eslicarbazepine acetate

Action and Spectrum

Actions and spectrum:

eslicarbazepine acetate is an antiepileptic medication. It acts by blocking voltage-gated sodium channels in the brain, reducing the excessive electrical activity, and preventing seizures. It is used to treat partial-onset seizures in patients with epilepsy.

The spectrum of eslicarbazepine acetate primarily targets partial-onset seizures, which are a type of focal seizures that originate in one part of the brain. It is effective in reducing frequency and severity of these seizures, thereby helping to improve the quality of life for individuals with epilepsy.

Drug Interaction

Adverse Reaction

Frequency defined

1-10%

1200 mg dose

• Ataxia (6%)
• Tremor (4%)
• Balance disorder (3%)
• Rash (3%)
• Dysarthria (2%)
• Nystagmus (2%)
• Diarrhea & constipation (2%)
• Fatigue (7%)
• Blurred vision (5%)
• Asthenia (3%)
• Depression (3%)
• Insomnia (2%)
• Memory disturbance (2%)
• Gait disturbances (2%)
• Abdominal pain (2%)

800 mg dose

• Diplopia (9%)
• Vomiting (6%)
• Fatigue (4%)
• Balance disorder (3%)
• Tremor (2%)
• Asthenia (2%)
• Peripheral edema (2%)
• Nausea (10%)
• Blurred vision (6%)
• Diarrhea (6%)
• Ataxia (4%)
• Falls (3%)
• Hyponatremia (2%)
• Gait disturbance (2%)
• Urinary tract infections (2%)

>10%

1200 mg dose

• Somnolence (18%)
• Headache (15%)
• Dizziness (28%)
• Nausea (16%)
• Diplopia (11%)

800 mg dose

• Headache (13%)
• Dizziness (20%)
• Somnolence (11%)

Postmarketing Reports

Nutrition and Metabolism Disorders: Syndrome of inappropriate antidiuretic hormone secretion

Lymphatic and Hematologic Systems: agranulocytosis, megaloblastic anemia, Leukopenia, thrombocytopenia, and pancytopenia

Black Box Warning

Black Box Warning:

There were no black box warnings specific to eslicarbazepine acetate.

Contraindication / Caution

Contraindication/Caution:

Contraindication:

• Hypersensitivity: eslicarbazepine acetate is contraindicated in individuals with a known hypersensitivity or allergy to the drug or its components.
• Hypersensitivity to other carbamazepine derivatives: Since eslicarbazepine is a derivative of carbamazepine, individuals with a history of hypersensitivity to other carbamazepine derivatives should avoid using eslicarbazepine acetate.
• Severe liver impairment: The use of eslicarbazepine acetate is contraindicated with severe liver impairment as it may worsen the condition.
• Inherited metabolic disorders: Individuals with known inherited metabolic disorders, such as porphyria, should not use eslicarbazepine acetate as it may exacerbate these conditions.
• Concurrent use with monoamine oxidase inhibitors (MAOIs): eslicarbazepine acetate should not be used in combination with MAOI therapy due to the risk of serotonin syndrome.

Caution:

• Suicidal thoughts and behaviour: eslicarbazepine acetate may increase the risk of suicidal thoughts and behavior. Patients should be monitored for mood or behavioral changes, especially when starting or adjusting the dosage.
• Hypersensitivity reactions: Although rare, hypersensitivity reactions, including serious skin reactions, have been reported with eslicarbazepine acetate. If any signs of hypersensitivity, such as rash or fever, occur, medical attention should be sought immediately.
• Hyponatremia: eslicarbazepine acetate may cause hyponatremia (low sodium levels), especially in elderly patients or those taking other medications that can affect sodium levels. Regular monitoring of sodium levels is recommended, and caution should be used in patients at risk for hyponatremia.
• Dose-related adverse effects: The risk of certain adverse effects, such as dizziness, somnolence, and coordination difficulties, may increase with higher doses of eslicarbazepine acetate. Individual response to the medication may vary, and dosage adjustments may be necessary.
• Drug interactions: eslicarbazepine acetate may interact with other medications, affecting their efficacy or safety.
• Pregnancy and breastfeeding: eslicarbazepine acetate should be used during pregnancy only if the potential benefits the potential risks to the fetus. It may also pass into breast milk, so its use during breastfeeding should be discussed with a healthcare professional.

Comorbidities:

• Mood disorders: Depression & anxiety are more common in people with epilepsy, and these conditions may require additional management alongside epilepsy treatment.
• Cognitive impairments: Epilepsy can be associated with cognitive difficulties, such as memory problems and attention deficits, which may impact daily functioning.
• Sleep disorders: Some individuals with epilepsy may experience sleep disturbances like insomnia or excessive daytime sleepiness.
• Migraine: Epilepsy and migraine have been found to be comorbid conditions in some cases.
• Cardiovascular conditions: Certain heart-related conditions, such as arrhythmias, may occur more frequently in people with epilepsy.
• Metabolic disorders: Epilepsy or its treatments could potentially be associated with metabolic changes, including weight gain or metabolic syndrome.
• Osteoporosis: Long-term use of antiepileptic drugs, including eslicarbazepine acetate, may be associated with reduced bone mineral density, increasing the risk of osteoporosis.

Respiratory issues: Some studies have suggested an association between epilepsy and respiratory problems, including an increased risk of sudden unexpected death in epilepsy.

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned

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:

eslicarbazepine acetate is an antiepileptic drug (AED) that is used for the treatment of partial-onset seizures in epilepsy. It is a prodrug, meaning it is converted in the body to its active form, eslicarbazepine. The pharmacology of eslicarbazepine acetate involves its interaction with voltage-gated sodium channels in the brain.

eslicarbazepine inhibits the activity of these sodium channels, which are responsible for the rapid depolarization and propagation of electrical signals in neurons. By doing so, eslicarbazepine reduces the excitability of neurons and stabilizes the electrical activity in the brain, preventing the uncontrolled and excessive firing of neurons that leads to seizures.

Pharmacodynamics:

• Sodium Channel Inhibition: eslicarbazepine inhibits the activity of voltage-gated Na channels, which are responsible for the rapid depolarization and propagation of electrical signals in neurons. By blocking these channels, eslicarbazepine reduces the influx of sodium ions into neurons, leading to a decrease in neuronal excitability.
• Stabilization of Neuronal Activity: By inhibiting voltage-gated sodium channels, eslicarbazepine stabilizes the electrical activity of neurons. This prevents the uncontrolled and excessive firing of neurons, which is associated with seizures in epilepsy.
• Selectivity for Brain Tissue: eslicarbazepine acetate exhibits a higher affinity for sodium channels in brain tissue compared to other tissues. This selectivity allows for its antiepileptic effects without significant systemic side effects.
• Effects on Other Ion Channels: In addition to its effects on sodium channels, eslicarbazepine may also modulate other ion channels, such as calcium and potassium channels, although its primary mechanism of action is sodium channel inhibition.

Pharmacokinetics:

Absorption

eslicarbazepine acetate is well absorbed after oral administration. It is rapidly and extensively hydrolyzed in the intestinal wall to its active metabolite, eslicarbazepine. Food does not significantly affect its absorption, and the drug can be taken with or without food.

Distribution

eslicarbazepine is highly bound to plasma proteins, primarily albumin. It has a moderate volume of distribution, indicating that it is distributed throughout the body but remains predominantly in the plasma.

Metabolism

eslicarbazepine undergoes minimal metabolism in the liver, primarily through glucuronidation to inactive metabolites. The main enzyme involved in this process is UDP-glucuronosyltransferase (UGT). The parent compound, eslicarbazepine acetate, is not pharmacologically active.

Elimination and excretion

The primary route of elimination for eslicarbazepine and its metabolites is through the kidneys. Approximately 90% of the dosage is excreted in the urine, with the majority of the excretion occurring as glucuronide conjugates. A smaller portion is excreted in feces.

Adminstartion

Administration:

• Dosage: The dosage of eslicarbazepine acetate varies depending on age, weight, and response to treatment. It is typically initiated at a low dose and gradually increased as required to achieve the desired therapeutic effect.
• Frequency: eslicarbazepine acetate is usually taken once daily. It is essential to take the medication at the same time each day to maintain a steady level in the blood.
• With or Without Food: eslicarbazepine acetate can be taken with or without food. However, it is advisable to take it consistently with the same meal preference to help ensure uniform absorption.
• Swallow Whole: The tablets should be administered whole with a glass of water. Do not chew, crush, or break tablets, as this may alter the drug’s release and absorption characteristics.

Avoid Abrupt Discontinuation: It is crucial not to suddenly stop taking eslicarbazepine acetate without consulting a healthcare professional. Abrupt discontinuation can lead to an increased risk of seizures.

Patient Information Leaflet

Patient information leaflet

Generic Name: eslicarbazepine acetate

Pronounced: [ ES-li-kar-BAZ-e-peen]

Why do we use eslicarbazepine acetate?

eslicarbazepine acetate is an antiepileptic medication primarily used for the treatment of partial-onset seizures.

• Adjunctive Therapy for Partial-Onset Seizures: eslicarbazepine acetate is used in combination with other antiepileptic medications to help control partial-onset seizures in adults with epilepsy.

Monotherapy for Partial-Onset Seizures: In some cases, eslicarbazepine acetate may also be used as a monotherapy, meaning it is the sole medication used to control seizures, depending on the patient’s specific condition and response to treatment.