Brivaracetam (brivaracetam)

Anticonvulsants Oral Tablet

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Last reviewed · Source: First Databank (FDB) drug data

Overview

Brivaracetam, a pyrrolidine derivative, is an anticonvulsant.

Brivaracetam, a pyrrolidine derivative, is an anticonvulsant. The drug is structurally and chemically related to levetiracetam. The exact mechanism of action by which brivaracetam exerts its anticonvulsant effects has not been fully elucidated, but may be related to its potent and selective binding affinity for synaptic vesicle protein 2A (SV2A).

SV2A is a transmembrane glycoprotein that is widely distributed in the CNS; although its precise role in neurotransmission is not fully understood, it is thought to modulate synaptic vesicle exocytosis and neurotransmitter release. Reduced expression of SV2A has been demonstrated in patients with epilepsy, which correlates with data from animal models suggesting that SV2A deficiency increases seizure vulnerability. The anticonvulsant potency of selective SV2A ligands has been shown to be strongly correlated with their in-vitro binding affinity.

Brivaracetam demonstrates 15- to 30-fold higher affinity for SV2A than levetiracetam.

Brivaracetam does not appear to have effects on other known targets potentially involved in epilepsy, including voltage-gated potassium or calcium channels, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid A (GABAA), glycine, or N-methyl-D-aspartate (NMDA) receptors at therapeutic concentrations. Although brivaracetam has demonstrated inhibitory effects on voltage-gated sodium channels, this effect appears to be unrelated to the drug's anticonvulsant activity.

Brivaracetam exhibits dose-proportional pharmacokinetics over a dose range of 10-600 mg. The drug is rapidly and almost completely absorbed following oral administration; peak plasma concentrations are attained at a median of 1 hour (range: 0.25-3 hours) under fasting conditions. Administration with a high-fat meal slows the rate but not extent of absorption.

Following IV administration of a single 100-mg dose, plasma brivaracetam concentrations were initially higher within the first hour of dosing than with oral administration of the 50- and 100-mg tablets, but the dosage forms were bioequivalent in terms of overall exposure. Bioequivalence also has been demonstrated between the tablet and oral solution formulations of the drug. Brivaracetam distributes readily and rapidly into the CNS; in vitro and animal studies indicate that the drug crosses the blood-brain barrier faster and to a greater extent than levetiracetam, likely due to its increased lipophilicity.

Metabolism of brivaracetam occurs primarily via hydrolysis of the amide moiety by hepatic and extrahepatic amidase to form the carboxylic acid metabolite; a secondary pathway involves hydroxylation (mediated principally by CYP2C19) to form the hydroxy metabolite. An additional hydroxy acid metabolite is created by further biotransformation of these metabolites. None of the identified metabolites are pharmacologically active.

Brivaracetam and its metabolites are eliminated principally by renal excretion. Over 95% of a dose is excreted in the urine within 72 hours, with less than 10% as unchanged brivaracetam; fecal excretion accounts for less than 1% of the dose. The elimination half-life of brivaracetam is approximately 9 hours.

The drug is weakly bound (no more than 20%) to plasma proteins.

USES: Brivaracetam is used to treat seizures.

Generic name: brivaracetam
Pronunciation: (BRIV-a-RA-se-tam)
Drug class: Anticonvulsants
Therapeutic class: Central Nervous System Agents

Reference product & biosimilars

No reference, biosimilar or interchangeable associated with this drug.

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Indications

The following indications are listed for Brivaracetam:

  • Focal Epilepsy

Also known as: Cortical Epilepsy, Focal Seizures, Local Epilepsy, Partial Epilepsy, Partial Onset Seizures, Partial Seizures.

Dosing

No dosing information is available for this tab.

Drug interactions

Brivaracetam is metabolized to some extent by cytochrome P-450 (CYP) isoenzyme 2C19; additional biotransformation of the metabolites is mediated by CYP2C9. (See Description.)

Brivaracetam is a weak inhibitor of CYP2C19; however, this inhibition is not expected to be clinically important. The drug inhibits epoxide hydrolase in vitro. Brivaracetam does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2D6, or 3A4, nor induce CYP1A2, 2B6, 2C9, 2C19, 3A4, or epoxide hydrolase.

Brivaracetam is not a substrate of the efflux transporters P-glycoprotein (P-gp) or multidrug resistance proteins (MRP) 1 and MRP2. The drug does not inhibit P-gp, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug and toxin extrusion transporters (MATE) 1 and MATE2/K, MRP2, organic anion transporters (OAT) 1 and OAT3, organic cation transporters (OCT) 1 and OCT2, or organic anion transport proteins (OATP) 1B1 and OATP1B3.

Contraindications

Known hypersensitivity to brivaracetam or any ingredients in the formulation. (See Sensitivity Reactions under Cautions: Warnings/Precautions.)

Adverse reactions

Adverse effects reported in at least 5% of patients with partial-onset seizures receiving brivaracetam in controlled clinical trials and at least 2% more frequently than with placebo include somnolence/sedation, dizziness, fatigue, nausea/vomiting, diarrhea, headache, insomnia, and nasopharyngitis.

Precautions

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ICD codes

CodeTypeDescription
Focal epilepsy
G40.0ICD10CMLocalization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset
G40.00ICD10CMLocalization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable
G40.009ICD10CMLocalization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable, without status epilepticus
G40.01ICD10CMLocalization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable
G40.019ICD10CMLocalization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable, without status epilepticus
G40.1ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures
G40.10ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable
G40.109ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable, without status epilepticus
G40.11ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable
G40.119ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable, without status epilepticus
G40.2ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures
G40.20ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable
G40.209ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable, without status epilepticus
G40.21ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable
G40.219ICD10CMLocalization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, without status epilepticus
G40.CICD10CMLafora progressive myoclonus epilepsy
G40.C0ICD10CMLafora progressive myoclonus epilepsy, not intractable
G40.C01ICD10CMLafora progressive myoclonus epilepsy, not intractable, with status epilepticus
G40.C09ICD10CMLafora progressive myoclonus epilepsy, not intractable, without status epilepticus
G40.C1ICD10CMLafora progressive myoclonus epilepsy, intractable
G40.C11ICD10CMLafora progressive myoclonus epilepsy, intractable, with status epilepticus
G40.C19ICD10CMLafora progressive myoclonus epilepsy, intractable, without status epilepticus

ICD code information from First Databank (FDB).

Formulary status

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Last reviewed · Source: First Databank (FDB) drug data