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Table 2 Summary of the pharmacological and clinical profile of antiseizure medications (ASMs) introduced in the market after 2015

From: The pharmacological treatment of epilepsy: recent advances and future perspectives

  Brivaracetam Cannabidiol Cenobamate Everolimus Fenfluramine
Chemical structure Levetiracetam derivative Cannabinoid Carbamate derivative Rapamycin derivative Amphetamine derivative
Approved epilepsy indications (United States) Treatment of focal seizures in patients aged 1 month and older Treatment of seizures associated with LGS, DS or TSC in patients 1 year of age and older Treatment of focal seizures in adults Add-on treatment of focal seizures associated with TSC in patients aged 2 years and older Treatment of seizures associated with DS in patients 2 years of age and older.
Main mechanisms of action SV2A modulator Several, including
GPR55 antagonism, desensitization of TRPV1channels, enhanced adenosine-mediated signaling, and GABAergic effects.
Blockade of persistent sodium currents and increase of phasic and tonic GABA inhibition. mTOR inhibition Several, including indirect stimulation of 5-HT2C and 5-HT1D receptors as well as interactions with σ1-receptors
Oral bioavailability Complete (100%) About 6% in the fasting state. About 25% when taken with a high-fat meal About 90% Variable About 80%
Main route of elimination CYP2C19-mediated hydroxylation and hydrolysis CYP2C19 and CYP3A4-mediated oxidation, and other metabolic pathways UGT2B7- and UGT2B4-mediated glucuronidation and CYP-mediated oxidation CYP3A4-mediated metabolism CYP-mediated metabolism, involving conversion to the active metabolite norfenfluramine
Half-life About 9 h About 15 h after a single dose, and about 60 h after multiple dosing About 50–60 h About 30 h Fenfluramine = about 20 h. Norfenfluramine = about 24 to 48 h
Most common adverse effects Sommnolence, fatigue, dizziness, coordination disturbances, mood and behavioural disturbances Somnolence, anorexia, diarrhea, fatigue, sleep disorders, behavioral disturbances Dizziness, fatigue, somnolence, ataxia, dysarthria, visual disturbances, gastrointestinal disturbances Stomatitis, pyrexia, pneumonia, diarrhea, hypercholesterolemia Anorexia, decreased weight, diarrhea, constipation, somnolence, fatigue, coordination disturbances, behavioral disturbances
Other adverse effects of potential concern Hypersensitivity reactions Hypersensitivity reactions, increased liver enzymes, pneumonia Hypersensitivity reactions Hypersensitivity reactions, infections, renal failure, myelosuppression Cardiac valvulopathy, pulmonary hypertension, serotonin syndrome
Main drug interactions Serum brivaracetam levels can be increased by cannabidiol, and moderately reduced by enzyme inducing ASMs. Brivaracetam increases serum levels of carbama-zepine-10,11-epoxide Cannabidiol inhibits the metabolism of several drugs. In particular, it increases markedly the serum levels of norclobazam, the active metabolite of clobazam Serum cenobamate levels are decreased by phenytoin. Cenobamate increases serum phenytoin levels, and can modify the serum levels of several other drugs Serum everolimus levels can be increased by inhibitors of P-gp and by CYP3A4 inhibitors, and decreased by inducers of P-gp / CYP3A4 Serum fenfluramine levels are increased by the combination of stiripentol with clobazam. Use together with other serotoninergic drugs may involve a risk of precipitating a serotonin syndrome
  1. Abbreviations: CYP cytochrome P450; DS Dravet syndrome; GABA gamma-aminobutyric acid, GPR55 G protein-coupled receptor 55, LGS Lennox-Gastaut syndrome; mTOR mechanistic target of rapamycin; P-gp P-glycoprotein, TRPV1 transient receptor potential vanilloid type 1, TSC tuberous sclerosis complex, UGT uridine 5′-diphospho-glucuronosyltransferase