ESLICARBAZEPINE AMAROX

Posology Adults Eslicarbazepine acetate may be taken as monotherapy or 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 1,200 mg once daily. 1). Special populations Elderly (over 65 years of age) No dose adjustment is needed in the elderly population provided that the renal function is not disturbed.

Due to very limited data on the 1,600 mg monotherapy regimen in the elderly, this dose is not recommended for this population. Renal impairment Caution should be exercised in the treatment of patients, adult and children above 6 years of age, 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 200 mg (or 5 mg/kg in children above 6 years) once daily or 400 mg (or 10 mg/kg in children above 6 years) every other day for 2 weeks followed by a once daily dose of 400 mg (or 10 mg/kg in children above 6 years).

However, based on individual response, the dose may be increased. − CLCR <30 ml/min: use is not recommended in patients with severe renal impairment due to insufficient data. Hepatic impairment No dose adjustment is needed in patients with mild to moderate hepatic impairment.

2) and use in these patients is, therefore, not recommended. Paediatric population Children above 6 years of age The recommended starting dose is 10 mg/kg/day once daily. Dosage should be increased in weekly or bi-weekly increments of 10 mg/kg/day up to 30 mg/kg/day, based on individual response.

1). Children with a body weight of ≥60 kg Children with a body weight of 60 kg or more should be given the same dose as for adults. The safety and efficacy of Eslicarbazepine acetate in children aged 6 years and below has not yet been established.

2 but no recommendation on a posology can be made. Method of administration Oral use. Eslicarbazepine acetate may be taken with or without food. For patients who are unable to swallow whole tablets, the tablets may be crushed and mixed with water or soft foods, such as apple sauce, immediately prior to use and administered orally.

Summary of the safety profile In clinical studies (adjunctive therapy treatment and monotherapy), 2,434 patients with partial-onset seizures were treated with Eslicarbazepine acetate (1,983 adult patients and 451 paediatric patients) and 51% of those patients experienced adverse reactions.

Adverse reactions were usually mild to moderate in intensity and occurred predominantly during the first weeks of treatment with Eslicarbazepine acetate. The risks that have been identified for eslicarbazepine are mainly class-based, dose- dependent undesirable effects.

The most common adverse reactions reported, in placebo controlled adjunctive therapy studies with adult epileptic patients and in an active controlled monotherapy study comparing Eslicarbazepine acetate with carbamazepine controlled release, were dizziness, somnolence, headache, and nausea.

The majority of adverse reactions were reported in <3% of subjects in any treatment group. 4). Tabulated list of adverse reactions Adverse reactions associated with Eslicarbazepine acetate obtained from clinical studies and post-marketing surveillance are tabulated below.

The following convention has been used for the classification of adverse reactions very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and not known (frequency cannot be estimated from available data). Within each frequency category, adverse reactions are presented in order of decreasing seriousness.

5. PR interval The use of Eslicarbazepine acetate is associated with increase in the PR interval. g. AV block, syncope, bradycardia) may occur. Class related adverse reactions Rare adverse reactions such as bone marrow depression, anaphylactic reactions, systemic lupus erythematosus or serious cardiac arrhythmias did not occur during the placebo-controlled studies of the epilepsy program with Eslicarbazepine acetate.

Suicidal ideation Suicidal ideation and behaviour have been reported in patients treated with antiepileptic active substances in several indications. A meta-analysis of randomised placebo-controlled trials of antiepileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour.

The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Eslicarbazepine acetate. Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Nervous system disorders 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.

Other warnings and precautions If eslicarbazepine is to be discontinued it is recommended to withdraw it gradually to minimise the potential of increased seizure frequency. 2% of total population treated with eslicarbazepine in clinical studies in epileptic patients.

Urticaria and angioedema cases have been reported in patients taking eslicarbazepine. Angioedema in the context of hypersensitivity/anaphylactic reaction associated with laryngeal oedema can be fatal. If signs or symptoms of hypersensitivity develop, Eslicarbazepine acetate must be discontinued immediately and alternative treatment should be initiated.

Severe cutaneous adverse reactions (SCARS) including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in post-marketing experience with eslicarbazepine treatment.

g. 1. Second or third degree atrioventricular (AV) block.