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| Clinical data | |
|---|---|
| Trade names | Aptiom, Zebinix, Exalief |
| AHFS/Drugs.com | Monograph |
| License data | |
| Pregnancy category | |
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | ~30%[5] |
| Metabolism | UGT (?) |
| Metabolites | Eslicarbazepine (active),glucuronides (inactive), etc. |
| Eliminationhalf-life | 10–20 hours |
| Excretion | ~90% renal |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.164.398 |
| Chemical and physical data | |
| Formula | C17H16N2O3 |
| Molar mass | 296.326 g·mol−1 |
| 3D model (JSmol) | |
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Eslicarbazepine acetate (ESL), sold under the brand namesAptiom andZebinix among others, is ananticonvulsant medication approved for use in Europe and the United States as monotherapy or as additional therapy for partial-onset seizuresepilepsy.[6][4][3]
Similarly tooxcarbazepine, ESL behaves as aprodrug to (S)-(+)-licarbazepine.[7] As such, theirmechanisms of action are identical.[8]
Eslicarbazepine acetate is contraindicated in people with second- or third-degreeatrioventricular block, a type of heart block, in the Austria-Codex. However heart block is not mentioned as a contraindication by the US FDA.[9] It is contraindicated for people who are hypersensitive to eslicarbazepine,oxcarbazepine orcarbamazepine.[10]
Adverse effects are similar to oxcarbazepine. The most common ones (more than 10% of patients) are tiredness and dizziness. Other fairly common side effects (1 to 10%) include impaired coordination,gastrointestinal disorders such asdiarrhoea, nausea and vomiting,rash (1.1%), andhyponatremia (lowsodium blood levels, 1.2%).[3][10] There may also be an increased risk ofsuicidal thoughts.[11]
Symptoms of overdosing are similar to adverse effects of standard doses: severe hyponatraemia,somnolence, uncoordinated/unsteady gait,hemiparesis (weakness of one side of the body), along with visual and gastrointestinal disturbances. No specificantidote is available. Eslicarbazepine and metabolites can bedialyzed.[3][10]
Like oxcarbazepine, eslicarbazepine can reduce plasma levels of drugs that are metabolized by the liver enzymesCYP3A4 (verified in studies forsimvastatin and the oral contraceptivelevonorgestrel/ethinylestradiol) andUDP-glucuronosyltransferase, and increase plasma levels of drugs metabolized byCYP2C19.[3][10]
Interaction studies have been conducted with a number of common anticonvulsants.Carbamazepine reducesblood plasma concentrations of eslicarbazepine, probably because it inducesglucuronidation. This drug combination also increased the risk fordiplopia, impaired coordination and dizziness in a clinical study.Phenytoin also reduces eslicarbazepine plasma concentrations, which may be due to increased glucuronidation of eslicarbazepine; and concomitant administration results in an increase in phenytoin serum concentrations, which is probably due to inhibition of CYP2C19.[11] Combinations withlamotrigine,topiramate,valproic acid orlevetiracetam showed no significant interactions in studies, although eslicarbazepine has been shown to cause a minor reduction in lamotrigine levels.[10][11]
The active component, eslicarbazepine, has the same mechanism of action as oxcarbazepine (which is a prodrug for licarbazepine, theracemate of eslicarbazepine) and most likely the closely related carbamazepine. It stabilises the inactive state ofvoltage-gated sodium channels, allowing for less sodium to enter neural cells, which leaves them less excitable.[12] According to some sources, it has not been shown conclusively that this is the actual mechanism.[3][10]
Eslicarbazepine acetate is absorbed to at least 90% from the gut, independently of food intake. It is quickly metabolised to eslicarbazepine, so that the original substance cannot be detected in the bloodstream. Peak plasma levels of eslicarbazepine are reached after 2–3 (1–4) hours, andplasma protein binding is somewhat less than 40%.Biological half-life is 10 to 20 hours, and steady-state concentrations are reached after four to five days after start of the treatment.[3][10] Oxcarbazepine, for comparison, is also nearly completely absorbed from the gut, and peak plasma concentrations of licarbazepine are reached after 4.5 hours on average after oxcarbazepine intake. Plasma protein binding and half-life are of course the same.[13]
Other metabolites of ESL are the less active (R)-(−)-licarbazepine (5%; thestereoisomer of eslicarbazepine), the pharmacologically active oxcarbazepine (1%), and inactiveglucuronides of all of these substances. The drug is excreted mainly via the urine, of which two thirds are in the form of eslicarbazepine and one third in the form of eslicarbazepine glucuronide. The other metabolites only account for a few percent of the excreted drug.[3][10]
Persons with certain genetic variations inhuman leukocyte antigens (HLAs) are under increased risk of developing skin reactions such asacute generalized exanthematous pustulosis (AGEP), but also severe ones such asStevens–Johnson andDRESS syndrome, under treatment with carbamazepine and drugs with related chemical structures. This is true for theHLA-A*3101 allele, which occurs in 2 to 5% of Europeans and 10% of Japanese people, and theHLA-B*1502 allele, which is mainly found in people of Asian descent. Theoretically, this may also apply to ESL.[10]
As the name suggests, eslicarbazepine acetate is theacetateesterprodrug of eslicarbazepine. Eslicarbazepine itself is the pharmacologically more active of the two stereoisomers of licarbazepine.[3] More specifically, it is (S)-(+)-licarbazepine.
Eslicarbazepine acetate was developed by the Portuguese pharmaceutical companyBial. In early 2009, Bial sold the marketing rights in Europe to the Japanese companyEisai.[14] The drug was approved in the European Union in April 2009 under the trade namesZebinix andExalief, but was marketed only under the first name.[15][16] In the US it is marketed bySunovion (formerly Sepracor) and was approved in November 2013.[6]
In May 2025, the medication's primary US patents expired, and generic versions of the medication became available as a generic drug.[17] This lowered the all-discounted retail cost from thousands of dollars to as little as $67.25 for the consumer - even more significant as alternative studied treatments such as trigeminal neuralgia are excluded from most US insurance coverage, due to Bial/Sunovion not submitting approval for additional treatments to the FDA.[18]
Studies for the use of ESL as an anticonvulsant for children are under way as of 2016[update].[19]
Like oxcarbazepine, ESL has potential uses for the treatment oftrigeminal neuralgia[20] andbipolar disorder. A 2015 assessment showed no statistical difference to placebo for the latter disorder.[21]
