oxcarbazepine

Action and Spectrum

Actions and Spectrum: 

oxcarbazepine is an antiepileptic medication used to treat various types of seizures, particularly partial ones. It was developed as a derivative of carbamazepine, another widely used AED. oxcarbazepine is primarily prescribed for epilepsy but can also be used for conditions like trigeminal neuralgia and mood disorders. 

Action: The exact mechanism of action of oxcarbazepine is not fully understood, but it is believed to involve several mechanisms that contribute to its antiepileptic effects: 

• Sodium channel modulation: oxcarbazepine and its active metabolite, 10-hydroxycarbazepine, can inhibit voltage-gated sodium channels in the brain. By blocking these channels, the drug reduces the excitability of neurons and decreases the generation and propagation of abnormal electrical impulses responsible for seizures. 
• Potassium channel modulation: oxcarbazepine may also enhance the activity of specific potassium channels, which can further stabilize neuronal membranes and reduce abnormal electrical activity. 
• Attenuation of glutamate release: Glutamate is a major excitatory neurotransmitter in the brain. oxcarbazepine has been found to reduce the release of glutamate, which can help prevent excessive neuronal excitability. 

Spectrum: oxcarbazepine is primarily indicated for treating partial seizures in adults and children over the age of 2 years. Partial seizures involve abnormal electrical discharges limited to a specific brain area and can lead to localized or focal symptoms. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Abnormal gait (16-20%) 

Vision abnormalities (11-15%) 

Nausea/vomiting (26-30%) 

Dizziness (30-50%) 

Tremor (16-20%) 

Ataxia (10-30%) 

Somnolence (26-30%) 

Diplopia (30-50%) 

Fatigue (11-15%) 

Vertigo (11-15%) 

Abdominal pain (11-15%) 

Nystagmus (26-30%) 

Headache (26-30%) 

1-10% 

Asthenia 

Dyspepsia (5-6%) 

Rash (4%) 

Hyponatremia (1-3%) 

Abnormal thinking (<4%) 

Hypotension (<2%) 

Insomnia (2-4%) 

Speech disorder (1%) 

Muscle weakness (1-2%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity to oxcarbazepine: Individuals with a known allergy or hypersensitivity to oxcarbazepine or its components should not take this medication. 
• Hypersensitivity to Carbamazepine: Since oxcarbazepine is structurally related to carbamazepine, patients who have experienced a hypersensitivity reaction to carbamazepine in the past may also be at risk of reacting to oxcarbazepine and should avoid its use. 
• Severe Liver Impairment: oxcarbazepine is metabolized by the liver, and severe liver impairment can lead to an accumulation of the drug and its active metabolite, potentially causing adverse effects. Therefore, it is generally not recommended for individuals with severe liver disease. 
• Hypersensitivity to Eslicarbazepine Acetate: Eslicarbazepine acetate is another antiepileptic drug related to oxcarbazepine. Patients who are hypersensitive to eslicarbazepine acetate should avoid taking oxcarbazepine. 
• Hereditary Disorders: Some hereditary conditions, such as rare genetic disorders like porphyria, may be worsened by the use of oxcarbazepine due to its potential effects on porphyrin metabolism. Therefore, it is generally not recommended for individuals with a history of porphyria or related disorders. 
• Concomitant Use with Monoamine Oxidase Inhibitors (MAOIs): Concurrent use of oxcarbazepine and MAOIs or within 14 days of stopping MAOIs is contraindicated due to the potential risk of serotonin syndrome, a severe and potentially life-threatening condition. 
• Pregnancy and Breastfeeding: The safety of oxcarbazepine during pregnancy and breastfeeding is not fully established. It might pose risks to the developing fetus/nursing infant. Therefore, its use in pregnant or breastfeeding individuals may be contraindicated or require careful consideration and supervision by a healthcare professional. 

Caution 

• Hypersensitivity Reactions: Although rare, oxcarbazepine can cause allergic reactions in some individuals. If you experience symptoms such as rash, itching, hives, swelling of the face/throat, or difficulty breathing, seek immediate medical attention and discontinue the medication. 
• Hyponatremia: oxcarbazepine can lead to low sodium levels in the blood (hyponatremia), especially in elderly patients or those taking other medications that can lower sodium levels. Symptoms of hyponatremia may include headache, nausea, confusion, and seizures. Regular monitoring of sodium levels is necessary, especially during the first few months of treatment. 
• Dizziness and Drowsiness: oxcarbazepine can cause dizziness and drowsiness and impair concentration and coordination.  
• Birth Control and Hormonal Contraceptives: oxcarbazepine might decrease the effectiveness of hormonal contraceptives. Women of childbearing age should use alternative or additional non-hormonal contraceptive methods while taking oxcarbazepine. 
• Withdrawal Risk: Abruptly stopping oxcarbazepine can increase the risk of seizure recurrence. If discontinuing the medication is necessary, it should be done under the supervision of a healthcare professional and with a gradual tapering of the dosage. 
• Psychiatric Symptoms: Some patients may experience mood changes, depression, or other psychiatric symptoms while taking oxcarbazepine.  
• Interactions with Other Medications: oxcarbazepine can interact with other medications, including antiepileptic drugs, antidepressants, and antipsychotics.  
• Renal Impairment: oxcarbazepine is eliminated mainly through the kidneys. Patients with renal impairment might require dosage adjustments, and their kidney function have to be monitored regularly during treatment. 
• Pregnancy and Breastfeeding: As mentioned earlier, the safety of oxcarbazepine during pregnancy and breastfeeding is not fully established.

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: D 

US FDA pregnancy category: C 

Lactation:   

Excreted into human milk: Yes. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

oxcarbazepine is an antiepileptic drug (AED) with a complex pharmacology. It is a prodrug rapidly converted to its active metabolite, 10-hydroxycarbazepine, contributing to its anticonvulsant effects. The primary mechanism of action involves the modulation of voltage-gated sodium channels, reducing the excitability of neurons and inhibiting the generation and propagation of abnormal electrical impulses responsible for seizures.

Additionally, oxcarbazepine may enhance the activity of specific potassium channels, stabilize neuronal membranes, and reduce glutamate release, further contributing to its antiepileptic properties. The drug is primarily used for partial seizures in adults and children, and it may also be effective in treating trigeminal neuralgia and off-label use for bipolar disorder. Regular monitoring and caution are needed for possible side effects, including hyponatremia, dizziness, and drowsiness. 

Pharmacodynamics: 

Mechanism of action: oxcarbazepine is an antiepileptic drug (AED) used to treat various types of seizures, particularly partial seizures. Its mechanism of action is not fully understood, but it is believed to involve multiple mechanisms that contribute to its antiepileptic effects: 

• Sodium Channel Modulation: The primary mechanism of action of oxcarbazepine is the modulation of voltage-gated sodium channels in the brain. Its active metabolite, 10-hydroxycarbazepine (MHD), can bind to and inhibit these channels. Specifically, the sodium channel subtypes Nav1.1, Nav1.2, and Nav1.3. By blocking these channels, oxcarbazepine reduces the excitability of neurons and prevents the abnormal and excessive firing of electrical impulses that lead to seizures. 
• Potassium Channel Modulation: oxcarbazepine may also enhance the activity of specific potassium channels in the brain. Promoting the efflux of potassium ions from neurons can stabilize neuronal membranes and further reduce neuronal excitability. 
• Attenuation of Glutamate Release: Glutamate is a major excitatory neurotransmitter in the brain. oxcarbazepine has been found to reduce the release of glutamate, which can help prevent excessive neuronal excitability and the spread of seizure activity. 

Pharmacokinetics: 

Absorption 

oxcarbazepine is well absorbed after oral administration. The absorption process occurs in the gastrointestinal tract. Food intake does not significantly affect absorption so it can be taken with or without food. However, high-fat meals may slightly increase the rate of absorption. 

Distribution 

oxcarbazepine and its active metabolite, 10-hydroxycarbazepine (MHD), have moderate to high protein binding (40-42% for oxcarbazepine and 49-68% for MHD). They bind primarily to plasma albumin. The drug and its metabolite distribute throughout the body, crossing the blood-brain barrier, and have a volume of distribution of approximately 49 liters. 

Metabolism 

oxcarbazepine undergoes extensive metabolism in the liver. The major metabolite is 10-hydroxycarbazepine (MHD), which possesses anticonvulsant properties similar to the parent compound. MHD is responsible for most of the pharmacological effects of oxcarbazepine. The metabolism is primarily mediated by the enzyme cytosolic enzyme UGT2B7 and, to a lesser extent, by CYP3A4 and CYP3A5 enzymes. 

Elimination and Excretion 

The elimination half-life of oxcarbazepine is relatively short, approximately 1 to 5 hours, while the half-life of MHD is more prolonged, ranging from 8 to 15 hours. 

Adminstartion

Administration: 

Oral administration 

oxcarbazepine is available in different formulations, including tablets and oral suspension. The administration of oxcarbazepine may vary depending on the patient’s age, the specific condition being treated, and the prescribed dosage. It’s essential to follow your healthcare provider’s instructions and the information on the prescription label.  

• Dosage: The dosage of oxcarbazepine will be determined by your healthcare provider depending on the age, weight, medical condition, and response to the drug. Always take the prescribed dosage as directed and avoid altering the dosage without consulting your doctor. 
• Timing: oxcarbazepine is usually taken twice daily with or without food. It’s essential to take the medication simultaneously each day to maintain a consistent level of the drug in your system. 
• Tablets: If prescribed oxcarbazepine tablets, swallow them whole with water. Do not crush, break/chew the tablets unless your doctor instructs you. 
• Oral Suspension: If prescribed the oral suspension form of oxcarbazepine, shake the bottle well before each use. Measure the correct dose using the provided measuring device (usually an oral syringe or a dosing spoon). If preferred, the suspension can be taken directly or mixed with a small amount of water or juice. 
• Missing Doses: If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time.
• Do Not Discontinue Abruptly: If you need to stop taking oxcarbazepine for any reason, it should be done gradually under the supervision of your healthcare provider. Suddenly stopping the medication may increase the risk of seizures. 
• Interactions: Be cautious about potential interactions with other medications, supplements/herbal products you are taking.  
• Special Instructions: If you take other antiepileptic medications, your doctor may adjust the dosage or schedule to avoid interactions and optimize treatment. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: oxcarbazepine 

Pronounced: [ ox-kar-BAY-zeh-peen ] 

Why do we use oxcarbazepine? 

oxcarbazepine is an antiepileptic drug (AED) primarily used to treat epilepsy and related conditions. Its main indication is the management of various types of seizures, particularly partial seizures.  

• Partial Seizures: oxcarbazepine is approved for treating partial seizures in adults and children over the age of 2 years. Partial seizures are characterized by abnormal electrical discharges localized to a specific brain area and can lead to localized or focal symptoms. oxcarbazepine helps to control these seizures by stabilizing neuronal membranes and reducing abnormal electrical activity. 
• Epilepsy: As an antiepileptic drug, oxcarbazepine is prescribed as a maintenance treatment for epilepsy. It is used to prevent the occurrence of seizures and improve seizure control in individuals with epilepsy. 
• Trigeminal Neuralgia: It is a neurological condition characterized by severe, recurrent facial pain. oxcarbazepine effectively reduces the frequency and intensity of pain attacks in some patients with trigeminal neuralgia. 
• Bipolar Disorder (Off-label use): While not an FDA-approved indication, some healthcare providers may prescribe oxcarbazepine off-label for treating mood disorders, particularly bipolar disorder. It may help stabilize mood swings and reduce manic episodes.