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 known as 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.
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. 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 induce autoinduction of its metabolism such as carbamazepine.
Oxcarbazepine is known to be a weak inducer of the CYP 3A4. CYP 3A4 plays a role in estrogen metabolism. Thus oxcarbazepine can reduce the efficacy of oral contraceptives when used in high doses. Oxcarbazepine is a weak inhibitor of CYP 2C19 and can, therefore, arise phenytoin levels when used very high doses. Oxcarbazepine itself is not affected by CYP 3A4 inhibitors like carbamazepine is.
Oxcarbazepine is only available in the oral 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 physician may increase by 300 mg every 3 days to a dose of 1200 mg daily. Doses as high as oxcarbazepine 2400 mg daily have been shown to be effective when changing to monotherapy. For adjunctive therapy for seizure control may increase at 600 mg at 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 physician should slowly titrate medication for the patient to best tolerate the sedating side effects of medications.
Immediate release medication should be taken 2 times a day, can take with or without food. The liquid formulation may be mixed with water for better tolerability of medications.
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 epilepsy patient to seize or may cause a relapse of a bipolar patient.
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 increase suicidal ideation are 2 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. 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.
Avoid abrupt withdrawal of oxcarbazepine. Please use with caution in children, elderly, pregnancy, renal impairment, patients that had a hypersensitivity reaction to carbamazepine.
It is very important to monitor serum sodium level. 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 known as sodium levels 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 levels through the syndrome of inappropriate antidiuretic hormone production.
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.
Oxcarbazepine is a category C drug. Category C means that no human trials have been done on this medication, but some animal studies done using oxcarbazepine have shown adverse effects. When used in the first trimester is may increase the risk of CNS teratogenic effects such as neural tube defects. It must be assessed for risks and benefits when considering starting or continuing oxcarbazepine in a pregnant woman. If oxcarbazepine is to be used during pregnancy, it is important to start folate to reduce the risk of neural tube defects.
May need to start a lower starting dose and titrate more slowly in patients with renal complications because the kidney excretes oxcarbazepine.
No adjustment in oxcarbazepine dose required.
No adjustment in oxcarbazepine dose required.
Geriatric population may have decreased renal clearance and thus should be started at lower doses and titrated more slowly as oxcarbazepine is renally excreted.
Oxcarbazepine studies done in rats and dogs over a 3 and 6-month period have shown reversible dose-dependent liver weight increases, 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.