Elsevier

Epilepsy Research

Volume 163, July 2020, 106327
Epilepsy Research

A review of the drug−drug interactions of the antiepileptic drug brivaracetam

https://doi.org/10.1016/j.eplepsyres.2020.106327Get rights and content
Under a Creative Commons license
open access

Highlights

  • Brivaracetam (50–200 mg/day) has a low risk of clinically relevant DDIs.

  • No dose modification is needed when given with other AEDs or oral contraceptives.

  • Brivaracetam dose should be adjusted when coadministered with rifampin.

  • Brivaracetam inhibits epoxide hydrolase and increases carbamazepine epoxide levels.

  • Supratherapeutic doses of brivaracetam moderately increase phenytoin levels.

Abstract

Brivaracetam is an antiepileptic drug (AED) indicated for the treatment of focal seizures, with improved safety and tolerability vs first-generation AEDs. Brivaracetam binds with high affinity to synaptic vesicle protein 2A in the brain, which confers its antiseizure activity. Brivaracetam is rapidly absorbed and extensively biotransformed, and exhibits linear and dose-proportional pharmacokinetics at therapeutic doses. Brivaracetam does not interact with most metabolizing enzymes and drug transporters, and therefore does not interfere with drugs that use these metabolic routes. The favorable pharmacokinetic profile of brivaracetam and lack of clinically relevant drug−drug interactions with commonly prescribed AEDs or oral contraceptives allows administration without dose adjustment, and avoids potential untoward events from decreased efficacy of an AED or oral contraceptive due to a drug−drug interaction. Few agents have been reported to affect the pharmacokinetics of brivaracetam. The strong enzyme-inducing AEDs carbamazepine, phenytoin and phenobarbital/primidone have been shown to moderately lower brivaracetam plasma concentrations, with no adjustment of brivaracetam dose needed. Dose adjustment should be considered when brivaracetam is coadministered with the more potent CYP inducer, rifampin. Additionally, caution should be used when adding or ending treatment with the strong enzyme inducer, St. John’s wort. In summary, brivaracetam (50–200 mg/day) has a favorable pharmacokinetic profile and is associated with few clinically relevant drug–drug interactions.

Keywords

Antiepileptic drug
Brivaracetam
Drug-drug interaction
Pharmacokinetics
SV2A

Abbreviations

AED
antiepileptic drug
AUC
area under the plasma concentration–time curve
BCRP
breast cancer resistance protein
bid
twice daily
BRV
brivaracetam
BSEP
bile salt export pump
CL/F
apparent plasma clearance
Cmax
maximal plasma concentration
CBZ-E
carbamazepine epoxide
CI
confidence interval
CLCR
creatinine clearance
CLB
clobazam
CYP
cytochrome P450
CZP
clonazepam
DDI
drug–drug interaction
EM
homozygous extensive metabolizer
hEM
heterozygous extensive metabolizer
IC50
half maximal inhibitory concentration
LCM
lacosamide
LEV
levetiracetam
LTG
lamotrigine
MATE
multi-drug and toxin extrusion protein
MHD
mono-hydroxy derivative of oxcarbazepine
MRP
multidrug resistance protein
OAT
organic anion transporter
OATP
organic anion transporting polypeptide
OC
oral contraceptive
OCT
organic cation transporter
P-gp
P-glycoprotein
PB
phenobarbital
PGN
pregabalin
PHT
phenytoin
PM
poor metabolizer
SV2A
synaptic vesicle protein 2A
t1/2
elimination half-life
TPM
topiramate
VPA
valproate
ZNS
zonisamide

Cited by (0)