Clinical data | |
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Pronunciation | /ɒks.kɑːrˈbæz.ɪˌpiːn/ |
Trade names | Trileptal, Oxtellar XR, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a601245 |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | >95% |
Metabolism | Liver (cytosolic enzymes and glucuronic acid) |
Elimination half-life | 1–5 hours (healthy adults) |
Excretion | Kidney (<1%) [3] |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.044.702 |
Chemical and physical data | |
Formula | C15H12N2O2 |
Molar mass | 252.273 g·mol−1 |
3D model (JSmol) | |
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Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy. [3] [5] For epilepsy it is used for both focal seizures and generalized seizures. [6] It has been used both alone and as add-on therapy in people with bipolar disorder who have had no success with other treatments. [7] [5] It is taken by mouth. [3] [5]
Common side effects include nausea, vomiting, dizziness, drowsiness, double vision and trouble with walking. [3] Serious side effects may include anaphylaxis, liver problems, pancreatitis, suicide ideation, and an abnormal heart beat. [3] [6] While use during pregnancy may harm the baby, use may be less risky than having a seizure. [1] [8] Use is not recommended during breastfeeding. [1] In those with an allergy to carbamazepine there is a 25% risk of problems with oxcarbazepine. [3] How it works is not entirely clear. [5]
Oxcarbazepine was patented in 1969 and came into medical use in 1990. [9] It is available as a generic medication. [6] In 2022, it was the 167th most commonly prescribed medication in the United States, with more than 3 million prescriptions. [10] [11]
Oxcarbazepine is an anticonvulsant used to reduce the occurrence of epileptic episodes, and is not intended to cure epilepsy. [12] Oxcarbazepine is used alone or in combination with other medications for the treatment of focal (partial) seizures in adults. [3] In pediatric populations, it can be used by itself for the treatment of partial seizures for children 4 years and older, or in combination with other medications for children 2 years and older. [3] There is some evidence to support its effectiveness in reducing seizure frequency when used as an add-on therapy for drug-resistant focal epilepsy but there are concerns over tolerability. [13]
Oxcarbazepine (brand name Trileptal), has been historically used off-label by psychiatrists as a mood stabilizer. However, due to the limited data supporting efficacy it is typically reserved for patients for whom other medications have not worked or are contraindicated. [14] [15]
Side effects are dose-dependent. The most common include dizziness, blurred or double vision, nystagmus, ataxia, fatigue, headaches, nausea, vomiting, sleepiness, difficulty in concentration, and mental sluggishness. [3] The incidence of movement disorders appears to be lower compared to carbamazepine. [16]
Other, rare, side effects of oxcarbazepine include severe low blood sodium (hyponatremia), anaphylaxis / angioedema, hypersensitivity (especially if experienced with carbamazepine), toxic epidermal necrolysis, Stevens–Johnson syndrome, and thoughts of suicide. [3]
Measurement of serum sodium levels should be considered in maintenance treatment or if symptoms of hyponatremia develop. [3] Low blood sodium is seen in 20–30% of people taking oxcarbazepine, and 8–12% of those experience severe hyponatremia. Some side effects, such as headaches, are more pronounced shortly after a dose is taken and tend to fade with time (60 to 90 minutes). Other side effects include stomach pain, tremor, rash, diarrhea, constipation, decreased appetite, and dry mouth. Photosensitivity is a potential side-effect and people could experience severe sunburns as a result of sun exposure. [3]
Oxcarbazepine may lead to hypothyroxinemia. The well-known reduction in free and total thyroxine concentration may be due to both peripheral and central mechanisms. [17]
Oxcarbazepine is pregnancy category C in the US. [18] There is limited data supporting its safety in pregnancy. Several alternative medications with similar efficacy profiles provide significantly more robust data to support safety during pregnancy. [19] However limited recent research shows similar rates of fetal malformations in exposed pregnancies to the general non-teratogen exposed population. [20] Careful consideration of the risks, benefits, alternatives, and expert advise is needed when considering Oxcarbazepine use during pregnancy.[ citation needed ]
Historically Oxcarbazepine was considered to be teratogenic in humans due to animal studies which have shown increased fetal abnormalities in pregnant rats and rabbits exposed to oxcarbazepine during pregnancy. Additionally it's similar structure of to carbamazepine, raised concern as it is teratogenic in humans (pregnancy category D). [21] [22]
Oxcarbazepine and its metabolite licarbazepine are both present in human breast milk and thus, some of the active drug can be transferred to a nursing infant. [3] When considering whether to continue this medication in nursing mothers, the impact of the drug's side effect profile on the infant should be weighed against its anti-epileptic benefit for the mother. [3]
Oxcarbazepine, licarbazepine and many other common drugs influence each other through interaction with the cytochrome P450 family of enzymes. This leads to a cluster of dozens of common drugs interacting with one another to varying degrees, some of which are especially noteworthy.[ citation needed ]
Oxcarbazepine and licarbazepine are potent inhibitors of CYP2C19 and thus have the potential to increase plasma concentration of drugs, which are metabolized through this pathway. [3] Other antiepileptics, which are CYP2C19 substrates and thus may be metabolised at a reduced rate when combined with oxcarbazepine, include diazepam, [23] [24] hexobarbital, [23] mephenytoin, [23] [24] methylphenobarbital, [23] nordazepam, [24] phenobarbital, [23] phenytoin, [24] and primidone. [23]
In addition, oxcarbazepine and licarbazepine are CYP3A4 and CYP3A5 inducers and thus have the potential to decrease the plasma concentration of CYP3A4 and CYP3A5 substrates, [3] including calcium channel antagonists against high blood pressure and oral contraceptives. [3] [12] However, whether the extent of CYP3A4/5 induction at therapeutic doses reaches clinical significance is unclear. [3]
Oxcarbazepine is a prodrug, which is largely metabolized to its pharmacologically active 10-monohydroxy derivative licarbazepine (sometimes abbreviated MHD). [3] [25] Oxcarbazepine and MHD exert their action by blocking voltage-sensitive sodium channels, thus leading to the stabilization of hyper-excited neural membranes, suppression of repetitive neuronal firing and diminishment propagation of synaptic impulses. [3] Furthermore, anticonvulsant effects of these compounds could be attributed to enhanced potassium conductance and modulation of high-voltage activated calcium channels. [3]
Oxcarbazepine has high bioavailability upon oral administration. [3] In a study in humans, only 2% of oxcarbazepine remained unchanged, 70% were reduced to licarbazepine; the rest were minor metabolites. [3] The half-life of oxcarbazepine is considered to be about 2 hours, whereas licarbazepine has a half-life of nine hours. Through its chemical difference to carbamazepine metabolic epoxidation is avoided, reducing hepatic risks. [26] Licarbazepine is metabolised by conjugation with Glucuronic acid. Approximately 4% are oxidised to the inactive 10,11-dihydroxy derivative. Elimination is almost completely renal, with faeces accounting to less than 4%. 80% of the excreted substances are to be attributed to licarbazepine or its glucuronides.[ citation needed ]
Both oxcarbazepine and licarbazepine were found to show anticonvulsant properties in seizure models done on animals. [3] These compounds had protective functions whenever tonic extension seizures were induced electrically, but such protection was less apparent whenever seizures were induced chemically. [3] There was no observable tolerance during a four weeks course of treatment with daily administration of oxcarbazepine or licarbazepine in electroshock test on mice and rats. [3] Most of the antiepileptic activity can be attributed to licarbazepine. [3] Aside from its reduction in side effects, it is presumed to have the same main mechanism as carbamazepine, sodium channel inhibition, and is generally used to treat the same conditions.[ citation needed ]
The human leukocyte antigen (HLA) allele B*1502 has been associated with an increased incidence of Stevens–Johnson syndrome and toxic epidermal necrolysis in people treated with carbamazepine, and thus those treated with oxcarbazepine might have similar risks. [3] People of Asian descent are more likely to carry this genetic variant, especially some Malaysian populations, Koreans (2%), Han Chinese (2–12%), Indians (6%), Thai (8%), and Philippines (15%). [3] Therefore, it has been suggested to consider genetic testing in these people prior to initiation of treatment. [3]
Oxcarbazepine is a structural derivative of carbamazepine, with a ketone in place of the carbon–carbon double bond on the dibenzazepine ring at the 10 position (10-keto). This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia or agranulocytosis occasionally associated with carbamazepine. [ citation needed ] Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine — sodium channel inhibition (presumed to be the main mechanism of action) – and is generally used to treat the same conditions.[ citation needed ]
Oxcarbazepine is a prodrug which is activated to licarbazepine in the liver. [25]
First made in 1966, [26] it was patent-protected by Geigy in 1969 through DE 2011087 . It was approved for use as an anticonvulsant in Denmark in 1990, Spain in 1993, Portugal in 1997, and eventually for all other EU countries in 1999. It was approved in the US in 2000. [5] In September 2010, Novartis, of which Geigy are part of its corporate roots, pleaded guilty to marketing Trileptal for the unapproved uses of neuropathic pain and bipolar disorder. [27]
Antiepileptics are a key pharmacological therapy used in the treatment of bipolar disorder. [28] Research has investigated the use of oxcarbazepine as a mood stabilizer in bipolar disorder, with further evidence needed to fully assess its suitability. [7] [29] [30] [31] Oxcarbazepine used in conjunction with lithium has been shown to be effective in the maintenance phase. [32]
It may be beneficial in trigeminal neuralgia. [33]
Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures.
Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.
A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder.
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures and focal seizures, but not absence seizures. The intravenous form, fosphenytoin, is used for status epilepticus that does not improve with benzodiazepines. It may also be used for certain heart arrhythmias or neuropathic pain. It can be taken intravenously or by mouth. The intravenous form generally begins working within 30 minutes and is effective for roughly 24 hours. Blood levels can be measured to determine the proper dose.
Valproate are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.
Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.
Topiramate, sold under the brand name Topamax among others, is a medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence and essential tremor. For epilepsy this includes treatment for generalized or focal seizures. It is taken orally.
Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression in any groups except for the severely depressed; but for patients with bipolar disorder who are not currently symptomatic, it appears to reduce the risk of future episodes of depression.
Levetiracetam, sold under the brand name Keppra among others, is a novel antiepileptic drug (medication) used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures, and is taken either by mouth as an immediate or extended release formulation or by injection into a vein.
Clonazepam, sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, obsessive–compulsive disorder (OCD), and akathisia. It is a long-acting tranquilizer of the benzodiazepine class. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. It is typically taken orally but is also used intravenously. Effects begin within one hour and last between eight and twelve hours in adults.
Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures and essential tremors. It is taken by mouth.
Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder.
Felbamate is an anticonvulsant used in the treatment of epilepsy. It is used to treat partial seizures in adults and partial and generalized seizures associated with Lennox–Gastaut syndrome in children. However, an increased risk of potentially fatal aplastic anemia and/or liver failure limit the drug's usage to severe refractory epilepsy.
Lacosamide, sold under the brand name Vimpat among others, is a medication used for the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. It is used by mouth or intravenously.
Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai Co. that is used in addition to other drugs to treat partial seizures and generalized tonic-clonic seizures for people older than twelve years. It was first approved in 2012, and as of 2016, its optimal role in the treatment of epilepsy relative to other drugs was not clear. It was the first antiepileptic drug in the class of selective non-competitive antagonist of AMPA receptors.
Eslicarbazepine acetate (ESL), sold under the brand names Aptiom and Zebinix among others, is an anticonvulsant medication approved for use in Europe and the United States as monotherapy or as additional therapy for partial-onset seizures epilepsy.
Antimanic drugs are psychotropic drugs that are used to treat symptoms of mania. Though there are different causes of mania, the majority is caused by bipolar disorder, therefore antimanic drugs are mostly similar to drugs treating bipolar disorder. Since 1970s, antimanic drugs have been used specifically to control the abnormal elevation of mood or mood swings during manic episodes. One purpose of antimanic drugs is to alleviate or shorten the duration of an acute mania. Another objective is to prevent further cycles of mania and maintain the improvement achieved during the acute episode. The mechanism of antimanic drugs has not yet been fully known, it is proposed that they mostly affect chemical neurotransmitters in the brain. However, the usage of antimanic drugs should be consulted with a doctor or pharmacist due to their side effects and interactions with other drugs and food.
Women with epilepsy can have safe, healthy pregnancies and healthy babies. However, proper planning and care is essential. The goal of planning is to minimize the risk of congenital malformations and neurodevelopmental disorders for the fetus while maintaining the mother's seizure control.
Fetal valproate spectrum disorder (FVSD), previously known as fetal valproate syndrome (FVS), is a rare disease caused by prenatal exposure to valproic acid (VPA), a medication commonly used to treat epilepsy, bipolar disorder, and migraines. This exposure can lead to a range of neurodevelopmental and physical symptoms, including cognitive impairments, developmental delays, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and congenital malformations.