eslicarbazepine acetate

Eslicarbazepine acetate is an anticonvulsant medication used as a single agent or an adjunctive therapy to treat partial-onset seizures in patients 4 years or older. Seizures are caused by abnormal electrical activity in the brain. Partial (focal) onset seizure is a type of seizure in which the abnormal electrical activity is confined to a limited area of the brain. Eslicarbazepine acetate inhibits the excessive electrical activity in the brain, reduces the incidence and frequency of seizures, and prevents their propagation to other parts of the brain.

Eslicarbazepine acetate is converted to its active metabolite eslicarbazepine in the body. The exact mechanism of eslicarbazepine’s anticonvulsant effect is not clear, but it is thought to inhibit the voltage-gated sodium channels, especially in rapidly firing neurons. Eslicarbazepine inhibits repeated neuronal firing and generation and propagation of nerve impulses by stabilizing the inactivated state of the sodium channels and preventing their return to the activated state. Eslicarbazepine also inhibits T-type calcium channels which may play a role in seizures.

• Do not use eslicarbazepine acetate in patients with hypersensitivity to oxcarbazepine, eslicarbazepine or any component of the formulation.
• Antiepileptic drugs including eslicarbazepine acetate can increase the risk of suicidal thoughts and behavior in patients. Caution patients, their family and caregivers about this risk, and advise them to be alert for and report any emergence or worsening of depression or suicidal thoughts, or unusual changes in mood and behavior.
• Eslicarbazepine acetate may cause serious, life-threatening, and sometimes fatal dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Risk factors for such reactions have not been identified.
  • Do not use eslicarbazepine acetate in patients with previous such reactions to eslicarbazepine, oxcarbazepine or carbamazepine.
  • Discontinue eslicarbazepine if a patient develops dermatological reactions during therapy, unless the reaction is established to be not drug related.
• Eslicarbazepine acetate can cause a drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multi-organ hypersensitivity that can be life-threatening or fatal.
  • If a patient develops fever, rash, facial and/or lymph node swelling, assess the patient for DRESS and discontinue the drug immediately if there are no alternate reasons for the symptoms.
  • Do not use eslicarbazepine in patients who have had a prior DRESS reaction to oxcarbazepine or eslicarbazepine.
• Although rare, eslicarbazepine acetate can cause severe hypersensitivity reactions including anaphylaxis with angioedema and laryngeal edema that can be fatal.
  • Discontinue eslicarbazepine immediately if a patient develops signs of serious hypersensitivity reactions.
  • Do not use eslicarbazepine in patients who have had an anaphylactic reaction to oxcarbazepine or eslicarbazepine.
• Eslicarbazepine acetate may cause sodium levels to drop and lead to hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Patients may also have concurrently low chloride levels (hypochloremia). Monitor patient’s sodium and chloride levels and reduce or discontinue eslicarbazepine based on the severity of hyponatremia.
• Eslicarbazepine can cause neurological adverse effects including dizziness, fatigue, somnolence, impairment of motor and cognitive functions, and visual changes. Advise patients to avoid hazardous activities until the effects of eslicarbazepine can be determined.
• Eslicarbazepine may cause liver injury. Monitor patient’s levels of liver enzymes and bilirubin. Discontinue the drug in patients with jaundice or other symptoms and signs of significant liver injury.
• Dose-dependent increase in serum levels of T3 and T4 thyroid hormones was observed in some patients, which were not associated with other abnormal thyroid function tests suggesting hypothyroidism. Clinically evaluate abnormal thyroid function tests.
• There have been rare reports of blood disorders that include reduced counts of leukocytes, granulocytes and all types of blood cells. Monitor complete blood count in patients and consider discontinuing eslicarbazepine in patients who develop leukopenia, agranulocytosis or pancytopenia.
• When discontinuing eslicarbazepine withdraws gradually because abrupt discontinuation may increase seizure frequency or precipitate status epilepticus, a state of prolonged seizure that’s a medical emergency. If withdrawal is required because of a serious adverse event, rapid discontinuation may be considered.
• Concurrent use of eslicarbazepine with hormonal contraceptives may reduce the contraceptive efficacy, caution patients to use alternate or additional nonhormonal methods of contraception.

Common side effects of eslicarbazepine acetate include:

• Dizziness
• Drowsiness (somnolence)
• Headache
• Fatigue
• Cognitive dysfunction
• Depression
• Memory impairment
• Insomnia
• Impairment of balance, coordination and speech (ataxia)
• Speech difficulty (dysarthria)
• Vertigo
• Equilibrium disturbance
• Abnormal gait
• Falling
• Tremor
• Weakness
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Gastritis
• Double vision (diplopia)
• Blurred vision
• Diminished visual acuity
• Uncontrolled eye movements (nystagmus)
• Cough
• Low sodium in blood (hyponatremia)
• High blood pressure (hypertension)
• Swelling from fluid collection in extremities (peripheral edema)
• Skin rash
• Urinary tract infection

Less common side effects of eslicarbazepine acetate include:

• Increase in triglyceride levels in blood
• Increase in total and LDL cholesterol in blood
• High blood cholesterol levels (hypercholesterolemia)
• Low chloride levels in blood (hypochloremia)
• Decrease in hematocrit
• Decrease in hemoglobin
• Increase in creatine phosphokinase
• Decrease in thyroid hormones T3 and T4
• Elevated liver enzymes ALT and AST
• Increase in serum bilirubin
• Hypersensitivity reactions including:
  • Swelling of tissue beneath the skin and mucous membranes (angioedema)
  • Severe allergic reaction (anaphylaxis)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Blood disorders including:
  • Low count of leukocyte immune cells (leukopenia)
  • Severely low count of granulocyte immune cells (agranulocytosis)
  • Anemia from production of abnormally large red blood cells (megaloblastic anemia)
  • Low platelet count (thrombocytopenia)
  • Low count of all types of blood cells (pancytopenia)
• Severe skin reactions including:
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Abnormal ECG reading (prolongation of P-R interval)
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 200 mg
• 400 mg
• 600 mg
• 800 mg

Adult:

Partial-Onset Seizures

• Indicated for partial-onset seizures as monotherapy or adjunctive therapy

Initial

• 400 mg orally once daily
• For some patients, treatment may be initiated at 800 mg once daily if the need for additional seizure reduction outweighs an increased risk of adverse reactions during initiation

Titration and maintenance

• Increase dose by weekly increments of 400-600 mg, based on clinical response and tolerability
• Recommended maintenance dose is 800-1600 mg once daily
• Monotherapy: Consider 800 mg/day maintenance dose in patients unable to tolerate 1200 mg/day
• Adjunctive therapy: 1600 mg/day should be considered in patients who did not achieve a satisfactory response with 1200 mg/day

Pediatric:

Partial-Onset Seizures

• Indicated for partial-onset seizures as monotherapy or adjunctive therapy

Children below 4 years:

• Safety and efficacy not established

Children 4-17 years

• Recommended initial weight based dosage
  • 11-21 kg: 200 mg orally once daily initially; titration increment not to exceed 200 mg/day
  • 22-38 kg: 300 mg orally once daily; titration increment not to exceed 300 mg/day
  • Above 38 kg: 400 mg orally once daily; titration increment not to exceed 400 mg/day
  • Dosage should be increased based on clinical response and tolerability, no more frequently than once per week
• Maintenance dosage
  • 11-21 kg: Not to exceed 400-600 mg/day
  • 22-31 kg: Not to exceed 500-800 mg/day
  • 32-38 kg: Not to exceed 600-900 mg/day
  • Above 38 kg: Not to exceed 800-1200 mg/day

Dosage Modifications

• Do not take adjunctively with oxcarbazepine
• Coadministration with enzyme-inducing AEDs (e.g., carbamazepine, phenytoin, phenobarbital, primidone): May need to increase eslicarbazepine dose

Renal impairment

• Mild (creatinine clearance [CrCl] 50 mL/minute or above): No dosage adjustment necessary
• Moderate-to-severe (CrCl below 50 mL/minute): Reduce the initial, titration, and maintenance doses by 50%; may adjust titration and maintenance doses according to clinical response

Hepatic impairment

• Mild-to-moderate: No dosage adjustment required
• Severe: Not recommended (not studied)

Dosing Considerations

• When discontinuing eslicarbazepine acetate, gradually reduce dose and avoid abrupt discontinuation in order to minimize risk of increased seizure frequency and status epilepticus

Overdose

• Eslicarbazepine overdose symptoms are consistent with its side effects profile and can include nausea, vomiting, low sodium levels (hyponatremia), dizziness, drowsiness, euphoria, impairment of speech, balance and coordination (ataxia), walking difficulties, double vision (diplopia) and abnormal skin sensations (paresthesia).
• There is no known antidote for eslicarbazepine acetate. Overdose is treated with symptomatic and supportive care, including gastric lavage and activated charcoal administration to eliminate the undigested drug. Hemodialysis may be considered based on the patient’s condition or in patients with significant impairment of kidney function.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of eslicarbazepine acetate include:
  • artemether/lumefantrine
  • artemether/lumefantrine
  • cariprazine
  • cobimetinib
  • dienogest/estradiol valerate
  • doravirine
  • elbasvir/grazoprevir
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • lonafarnib
  • lumacaftor/ivacaftor
  • lumefantrine
  • lurasidone
  • mavacamten
  • naloxegol
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • oxcarbazepine
  • pacritinib
  • panobinostat
  • praziquantel
  • regorafenib
  • rilpivirine
  • roflumilast
  • vandetanib
• Eslicarbazepine acetate has serious interactions with at least 96 different drugs.
• Eslicarbazepine acetate has moderate interactions with at least 173 different drugs.
• Eslicarbazepine acetate has mild interactions with at least 77 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There is insufficient information on the safety of eslicarbazepine acetate use in pregnant women, however, animal reproductive studies show it can cause fetal harm if used during pregnancy.
• Animal studies show eslicarbazepine acetate can impair fertility in women.
• Eslicarbazepine acetate can reduce the efficacy of hormonal contraceptives such as ethinylestradiol and levonorgestrel. Women on hormonal contraceptives should use additional or alternate non-hormonal methods of contraception.
• Eslicarbazepine acetate is present in breastmilk. The effects on milk production and the breastfed infant are not known. Decision to breastfeed must be made considering the importance of the drug to the nursing mother, and the risks to the infant from exposure to the drug or the mother’s underlying condition.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as eslicarbazepine acetate, during pregnancy. Women taking eslicarbazepine acetate during pregnancy should be encouraged to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.

• Take eslicarbazepine acetate exactly as prescribed.
• Do not stop taking eslicarbazepine except under your physician’s guidance. Abrupt discontinuation can increase seizure frequency and the risk for a prolonged state of seizure that can be a medical emergency.
• Eslicarbazepine acetate may induce or worsen depression and suicidal thoughts and behavior. Seek support from family, friends and your healthcare provider if you feel depressed.
• If you are a family member or caregiver of a patient receiving eslicarbazepine treatment, be alert for signs and symptoms of depression in the patient and contact the healthcare provider if you notice unusual changes in the patient’s mood or behavior.
• Contact your physician immediately if you experience any of the following:
  • Severe skin reactions
  • Hypersensitivity reactions such as swelling of face and/or throat
  • Symptoms of multi-organ hypersensitivity known as drug reaction with eosinophilia and systemic symptoms (DRESS), which may include fever, rash, lymph node swelling and/or facial swelling
  • Low sodium symptoms such as nausea, headache, lethargy and confusion
  • Neurological symptoms including dizziness, fatigue, drowsiness, impairment of cognitive function, gait disturbance and visual changes
  • Symptoms suggestive of blood disorders including infections or bruising
• Eslicarbazepine can impair mental and physical abilities, avoid engaging in hazardous activities such as driving and operating heavy machinery until the drug effects can be determined.
• Store eslicarbazepine acetate safely out of reach of children.
• In case of overdose, seek immediate medical help or contact Poison Control.