Oxcarbazepine


Article Author:
Charles Preuss
Gagandeep Randhawa
Tom Joshua Wy


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Abdolreza Saadabadi


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Nazia Sadiq
Hajira Basit
Phillip Hynes
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Sandeep Sekhon


Updated:
10/10/2019 3:38:50 PM

Indications

Oxcarbazepine is a 10-keto derivative of carbamazepine which came to the market in 2000. However, the minor structural differences between oxcarbazepine and carbamazepine have led to significant 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 is useful as monotherapy or adjunctive to another medication for the management of seizures. Oxcarbazepine is also an option 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 gets metabolized by the liver and excreted by the kidneys. Oxcarbazepine very rapidly converts 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 two separate doses. For monotherapy of patient with a seizure disorder, the physician may increase by 300 mg every three 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 to best tolerate the sedating side effects of the medications.

Immediate-release dosage form dosing should be two times a day, and dowsing can be with or without food. The patient may mix the liquid formulation 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 essential to taper off oxcarbazepine slowly. If the patient discontinues oxcarbazepine suddenly, 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 cease. 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 essential 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 three 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 registries suggest congenital malformations can occur, e.g., craniofacial, cardiac. Pregnant patients taking oxcarbazepine are encouraged 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 the oxcarbazepine dose required.

Cardiac Impairment

No adjustment in oxcarbazepine dose required.

Elderly

The geriatric population may have decreased renal clearance and thus should be started at lower doses and titrated more slowly as oxcarbazepine undergoes renal excretion.

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.

Nursing should actively participate in this monitoring since they often have more frequent contact with the patient. They can also assess treatment effectiveness on follow-up visits, as well as monitoring for adverse drug effects. They will report any issues to the doctor and/or pharmacist. Pharmacists need to verify dosing and in cases of drugs like oxcarbazepine, checking for potential drug-drug interactions crucial since they can impair the therapeutic effectiveness of oxcarbazepine.  If any interactions are present, the pharmacist must contact the prescriber immediately. If the patient is receiving cognitive therapy as well from a different provider, that individual also needs to know about the patient's regimen so that they can monitor for adverse effects as well.

All medications require interprofessional coordination, but it may even be more crucial for drugs such as oxcarbazepine; all members of the healthcare team need to participate, collaborate, and communicate to optimize results and minimize adverse effects. [Level V]


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Oxcarbazepine - Questions

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A 21-year-old woman presents to the clinician with concerns about weekly muscle contractions on the left side of her body. The patient states that she is fully conscious during the muscle contractions, but she has no control over them. The muscle contractions started a month ago. Her vital signs include a blood pressure of 114/78 mmHg, a temperature of 98.7 degrees Fahrenheit, respiration of 15 breaths per minute, and a pulse of 75 beats per minute. The physical exam is unremarkable. The patient is prescribed oxcarbazepine for treatment. Which of the following is the most likely mechanism of action of the prescribed drug?



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A 55-year- old female patient presents to her primary care practitioner with fatigue, weight gain, and profound sadness. The patient has a history of seizures and Hashimoto disease. Her vital signs are blood pressure of 110/71 mmHg, the temperature of 98.4 F, and a pulse of 70 beats per minute. The patient’s laboratory values are sodium of 141 mmol/L, potassium of 4.5 mmol/L, magnesium of 1.1 mmol/L, the glucose of 5 mmol/L, and thyroid-stimulating hormone of 5 mU/L. The physical exam is unremarkable. The patient is currently prescribed levothyroxine and oxcarbazepine. Which of the following is the most likely explanation for the patient presentation?



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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 patient’s electronic record documents the presence of the HLA-B*1502 allele. Her vital signs include a blood pressure of 115/77 mmHg, a temperature of 98.5 degrees Fahrenheit, respiration of 14 breaths per minute, and a pulse of 79 beats per minute. Physical examination is unremarkable. The patient is prescribed oxcarbazepine for treatment. Which of the following does the patient have the highest risk of developing because of her treatment with oxcarbazepine?



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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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