eslicarbazepine

Action and Spectrum

Actions and spectrum: 

eslicarbazepine is an antiepileptic medication that belongs to the dibenzazepine carboxamide class. Its primary mechanism of action is believed to be the inhibition of voltage-gated sodium channels, which reduces the repetitive neuronal firing and stabilizes hyperexcitable neuronal membranes. This action helps to control seizures. 

eslicarbazepine is primarily used in the treatment of partial-onset seizures, which are a common type of epilepsy characterized by seizures that start in a specific region of the brain. It can be used as monotherapy or as adjunctive therapy in combination with other antiepileptic drugs. 

The spectrum of eslicarbazepine’s activity is focused on partial-onset seizures, including simple and complex partial seizures. It is not typically used for the treatment of other types of seizures or conditions unrelated to epilepsy. The specific effectiveness and safety of eslicarbazepine may vary depending on the individual patient and their specific seizure disorder. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

1200 mg dose 

• Ataxia (6%) 
• Tremor (4%) 
• Balance disorder (3%) 
• Rash (3%) 
• Dysarthria (2%) 
• Nystagmus (2%) 
• Constipation and Diarrhea (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%) 
• Hyponatremia (2%) 
• Gait disturbance (2%) 
• UTI (2%) 
• Nausea (10%) 
• Blurred vision (6%) 
• Diarrhoea (6%) 
• Ataxia (4%) 
• Falls (3%) 
• Tremor (2%) 
• Asthenia (2%) 
• Peripheral edema (2%) 

>10% 

1200 mg dose 

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

800 mg dose 

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

Post marketing Reports 

Nutrition and Metabolism Disorders: SIADH 

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

Black Box Warning

Black Box Warning: 

There were no black box warnings specifically associated with eslicarbazepine 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: eslicarbazepine is contraindicated in individuals who have a known hypersensitivity or allergic reaction to eslicarbazepine acetate or any of the other components of the medication. 
• Hypersensitivity to Other Carbamazepine Derivatives: Since eslicarbazepine is structurally related to carbamazepine and oxcarbazepine, individuals who have experienced hypersensitivity reactions to these medications should not use eslicarbazepine. 
• Familial Short QT Syndrome: eslicarbazepine is contraindicated in patients with known or suspected familial short QT syndrome, as it may further shorten the QT interval and increase the risk of potentially life-threatening ventricular arrhythmias. 
• Concurrent Use with Monoamine Oxidase Inhibitors (MAOIs): eslicarbazepine should not be used in combination with MAOIs or within 14 days after discontinuation of an MAOI. Concurrent use can increase the risk of serotonin syndrome, a potentially serious condition characterized by symptoms such as agitation, hallucinations, rapid heartbeat, and increased body temperature.

Caution: 

• Hypersensitivity Reactions: eslicarbazepine may cause hypersensitivity reactions, including rash, DRESS, and Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). If any signs of hypersensitivity reaction occur, such as rash, fever, or swollen lymph nodes, immediate medical attention should be sought. 
• Suicidal Thoughts and Behaviours: Antiepileptic drugs (AEDs), including eslicarbazepine, may increase the risk of suicidal thoughts or behaviours. Patients and caregivers should be alert for any changes in mood, behaviour, or symptoms and seek medical advice if such changes occur. 
• Cardiovascular Events: eslicarbazepine may cause cardiovascular events, including QT prolongation, atrial fibrillation, and ventricular arrhythmias. It should be used with caution in patients with a history of cardiac disease or those at risk for cardiovascular events. 
• Hepatic Adverse Reactions: eslicarbazepine can cause hepatotoxicity, including potentially life-threatening liver failure. Liver function should be monitored before initiating treatment and periodically during treatment. Discontinue eslicarbazepine if significant liver injury is suspected. 
• Hyponatremia: eslicarbazepine can cause hyponatremia (low sodium levels), which may be life-threatening, especially in elderly patients. Serum sodium levels should be monitored before treatment initiation and during treatment, especially during the first few months and in patients at higher risk. 
• Renal Impairment: eslicarbazepine is primarily eliminated by the kidneys, and dosage adjustment may be necessary in patients with renal impairment. Renal function should be assessed before starting treatment and regularly during treatment. 
• Drug Interactions: eslicarbazepine may interact with other medications, including hormonal contraceptives, causing reduced contraceptive efficacy. Close monitoring and potential dose adjustments of both eslicarbazepine and interacting medications may be necessary.

Comorbidities: 

• Mood Disorders: Patients with epilepsy may have an increased risk of depression and anxiety. 
• Cognitive Impairment: Epilepsy can be associated with cognitive dysfunction and impaired memory. 
• Sleep Disorders: Sleep disorders, including insomnia and excessive daytime sleepiness, are commonly observed in patients with epilepsy. 
• Neurodevelopmental Disorders: Epilepsy can coexist with neurodevelopmental disorders such as autism spectrum disorder and ADHD. 
• Psychiatric Disorders: Psychiatric conditions like schizophrenia and bipolar disorder may occur concurrently with epilepsy. 
• Neurological Disorders: Other neurological conditions, such as migraine, multiple sclerosis, and stroke, may be present in patients with 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 is an antiepileptic drug that belongs to the class of sodium channel blockers. It is chemically related to carbamazepine and oxcarbazepine. The pharmacological effects of eslicarbazepine are primarily mediated through its active metabolite, eslicarbazepine acetate (ESA). ESA is formed by hydrolysis of eslicarbazepine in the gastrointestinal tract and further metabolized to its pharmacologically active metabolite, eslicarbazepine. 

The primary mechanism of action of eslicarbazepine is the blockade of voltage-gated sodium channels, specifically the persistent sodium current. By inhibiting the influx of sodium ions into neurons, eslicarbazepine reduces neuronal excitability and prevents the generation and propagation of epileptic activity. 

eslicarbazepine has selective effects on sodium channels, preferentially inhibiting the channels in the inactivated state. This selectivity allows for a more pronounced effect on hyperexcitable neurons, such as those involved in epileptic activity, while having minimal impact on normal neuronal function.  

Pharmacodynamics: 

• Blockade of voltage-gated sodium channels: eslicarbazepine inhibits the persistent sodium current, which reduces neuronal excitability and prevents the generation and propagation of epileptic activity. It selectively targets sodium channels in the inactivated state, preferentially affecting hyperexcitable neurons involved in epileptic activity. 
• Modulation of other ion channels: eslicarbazepine may also modulate other ion channels, including calcium channels and potassium channels, although the precise significance of these effects in its antiepileptic action is not fully understood. 
• Antiepileptic activity: By reducing neuronal excitability and inhibiting abnormal electrical activity in the brain, eslicarbazepine helps control seizures and is indicated for the treatment of epilepsy. It may be effective against partial-onset seizures in adults and children. 
• Pharmacokinetic interactions: eslicarbazepine may interact with other drugs that are substrates, inducers, or inhibitors of CYP450 enzymes, affecting their pharmacokinetics and potentially altering their therapeutic effects or toxicity.

Pharmacokinetics: 

Absorption 

• eslicarbazepine is rapidly and completely absorbed from the gastrointestinal tract after oral administration. 
• It is primarily absorbed as the prodrug eslicarbazepine acetate, which is then rapidly converted to the active metabolite eslicarbazepine. 

Distribution 

• eslicarbazepine is extensively distributed throughout the body, including the central nervous system. 
• It binds moderately (40%) to plasma proteins. 

Metabolism 

• eslicarbazepine undergoes extensive hepatic metabolism via enzymatic hydrolysis to form the active metabolite, eslicarbazepine. 
• The conversion of eslicarbazepine acetate to eslicarbazepine is mediated by carboxylesterases. 
• eslicarbazepine is primarily metabolized by glucuronidation and to a lesser extent by oxidation, through the cytochrome P450 enzyme CYP3A4. 

Elimination and excretion 

• The primary route of excretion of eslicarbazepine and its metabolites is through the urine. 
• Approximately 80% of the administered dose is eliminated in the urine as glucuronide conjugates of eslicarbazepine. 
• A small portion (less than 4%) is excreted in the feces. 

Adminstartion

Administration: 

• Dosage: The dosage of eslicarbazepine is determined by the healthcare provider based on factors such as the patient’s age, weight, renal function, and the specific condition being treated.  
• Timing: eslicarbazepine can be taken with or without food. However, taking it consistently with or without food is recommended to maintain consistent blood levels of the medication. 
• Swallowing: The tablet should be swallowed whole with enough water. It should not be crushed, chewed, or broken. 
• Compliance: It is important to take eslicarbazepine regularly and at the same time(s) each day to maintain consistent blood levels and maximize its effectiveness. Missing doses may reduce the control of seizures or other conditions being treated. 
• Duration: The duration of treatment with eslicarbazepine is to continue taking the medication, if symptoms improve, unless instructed otherwise by the healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: eslicarbazepine 

Pronounced: (es-lih-car-baz-uh-peen)  

Why do we use eslicarbazepine? 

eslicarbazepine is primarily used for the treatment of epilepsy. It is indicated as an adjunctive therapy for partial seizures in adults and children aged 4 years and older. Adjunctive therapy means it is used in combination with other antiepileptic medications to help control seizures. 

eslicarbazepine works by blocking voltage-gated sodium channels in the brain, which helps to stabilize the overactive electrical activity that can lead to seizures. It can be prescribed for individuals who have not achieved adequate seizure control with other antiepileptic medications or who are experiencing intolerable side effects from their current treatment.