Brivaracetam for the treatment of focal-onset seizures: pharmacokinetic and pharmacodynamic evaluations

Biase, Stefano de; Gigli, Gian Luigi; Valente, Mariarosaria

doi:10.1080/17425255.2020.1813277

Cited by 7 publications

(8 citation statements)

References 73 publications

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“…Brivaracetam is a chemical analogue of levetiracetam and a high-affinity ligand of the SV2A glycoprotein. Common side effects of brivaracetam, include headache, drowsiness, dizziness, fatigue and nausea [ 119 ]. Brivaracetam-related CNS side effects have been shown to peak during the first week, followed by a decrease in the first 6 weeks in prevalence and in the first 3 weeks in incidence, suggesting adaption of the ASD [ 120 ].…”

Section: Broad and Narrow Spectrum Anti-seizure Drugsmentioning

confidence: 99%

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Akyüz

Köklü

Ozenen

et al. 2021

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: Over the decades, various interventions have been developed and utilized to treat epilepsy. However, majority of epileptic patients are often first prescribed with anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as a first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action including regulation of ion channels, blocking of glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggest that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile, by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.

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Section: Broad and Narrow Spectrum Anti-seizure Drugsmentioning

confidence: 99%

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Akyüz

Köklü

Ozenen

et al. 2021

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“…The AUC of BRV was increased by 39% in CYP2C19 poor metabolizers compared to extensive metabolizers 16 . Regarding its drug–drug interaction potential, BRV exposure is decreased by strong inducers, and BRV inhibits epoxide hydrolase resulting in raised carbamazepine epoxide; the potential for clinically relevant drug–drug interactions is considered to be low 17–19 …”

Section: Figurementioning

confidence: 99%

Pharmacokinetics, Safety, and Tolerability of Brivaracetam in Healthy Elderly Participants

Stockis

Nicolas

Sargentini‐Maier

et al. 2023

Clinical Pharm in Drug Dev

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The pharmacokinetics, metabolism, safety, and tolerability of the antiseizure medication brivaracetam (BRV) were characterized in 16 healthy elderly participants (8 men/8 women) aged 65–78 years who received a single 200‐mg oral dose of BRV on day 1, followed by 200 mg twice daily from day 3 until day 12. BRV and three metabolites were determined in plasma and urine. Adverse events, vital signs, electrocardiograms, laboratory tests, general and neurological examinations, and psychometric rating scales were recorded at regular intervals. No clinically relevant changes or abnormalities were detected. The adverse events were similar to those observed in pivotal trials. Rating scales indicated transiently increased sedation and decreased alertness. BRV pharmacokinetics and metabolism were unchanged relative to younger populations. Based on our observations in this healthy elderly population receiving oral BRV 200 mg twice daily (twice the maximum recommended dose), dose reductions are not warranted relative to other, younger populations. Further investigations may be necessary in frail elderly populations aged >80 years.

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“…Brivaracetam is a selective, reversible, high-affinity ligand of SV2A (15–30 fold higher than levetiracetam) ( de Biase et al, 2020 ). Pharmacokinetically, brivaracetam has the ability to rapidly cross the blood-brain barrier due to its lipophilicity, which is similar to that of benzodiazepines and higher than levetiracetam ( Niespodziany et al, 2017 ).…”

Section: Antiseizure Medication For Brain Tumor-related Epilepsymentioning

confidence: 99%

“…Brivaracetam is extensively metabolized in the liver. Thus, its dose needs to be reduced in patients with liver damage regardless of the Child-Pugh score ( de Biase et al, 2020 ). In contrast, brivaracetam does not induce or inhibit CYP enzymes or the known drug transport system, except for CYP2C19 (weakly inhibited in vitro studies).…”

Section: Antiseizure Medication For Brain Tumor-related Epilepsymentioning

confidence: 99%

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Epilepsy treatment in neuro-oncology: A rationale for drug choice in common clinical scenarios

et al. 2022

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Epilepsy represents a challenge in the management of patients with brain tumors. Epileptic seizures are one of the most frequent comorbidities in neuro-oncology and may be the debut symptom of a brain tumor or a complication during its evolution. Epileptogenic mechanisms of brain tumors are not yet fully elucidated, although new factors related to the underlying pathophysiological process with possible treatment implications have been described. In recent years, the development of new anti-seizure medications (ASM), with better pharmacokinetic profiles and fewer side effects, has become a paradigm shift in many clinical scenarios in neuro-oncology, being able, for instance, to adapt epilepsy treatment to specific features of each patient. This is crucial in several situations, such as patients with cognitive/psychiatric comorbidity, pregnancy, or advanced age, among others. In this narrative review, we provide a rationale for decision-making in ASM choice for neuro-oncologic patients, highlighting the strengths and weaknesses of each drug. In addition, according to current literature evidence, we try to answer some of the most frequent questions that arise in daily clinical practice in patients with epilepsy related to brain tumors, such as, which patients are the best candidates for ASM and when to start it, what is the best treatment option for each patient, and what are the major pitfalls to be aware of during follow-up.

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Brivaracetam for the treatment of focal-onset seizures: pharmacokinetic and pharmacodynamic evaluations

Cited by 7 publications

References 73 publications

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Pharmacokinetics, Safety, and Tolerability of Brivaracetam in Healthy Elderly Participants

Epilepsy treatment in neuro-oncology: A rationale for drug choice in common clinical scenarios

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