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BRIVARACETAM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Brivaracetam is an anticonvulsant agent used to treat partial-onset seizures. The exact mechanism for brivaracetam's anticonvulsive effects is unknown; however, it has a high and selective binding affinity for synaptic vesicle protein 2A in the brain.

Specific Substances

    1) Brivaracetamum
    2) UCB-34714
    3) CAS 357336-20-0

Available Forms Sources

    A) FORMS
    1) Brivaracetam is available as 10 mg, 25 mg, 50 mg, 75 mg, 100 mg tablets, 10 mg/mL oral solution, and 50 mg/5 mL single-dose vials for injection (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    B) USES
    1) Brivaracetam is indicated for the adjunctive treatment of partial-onset seizures in patients with epilepsy (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Brivaracetam is indicated for the adjunctive treatment of partial-onset seizures in patients with epilepsy.
    B) PHARMACOLOGY: The exact mechanism for brivaracetam's anticonvulsive effects is unknown; however, it has a high and selective binding affinity for synaptic vesicle protein 2A in the brain.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) MOST COMMON (at least 5%): Somnolence/sedation, dizziness, fatigue, and nausea/vomiting. OTHER EFFECTS: Cerebellar coordination and balance disturbances (ie, ataxia, balance disorder, abnormal coordination, and nystagmus), hypersensitivity reaction (including bronchospasm and angioedema), irritability, anxiety, nervousness, aggression, belligerence, anger, agitation, restlessness, depression, depressed mood, tearfulness, apathy, altered mood, mood swings, affect lability, psychomotor hyperactivity, abnormal behavior, adjustment disorder, irritability, psychiatric adverse effects (ie, psychotic disorder with hallucination, paranoia, acute psychosis, and psychotic behavior), and suicidal thoughts.
    E) WITH POISONING/EXPOSURE
    1) In general, overdose effects are anticipated to be an extension of adverse effects following therapeutic administration. A patient developed somnolence and dizziness after receiving a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose). Vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia have also been reported following brivaracetam overdose.
    0.2.20) REPRODUCTIVE
    A) There are not sufficient data on the use of brivaracetam in pregnant women to determine the potential risk for humans. Administer brivaracetam to a pregnant woman only if the potential benefit outweighs the potential risk to the fetus. It is not known if brivaracetam is excreted into human breast milk. In animal studies, brivaracetam was excreted in breast milk. Discontinue brivaracetam therapy or discontinue breastfeeding taking into account the importance of the drug to the mother.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, human carcinogenicity studies with brivaracetam have not been conducted.

Laboratory Monitoring

    A) Monitor vital signs and mental status following significant overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. Bradycardia usually does not require treatment. Treat bradycardia with atropine; if unresponsive, use beta adrenergic agonists (eg, isoproterenol). Consider temporary pacemaker insertion. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended because of the potential for somnolence and rarely, seizures.
    2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    D) AIRWAY MANAGEMENT
    1) Endotracheal intubation may be necessary if significant CNS depression develops.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) No information is available regarding the use of hemodialysis in removing brivaracetam; however, hemodialysis is not expected to increase brivaracetam clearance because less than 10% of the drug is excreted in the urine.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) When managing a suspected overdose, the treating physician should be cognizant of the possibility of multi-drug involvement.
    I) PHARMACOKINETICS
    1) Tmax, oral tablets: 1 hour (range, 0.25 to 3 hours). Bioavailability, oral: Rapidly and almost completely absorbed. Protein binding, plasma proteins: 20% or less. Vd: 0.5 L/kg. Excretion: Greater than 95% of a brivaracetam dose, including metabolites, is excreted in urine within 72 hours and less than 10% is excreted as unchanged drug in urine. Elimination half-life: 9 hours.
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause neurologic disorders.

Range Of Toxicity

    A) TOXICITY: A specific minimum toxic dose has not been established for brivaracetam. A patient developed somnolence and dizziness after taking a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose). Vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia have also been reported following brivaracetam overdose.
    B) THERAPEUTIC DOSE: ADULTS AND CHILDREN 16 YEARS OR OLDER: 25 mg twice daily up to 100 mg twice daily.

Clinical Effects

Summary Of Exposure

    A) USES: Brivaracetam is indicated for the adjunctive treatment of partial-onset seizures in patients with epilepsy.
    B) PHARMACOLOGY: The exact mechanism for brivaracetam's anticonvulsive effects is unknown; however, it has a high and selective binding affinity for synaptic vesicle protein 2A in the brain.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) MOST COMMON (at least 5%): Somnolence/sedation, dizziness, fatigue, and nausea/vomiting. OTHER EFFECTS: Cerebellar coordination and balance disturbances (ie, ataxia, balance disorder, abnormal coordination, and nystagmus), hypersensitivity reaction (including bronchospasm and angioedema), irritability, anxiety, nervousness, aggression, belligerence, anger, agitation, restlessness, depression, depressed mood, tearfulness, apathy, altered mood, mood swings, affect lability, psychomotor hyperactivity, abnormal behavior, adjustment disorder, irritability, psychiatric adverse effects (ie, psychotic disorder with hallucination, paranoia, acute psychosis, and psychotic behavior), and suicidal thoughts.
    E) WITH POISONING/EXPOSURE
    1) In general, overdose effects are anticipated to be an extension of adverse effects following therapeutic administration. A patient developed somnolence and dizziness after receiving a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose). Vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia have also been reported following brivaracetam overdose.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) DIPLOPIA has been reported following brivaracetam overdose (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia has been reported following brivaracetam overdose (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) The following effects have been reported during clinical trials in patients receiving brivaracetam: irritability, anxiety, nervousness, aggression, belligerence, anger, agitation, restlessness, depression, depressed mood, tearfulness, apathy, altered mood, mood swings, affect lability, psychomotor hyperactivity, abnormal behavior, and adjustment disorder (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    B) DROWSY
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, somnolence and sedation developed in 16% of patients with partial-onset seizures (n=803) receiving brivaracetam (50 mg/kg, 100 mg/kg, and 200 mg/kg oral and IV; median length of treatment:12 weeks) as compared with 8% of patients receiving placebo (n=459) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A patient developed somnolence and dizziness after taking a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016)
    C) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, dizziness developed in 12% of patients with partial-onset seizures (n=803) receiving brivaracetam (50 mg/kg, 100 mg/kg, and 200 mg/kg oral and IV; median length of treatment:12 weeks) as compared with 7% of patients receiving placebo (n=459) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A patient developed somnolence and dizziness after taking a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016)
    D) CEREBELLAR ATAXIA
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, cerebellar coordination and balance disturbances (ie, ataxia, balance disorder, abnormal coordination, and nystagmus) developed in 3% of patients with partial-onset seizures (n=803) receiving brivaracetam (50 mg/kg, 100 mg/kg, and 200 mg/kg oral and IV; median length of treatment:12 weeks) as compared with 1% of patients receiving placebo (n=459) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    E) FEELING IRRITABLE
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, irritability developed in 3% of patients with partial-onset seizures (n=803) receiving brivaracetam (50 mg/kg, 100 mg/kg, and 200 mg/kg oral and IV; median length of treatment:12 weeks) as compared with 1% of patients receiving placebo (n=459) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    F) FATIGUE
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, fatigue developed in 9% of patients with partial-onset seizures (n=803) receiving brivaracetam (50 mg/kg, 100 mg/kg, and 200 mg/kg oral and IV; median length of treatment:12 weeks) as compared with 4% of patients receiving placebo (n=459). Risk is greatest early in treatment and may occur any time (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    2) WITH POISONING/EXPOSURE
    a) Fatigue has been reported following brivaracetam overdose (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    G) ANXIETY
    1) WITH POISONING/EXPOSURE
    a) Anxiety has been reported following brivaracetam overdose (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, nausea/vomiting developed in 5% of patients with partial-onset seizures (n=803) receiving brivaracetam (50 mg/kg, 100 mg/kg, and 200 mg/kg oral and IV; median length of treatment: 12 weeks) as compared with 3% of patients receiving placebo (n=459) (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    2) WITH POISONING/EXPOSURE
    a) Nausea has been reported following brivaracetam overdose (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) In pooled placebo-controlled adjunctive therapy studies, hypersensitivity reaction (including bronchospasm and angioedema) occurred in patients with partial-onset seizures receiving brivaracetam (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Reproductive

    3.20.1) SUMMARY
    A) There are not sufficient data on the use of brivaracetam in pregnant women to determine the potential risk for humans. Administer brivaracetam to a pregnant woman only if the potential benefit outweighs the potential risk to the fetus. It is not known if brivaracetam is excreted into human breast milk. In animal studies, brivaracetam was excreted in breast milk. Discontinue brivaracetam therapy or discontinue breastfeeding taking into account the importance of the drug to the mother.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) In animal studies, brivaracetam did not produce embryofetal toxicity at doses of up to 30 times the recommended human exposure (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    3.20.3) EFFECTS IN PREGNANCY
    A) RISK SUMMARY
    1) There are not sufficient data on the use of brivaracetam in pregnant women to determine the potential risk for humans. Administer brivaracetam to a pregnant woman only if the potential benefit outweighs the potential risk to the fetus (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    B) PREGNANCY REGISTRY
    1) Healthcare providers may enroll patients with brivaracetam exposure during pregnancy in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334. Information on the registry may also be obtained from the website http://www.aedpregnancyregistry.org/ (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    C) ANIMAL STUDIES
    1) In animal studies, embryofetal mortality and decreased body weight occurred in animals at doses about 4 times the human exposure. Decreased growth, neurobehavioral changes, and delayed sexual maturation in females occurred with doses about 7 times human exposure administered throughout pregnancy and lactation (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is not known if brivaracetam is excreted into human breast milk. In animal studies, brivaracetam was excreted in breast milk. Discontinue brivaracetam therapy or discontinue breastfeeding taking into account the importance of the drug to the mother(Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, human carcinogenicity studies with brivaracetam have not been conducted.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, human carcinogenicity studies with brivaracetam have not been conducted.
    3.21.4) ANIMAL STUDIES
    A) HEPATOCELLULAR ADENOMA AND CARCINOMA
    1) An increased incidence of liver tumors (hepatocellular adenoma and carcinoma) has been reported in animals that were administered oral brivaracetam doses 550 mg/kg/day and 700 mg/kg/day for 104 weeks. Brivaracetam 400 mg/kg (plasma exposures [AUC] about equal to those in humans at the maximum recommended dose of 200 mg/day) was also administered to animals but did not increase the incidence of liver tumors (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).
    B) THYMUS TUMORS
    1) Increased incidence of thymus tumors (benign thymoma) has been reported in animals that were administered oral brivaracetam doses 700 mg/kg/day for 104 weeks. Brivaracetam 450 mg/kg (plasma exposures [AUC] about 9 times those in humans at the maximum recommended dose of 200 mg/day) was also administered to animals but did not increase the incidence of thymus tumors (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Genotoxicity

    A) Genotoxicity tests in in vitro (Ames, mouse lymphoma, and CHO chromosomal aberration) and in vivo (rat bone marrow micronucleus) assays were negative for brivaracetam (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status following significant overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Monitor vital signs and mental status following significant overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is not recommended because of the potential for somnolence and rarely, seizures.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. Bradycardia usually does not require treatment. Treat bradycardia with atropine; if unresponsive, use beta adrenergic agonists (eg, isoproterenol). Consider temporary pacemaker insertion. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) MONITORING OF PATIENT
    1) Monitor vital signs and mental status following significant overdose.
    2) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) BRADYCARDIA
    1) SUMMARY: Usually does not require treatment. Treat bradycardia with atropine; if unresponsive, use beta adrenergic agonists (eg, isoproterenol). Consider temporary pacemaker insertion.
    2) ATROPINE/DOSE
    a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
    b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.
    1) There is no minimum dose (de Caen et al, 2015).
    2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).
    3) ISOPROTERENOL INDICATIONS
    a) Used for temporary control of hemodynamically significant bradycardia in a patient with a pulse; generally other modalities (atropine, dopamine, epinephrine, dobutamine, pacing) should be used first because of the tendency to develop ischemia and dysrhythmias with isoproterenol (Neumar et al, 2010).
    b) ADULT DOSE: Infuse 2 micrograms per minute, gradually titrating to 10 micrograms per minute as needed to desired response (Neumar et al, 2010).
    c) CAUTION: Decrease infusion rate or discontinue infusion if ventricular dysrhythmias develop(Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    d) PEDIATRIC DOSE: Not well studied. Initial infusion of 0.1 mcg/kg/min titrated as needed, usual range is 0.1 mcg/kg/min to 1 mcg/kg/min (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

Enhanced Elimination

    A) HEMODIALYSIS
    1) No information is available regarding the use of hemodialysis in removing brivaracetam; however, hemodialysis is not expected to increase brivaracetam clearance because less than 10% of the drug is excreted in the urine (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Range Of Toxicity

Summary

    A) TOXICITY: A specific minimum toxic dose has not been established for brivaracetam. A patient developed somnolence and dizziness after taking a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose). Vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia have also been reported following brivaracetam overdose.
    B) THERAPEUTIC DOSE: ADULTS AND CHILDREN 16 YEARS OR OLDER: 25 mg twice daily up to 100 mg twice daily.

Therapeutic Dose

    7.2.1) ADULT
    A) 25 mg twice daily up to 100 mg twice daily (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016)
    7.2.2) PEDIATRIC
    A) 16 YEARS OR OLDER: 25 mg twice daily up to 100 mg twice daily (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016)

Maximum Tolerated Exposure

    A) A patient developed somnolence and dizziness after taking a single brivaracetam dose of 1400 mg (14 times the highest recommended single dose). Vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia have also been reported following brivaracetam overdose (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) The exact mechanism for brivaracetam's anticonvulsive effects is unknown; however, it has a high and selective binding affinity for synaptic vesicle protein 2A in the brain (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Physicochemical

Physical Characteristics

    A) A white to off white crystalline powder, soluble in water and ethanol (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

Molecular Weight

    A) 212.29 (Prod Info BRIVIACT(R) oral tablets oral solution intravenous injection solution, 2016).

References

General Bibliography

    1) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    2) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    3) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    4) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    5) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    6) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    7) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    8) Neumar RW , Otto CW , Link MS , et al: Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S729-S767.
    9) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    10) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    11) Product Information: BRIVIACT(R) oral tablets oral solution intravenous injection solution, brivaracetam oral tablets oral solution intravenous injection solution. UCB, Inc (per manufacturer), Smyrna, GA, 2016.
    12) Product Information: Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, isoproterenol HCl intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection. Hospira, Inc. (per FDA), Lake Forest, IL, 2013.
    13) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    14) de Caen AR, Berg MD, Chameides L, et al: Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S526-S542.