Addition of the following:

Pediatric Patients (4 Years to less than 16 Years of Age)

Safety of BRIVIACT was evaluated in two open-label, safety and pharmacokinetic trials in pediatric patients 4 years to less than 16 years of age. Across studies of pediatric patients with partial onset seizures, 149 patients 4 years to less than 16 years of age received BRIVIACT oral solution or tablet, of whom 107 received BRIVIACT for at least 12 months. Adverse reactions reported in clinical studies of pediatric patients 4 years to less than 16 years of age were generally similar to those seen in adult patients.

Adverse Reactions with BRIVIACT Injection

Additions and/or revisions underlined:

Adverse reactions with BRIVIACT injection administered to adult patients were generally similar to those observed with BRIVIACT tablet ….

8 Use in Specific Populations

8.4 Pediatric Use

Addition of the following:

Safety and effectiveness of BRIVIACT tablets and oral solution have been established in pediatric patients 4 years to less than 16 years of age. Use of BRIVIACT in these age groups is supported by evidence from adequate and well-controlled studies of BRIVIACT in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 149 pediatric patients 4 years to less than 16 years of age.

Safety of BRIVIACT injection in pediatric patients has not been established.

Additions and/or revisions underlined:

Safety and effectiveness in pediatric patients below the age of 4 years have not been established.

Juvenile Animal Toxicity Data

… Oral administration (0, 150, 300, or 600 mg/kg/day) to rats during the neonatal and juvenile periods of development (approximately equivalent to neonatal through adolescent development in humans) resulted in increased mortality … Therefore, a no-effect dose was not established; the lowest dose tested in juvenile rats was associated with plasma exposures (AUC) approximately 2 times those in children and adolescents at the recommended maintenance dose.

The overall no-effect dose (30 mg/kg/day) and the no-effect dose for adverse effects on developmental parameters (100 mg/kg/day) were associated with plasma exposures approximately equal to and 4 times, respectively, those in children and adolescents at the recommended maintenance dose.

09/14/2017 (SUPPL-3)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion, as below:

Pregnancy Exposure Registry

Risk Summary

There are no adequate data on the developmental risks associated with use of BRIVIACT in pregnant women. In animal studies, brivaracetam produced evidence of developmental toxicity (increased embryofetal mortality and decreased fetal body weights in rabbits; decreased growth, delayed sexual maturation, and long-term neurobehavioral changes in rat offspring) at maternal plasma exposures greater than clinical exposures

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. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data

Animal Data

Oral administration of brivaracetam (0, 150, 300, or 600 mg/kg/day) to pregnant rats during the period of organogenesis did not produce any significant maternal or embryofetal toxicity. The highest dose tested was associated with maternal plasma exposures (AUC) approximately 30 times exposures in humans at the maximum recommended dose (MRD) of 200 mg/day.

Oral administration of brivaracetam (0, 30, 60, 120, or 240 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal mortality and decreased fetal body weights at the highest dose tested, which was also maternally toxic. The highest no-effect dose (120 mg/kg/day) was associated with maternal plasma exposures approximately 4 times human exposures at the MRD.

When brivaracetam (0, 150, 300, or 600 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, decreased growth, delayed sexual maturation (female), and long-term neurobehavioral changes were observed in the offspring at the highest dose. The highest no-effect dose (300 mg/kg/day) was associated with maternal plasma exposures approximately 7 times human exposures at the MRD.

Brivaracetam was shown to readily cross the placenta in pregnant rats after a single oral (5 mg/kg) dose of 14C-brivaracetam. From 1 hour post dose, radioactivity levels in fetuses, amniotic fluid, and placenta were similar to those measured in maternal blood.

8.2 Lactation

PLLR conversion; as below:

Risk Summary

No data are available regarding the presence of brivaracetam in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Studies in lactating rats have shown excretion of brivaracetam or metabolites in milk.

Data

Animal Data

Following a single oral (5 mg/kg) dose of 14C-brivaracetam to lactating rats, radioactivity was secreted in milk and rapidly reached levels similar to those in plasma.