LACOSAMIDE AMAROX

Posology The physician should prescribe the most appropriate formulation and strength according to weight and dose. Lacosamide therapy can be initiated with either oral administration (either tablets or syrup) or intravenous administration (solution for infusion).

Solution for infusion is an alternative for patients when oral administration is temporarily not feasible. The overall duration of treatment with intravenous lacosamide is at the physician’s discretion; there is experience from clinical studies with twice daily infusions of lacosamide for up to 5 days in adjunctive therapy.

Conversion to or from oral and intravenous administration can be done directly without titration. The total daily dose and twice daily administration should be maintained. g. 4). Lacosamide must be taken twice a day (approximately 12 hours apart).

The recommended posology for adults, adolescents and children from 2 years of age is summarised in the following table. Adolescents and children weighing 50 kg or more, and adults Starting dose Titration (incremental steps) Maximum recommended dose Monotherapy: 50 mg twice a day (100 mg/day) or 100 mg twice a day (200 mg/day) Adjunctive therapy: 50 mg twice a day (100 mg/day) 50 mg twice a day (100 mg/day) at weekly intervals Monotherapy: up to 300 mg twice a day (600 mg/day) Adjunctive therapy: up to 200 mg twice a day (400 mg/day) Alternate initial dosage* (If applicable): 200 mg single loading dose followed by 100 mg twice a day (200 mg/day) * A loading dose may be initiated in patients in situations when the physician determines that rapid attainment of lacosamide steady state plasma concentration and therapeutic effect is warranted.

8). Administration of a loading dose has not been studied in acute conditions such as status epilepticus. Children from 2 years of age and adolescents weighing less than 50 kg Starting dose Titration (incremental steps) Maximum recommended dose Monotherapy and 1 mg/kg twice Monotherapy: − up to 6 mg/kg twice a day (12 mg/kg/day) in patients ≥ 10 kg to < 40 kg − up to 5 mg/kg twice a day (10 mg/kg/day) in patients ≥ 40 kg to < 50 kg Adjunctive therapy: 1 mg/kg twice a day (2 mg/kg/day) a day (2 mg/kg/day) at weekly intervals Adjunctive therapy: − up to 6 mg/kg twice a day (12 mg/kg/day) in patients ≥ 10 kg to < 20 kg − up to 5 mg/kg twice a day (10 mg/kg/day) in patients ≥ 20 kg to < 30 kg − up to 4 mg/kg twice a day (8 mg/kg/day) in patients ≥ 30 kg to < 50 kg Adolescents and children weighing 50 kg or more, and adults Monotherapy (in the treatment of partial-onset seizures) The recommended starting dose is 50 mg twice a day (100 mg/day) which should be increased to an initial therapeutic dose of 100 mg twice a day (200 mg/day) after one week.

2 % of patients randomised to placebo reported at least 1 adverse reaction. The most frequently reported adverse reactions (≥ 10 %) with lacosamide treatment were dizziness, headache, nausea and diplopia. They were usually mild to moderate in intensity.

Some were dose-related and could be alleviated by reducing the dose. Incidence and severity of central nervous system (CNS) and gastrointestinal (GI) adverse reactions usually decreased over time. 6 % for patients randomised to placebo.

The most common adverse reaction resulting in discontinuation of lacosamide therapy was dizziness. Incidence of CNS adverse reactions such as dizziness may be higher after a loading dose. Based on the analysis of data from a non-inferiority monotherapy clinical study comparing lacosamide to carbamazepine controlled release (CR), the most frequently reported adverse reactions (≥ 10 %) for lacosamide were headache and dizziness.

6 % for patients treated with carbamazepine CR. The safety profile of lacosamide reported in a study conducted in patients aged 4 years and older with idiopathic generalised epilepsy with primary generalised tonic- clonic seizures (PGTCS) was consistent with the safety profile reported from the pooled placebo-controlled clinical studies in partial-onset seizures.

3 % in the lacosamide- group and 0 % in the placebo-group). The most frequently reported adverse reactions were dizziness and somnolence. The most common adverse reactions resulting in discontinuation of lacosamide therapy were dizziness and suicidal ideation.

1 % in the placebo group. Tabulated list of adverse reactions The table below shows the frequencies of adverse reactions which have been reported in clinical studies and post-marketing experience. The frequencies are defined as follows: 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).

Suicidal ideation and behaviour Suicidal ideation and behaviour have been reported in patients treated with antiepileptic medicinal products in several indications. A meta-analysis of randomised placebo-controlled clinical studies 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 lacosamide. Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

8). Cardiac rhythm and conduction Dose-related prolongations in PR interval with lacosamide have been observed in clinical studies. g. 5), as well as in elderly patients. In these patients it should be considered to perform an ECG before a lacosamide dose increase above 400 mg/day and after lacosamide is titrated to steady-state.

In the placebo-controlled clinical studies of lacosamide in epilepsy patients, atrial fibrillation or flutter were not reported; however, both have been reported in open- label epilepsy studies and in post-marketing experience. In post-marketing experience, AV block (including second degree or higher AV block) has been reported.

In patients with proarrhythmic conditions, ventricular tachyarrhythmia has been reported. In rare cases, these events have led to asystole, cardiac arrest and death in patients with underlying proarrhythmic conditions. g. slow, rapid or irregular pulse, palpitations, shortness of breath, feeling lightheaded, fainting).

Patients should be counselled to seek immediate medical advice if these symptoms occur. Dizziness Treatment with lacosamide has been associated with dizziness which could increase the occurrence of accidental injury or falls. 8). 8 mg sodium per vial, equivalent to 3 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1. Known second- or third-degree atrioventricular (AV) block.