Oxcarbazepine


Article Author:
Charles Preuss
Gagandeep Randhawa
Radia Jamil


Article Editor:
Abdolreza Saadabadi


Editors In Chief:
Lauren Camaione


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
5/30/2019 9:42:17 PM

Indications

Oxcarbazepine is a 10-keto derivative of carbamazepine which came to the market in 2000. However, the minor structural differences in between oxcarbazepine and carbamazepine have led to major differences in the induction of metabolic pathways and the metabolism of the two medications.

Oxcarbazepine is available as an extended release (XR). It is a member of a class of medications known as anticonvulsants and voltage-sensitive sodium channel antagonists. Oxcarbazepine is FDA-approved for partial seizures in adults with epilepsy or partial seizures in children with epilepsy ages 4 to 16. This medication can be used as monotherapy or adjunctive to another medication for the management of seizures. Oxcarbazepine is also used for bipolar disorder; however, this medication is not yet FDA-approved for bipolar disorder.[1][2][3][4]

Mechanism of Action

Oxcarbazepine binds to sodium channels and inhibits the high-frequency repetitive neuronal firing. Oxcarbazepine also inhibits the release of glutamate. This medication is metabolized by the liver and excreted by the kidneys. Oxcarbazepine is very rapidly converted to licarbazepine which is its active metabolite (monohydroxy metabolite, MHD). Licarbazepine is responsible for the antiseizure activity of oxcarbazepine. The half-life of oxcarbazepine is 1 to 3.7 hours while the half-life of licarbazepine is 8 to 10 hours. Oxcarbazepine has not been shown to cause autoinduction of its metabolism such as carbamazepine.[5][6][7]

Oxcarbazepine is known to be a weak inducer of the CYP3A4 which plays a role in estrogen metabolism. Thus oxcarbazepine can reduce the efficacy of oral contraceptives when used in high doses. Oxcarbazepine is also a weak inhibitor of CYP2C19 and can cause an increase in phenytoin concentrations when used very high doses. Oxcarbazepine itself is not affected by CYP3A4 inhibitors like carbamazepine is.

Administration

Oxcarbazepine is only available in the oral dosage form at this time; both tablets and liquid formulations are available. Oxcarbazepine shows rapid and nearly complete absorption after oral administration, about 95% absorption. The usual doses range for oxcarbazepine is 1200 to 2400 mg per day. Whether using oxcarbazepine for monotherapy or adjunct for seizure control, the initial dose can be 600 mg per day divided into 2 separate doses. For monotherapy of patient with a seizure disorder, the physician may increase by 300 mg every 3 days to a dose of 1200 mg daily. Doses as high as 2400 mg daily have been shown to be effective when changing to monotherapy. For adjunctive therapy for seizure control, the dose may be increased in 600 mg weekly intervals to a total of 1200 mg daily in 2 divided doses for immediate release and 1200 to 2400 mg daily for extended release.

When using oxcarbazepine with other sedating medications, the physician should slowly titrate the medication for the patient inorder to best tolerate the sedating side effects of the medications.

Immediate release dosage form should be taken 2 times a day and it can be taken with or without food. The liquid formulation may be mixed with water for better tolerability.

Extended-release medication should be taken one time a day. It is important to take the extended-release oxcarbazepine on an empty stomach and not to cut or crush the medication before ingesting it.

It is very important to slowly taper off oxcarbazepine. If oxcarbazepine is suddenly discontinued, it may cause the epilepsy patient to seize or may cause a relapse of a bipolar patient.

Adverse Effects

Oxcarbazepine can lead to central nervous system (CNS) side effects due to its blockade of voltage-sensitive sodium channels. Some common side effects that patients experience when taking oxcarbazepine are sedation, dizziness, abnormal gait, headache, ataxia, fatigue, confusion, nausea, vomiting, abdominal pain, or rash. Hyponatremia and increased suicidal ideation are two of the most dangerous and life-threatening side effects which patients may experience while taking oxcarbazepine. Weight gain and sedation can occur as well in a minority of patients. If patients have experienced hypersensitivity with carbamazepine, they are more likely to experience hypersensitivity with oxcarbazepine. Oxcarbazepine is structurally similar to carbamazepine and thus an increased risk of Stevens-Johnson syndrome or toxic epidermal necrolysis in Asian patients with the HLA-B*1502 allele. When experiencing a side effect, it is recommended to wait and continue medication if the side effect is not disruptive to life or dangerous, with time most side effects do end. If side effects continue, physicians should consider switching to another agent, and augmenting oxcarbazepine with another agent is usually not successful. It is important to note that side effects may increase when increasing the dose of oxcarbazepine.[8][9]

Contraindications

Avoid abrupt withdrawal of oxcarbazepine. Please use with caution in children, elderly, pregnancy, and renal impairment patients that had a hypersensitivity reaction to carbamazepine.

Monitoring

It is very important to monitor serum sodium concentrations. Hyponatremia is a severe risk that can occur with the use of oxcarbazepine. The risk for hyponatremia is the highest in the first 3 months of medication use, and 2% to 3% of patients may experience hyponatremia. Hyponatremia is when sodium concentrations are below 125 mmol/L.  It is important to monitor the use of selective serotonin reuptake inhibitor (SSRI) use with oxcarbazepine, as these medications can cause a decrease in sodium concentrations through the syndrome of inappropriate antidiuretic hormone (SIADH) production.

Special Populations

Children

Approved for use in children four years and older as monotherapy or adjunctive therapy for partial seizures. The initial dose should be 8 to 10 mg/kg per day separated in two divided doses.

Pregnancy

Oxcarbazepine and licarbazepine (MHD) can cross the placenta and they have been found in the newborn. Data from a limited number of pregnancy regisitries suggest congentital malformations can occur, e.g., craniofacial, cardiac. Pregnant patients taking oxcarbazepine are encourage to enroll in a pregnancy registry (www.aedpregnancyregistry.org).

Renal Impairment

May need to start a lower starting dose and titrate more slowly in patients with renal complications because the kidney excretes oxcarbazepine.

Hepatic Impairment

No adjustment in oxcarbazepine dose required.

Cardiac Impairment

No adjustment in oxcarbazepine dose required.

Elderly

Geriatric population may have decreased renal clearance and thus should be started at lower doses and titrated more slowly as oxcarbazepine is renally excreted.

Toxicity

Oxcarbazepine studies done in rats and dogs over a 3 and 6-month period have shown reversible dose-dependent liver weight increases, and this is considered to be due to centrilobular megalocytosis. Oxcarbazepine metabolism differs significantly between humans and rats, and therefore this toxicity cannot be generalized to human patients.

Enhancing Healthcare Team Outcomes

Healthcare workers (including the primary physician, nurse practitioner) who prescribe oxcarbazepine should be aware of it is indications and adverse effect profile. The drug is known to cause many CNS adverse effects including sedation, dizziness, abnormal gait, headache, ataxia, fatigue, confusion, nausea, vomiting, abdominal pain, or rash. Hyponatremia and increase suicidal ideation are two of the most dangerous and life-threatening side effects which patients may experience while taking oxcarbazepine. Weight gain and sedation can occur as well in a minority of patients. If side effects continue, physicians should consider switching to another agent because augmenting oxcarbazepine with another agent is usually not successful. It is important to note that side effects may increase with higher doses of oxcarbazepine.


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Oxcarbazepine - Questions

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A 25-year-old man presents to the emergency department with nausea, malaise, headache, lethargy, and confusion. The patient’s serum sodium is 120 mmol/L. The patient has a history of seizures, and he started a new antiseizure medication four months ago. Which of the following is the most likely cause of this clinical presentation?



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A 36-year-old Asian woman is diagnosed with new-onset partial seizures. The clinician selects oxcarbazepine for treatment. The patient’s electronic record documents the HLA-B*1502 allele. For which of the following does the patient have the highest risk?



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Oxcarbazepine - References

References

Bosak M,Słowik A,Iwańska A,Lipińska M,Turaj W, Co-medication and potential drug interactions among patients with epilepsy. Seizure. 2019 Jan 16;     [PubMed]
Di Stefano G,Maarbjerg S,Truini A, Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options. The journal of headache and pain. 2019 Feb 19;     [PubMed]
Jansen AC,Andermann E, Progressive Myoclonus Epilepsy, Lafora Type 1993;     [PubMed]
Caraballo RH,Cachia P,Valenzuela GR,Calvo A, Rasmussen syndrome: absence seizures may be induced by oxcarbazepine. Epileptic disorders : international epilepsy journal with videotape. 2019 Feb 15;     [PubMed]
Golpayegani M,Salari F,Gharagozli K, Newer Antiepileptic Drugs Discontinuation due to Adverse Effects: An Observational Study. Annals of Indian Academy of Neurology. 2019 Jan-Mar;     [PubMed]
Tomson T,Battino D,Perucca E, Teratogenicity of antiepileptic drugs. Current opinion in neurology. 2019 Jan 16;     [PubMed]
Li W,Jayagopal LA,Taraschenko O, Ictal asystole with isolated syncope: A case report and literature review. Epilepsy     [PubMed]
Thelengana A,Shukla G,Srivastava A,Singh MB,Gupta A,Rajan R,Vibha D,Pandit AK,Prasad K, Cognitive, behavioural and sleep-related adverse effects on introduction of levetiracetam versus oxcarbazepine for epilepsy. Epilepsy research. 2019 Feb;     [PubMed]
Khalid K,Kwak BS,Leo RJ, Oxcarbazepine-Induced Stevens-Johnson Syndrome. The primary care companion for CNS disorders. 2018 Dec 20;     [PubMed]

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