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| Clinical data | |
|---|---|
| Trade names | Xcopri, Ontozry |
| Other names | YKP3089 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a620021 |
| License data | |
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | ≥88% |
| Protein binding | 60% |
| Metabolism | Mainlyglucuronidation viaUGT2B7 |
| Eliminationhalf-life | 50–60 hours |
| Excretion | Mainly via urine |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C10H10ClN5O2 |
| Molar mass | 267.67 g·mol−1 |
| 3D model (JSmol) | |
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Cenobamate, sold under the brand namesXcopri (US) andOntozry (EU), is amedication used for the treatment ofpartial-onset seizures, a kind ofepilepsy, in adults.[3][7][8] It is takenby mouth.[3]
Cenobamate was approved for medical use in the United States in November 2019,[3][7][8][9] and placed in Schedule V of theControlled Substances Act in March 2020.[10] Cenobamate was authorized for medical use in the European Union in March 2021,[5] approved for use in the UK in December 2021,[11] and approved for use in Canada in June 2023.[12]
In the United States, cenobamate isindicated for the treatment ofpartial-onset seizures in adults.[3]
In the European Union, it is indicated for theadjunctive treatment of focal-onset seizures with or without secondary generalization in adults withepilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medications.[5]
In the UK, it is used as an add-on treatment, after at least 1 other add-on treatment has not controlled seizures and only when treatment is started in a specialised epilepsy service (tertiary care).[11]
Cenobamate shortens theQT interval of the heart rhythm. It is therefore contraindicated in people with familialshort QT syndrome, a very rare disease of the electrical system of the heart.[13][14]
The most common side effects are drowsiness (in 37% of people taking the drug), dizziness (33%), andfatigue (24%). Sight disorders, headache and elevatedpotassium levels in the blood (over 5 mmol/L) are also common.[13]Hypersensitivity occurs in fewer than 1% of patients,drug reaction with eosinophilia and systemic symptoms (DRESS) in fewer than 0.1%.[14]
There are few data regarding cenobamate overdose. It is expected that the described adverse effects such as drowsiness, dizziness and fatigue would occur, as well as possibly problems with the heart rhythm. No specificantidote exists.[13][14]
Using cenobamate together with othercentral nervous system depressants such asbarbiturates,benzodiazepines oralcohol may result in increased drowsiness and othercentral nervous system symptoms.[13][14]
Cenobamateinduces the enzymesCYP3A4 andCYP2B6 and can therefore decrease blood concentrations of drugs that aremetabolized by these enzymes (for examplemidazolam andbupropion, respectively). Conversely, itinhibits the enzymeCYP2C19, potentially increasing concentrations of drugs metabolized by this enzyme (for exampleomeprazole).[13][14]
Cenobamate is avoltage-gated sodium channel (VGSC)blocker.[15] It is aselective blocker of the inactivated state of VGSCs, preferentially inhibiting persistent sodium current.[15] It has been proposed that cenobamate additionally enhancespresynapticrelease ofγ-aminobutyric acid (GABA), thereby increasinginhibitoryGABAergicneurotransmission.[15]
Cenobamate is absorbed from the gut to at least 88% and reaches highest concentrations in theblood plasma after one to four hours. When in the bloodstream, 60% of the substance are bound toplasma proteins, mostly toalbumin. Cenobamate is inactivated mainly byglucuronidation via the enzymeUGT2B7 and to a lesser extentUGT2B4. The enzymesCYP2E1,CYP2A6,CYP2B6,CYP2C19 andCYP3A4 play smaller roles in the drug's metabolism.[14]
Steady state conditions are reached after 14 days. Cenobamate and itsmetabolites are mostly eliminated via the urine and only to 5.2% via the faeces. Theterminal half-life is 50 to 60 hours.[14]
The safety and efficacy of cenobamate to treat partial-onset seizures was established in two randomized, double-blind,placebo-controlled studies that enrolled 655 adults. In these studies, patients had partial-onset seizures with or without secondary generalization for an average of approximately 24 years and median seizure frequency of 8.5 seizures per 28 days during an 8-week baseline period. During the trials, doses of 100, 200, and 400 milligrams (mg) daily reduced the number of seizures per 28 days compared with the placebo group.[7]
The USFood and Drug Administration (FDA) approved cenobamate in November 2019, and granted the application for Xcopri to SK Life Science Inc.[7][8][9][16]
In January 2021, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization.[17] The applicant for this medicinal product is Arvelle Therapeutics Netherlands B.V.[17] Ontozry was authorized for medical use in the European Union in March 2021.[5][18]
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