Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

. For epilepsy it is used for both

focal seizure Focal seizures are seizures that originate within brain networks limited to one hemisphere of the brain. In most cases, each seizure type has a consistent site of onset and characteristic patterns of spread, although some individuals experience mo ...

s and

generalized seizure Generalized epilepsy is a form of epilepsy characterized by generalized seizures that occur with no obvious cause. Generalized seizures, as opposed to focal seizures, are a type of seizure that manifests as impaired consciousness, bilateral motor ...

s. It has been used both alone and as add-on therapy in people with

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

who have had no success with other treatments. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. Common side effects include nausea, vomiting, dizziness, drowsiness,

double vision Diplopia is the simultaneous perception of two images of a single object that may be displaced in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often voluntary. However, when occ ...

and trouble with walking. Serious side effects may include

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

, liver problems,

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...

suicide ideation Suicide is the act of intentionally causing one's own death. Risk factors for suicide include mental disorders, physical disorders, and substance abuse. Some suicides are impulsive acts driven by stress (such as from financial or ac ...

, and an abnormal heart beat. While use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

may harm the baby, use may be less risky than having a seizure. Use is not recommended during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

. In those with an allergy to

carbamazepine 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 ...

there is a 25% risk of problems with oxcarbazepine. How it works is not entirely clear. Oxcarbazepine was patented in 1969 and came into medical use in 1990. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 167th most commonly prescribed medication in the United States, with more than 3million prescriptions.

Medical uses

Neurology

Oxcarbazepine is an

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

used to reduce the occurrence of epileptic episodes, and is not intended to cure epilepsy. Oxcarbazepine is used alone or in combination with other medications for the treatment of focal (partial) seizures in adults. 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. 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.

Psychiatry

Oxcarbazepine (brand name Trileptal), has been historically used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...

by psychiatrists as a

mood stabilizer 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. Uses Mood stabilizers are best known for t ...

. However, due to the limited data supporting efficacy it is typically reserved for patients for whom other medications have not worked or are

contraindicated In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...

Side effects

Side effects are dose-dependent. The most common include dizziness, blurred or double vision,

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

, headaches, nausea, vomiting, sleepiness, difficulty in concentration, and mental sluggishness. The incidence of

movement disorder Movement disorders are clinical syndromes with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders present with extrapyramidal symptoms and are caused by basa ...

s appears to be lower compared to

. Other, rare, side effects of oxcarbazepine include severe low blood sodium (hyponatremia), anaphylaxis /

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

, hypersensitivity (especially if experienced with carbamazepine),

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...

, and thoughts of suicide. Measurement of serum sodium levels should be considered in maintenance treatment or if symptoms of hyponatremia develop. 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 A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

, rash, diarrhea, constipation, decreased appetite, and dry mouth.

Photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...

is a potential side-effect and people could experience severe

sunburn Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and other animals include red or reddish skin tha ...

s as a result of sun exposure. Oxcarbazepine may lead to hypothyroxinemia. The well-known reduction in free and total

thyroxine Thyroxine, also known as T4, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T3). Thyroxine and its acti ...

concentration may be due to both peripheral and central mechanisms.

Pregnancy

Oxcarbazepine is pregnancy category C in the US. 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. However limited recent research shows similar rates of fetal malformations in exposed pregnancies to the general non- teratogen exposed population. Careful consideration of the risks, benefits, alternatives, and expert advise is needed when considering Oxcarbazepine use during pregnancy. 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).

Breastfeeding

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. 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.

Interactions

Oxcarbazepine, licarbazepine and many other common drugs influence each other through interaction with the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

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. Oxcarbazepine and licarbazepine are potent inhibitors of

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some ...

and thus have the potential to increase plasma concentration of drugs, which are metabolized through this pathway. Other antiepileptics, which are CYP2C19 substrates and thus may be metabolised at a reduced rate when combined with oxcarbazepine, include

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

hexobarbital Hexobarbital or hexobarbitone, sold both in acid and sodium salt forms as Citopan, Evipan, and Tobinal, is a barbiturate derivative having hypnotic and sedative effects. It was used in the 1940s and 1950s as an agent for inducing anesthesia for s ...

, mephenytoin,

methylphenobarbital Methylphenobarbital (INN), also known as mephobarbital (USAN, JAN) and mephobarbitone ( BAN), marketed under brand names such as Mebaral, Mephyltaletten, Phemiton, and Prominal, is a drug which is a barbiturate derivative and is used primarily ...

nordazepam Nordazepam (INN; marketed under brand names Nordaz, Stilny, Madar, Vegesan, and Calmday; also known as nordiazepam, desoxydemoxepam, and desmethyldiazepam) is a 1,4-benzodiazepine derivative. Like other benzodiazepine derivatives, it has amnesi ...

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...

, and

primidone Primidone, sold under various brand names (including Mysoline), is a barbiturate medication that is used to treat partial seizure, partial and generalized seizures and essential tremors. It is taken Oral administration, by mouth. Its common ...

. In addition, oxcarbazepine and licarbazepine are

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

and

CYP3A5 Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene. Tissue distribution ''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...

inducers and thus have the potential to decrease the plasma concentration of CYP3A4 and CYP3A5 substrates, including calcium channel antagonists against high blood pressure and

oral contraceptives Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. The introduction of the birth control pill ("the Pill") in 1960 revolutionized the options for contraception, ...

. However, whether the extent of CYP3A4/5 induction at therapeutic doses reaches clinical significance is unclear.

Pharmacology

Oxcarbazepine is a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

, which is largely

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

to its pharmacologically active 10-monohydroxy derivative licarbazepine (sometimes abbreviated ''MHD''). 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. Furthermore, anticonvulsant effects of these compounds could be attributed to enhanced potassium conductance and modulation of high-voltage activated calcium channels.

Pharmacokinetics

Oxcarbazepine has high

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

upon oral administration. In a study in humans, only 2% of oxcarbazepine remained unchanged, 70% were reduced to licarbazepine; the rest were minor metabolites. The

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''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. Licarbazepine is metabolised by conjugation with

Glucuronic acid Glucuronic acid (GCA, from ) is a uronic acid that was first isolated from urine (hence the name "uronic acid"). It is found in many natural gum, gums such as gum arabic ( 18%), xanthan, and kombucha tea and is important for the metabolism of ...

. 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.

Pharmacodynamics

Both oxcarbazepine and licarbazepine were found to show anticonvulsant properties in seizure models done on animals. These compounds had protective functions whenever tonic extension seizures were induced electrically, but such protection was less apparent whenever seizures were induced chemically. 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. Most of the antiepileptic activity can be attributed to licarbazepine. Aside from its reduction in side effects, it is presumed to have the same main mechanism as carbamazepine,

sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell (biology), cell's cell membrane, membrane. They belong to the Cation channel superfamily, superfamily of cation channels. Classific ...

inhibition, and is generally used to treat the same conditions.

Pharmacogenetics

The

human leukocyte antigen The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histo ...

(HLA) allele B*1502 has been associated with an increased incidence of

and

in people treated with carbamazepine, and thus those treated with oxcarbazepine might have similar risks. 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%). Therefore, it has been suggested to consider genetic testing in these people prior to initiation of treatment.

Structure

Oxcarbazepine is a structural derivative of

, with a

ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

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 The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

of metabolizing the drug, and also prevents the serious forms of

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...

occasionally associated with

. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine —

inhibition (presumed to be the main mechanism of action) – and is generally used to treat the same conditions. Oxcarbazepine is a

which is activated to licarbazepine in the liver.

History

First made in 1966, it was

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

-protected by

Geigy Novartis AG is a Swiss multinational pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by revenue in 2024. Novartis manufactures the drugs ...

in 1969 through . It was approved for use as an anticonvulsant in

Denmark Denmark is a Nordic countries, Nordic country in Northern Europe. It is the metropole and most populous constituent of the Kingdom of Denmark,, . also known as the Danish Realm, a constitutionally unitary state that includes the Autonomous a ...

in 1990,

Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...

in 1993,

Portugal Portugal, officially the Portuguese Republic, is a country on the Iberian Peninsula in Southwestern Europe. Featuring Cabo da Roca, the westernmost point in continental Europe, Portugal borders Spain to its north and east, with which it share ...

in 1997, and eventually for all other EU countries in 1999. It was approved in the US in 2000. In September 2010,

Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...

, of which Geigy are part of its corporate roots, pleaded guilty to marketing Trileptal for the unapproved uses of neuropathic pain and bipolar disorder.

Research

Antiepileptics are a key pharmacological therapy used in the treatment of bipolar disorder. Research has investigated the use of oxcarbazepine as a mood stabilizer in bipolar disorder, with further evidence needed to fully assess its suitability. Oxcarbazepine used in conjunction with

lithium Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...

has been shown to be effective in the maintenance phase. It may be beneficial in

trigeminal neuralgia Trigeminal neuralgia (TN or TGN), also called Fothergill disease, tic douloureux, trifacial neuralgia, is a chronic pain, long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor funct ...

References

{{Portal bar , Medicine Wikipedia medicine articles ready to translate Anticonvulsants CYP3A4 inducers Dibenzazepines Embryotoxicants Drugs developed by Novartis Ketones Mood stabilizers Prodrugs Teratogens Ureas