Identification

Name
Eslicarbazepine acetate
Accession Number
DB09119
Type
Small Molecule
Groups
Approved
Description

Eslicarbazepine acetate (ESL) is an anticonvulsant medication approved for use in Europe, the United States and Canada as an adjunctive therapy for partial-onset seizures that are not adequately controlled with conventional therapy. Eslicarbazepine acetate is a prodrug that is rapidly converted to eslicarbazepine, the primary active metabolite in the body. Eslicarbazepine's mechanism of action is not well understood, but it is known that it does exert anticonvulsant activity by inhibiting repeated neuronal firing and stabilizing the inactivated state of voltage-gated sodium channels, thus preventing their return to the activated state during which seizure activity can occur.

Eslicarbazepine acetate is marketed as Aptiom in North America and Zebinix or Exalief in Europe. It is available in 200, 400, 600, or 800mg tablets that are taken once daily, with or without food. Eslicarbazepine acetate is associated with numerous side effects including dizziness, drowsiness, nausea, vomiting, diarrhea, headache, aphasia, lack of concentration, psychomotor retardation, speech disturbances, ataxia, depression and hyponatremia. It is recommended that patients taking eslicarbazepine acetate be monitored for suicidality.

Structure
Thumb
Synonyms
  • (10S)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide
  • (10S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate
  • ESL
  • Stedesa
External IDs
BIA 2-093 / BIA-2-093 / BIA2-093 / SEP 0002093 / SEP-0002093 / SEP0002093
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AptiomTablet200 mgOralSunovion2014-08-07Not applicableCanada
AptiomKitOralSunovion2014-04-07Not applicableUs
AptiomTablet600 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet400 mg/1OralSunovion2014-04-07Not applicableUs
AptiomTablet800 mg/1OralSunovion2014-04-07Not applicableUs
AptiomTablet400 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet200 mg/1OralSunovion2014-04-07Not applicableUs
AptiomTablet800 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet600 mg/1OralSunovion2014-04-07Not applicableUs
ZebinixTablet400 mgOralBial Portela & Ca, S.A.2009-04-21Not applicableEu
International/Other Brands
Eksaliyef (Bial-Portela & Ca. S.A.) / Erelib (Bial-Portela & Ca. S.A.) / Eslicar (Emcure Pharmaceuticals Ltd) / Eslify (Torrent Pharmaceuticals Ltd) / Eslistar (Lupin Ltd) / Eslizen (Intas Pharmaceuticals Ltd) / Exalief (Bial-Portela & Ca. S.A.) / Normictal (Abbott India Ltd ) / Zebinix (Bial-Portela & Ca. S.A., Esai Co. Ltd.) / Zefretol (Sun Pharma Laboratories Ltd)
Categories
UNII
BEA68ZVB2K
CAS number
236395-14-5
Weight
Average: 296.326
Monoisotopic: 296.116092383
Chemical Formula
C17H16N2O3
InChI Key
QIALRBLEEWJACW-INIZCTEOSA-N
InChI
InChI=1S/C17H16N2O3/c1-11(20)22-16-10-12-6-2-4-8-14(12)19(17(18)21)15-9-5-3-7-13(15)16/h2-9,16H,10H2,1H3,(H2,18,21)/t16-/m0/s1
IUPAC Name
(9S)-2-carbamoyl-2-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-9-yl acetate
SMILES
CC(=O)O[[email protected]]1CC2=CC=CC=C2N(C(N)=O)C2=CC=CC=C12

Pharmacology

Indication

Eslicarbazepine acetate is indicated as adjunctive therapy in the treatment of partial-onset seizures that are not adequately controlled with conventional therapy in epileptic patients.

Structured Indications
Pharmacodynamics

Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval.

Mechanism of action

Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity.

TargetActionsOrganism
AP2X purinoceptor 4
antagonist
Human
Absorption

Eslicarbazepine active metabolite has a high bioavailability and reaches peak serum concentration 1-4 hours after a given dose. Eslicarbazepine acetate absorption is not affected by food.

Volume of distribution

The apparent volume of distribution of eslicarbazepine is 61.3 L for a body weight of 70 kg based on population PK analysis.

Protein binding

Eslicarbazepine is bound to plasma proteins at a relatively low rate of <40%, independent of concentration. In vitro studies have shown that plasma protein binding is not relevantly affected by the presence of other medications such as warfarin, diazepam, digoxin, phenytoin or tolbutamide. Similarly, the binding of these medications was not significantly affected by the presence of eslicarbazepine.

Metabolism

Eslicarbazepine acetate is rapidly and extensively metabolized to its major active metabolite, eslicarbazepine, via hydrolytic first-pass metabolism. Eslicarbazepine corresponds to about 92% of systemic exposure. Minor active metabolites (R)-licarbazepine and oxcarbazepine consist of <5% of systemic exposure. Active metabolites are then metabolized to inactive glucuronides that correspond to about 3% of systemic exposure.

Eslicarbazepine had a moderate inhibitory effect on CYP2C19 and a mild activation of UGT1A1-mediated glucuronidation when studied in human hepatic microsomes. It has been shown to induce CYP3A4 enzymes in vivo.

Route of elimination

Eslicarbazepine acetate and its metabolites are eliminated primarily via renal excretion. Eslicarbazepine active metabolite is excreted two-thirds in the unchanged form and one-third as a glucuronide conjugate. This accounts for around 90% of total metabolites excreted, with the remaining 10% being minor metabolites. Renal tubular reabsorption is expected to occur with eslicarbazepine.

Half life

The apparent plasma half-life of eslicarbazepine is 10-20 hours in healthy subjects and 13-20 hours in epilepsy patients. Steady-state plasma concentrations are attained after 4 to 5 days of once daily dosing.

Clearance

Renal clearance of eslicarbazepine was found to be approximately 20 mL/min in healthy subjects with normal renal function.

Toxicity

There are no adequate and well-controlled studies of the use of eslicarbazepine acetate in pregnant women. In studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate did show developmental toxicities, including teratogenicity, embryolethality, and fetal growth retardation, at clinically relevant doses. Drug-induced liver injury ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases with concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported with the use of eslicarbazepine. Overdose with eslicarbazepine acetate appears similar to its known adverse reactions and includes symptoms of hyponatremia, dizziness, nausea, vomiting, somnolence, euphoria, oral paraesthesias, ataxia, and diplopia. There is no specific antidote for eslicarbazepine acetate overdose and it should be treated primarily with supportive measures. If required, the drug may be removed by gastric lavage, partially by hemodialysis or inactivated with activated charcoal.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Eslicarbazepine acetate.Approved
AdinazolamThe metabolism of Adinazolam can be decreased when combined with Eslicarbazepine acetate.Approved
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
AmbrisentanThe metabolism of Ambrisentan can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Eslicarbazepine acetate.Approved, Withdrawn
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Eslicarbazepine acetate.Approved
AmoxicillinThe metabolism of Amoxicillin can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Eslicarbazepine acetate.Approved
ApixabanThe metabolism of Apixaban can be decreased when combined with Eslicarbazepine acetate.Approved
AprepitantThe metabolism of Aprepitant can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
ArtemetherThe metabolism of Artemether can be decreased when combined with Eslicarbazepine acetate.Approved
AtomoxetineThe metabolism of Atomoxetine can be decreased when combined with Eslicarbazepine acetate.Approved
AxitinibThe metabolism of Axitinib can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
AzelastineThe metabolism of Azelastine can be decreased when combined with Eslicarbazepine acetate.Approved
BenzatropineThe metabolism of Benzatropine can be decreased when combined with Eslicarbazepine acetate.Approved
BortezomibThe metabolism of Bortezomib can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
BrivaracetamThe metabolism of Brivaracetam can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
BromazepamThe metabolism of Bromazepam can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Eslicarbazepine acetate.Approved
BupivacaineThe metabolism of Bupivacaine can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Eslicarbazepine acetate.Approved, Investigational
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Eslicarbazepine acetate.Approved
CarisoprodolThe metabolism of Carisoprodol can be decreased when combined with Eslicarbazepine acetate.Approved
ChloramphenicolThe metabolism of Chloramphenicol can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Eslicarbazepine acetate.Investigational, Withdrawn
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Eslicarbazepine acetate.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Eslicarbazepine acetate.Approved
CisaprideThe metabolism of Cisapride can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational, Withdrawn
CitalopramThe serum concentration of Citalopram can be increased when it is combined with Eslicarbazepine acetate.Approved
ClarithromycinThe metabolism of Clarithromycin can be decreased when combined with Eslicarbazepine acetate.Approved
ClobazamThe metabolism of Clobazam can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
clomethiazoleThe metabolism of clomethiazole can be decreased when combined with Eslicarbazepine acetate.Investigational
ClomipramineThe metabolism of Clomipramine can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
ClopidogrelThe serum concentration of the active metabolites of Clopidogrel can be reduced when Clopidogrel is used in combination with Eslicarbazepine acetate resulting in a loss in efficacy.Approved, Nutraceutical
ClotiazepamThe metabolism of Clotiazepam can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
ClozapineThe metabolism of Clozapine can be decreased when combined with Eslicarbazepine acetate.Approved
Conjugated estrogensThe serum concentration of Conjugated estrogens can be decreased when it is combined with Eslicarbazepine acetate.Approved
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
DapsoneThe metabolism of Dapsone can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
DesipramineThe metabolism of Desipramine can be decreased when combined with Eslicarbazepine acetate.Approved
DesogestrelThe serum concentration of Desogestrel can be decreased when it is combined with Eslicarbazepine acetate.Approved
DexlansoprazoleThe metabolism of Dexlansoprazole can be decreased when combined with Eslicarbazepine acetate.Approved
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Eslicarbazepine acetate.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit, Vet Approved
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
DienestrolThe serum concentration of Dienestrol can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
DienogestThe serum concentration of Dienogest can be decreased when it is combined with Eslicarbazepine acetate.Approved
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Eslicarbazepine acetate.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Eslicarbazepine acetate.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Eslicarbazepine acetate.Approved
DoxazosinThe metabolism of Doxazosin can be decreased when combined with Eslicarbazepine acetate.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Eslicarbazepine acetate.Approved
DronabinolThe metabolism of Dronabinol can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
DrospirenoneThe serum concentration of Drospirenone can be decreased when it is combined with Eslicarbazepine acetate.Approved
EletriptanThe metabolism of Eletriptan can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
EnasidenibThe metabolism of Enasidenib can be decreased when combined with Eslicarbazepine acetate.Approved
EnfuvirtideThe metabolism of Enfuvirtide can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
EscitalopramThe metabolism of Escitalopram can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
EsomeprazoleThe metabolism of Esomeprazole can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be decreased when it is combined with Eslicarbazepine acetate.Approved
Estrogens, esterifiedThe serum concentration of Estrogens, esterified can be decreased when it is combined with Eslicarbazepine acetate.Approved
Estrone sulfateThe serum concentration of Estrone sulfate can be decreased when it is combined with Eslicarbazepine acetate.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Eslicarbazepine acetate.Approved
Ethynodiol diacetateThe serum concentration of Ethynodiol diacetate can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtizolamThe metabolism of Etizolam can be decreased when combined with Eslicarbazepine acetate.Approved
EtonogestrelThe serum concentration of Etonogestrel can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Eslicarbazepine acetate.Approved
FamotidineThe metabolism of Famotidine can be decreased when combined with Eslicarbazepine acetate.Approved
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
FlutamideThe metabolism of Flutamide can be decreased when combined with Eslicarbazepine acetate.Approved
FormoterolThe metabolism of Formoterol can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
FosphenytoinThe serum concentration of Eslicarbazepine acetate can be decreased when it is combined with Fosphenytoin.Approved
GestodeneThe serum concentration of Gestodene can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
GliclazideThe metabolism of Gliclazide can be decreased when combined with Eslicarbazepine acetate.Approved
GlucosamineThe metabolism of Glucosamine can be decreased when combined with Eslicarbazepine acetate.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Eslicarbazepine acetate.Approved
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Eslicarbazepine acetate.Approved
HexestrolThe serum concentration of Hexestrol can be decreased when it is combined with Eslicarbazepine acetate.Withdrawn
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Eslicarbazepine acetate.Approved
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Eslicarbazepine acetate.Approved
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Eslicarbazepine acetate.Approved
ImatinibThe metabolism of Imatinib can be decreased when combined with Eslicarbazepine acetate.Approved
ImipramineThe metabolism of Imipramine can be decreased when combined with Eslicarbazepine acetate.Approved
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
IxazomibThe metabolism of Ixazomib can be decreased when combined with Eslicarbazepine acetate.Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
LapatinibThe metabolism of Lapatinib can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
LevomilnacipranThe metabolism of Levomilnacipran can be decreased when combined with Eslicarbazepine acetate.Approved
LevonorgestrelThe serum concentration of Levonorgestrel can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
LorcaserinThe metabolism of Lorcaserin can be decreased when combined with Eslicarbazepine acetate.Approved
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
LynestrenolThe serum concentration of Lynestrenol can be decreased when it is combined with Eslicarbazepine acetate.Investigational
MacitentanThe metabolism of Macitentan can be decreased when combined with Eslicarbazepine acetate.Approved
Medroxyprogesterone acetateThe serum concentration of Medroxyprogesterone acetate can be decreased when it is combined with Eslicarbazepine acetate.Approved, Investigational
MefloquineThe therapeutic efficacy of Eslicarbazepine acetate can be decreased when used in combination with Mefloquine.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Eslicarbazepine acetate.Approved, Nutraceutical, Vet Approved
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Eslicarbazepine acetate.Investigational, Withdrawn
MeprobamateThe metabolism of Meprobamate can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Eslicarbazepine acetate.Approved
MethadoneThe metabolism of Methadone can be decreased when combined with Eslicarbazepine acetate.Approved
MethallenestrilThe serum concentration of Methallenestril can be decreased when it is combined with Eslicarbazepine acetate.Experimental
MethsuximideThe metabolism of Methsuximide can be decreased when combined with Eslicarbazepine acetate.Approved
MethylphenobarbitalThe metabolism of Methylphenobarbital can be decreased when combined with Eslicarbazepine acetate.Approved
MetoprololThe metabolism of Metoprolol can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
MianserinThe therapeutic efficacy of Eslicarbazepine acetate can be decreased when used in combination with Mianserin.Approved, Investigational
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Eslicarbazepine acetate.Approved
NelfinavirThe metabolism of Nelfinavir can be decreased when combined with Eslicarbazepine acetate.Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Eslicarbazepine acetate.Approved
NilutamideThe metabolism of Nilutamide can be decreased when combined with Eslicarbazepine acetate.Approved
NorelgestrominThe serum concentration of Norelgestromin can be decreased when it is combined with Eslicarbazepine acetate.Approved
NorgestimateThe serum concentration of Norgestimate can be decreased when it is combined with Eslicarbazepine acetate.Approved
NorgestrelThe serum concentration of Norgestrel can be decreased when it is combined with Eslicarbazepine acetate.Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Eslicarbazepine acetate.Approved
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational, Vet Approved
OrlistatThe serum concentration of Eslicarbazepine acetate can be decreased when it is combined with Orlistat.Approved, Investigational
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Eslicarbazepine acetate.Approved
OxcarbazepineThe risk or severity of adverse effects can be increased when Eslicarbazepine acetate is combined with Oxcarbazepine.Approved
OxiconazoleThe metabolism of Oxiconazole can be decreased when combined with Eslicarbazepine acetate.Approved
PantoprazoleThe metabolism of Pantoprazole can be decreased when combined with Eslicarbazepine acetate.Approved
PentamidineThe metabolism of Pentamidine can be decreased when combined with Eslicarbazepine acetate.Approved
PentobarbitalThe metabolism of Pentobarbital can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Eslicarbazepine acetate.Approved
PethidineThe metabolism of Pethidine can be decreased when combined with Eslicarbazepine acetate.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Eslicarbazepine acetate.Withdrawn
PhenobarbitalThe serum concentration of Eslicarbazepine acetate can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Eslicarbazepine acetate can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PipotiazineThe metabolism of Pipotiazine can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
PodofiloxThe metabolism of Podofilox can be decreased when combined with Eslicarbazepine acetate.Approved
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Eslicarbazepine acetate.Approved
PraziquantelThe metabolism of Praziquantel can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
PrimidoneThe serum concentration of Eslicarbazepine acetate can be decreased when it is combined with Primidone.Approved, Vet Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Eslicarbazepine acetate.Approved
PromazineThe metabolism of Promazine can be decreased when combined with Eslicarbazepine acetate.Approved, Vet Approved
PropofolThe metabolism of Propofol can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational, Vet Approved
PropranololThe metabolism of Propranolol can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
QuazepamThe metabolism of Quazepam can be decreased when combined with Eslicarbazepine acetate.Approved, Illicit
QuetiapineThe metabolism of Quetiapine can be decreased when combined with Eslicarbazepine acetate.Approved
QuinineThe metabolism of Quinine can be decreased when combined with Eslicarbazepine acetate.Approved
RabeprazoleThe metabolism of Rabeprazole can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
RamelteonThe metabolism of Ramelteon can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
RanitidineThe metabolism of Ranitidine can be decreased when combined with Eslicarbazepine acetate.Approved
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Eslicarbazepine acetate.Approved
RomidepsinThe metabolism of Romidepsin can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be decreased when it is combined with Eslicarbazepine acetate.Approved
RupatadineThe metabolism of Rupatadine can be decreased when combined with Eslicarbazepine acetate.Approved
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Eslicarbazepine acetate.Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational, Vet Approved
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Eslicarbazepine acetate.Approved
SertralineThe metabolism of Sertraline can be decreased when combined with Eslicarbazepine acetate.Approved
SildenafilThe metabolism of Sildenafil can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be decreased when it is combined with Eslicarbazepine acetate.Approved
Synthetic Conjugated Estrogens, AThe serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Eslicarbazepine acetate.Approved
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Eslicarbazepine acetate.Approved
TapentadolThe metabolism of Tapentadol can be decreased when combined with Eslicarbazepine acetate.Approved
TemazepamThe metabolism of Temazepam can be decreased when combined with Eslicarbazepine acetate.Approved
TeniposideThe metabolism of Teniposide can be decreased when combined with Eslicarbazepine acetate.Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational, Vet Approved
TestosteroneThe metabolism of Testosterone can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational, Withdrawn
ThioridazineThe metabolism of Thioridazine can be decreased when combined with Eslicarbazepine acetate.Approved, Withdrawn
TiclopidineThe metabolism of Ticlopidine can be decreased when combined with Eslicarbazepine acetate.Approved
TimololThe metabolism of Timolol can be decreased when combined with Eslicarbazepine acetate.Approved
TipranavirThe metabolism of Tipranavir can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
TofacitinibThe metabolism of Tofacitinib can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Eslicarbazepine acetate.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Eslicarbazepine acetate.Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Eslicarbazepine acetate.Approved
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Eslicarbazepine acetate.Investigational, Withdrawn
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Eslicarbazepine acetate.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Eslicarbazepine acetate.Approved
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Eslicarbazepine acetate.Approved, Investigational
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Eslicarbazepine acetate.Approved
WarfarinThe serum concentration of Warfarin can be decreased when it is combined with Eslicarbazepine acetate.Approved
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Eslicarbazepine acetate.Approved
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Eslicarbazepine acetate.Approved
Food Interactions
Not Available

References

Synthesis Reference
  • Ravinder B, Reddy SR, Sridhar M, Mohan MM, Srinivas K, Reddy AP, Bandichhor R. An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbamazepine. Tetrahedron Letters. 2013 May 29;54(22):2841-4.
  • Desai S, Poddar A, Sawant K: Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability. Mater Sci Eng C Mater Biol Appl. 2016 Jan 1;58:826-34. doi: 10.1016/j.msec.2015.09.019. Epub 2015 Sep 8. Pubmed.
General References
  1. Banach M, Borowicz KK, Czuczwar SJ: Pharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):639-48. doi: 10.1517/17425255.2015.1021686. Epub 2015 Mar 5. [PubMed:25740561]
  2. Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [PubMed:20043029]
  3. Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. [PubMed:22612290]
  4. Villanueva V, Serratosa JM, Guillamon E, Garces M, Giraldez BG, Toledo M, Salas-Puig J, Lopez Gonzalez FJ, Flores J, Rodriguez-Uranga J, Castillo A, Mauri JA, Camacho JL, Lopez-Gomariz E, Giner P, Torres N, Palau J, Molins A: Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study. Epilepsy Res. 2014 Sep;108(7):1243-52. doi: 10.1016/j.eplepsyres.2014.04.014. Epub 2014 May 14. [PubMed:24908564]
  5. Soares-da-Silva P, Pires N, Bonifacio MJ, Loureiro AI, Palma N, Wright LC: Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect. 2015 Mar;3(2):e00124. doi: 10.1002/prp2.124. Epub 2015 Mar 30. [PubMed:26038700]
  6. Rocamora R: A review of the efficacy and safety of eslicarbazepine acetate in the management of partial-onset seizures. Ther Adv Neurol Disord. 2015 Jul;8(4):178-86. doi: 10.1177/1756285615589711. [PubMed:26136845]
  7. Tomic MA, Pecikoza UB, Micov AM, Stepanovic-Petrovic RM: The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors. Anesth Analg. 2015 Dec;121(6):1632-9. doi: 10.1213/ANE.0000000000000953. [PubMed:26465930]
  8. Jacobson MP, Pazdera L, Bhatia P, Grinnell T, Cheng H, Blum D: Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study. BMC Neurol. 2015 Mar 28;15:46. doi: 10.1186/s12883-015-0305-5. [PubMed:25880756]
  9. Zaccara G, Giovannelli F, Cincotta M, Carelli A, Verrotti A: Clinical utility of eslicarbazepine: current evidence. Drug Des Devel Ther. 2015 Feb 10;9:781-9. doi: 10.2147/DDDT.S57409. eCollection 2015. [PubMed:25709402]
  10. Sperling MR, Abou-Khalil B, Harvey J, Rogin JB, Biraben A, Galimberti CA, Kowacs PA, Hong SB, Cheng H, Blum D, Nunes T, Soares-da-Silva P: Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial. Epilepsia. 2015 Feb;56(2):244-53. doi: 10.1111/epi.12894. Epub 2014 Dec 22. [PubMed:25528898]
  11. Shaikh S, Rizvi SM, Hameed N, Biswas D, Khan M, Shakil S, Kamal MA: Aptiom (eslicarbazepine acetate) as a dual inhibitor of beta-secretase and voltage-gated sodium channel: advancement in Alzheimer's disease-epilepsy linkage via an enzoinformatics study. CNS Neurol Disord Drug Targets. 2014;13(7):1258-62. [PubMed:25230222]
  12. Doeser A, Soares-da-Silva P, Beck H, Uebachs M: The effects of eslicarbazepine on persistent Na(+) current and the role of the Na(+) channel beta subunits. Epilepsy Res. 2014 Feb;108(2):202-11. doi: 10.1016/j.eplepsyres.2013.11.022. Epub 2013 Dec 8. [PubMed:24368131]
External Links
KEGG Drug
D09612
PubChem Compound
179344
PubChem Substance
310265036
ChemSpider
156110
BindingDB
50240669
ChEBI
87016
ChEMBL
CHEMBL87992
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eslicarbazepine_acetate
ATC Codes
N03AF04 — Eslicarbazepine
AHFS Codes
  • 28:12.92 — Miscellaneous Anticonvulsants
FDA label
Download (820 KB)
MSDS
Download (44.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentEpilepsies25
1CompletedTreatmentEpilepsy, Localization Related2
1CompletedTreatmentPain, Neuropathic1
1TerminatedTreatmentEpilepsies2
2CompletedNot AvailableEpilepsies1
2CompletedTreatmentBipolar I Disorder2
2CompletedTreatmentEpilepsies2
2CompletedTreatmentEpilepsy, Localization Related1
2CompletedTreatmentFibromyalgia1
2CompletedTreatmentMigraines1
2CompletedTreatmentPainful Diabetic Neuropathy1
2CompletedTreatmentPostherpetic Neuralgia1
2TerminatedTreatmentBipolar I Disorder1
3Active Not RecruitingTreatmentEpilepsy, Localization Related1
3Active Not RecruitingTreatmentPartial Epilepsy in Children and Adolescents1
3CompletedTreatmentEpilepsies3
3CompletedTreatmentEpilepsy With Simple or Complex Partial Onset Seizures1
3CompletedTreatmentEpilepsy, Localization Related2
3CompletedTreatmentRefractory Partial Epilepsy1
3Enrolling by InvitationTreatmentEpilepsies1
3TerminatedTreatmentEpilepsies1
3TerminatedTreatmentPainful Diabetic Neuropathy1
3TerminatedTreatmentPost-Herpetic Neuralgia (PHN)1
4CompletedTreatmentEpilepsies1
4RecruitingTreatmentEpilepsies1
4RecruitingTreatmentEpilepsy With Partial On-set Seizures1
Not AvailableCompletedNot AvailableEpilepsies2
Not AvailableCompletedNot AvailablePartial onset seizure Epilepsy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitOral
TabletOral200 mg
TabletOral200 mg/1
TabletOral400 mg/1
TabletOral400 mg
TabletOral600 mg/1
TabletOral600 mg
TabletOral800 mg/1
TabletOral800 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5753646No1996-06-272016-06-27Us
US8372431No2010-04-172030-04-17Us
US9206135No2006-04-212026-04-21Us
US9643929No2006-04-212026-04-21Us
US9566244No2008-10-232028-10-23Us
US9763954No2008-09-132028-09-13Us
US9750747No2012-08-242032-08-24Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityWater solubility of eslicarbazepine acetate is low at less than 1 mg/mL including at different pH values. Its main metabolite eslicarbazepine has a greater water solubility of 4.2 mg/mL.# Banach M, Borowicz KK, Czuczwar SJ: Pharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):639-48. doi: 10.1517/17425255.2015.1021686. Epub 2015 Mar 5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/25740561
logP8.8# Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/22612290
Predicted Properties
PropertyValueSource
Water Solubility0.11 mg/mLALOGPS
logP1.99ALOGPS
logP2.17ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)15.96ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.63 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity81.44 m3·mol-1ChemAxon
Polarizability30.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzazepines. These are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Dibenzazepines
Direct Parent
Dibenzazepines
Alternative Parents
Azepines / Benzenoids / Ureas / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Dibenzazepine / Azepine / Benzenoid / Carboxylic acid ester / Urea / Carbonic acid derivative / Carboxylic acid derivative / Monocarboxylic acid or derivatives / Azacycle / Organic nitrogen compound
show 8 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
acetate ester, carboxamide, dibenzoazepine (CHEBI:87016)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for ATP that acts as a ligand-gated ion channel. This receptor is insensitive to the antagonists PPADS and suramin.
Gene Name
P2RX4
Uniprot ID
Q99571
Uniprot Name
P2X purinoceptor 4
Molecular Weight
43368.725 Da
References
  1. Tian M, Abdelrahman A, Weinhausen S, Hinz S, Weyer S, Dosa S, El-Tayeb A, Muller CE: Carbamazepine derivatives with P2X4 receptor-blocking activity. Bioorg Med Chem. 2014 Feb 1;22(3):1077-88. doi: 10.1016/j.bmc.2013.12.035. Epub 2013 Dec 25. [PubMed:24411477]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. [PubMed:22612290]
  2. Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [PubMed:20043029]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. [PubMed:22612290]
  2. Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [PubMed:20043029]

Drug created on September 22, 2015 14:02 / Updated on December 11, 2017 13:01