Brivaracetam

Brivaracetam comes as a tablet and solution (liquid) to take by mouth. It is usually taken with or without food twice daily. Take brivaracetam at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

Swallow the tablets whole; do not split, chew, or crush them.

If you are taking the liquid, do not use a household spoon to measure your dose. Use the measuring spoon or cup that came with the medication or use a spoon made especially for measuring medication.

Your doctor may increase or decrease your dose depending on how well the medication works for you, and the side effects you experience. Be sure to tell your doctor how you are feeling during your treatment with brivaracetam.

Brivaracetam may be habit forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor.

Brivaracetam may help control your condition but will not cure it. Continue to take brivaracetam even if you feel well. Do not stop taking brivaracetam without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you suddenly stop taking brivaracetam, your seizures may become worse. Your doctor will probably decrease your dose gradually.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with brivaracetam and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.

Pregnancy

No adequate and well-controlled studies in pregnant women

In animal studies, brivaracetam produced evidence of developmental toxicity at plasma exposures greater than clinical exposure

Pregnancy Registry

• Recommend that pregnant patients enroll in the North American Antiepileptic Drug Pregnancy Registry; this can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves
• Information on the registry can also be found at the Web site http://www.aedpregnancyregistry.org/

Lactation

Unknown if distributed in human breast milk

Studies in rats have shown excretion in milk

Because many drugs are excreted into human milk, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Brivaracetam falls into category C. There are no adequate and well-controlled studies in pregnant women. However, bBased on animal data, brivaracetam may cause harm to your unborn baby. It is not known if brivaracetam will harm your unborn baby. 

Tell your healthcare provider right away if you become pregnant while taking brivaracetam. You and your healthcare provider will have to decide if you should take brivaracetam while you are pregnant.

If you become pregnant while taking brivaracetam, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of brivaracetam and other antiepileptic medicines during pregnancy. 

Brivaracetam is an anti-epileptic drug, also called an anticonvulsant.

Brivaracetam is used together with other medicines to treat partial onset seizures in people with epilepsy who are at least 16 years old.

Brivaracetam may also be used for purposes not listed in this medication guide.

Some people have thoughts about suicide while taking seizure medicine. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• rifampin; or

• other seizure medications, especially carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), or phenytoin (Dilantin).

Your dosages of other medicines may be different while you are taking brivaracetam. Do not change your doses or medication schedule without your doctor's advice.

This list is not complete. Other drugs may interact with brivaracetam, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Seizure Disorders

Management (in combination with other anticonvulsants) of partial-onset seizures in adults and adolescents ≥16 years of age.1 2 3 4 24 25

Contraindications

• Known hypersensitivity to brivaracetam or any ingredients in the formulation.1 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

General Precautions

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).1 10 11 12 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.1 10 11 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1 10

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 Anxiety, agitation, hostility, insomnia, and mania may be precursors to emerging suicidality.1 10

Balance risk of suicidality with risk of untreated illness.1 10 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.1 12 If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.1 12 (See Advice to Patients.)

Adverse neurologic effects may occur; dizziness, disturbances in gait or coordination (e.g., vertigo, nystagmus, balance disorder, ataxia, abnormal coordination), somnolence, and fatigue reported.1 Generally observed early in treatment but can occur at any time during therapy.1

Monitor patients for adverse neurologic effects and advise patients not to drive or operate machinery until the effects of the drug are known.1 (See Advice to Patients.)

Adverse psychiatric effects may occur, including nonpsychotic symptoms (e.g., irritability, anxiety, nervousness, aggression, belligerence, anger, agitation, restlessness, depression, tearfulness, apathy, altered mood, labile affect, psychomotor hyperactivity, abnormal behavior, adjustment disorder) and psychotic symptoms (e.g., psychotic disorder, hallucination, paranoia, acute psychosis).1

Monitor patients for adverse psychiatric effects.1

Hypersensitivity reactions (i.e., bronchospasm, angioedema) reported; discontinue immediately if patients experience a hypersensitivity reaction.1

Abrupt withdrawal of anticonvulsants may increase seizure frequency and risk of status epilepticus.1 In general, gradual withdrawal is recommended; however, manufacturer states that prompt withdrawal may be considered if discontinuance of brivaracetam is necessary because of serious adverse effects.1

Brivaracetam is subject to control as a schedule V (C-V) drug.1 23 Sedative and euphoric effects reported less frequently than with alprazolam (a schedule IV drug) at recommended therapeutic doses; however, such effects were similar to those produced by alprazolam when brivaracetam administered at supratherapeutic doses.1

No evidence of physical dependence or withdrawal symptoms.1

Specific Populations

Category C.1

North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or .1

Not known whether distributed into human milk; distributes into milk in rats.1 Discontinue nursing or the drug.1

Safety and efficacy not established in pediatric patients <16 years of age.1

Insufficient experience in geriatric patients ≥65 years of age to establish efficacy.1 Consider greater frequency of decreased hepatic, renal, and/or cardiac function and other concomitant disease and drug therapy when selecting dosage in geriatric patients.1 (See Elimination: Special Populations, under Pharmacokinetics.)

Systemic exposure of brivaracetam is increased in patients with hepatic impairment.1 20 1 (See Hepatic Impairment under Dosage and Administration, and also see Absorption: Special Populations, under Pharmacokinetics.)

Pharmacokinetics not substantially affected by renal impairment.1 (See Renal Impairment under Dosage and Administration, and also see Absorption: Special Populations, under Pharmacokinetics.)

Not studied in patients undergoing dialysis; use not recommended.1

Increased plasma concentrations in patients who are poor metabolizers of CYP2C19.1 (See Poor CYP2C19 Metabolizers under Dosage and Administration, and also see Absorption: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Somnolence/sedation,1 3 4 dizziness,1 3 4 fatigue,1 2 3 4 nausea/vomiting,1 3 diarrhea,3 headache,2 insomnia,3 nasopharyngitis.3

(briv a RA se tam)

In patients with hepatic cirrhosis, Child-Pugh classes A, B, and C, showed 50%, 57%, and 59% increases in brivaracetam exposure, respectively.

Injection: Administer IV over 2 to 15 minutes; may administer undiluted or diluted with NS, LR, or D5W.

Oral solution: Administer with or without food. Use a calibrated measuring device to measure (household teaspoon or tablespoon is not an adequate measuring device). May also be administered using a nasogastric tube or gastronomy tube.

Tablets: Administer with or without food. Swallow tablets whole with liquid; do not chew or crush.

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Oral solution: Do not freeze. Discard any oral solution remaining after 5 months of first opening the bottle.

Injection: Do not freeze. May store solution diluted in NS, LR, or D5W for ≤4 hours at room temperature in polyvinyl chloride (PVC) bags. Discard any unused portion.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with a full glass of water. You may take brivaracetam with or without food.

Measure the oral solution (liquid) with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, or break a brivaracetam tablet. Swallow it whole.

Do not stop using brivaracetam suddenly, even if you feel fine. Stopping suddenly may cause serious medical problems or increased seizures. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture and heat.

Do not allow the liquid medicine to freeze. Throw away any unused brivaracetam liquid if it has been longer than 5 months since you first opened the bottle.

Keep track of the amount of medicine used from each new bottle. Brivaracetam may be a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

For all stages of hepatic impairment, the recommended starting dose is 25 mg 2 times a day (50 mg per day) and the recommended maximum dosage is 75 mg 2 times a day (150 mg per day)