Briviact

Unless your doctor tells you otherwise, continue your normal diet.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

• sleepiness
• extreme tiredness
• dizziness
• trouble keeping your balance
• blurred or double vision
• slowed heartbeat
• nausea
• feeling anxious

Mechanism of Action

Exact mechanism unknown

Displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect

Absorption

Highly permeable and is rapidly and almost completely absorbed after PO administration

Peak plasma time: 1 hr (without food); slower absorption with a high-fat meal

Distribution

Protein bound: ≤20%

Vd: 0.5 L/kg

Metabolism

Primarily metabolized by hydrolysis of the amide moiety to form the corresponding carboxylic acid metabolite and is mediated by hepatic and extra-hepatic amidase

Secondarily metabolized by hydroxylation on the propyl side chain to form the hydroxy metabolite that is mediated primarily by CYP2C19

An additional hydroxy acid metabolite is created by hydrolysis of the amide moiety on the hydroxy metabolite or hydroxylation of the propyl side chain on the carboxylic acid metabolite (mainly by CYP2C9)

The 3 metabolites are not pharmacologically active

Elimination

Half-life: 9 hr

Excretion

• Urine (>95%); feces (<1%)
• <10% of the dose is excreted unchanged in the urine
• 34% of the dose is excreted as the carboxylic acid metabolite in urine

Pharmacogenomics

In human subjects possessing genetic variations in CYP2C19, production of the hydroxy metabolite is decreased 2-fold or 10-fold, while the blood level of brivaracetam itself is increased by 22% or 42%, respectively, in individuals with one or both mutated alleles

CYP2C19 poor metabolizers and patients using inhibitors of CYP2C19 may require dose reduction

Oral Administration

May take with or without food

Tablet

• Swallow whole; do not chew or crush

Oral solution

• Use a calibrated measuring device to measure and deliver the prescribed dose accurately
• No dilution is necessary
• May also be administered using an NT-tube or G-tube

IV Compatibilities

0.9% NaCl

Dextrose 5%

Lactated Ringer injection

IV Preparation

Inspect visually for particulate matter and discoloration prior to administration; product with particulate matter or discoloration should not be used

Vial is for single dose only

IV Administration

Can be administered IV without further dilution or may be mixed with diluents (see IV Compatibilities)

Infuse IV over 2-15 minutes

Discontinuation

Avoid abrupt withdrawal in order to minimize the risk of increased seizure frequency and status epilepticus

Storage

Oral

• Store at 25°C (77°F); excursions permitted between 15-30°C (59-86°F)
• Oral solution: Do not freeze; discard any unused oral solution remaining after 5 months of first opening the bottle

IV

• Unopened vials: Store at 25°C (77°F); excursions permitted between 15-30°C (59-86°F); do not freeze
• Diluted solution: May store for up to 4 hr at room temperature in PVC bag
• Discard any unused portion

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Briviact, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Briviact crosses into human milk. Talk to your healthcare provider about the best way to feed your baby if you take Briviact. 

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• your liver function
• other medications you are taking
• how you respond to this medication

The recommended starting dose of Briviact is 50 mg twice daily. Your dose will be increased or decreased based on you respond to this medication and how well you tolerate the medication. Your dose will be decreased if you have liver dysfunction. 

Although appropriate studies on the relationship of age to the effects of brivaracetam have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related liver problems, which may require caution and an adjustment in the dose for patients receiving brivaracetam.

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.

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.

Brivaracetam may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule V (C-V) drug.1 23

It is very important that your doctor check your progress at regular visits, especially for the first few months you are taking this medicine. This is necessary to allow dose adjustments and to reduce any unwanted effects.

Brivaracetam may cause changes in mood or behavior, problems with coordination, or unusual tiredness or weakness. Tell your doctor right away if you start to feel depressed, anxious, angry, getting upset easily, restless, or have thoughts about hurting yourself. Report any unusual thoughts or behavior that trouble you, especially if they are new or getting worse quickly.

This medicine may cause some people to become dizzy, drowsy, tired, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

This medicine may cause serious allergic reactions, including bronchospasm and angioedema. Tell your doctor if you have difficulty in breathing or swallowing, a fever, large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, nausea, reddening of the skin, especially around the ears, swelling of the eyes, face, or inside of the nose, or unusual tiredness or weakness.

Do not stop using brivaracetam without first checking with your doctor. Stopping the medicine suddenly may cause your seizures to return or to occur more often. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

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.

You should not use brivaracetam if you are allergic to it.

Brivaracetam may be habit-forming. Never share brivaracetam with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Selling or giving away this medicine is against the law.

To make sure brivaracetam is safe for you, tell your doctor if you have ever had:

• depression or a mood disorder;
• suicidal thoughts or actions;
• liver disease; or
• alcoholism or drug addiction.

Some people have thoughts about suicide while taking seizure medicine. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Follow your doctor's instructions about taking seizure medication if you are pregnant. Seizure control is very important during pregnancy, and having a seizure could harm both mother and baby. Do not start or stop taking this medicine without your doctor's advice, and tell your doctor right away if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of brivaracetam on the baby.

It is not known whether brivaracetam passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Brivaracetam is not approved for use by anyone younger than 16 years old.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

• severe drowsiness;
• a light-headed feeling, like you might pass out;
• loss of balance or coordination;
• unusual changes in mood or behavior; or
• unusual thoughts, hallucinations (seeing or hearing things that are not real).

Common side effects may include:

• dizziness, drowsiness;
• nausea, vomiting; or
• feeling tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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

Common side effects of Briviact include: acute psychosis, dizziness, drowsiness, equilibrium disturbance, fatigue, sedation, abnormal behavior, abnormal gait, aggressive behavior, agitation, anxiety, apathy, asthenia, ataxia, depressed mood, depression, hallucination, hypersomnia, lacrimation, lethargy, nervousness, nystagmus, paranoia, psychomotor agitation, vertigo, irritability, emotional lability, malaise, and restlessness. See below for a comprehensive list of adverse effects.

Dosage Information

Monotherapy or Adjunctive Therapy

When initiating treatment, gradual dose escalation is not required. The recommended starting dosage is 50 mg twice daily (100 mg per day). Based on individual patient tolerability and therapeutic response, the dosage may be adjusted down to 25 mg twice daily (50 mg per day) or up to 100 mg twice daily (200 mg per day) [see Clinical Studies (14)].

Briviact injection may be used when oral administration is temporarily not feasible. Briviact injection should be administered at the same dosage and same frequency as Briviact tablets and oral solution.

The clinical study experience with Briviact injection is limited to 4 consecutive days of treatment.

Administration Instructions for Briviact Tablets and Briviact Oral Solution

Briviact can be initiated with either intravenous or oral administration.

Briviact tablets and oral solution may be taken with or without food.

Briviact Tablets

Briviact tablets should be swallowed whole with liquid. Briviact tablets should not be chewed or crushed.

Briviact Oral Solution

A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device.

When using Briviact oral solution, no dilution is necessary. Briviact oral solution may also be administered using a nasogastric tube or gastrostomy tube.

Discard any unused Briviact oral solution remaining after 5 months of first opening the bottle.

Preparation and Administration Instructions for Briviact Injection

Briviact injection is for intravenous use only.

Preparation

Briviact injection can be administered intravenously without further dilution or may be mixed with diluents listed below.

Administration

Briviact injection should be administered intravenously over 2 to 15 minutes.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Product with particulate matter or discoloration should not be used. Briviact injection is for single dose only.

Storage and Stability

The diluted solution should not be stored for more than 4 hours at room temperature and may be stored in polyvinyl chloride (PVC) bags. Discard any unused portion of the Briviact injection vial contents.

Discontinuation of Briviact

Avoid abrupt withdrawal from Briviact in order to minimize the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.5) and Clinical Studies (14)].

Patients with Hepatic Impairment

For all stages of hepatic impairment, the recommended starting dosage is 25 mg twice daily (50 mg per day) and the recommended maximum dosage is 75 mg twice daily (150 mg per day) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Co-administration with Rifampin

Increase the Briviact dosage in patients on concomitant rifampin by up to 100% (i.e., double the dosage) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including Briviact, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs.

The relative risk for suicidal thoughts or behavior was higher in clinical trials in patients with epilepsy than in clinical trials in patients with psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing Briviact or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Neurological Adverse Reactions

Briviact causes somnolence, fatigue, dizziness, and disturbance in coordination. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on Briviact to gauge whether it adversely affects their ability to drive or operate machinery.

Somnolence and Fatigue

Briviact causes dose-dependent increases in somnolence and fatigue-related adverse reactions (fatigue, asthenia, malaise, hypersomnia, sedation, and lethargy) [see Adverse Reactions (6.1)]. In the Phase 3 controlled adjunctive epilepsy trials, these events were reported in 25% of patients randomized to receive Briviact at least 50 mg/day (20% at 50 mg/day, 26% at 100 mg/day, and 27% at 200 mg/day) compared to 14% of patients who received placebo. The risk is greatest early in treatment but can occur at any time.

Dizziness and Disturbance in Gait and Coordination

Briviact causes adverse reactions related to dizziness and disturbance in gait and coordination (dizziness, vertigo, balance disorder, ataxia, nystagmus, gait disturbance, and abnormal coordination) [see Adverse Reactions (6.1)]. In the Phase 3 controlled adjunctive epilepsy trials, these events were reported in 16% of patients randomized to receive Briviact at least 50 mg/day compared to 10% of patients who received placebo. The risk is greatest early in treatment but can occur at any time.

Psychiatric Adverse Reactions

Briviact causes psychiatric adverse reactions. In the Phase 3 controlled adjunctive epilepsy trials, psychiatric adverse reactions were reported in approximately 13% of patients who received Briviact (at least 50 mg/day) compared to 8% of patients who received placebo. Psychiatric events included both non-psychotic symptoms (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) and psychotic symptoms (psychotic disorder along with hallucination, paranoia, acute psychosis, and psychotic behavior). A total of 1.7% of adult patients treated with Briviact discontinued treatment because of psychiatric reactions compared to 1.3% of patients who received placebo.

Hypersensitivity: Bronchospasm and Angioedema

Briviact can cause hypersensitivity reactions. Bronchospasm and angioedema have been reported in patients taking Briviact. If a patient develops hypersensitivity reactions after treatment with Briviact, the drug should be discontinued. Briviact is contraindicated in patients with a prior hypersensitivity reaction to brivaracetam or any of the inactive ingredients [see Contraindications (4)].

Withdrawal of Antiepileptic Drugs

As with most antiepileptic drugs, Briviact should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus [see Dosage and Administration (2.4) and Clinical Studies (14)]. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.