Brivaracetam Holsten
Antiepileptic medication for partial-onset seizures
Quick Facts About Brivaracetam Holsten
Key Takeaways About Brivaracetam Holsten
- Add-on therapy for focal seizures: Brivaracetam Holsten is used alongside other antiepileptic drugs to control partial-onset seizures in patients aged 2 years and older
- High SV2A affinity: Brivaracetam has 15-30 times higher binding affinity for SV2A compared to levetiracetam, potentially offering greater potency at lower doses
- Never stop suddenly: Abrupt discontinuation can trigger rebound seizures or status epilepticus; always taper gradually under medical supervision
- Common side effects are manageable: Dizziness and drowsiness are the most frequent side effects, typically improving over the first weeks of treatment
- Monitor for mood changes: As with all antiepileptic drugs, patients should be monitored for signs of depression, anxiety, or suicidal thoughts
What Is Brivaracetam Holsten and What Is It Used For?
Brivaracetam Holsten is a prescription antiepileptic drug (AED) containing brivaracetam as its active ingredient. It is approved as adjunctive (add-on) therapy for the treatment of partial-onset seizures with or without secondary generalisation in adults, adolescents, and children from 2 years of age with epilepsy.
Epilepsy is one of the most common neurological disorders worldwide, affecting approximately 50 million people according to the World Health Organization (WHO). Partial-onset seizures, also known as focal seizures, originate in a specific area of the brain and account for approximately 60% of all epilepsy cases. These seizures may remain localised (simple partial seizures) or spread to involve the entire brain (secondary generalisation), leading to loss of consciousness and convulsions.
Brivaracetam belongs to a class of medications known as antiepileptic drugs or anticonvulsants. It was developed as a structural analogue of levetiracetam, another widely used antiepileptic medication. However, brivaracetam exhibits significantly higher selectivity and binding affinity for its molecular target, synaptic vesicle protein 2A (SV2A), which is a transmembrane glycoprotein found in presynaptic nerve terminals throughout the brain. SV2A plays an essential role in regulating the release of neurotransmitters from synaptic vesicles.
By binding to SV2A with approximately 15 to 30 times higher affinity than levetiracetam, brivaracetam modulates synaptic vesicle function and neurotransmitter release more effectively. This mechanism helps stabilise overexcitable neuronal networks and prevents the abnormal, synchronised electrical discharges that characterise epileptic seizures. The precise downstream mechanisms by which SV2A modulation leads to seizure control are still being investigated, but the clinical benefits have been well established through multiple large-scale randomised controlled trials.
Brivaracetam Holsten is manufactured by Holsten Pharma GmbH and is available as 10 mg film-coated tablets. It is a generic formulation of the original brivaracetam product, which was first approved by the European Medicines Agency (EMA) in 2016 and by the U.S. Food and Drug Administration (FDA) in the same year. The medication has demonstrated bioequivalence with the originator product, meaning it delivers the same amount of active substance to the bloodstream at the same rate.
Brivaracetam Holsten is specifically approved for use in combination with other antiepileptic drugs, not as monotherapy (sole treatment). Your neurologist will determine the best combination of medications for your individual seizure type and overall health profile.
What Should You Know Before Taking Brivaracetam Holsten?
Before starting Brivaracetam Holsten, your doctor must assess your medical history, current medications, liver function, and mental health status. There are several important contraindications and precautions that apply to this medication.
Contraindications
You must not take Brivaracetam Holsten if you are allergic (hypersensitive) to brivaracetam, other pyrrolidone derivatives, or any of the other ingredients in the tablets. Hypersensitivity reactions, although rare, can include angioedema and bronchospasm. If you experience any signs of a severe allergic reaction such as swelling of the face, lips, tongue, or throat, or difficulty breathing, you should seek emergency medical attention immediately and discontinue the medication.
Warnings and Precautions
Several important precautions apply when using Brivaracetam Holsten. Discuss all of the following considerations with your healthcare provider before and during treatment:
Suicidal ideation and behaviour: Antiepileptic drugs, including brivaracetam, have been associated with an increased risk of suicidal thoughts and behaviour. A meta-analysis conducted by the FDA found that patients taking antiepileptic drugs had approximately twice the risk of suicidal ideation compared to those receiving placebo. This risk appears as early as one week after starting treatment and persists throughout the duration of therapy. Patients, family members, and caregivers should be vigilant for any emergence of or worsening of depression, anxiety, agitation, hostility, irritability, or suicidal thoughts. Any such changes should be reported to the prescribing physician immediately.
Hepatic impairment: Brivaracetam is metabolised in the liver, primarily through hydrolysis by amidase enzymes and secondarily through hydroxylation by CYP2C19. In patients with moderate to severe hepatic impairment (Child-Pugh Class B or C), the plasma concentration of brivaracetam may be significantly increased. A dose adjustment is therefore recommended in patients with hepatic impairment, and liver function should be monitored regularly throughout treatment. The maximum recommended dose should not exceed 150 mg per day in patients with any stage of hepatic impairment.
Central nervous system depression: Brivaracetam can cause somnolence (drowsiness) and dizziness, which may impair the ability to drive or operate machinery. Patients should be advised not to drive, use complex machinery, or engage in other hazardous activities until they have gained sufficient experience with the medication to gauge whether it adversely affects their alertness and coordination. These effects are most pronounced during the initial titration period and typically diminish over time.
Seizure withdrawal: As with all antiepileptic drugs, brivaracetam should not be stopped abruptly. Sudden discontinuation of antiepileptic therapy can provoke rebound seizures and potentially life-threatening status epilepticus. If it is necessary to discontinue Brivaracetam Holsten, the dose should be gradually reduced over a minimum period of one week under the supervision of a neurologist.
Never discontinue Brivaracetam Holsten without consulting your doctor. Abrupt withdrawal can trigger severe rebound seizures or status epilepticus, which is a medical emergency. If discontinuation is needed, your doctor will create a gradual tapering schedule over at least one week.
Pregnancy and Breastfeeding
There is limited clinical data on the use of brivaracetam in pregnant women. Animal reproductive studies have shown developmental toxicity, including increased embryo-fetal mortality and decreased fetal body weights at maternally toxic doses. Brivaracetam crosses the placental barrier in animal studies.
As a precautionary measure, brivaracetam should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus. This decision should be made jointly by the patient and her neurologist, taking into account the severity of the seizure disorder and the risks of uncontrolled seizures during pregnancy. Women of childbearing potential should use effective contraception during treatment.
Brivaracetam is excreted in human breast milk. A risk to the breastfed infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue brivaracetam therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. Discuss these options carefully with your healthcare provider.
How Does Brivaracetam Holsten Interact with Other Drugs?
Brivaracetam has a relatively favourable drug interaction profile compared to many other antiepileptic drugs. However, there are several clinically significant interactions that require attention, particularly with strong enzyme inducers and certain other antiepileptic medications.
Brivaracetam is metabolised primarily by hydrolysis (via amidase enzymes) and secondarily by CYP2C19-mediated hydroxylation. It does not significantly inhibit or induce cytochrome P450 enzymes at therapeutic doses, which contributes to its generally favourable interaction profile. However, medications that strongly induce hepatic enzymes can increase the clearance of brivaracetam and reduce its plasma concentrations.
The following table summarises the most clinically significant drug interactions with brivaracetam. Always inform your doctor and pharmacist about all medications you are currently taking, including over-the-counter products, herbal remedies, and dietary supplements.
| Interacting Drug | Effect | Severity | Clinical Recommendation |
|---|---|---|---|
| Rifampicin | Decreases brivaracetam plasma levels by up to 45% through enzyme induction | Major | Dose adjustment of brivaracetam may be needed; monitor seizure control closely |
| Carbamazepine | Brivaracetam increases carbamazepine-epoxide levels by approximately 30%; carbamazepine slightly reduces brivaracetam levels | Major | Monitor for carbamazepine toxicity symptoms (dizziness, diplopia, ataxia); may require carbamazepine dose reduction |
| Phenytoin | Brivaracetam can increase phenytoin plasma levels by up to 20% through CYP2C19 inhibition | Major | Monitor phenytoin levels and adjust dose if needed; watch for signs of phenytoin toxicity |
| Levetiracetam | No pharmacokinetic interaction, but both target SV2A; no additional clinical benefit expected from combination | Moderate | Combination generally not recommended due to overlapping mechanism; consider substitution rather than addition |
| Oral contraceptives | No clinically significant pharmacokinetic interaction at therapeutic doses | Minor | No dose adjustment necessary; hormonal contraception remains effective |
| Alcohol | May potentiate CNS-depressant effects including drowsiness and dizziness | Moderate | Avoid or limit alcohol consumption during treatment |
Major Interactions
The most significant interactions involve strong hepatic enzyme inducers such as rifampicin, which can reduce brivaracetam plasma concentrations by up to 45%. Similarly, the combination of brivaracetam with carbamazepine requires careful monitoring because brivaracetam inhibits the enzyme epoxide hydrolase, leading to elevated levels of carbamazepine-10,11-epoxide, the active and potentially toxic metabolite of carbamazepine. Symptoms of carbamazepine-epoxide toxicity include dizziness, double vision, unsteadiness, nausea, and headache.
The interaction with phenytoin is also clinically important. Brivaracetam can inhibit CYP2C19, the enzyme primarily responsible for phenytoin metabolism, leading to increased phenytoin levels. Since phenytoin has a narrow therapeutic index, even modest increases in its plasma concentration can lead to toxicity, manifesting as nystagmus, ataxia, slurred speech, and confusion.
Minor Interactions
Brivaracetam has a reassuringly minimal effect on oral contraceptives. Clinical studies have confirmed that co-administration of brivaracetam at doses up to 100 mg twice daily does not significantly alter the pharmacokinetics of ethinylestradiol or levonorgestrel. This is a notable advantage over several other antiepileptic drugs (such as carbamazepine, phenytoin, and topiramate) that can reduce the efficacy of hormonal contraceptives.
What Is the Correct Dosage of Brivaracetam Holsten?
The recommended starting dose of Brivaracetam Holsten for adults and adolescents weighing 50 kg or more is 50 mg per day (25 mg twice daily), which can be adjusted to between 50 mg and 200 mg per day based on individual clinical response and tolerability.
Dosing of Brivaracetam Holsten must be individualised based on the patient's age, body weight, hepatic function, concomitant medications, and clinical response. The tablets should be taken orally, swallowed whole with water, and can be taken with or without food. Food does not significantly affect the rate or extent of brivaracetam absorption, with an oral bioavailability of approximately 100%. Doses should be taken at approximately the same times each day, preferably one dose in the morning and one in the evening, to maintain stable blood levels.
Adults and Adolescents (50 kg and above)
Standard Adult Dosing
Starting dose: 50 mg per day, given as 25 mg twice daily
Dose range: 50 mg to 200 mg per day
Maximum dose: 200 mg per day (100 mg twice daily)
Based on individual patient response and tolerability, the dose may be adjusted within the therapeutic range. The dose can be started at 50 mg/day without the need for dose titration, although some clinicians prefer a more gradual approach in sensitive patients.
Children (2 years to <16 years, below 50 kg)
Paediatric Weight-Based Dosing
Starting dose: 1 mg/kg/day, given as 0.5 mg/kg twice daily
Dose range: 1 mg/kg/day to 5 mg/kg/day
Maximum dose: 5 mg/kg/day (2.5 mg/kg twice daily), not exceeding 200 mg/day
Dosing in children is weight-based and should be carefully calculated by the prescribing physician. The 10 mg tablet formulation may not be suitable for all paediatric doses; an oral solution formulation may be more appropriate for precise weight-based dosing in younger or lighter children.
Elderly Patients
No dose adjustment is specifically recommended for elderly patients based on age alone. However, as renal function naturally declines with age and elderly patients are more likely to have hepatic impairment or to be taking multiple medications, dose adjustments may be necessary on an individual basis. Elderly patients may also be more susceptible to the central nervous system effects of brivaracetam, including dizziness, somnolence, and falls. Starting at the lower end of the dosing range and titrating more slowly may be advisable in this population.
| Patient Group | Starting Dose | Dose Range | Maximum Dose |
|---|---|---|---|
| Adults & adolescents (≥50 kg) | 25 mg twice daily | 50-200 mg/day | 200 mg/day |
| Children (2-16 years, <50 kg) | 0.5 mg/kg twice daily | 1-5 mg/kg/day | 5 mg/kg/day (max 200 mg/day) |
| Elderly | 25 mg twice daily (consider lower) | 50-200 mg/day | 200 mg/day |
| Hepatic impairment | 25 mg twice daily | 50-150 mg/day | 150 mg/day |
Missed Dose
If you miss a dose of Brivaracetam Holsten, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and take the next dose at the regular time. Do not take a double dose to make up for a missed one. Consistent dosing is important for maintaining stable blood levels and optimal seizure control. If you frequently forget to take your medication, consider setting a daily alarm or using a pill organiser to help establish a routine.
Overdose
There is limited clinical experience with brivaracetam overdose. In clinical trials, doses up to 1400 mg/day have been administered without life-threatening effects. The most commonly reported symptoms following overdose include dizziness, somnolence, nausea, and vertigo. There is no specific antidote for brivaracetam overdose. Treatment should be supportive, including gastric lavage or activated charcoal if ingestion was recent. Haemodialysis is not expected to be effective in removing brivaracetam due to the drug's high protein binding. In the event of a suspected overdose, contact your local poison control centre or emergency services immediately.
What Are the Side Effects of Brivaracetam Holsten?
Like all medicines, Brivaracetam Holsten can cause side effects, although not everybody gets them. The most commonly reported side effects are dizziness and somnolence (drowsiness), which each affect more than 1 in 10 patients. Most side effects are mild to moderate and tend to decrease over time.
The safety profile of brivaracetam has been established through extensive clinical trials involving thousands of patients with epilepsy. In the pivotal phase III clinical trials, the most frequently reported adverse reactions leading to treatment discontinuation were dizziness (0.8%), somnolence (0.8%), and fatigue (0.4%). The overall discontinuation rate due to adverse events was comparable to placebo, indicating generally good tolerability.
Side effects are categorised below by frequency according to the internationally agreed convention used in European product information:
Very Common (affects more than 1 in 10 people)
- Dizziness – a sensation of lightheadedness or unsteadiness, most common during the initial weeks of treatment
- Somnolence (drowsiness) – excessive sleepiness or difficulty staying awake, usually decreasing over time
Common (affects 1 in 10 to 1 in 100 people)
- Fatigue – feeling unusually tired or lacking energy
- Nausea – feeling sick to the stomach, sometimes with vomiting
- Insomnia – difficulty falling asleep or staying asleep
- Upper respiratory tract infections – including common cold symptoms, sore throat, and nasal congestion
- Depression – low mood, loss of interest in activities
- Irritability – feeling easily annoyed or agitated
- Anxiety – excessive worry or nervousness
- Constipation – infrequent or difficult bowel movements
- Vertigo – a spinning sensation, distinct from general dizziness
Uncommon (affects 1 in 100 to 1 in 1,000 people)
- Neutropenia – reduced white blood cell count, potentially increasing infection risk
- Psychotic symptoms – including hallucinations and paranoia
- Suicidal ideation – thoughts of self-harm or suicide
- Aggression – unusually hostile or aggressive behaviour
Rare (affects fewer than 1 in 1,000 people)
- Hypersensitivity reactions – including angioedema (swelling of face, lips, tongue) and bronchospasm
- Suicidal behaviour and completed suicide – reported during post-marketing surveillance across all antiepileptic drugs
Contact your doctor or go to the nearest emergency department immediately if you experience: severe allergic reaction (swelling of face, lips, tongue, or throat; difficulty breathing; skin rash with itching), suicidal thoughts or intentions, severe mood changes, or new/worsening seizures after missing doses.
Psychiatric and behavioural side effects deserve particular attention. In clinical trials, psychiatric adverse reactions were reported in approximately 13% of patients treated with brivaracetam compared to 8% of those receiving placebo. The most common psychiatric effects include fatigue, insomnia, irritability, anxiety, and depression. Although the incidence of behavioural side effects with brivaracetam appears to be lower than that observed with levetiracetam, vigilance remains important, particularly in patients with a pre-existing history of psychiatric conditions.
Long-term safety data from open-label extension studies spanning up to 8 years of continuous treatment have shown that the safety profile of brivaracetam remains consistent over prolonged use, with no new safety signals emerging. The types and frequencies of adverse events observed during long-term treatment were generally consistent with those seen in the pivotal short-term trials.
How Should You Store Brivaracetam Holsten?
Brivaracetam Holsten should be stored below 25°C (77°F) in the original packaging, protected from moisture. Keep out of reach and sight of children.
Proper storage of medication is essential to maintain its effectiveness and safety throughout the shelf life. Brivaracetam Holsten film-coated tablets should be stored at room temperature, not exceeding 25°C (77°F). The tablets should be kept in the original blister packaging to protect them from moisture and light degradation. Do not transfer the tablets to a different container unless it is specifically designed for medication storage.
Do not use Brivaracetam Holsten after the expiry date printed on the carton and blister packaging. The expiry date refers to the last day of that month. Once expired, the chemical stability and therapeutic efficacy of the medication cannot be guaranteed, and using expired medication may result in suboptimal seizure control.
Do not dispose of unused or expired medications by flushing them down the toilet or throwing them in the household waste. Return them to your pharmacy for safe disposal in accordance with local environmental regulations. Many pharmacies and healthcare facilities offer take-back programmes for unused medications.
What Does Brivaracetam Holsten Contain?
Each Brivaracetam Holsten 10 mg film-coated tablet contains 10 mg of brivaracetam as the active substance, along with several inactive ingredients (excipients) necessary for tablet manufacture and stability.
The active substance in Brivaracetam Holsten is brivaracetam. Each film-coated tablet contains exactly 10 mg of brivaracetam. Brivaracetam (chemical name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide) is a white to off-white crystalline powder with a molecular weight of 212.29 g/mol.
The inactive ingredients (excipients) in the tablet core typically include:
- Croscarmellose sodium – a disintegrant that helps the tablet break apart in the gastrointestinal tract for rapid drug release
- Lactose monohydrate – a filler/diluent (patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should consult their doctor)
- Microcrystalline cellulose – a binder and filler for tablet integrity
- Povidone – a binding agent
- Magnesium stearate – a lubricant to prevent the tablet from sticking to manufacturing equipment
The film coating typically contains hypromellose, titanium dioxide (E171), macrogol/polyethylene glycol, and potentially iron oxide pigments depending on the tablet colour designation. The film coating serves to protect the active ingredient from environmental degradation, mask any unpleasant taste, and facilitate swallowing.
Brivaracetam Holsten tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Frequently Asked Questions About Brivaracetam Holsten
Brivaracetam Holsten is used as adjunctive (add-on) therapy for the treatment of partial-onset seizures (also known as focal seizures) with or without secondary generalisation in adults, adolescents and children from 2 years of age with epilepsy. It works by binding to synaptic vesicle protein 2A (SV2A) in the brain to help control seizure activity. It is not intended for use as a sole treatment (monotherapy) but is taken alongside other antiepileptic medications.
Both brivaracetam and levetiracetam target the synaptic vesicle protein 2A (SV2A), but brivaracetam has approximately 15 to 30 times higher affinity for SV2A compared to levetiracetam. This higher binding affinity may translate to greater potency at lower doses. Additionally, brivaracetam appears to have a lower incidence of behavioral and psychiatric side effects, particularly irritability and aggression, which are commonly reported with levetiracetam. Combining both drugs is generally not recommended as they share the same target.
No. Brivaracetam Holsten should never be stopped suddenly. Abrupt discontinuation of antiepileptic drugs can lead to rebound seizures and potentially life-threatening status epilepticus. If your doctor decides that you should stop taking brivaracetam, the dose will be gradually reduced over at least one week. Always follow your doctor's instructions for tapering the medication.
The most common side effects of brivaracetam are dizziness and somnolence (drowsiness), each affecting more than 1 in 10 patients. Other common side effects include fatigue, nausea, insomnia, and upper respiratory tract infections. Most side effects are mild to moderate and tend to decrease over time as the body adjusts to the medication. If side effects are bothersome or persistent, talk to your doctor about possible dose adjustments.
Brivaracetam should not be used during pregnancy unless clearly necessary and only after careful risk-benefit assessment by a neurologist. There is limited clinical data on the use of brivaracetam in pregnant women. Animal studies have shown reproductive toxicity. Women of childbearing potential should use effective contraception during treatment. If you are planning a pregnancy, discuss your epilepsy treatment plan with your neurologist well in advance so alternative options can be considered.
Yes, Brivaracetam Holsten can be taken with or without food. Food does not significantly affect the absorption of brivaracetam, which has an oral bioavailability of approximately 100%. The tablets should be swallowed whole with a glass of water and should be taken at approximately the same times each day to maintain consistent blood levels for optimal seizure control.
References
- European Medicines Agency (EMA). Brivaracetam Summary of Product Characteristics. EMA/CHMP. Last updated 2025. Available at: www.ema.europa.eu
- Klein P, Schiemann J, Sperling MR, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study of adjunctive brivaracetam in patients with partial-onset seizures. Epilepsia. 2015;56(12):1890-1898. doi:10.1111/epi.13212
- Ryvlin P, Werhahn KJ, Blaszczyk B, et al. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014;55(1):47-56. doi:10.1111/epi.12432
- Kwan P, Trinka E, Van Paesschen W, et al. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia. 2014;55(1):38-46. doi:10.1111/epi.12391
- Moseley BD, Cole D, Iwuora O, et al. The tolerability of oral brivaracetam in the treatment of adults with epilepsy: a comprehensive review. Expert Opinion on Drug Safety. 2020;19(9):1117-1128. doi:10.1080/14740338.2020.1796965
- U.S. Food and Drug Administration (FDA). BRIVIACT (brivaracetam) prescribing information. Revised 2024. Available at: www.fda.gov
- World Health Organization (WHO). Epilepsy: a public health imperative. Geneva: WHO; 2019. Available at: www.who.int
- International League Against Epilepsy (ILAE). Operational classification of seizure types. Epilepsia. 2017;58(4):522-530. doi:10.1111/epi.13670
- National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. NICE guideline [NG217]. Published 2022. Available at: www.nice.org.uk
- Steinhoff BJ, Bacher M, Bast T, et al. First clinical experiences with brivaracetam in daily clinical practice and development of psychiatric symptoms: a multicentre study. Epilepsia. 2017;58(12):e166-e171. doi:10.1111/epi.13905
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians specialising in neurology, epileptology, and clinical pharmacology. Our editorial process follows the principles of evidence-based medicine, relying on peer-reviewed research, international clinical guidelines (EMA, FDA, WHO, ILAE, NICE), and the GRADE evidence framework.
Board-certified neurologists and clinical pharmacologists with expertise in epilepsy management and anticonvulsant pharmacotherapy
Independent panel of medical experts ensuring accuracy, completeness, and adherence to current clinical evidence
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