Normictal

Uses

Eslicarbazepine acetate is used for an add-on therapy for partial seizure with or without secondary generalization.

Normictal is also used to associated treatment for these conditions: Partial-Onset Seizures

How Normictal works

Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity.

Dosage

Normictal dosage

Adult: Eslicarbazepine acetate must be added to existing anticonvulsant therapy. The recommended starting dose is 400 mg once daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response the dose may be increased to 1200 mg once daily

Elderly (over 65 years of age): Caution should be exercised in the treatment of elderly patients as there is limited safety information on the use of Eslicarbazepine acetate in these patients.

Paediatric: The safety and efficacy of Eslicarbazepine acetate below 18 years has not yet been established. No data are available

Side Effects

The use of Eslicarbazepine acetate is associated with increase in the PR interval. Adverse reactions associated with PR interval prolongation (e.g. AV block, syncope, bradycardia) may occur.

Toxicity

There are no adequate and well-controlled studies of the use of eslicarbazepine acetate in pregnant women. In studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate did show developmental toxicities, including teratogenicity, embryolethality, and fetal growth retardation, at clinically relevant doses. Drug-induced liver injury ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases with concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported with the use of eslicarbazepine. Overdose with eslicarbazepine acetate appears similar to its known adverse reactions and includes symptoms of hyponatremia, dizziness, nausea, vomiting, somnolence, euphoria, oral paraesthesias, ataxia, and diplopia. There is no specific antidote for eslicarbazepine acetate overdose and it should be treated primarily with supportive measures. If required, the drug may be removed by gastric lavage, partially by hemodialysis or inactivated with activated charcoal.

Precaution

Eslicarbazepine acetate has been associated with some central nervous system adverse reactions, such as dizziness and somnolence, which could increase the occurrence of accidental injury.

Eslicarbazepine acetate may decrease the effectiveness of hormonal contraceptives. Additional non-hormonal forms of contraception are recommended when using Eslicarbazepine acetate.

As with other anti-epileptic medicinal products, if Eslicarbazepine acetate is to be discontinued it is recommended to withdraw it gradually to minimize the potential of increased seizure frequency.

Concomitant use of Eslicarbazepine acetate with oxcarbazepine is not recommended because this may cause overexposure to the active metabolites.

Rash developed as an adverse reaction in 1.1% of total population treated with Eslicarbazepine acetate in placebo-controlled add-on studies in epileptic patients. If signs or symptoms of hypersensitivity develop, Eslicarbazepine acetate must be discontinued. Hyponatraemia has been reported as an adverse reaction in less than 1% of patients treated with Eslicarbazepine acetate.

Interaction

Carbamazepine: Based on individual response, the dose of Eslicarbazepine acetate may need to be increased if used concomitantly with carbamazepine.

Phenytoin: The dose of Eslicarbazepine acetate may need to be increased and the dose of phenytoin may need to be decreased.

Oral contraceptives: Administration of Eslicarbazepine acetate 1,200 mg once daily to female subjects using a combined oral contraceptive showed an average decrease of 37% and 42% in systemic exposure to levonorgestrel and ethinyloestradiol, respectively. Therefore, women of childbearing potential must use adequate contraception during treatment with Eslicarbazepine acetate.

Simvastatin: The dose of Simvastatin shall be increased if used with Eslicarbazepine.

Food Interaction

• Take with or without food.

Volume of Distribution

The apparent volume of distribution of eslicarbazepine is 61.3 L for a body weight of 70 kg based on population PK analysis.

Elimination Route

Eslicarbazepine active metabolite has a high bioavailability and reaches peak serum concentration 1-4 hours after a given dose. Eslicarbazepine acetate absorption is not affected by food.

Half Life

The apparent plasma half-life of eslicarbazepine is 10-20 hours in healthy subjects and 13-20 hours in epilepsy patients. Steady-state plasma concentrations are attained after 4 to 5 days of once daily dosing.

Clearance

Renal clearance of eslicarbazepine was found to be approximately 20 mL/min in healthy subjects with normal renal function.

Elimination Route

Eslicarbazepine acetate and its metabolites are eliminated primarily via renal excretion. Eslicarbazepine active metabolite is excreted two-thirds in the unchanged form and one-third as a glucuronide conjugate. This accounts for around 90% of total metabolites excreted, with the remaining 10% being minor metabolites. Renal tubular reabsorption is expected to occur with eslicarbazepine.

Pregnancy & Breastfeeding use

There are no data from the use of Eslicarbazepine acetate in pregnant women. Studies in animals have shown reproductive toxicity. If women receiving Eslicarbazepine acetate become pregnant or plan to become pregnant, the use of Exalief should be carefully re-evaluated.

It is unknown whether Eslicarbazepine acetate is excreted in human breast milk.

Contraindication

Hypersensitivity to the active substance, to other carboxamide derivatives (e.g. carbamazepine, oxcarbazepine) or to any of the excipients.

Special Warning

Patients with renal impairment: Caution should be exercised in the treatment of patients with renal impairment and the dose should be adjusted according to creatinine clearance (CLCR) as follows:

• CLCR >60 ml/min: no dose adjustment required
• CLCR 30-60 ml/min: initial dose of 400 mg every other day for 2 weeks followed by a once daily dose of 400 mg.
• CLCR <30 ml/min: use is not recommended in patients with severe renal impairment due to insufficient data

Patients with hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. The pharmacokinetics of Eslicarbazepine acetate has not been evaluated in patients with severe hepatic impairment and use in these patients is therefore not recommended.

Storage Condition

Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Innovators Monograph

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