LACOSAMIDE TORRENT

Posology Lacosamide must be taken twice a day (usually once in the morning and once in the evening). Lacosamide may be taken with or without food. If a dose is missed, the patient should be instructed to take the missed dose immediately, and then to take the next dose of lacosamide at the regularly scheduled time.

If the patient notices the missed dose within 6 hours of the next one, he/she should be instructed to wait to take the next dose of lacosamide at the regularly scheduled time. Patients should not take a double dose. Adolescents and children weighing 50 kg or more, and adults The following table summarises the recommended posology for adolescents and children weighing 50 kg or more, and for adults.

More details are provided in the table below. Monotherapy Adjunctive therapy 100 mg/day or 200 mg/day 100 mg/dayStarting dose Single loading dose (if applicable) 200 mg 200 mg Titration (incremental steps) 50 mg twice a day (100 mg/day) at weekly intervals 50 mg twice a day (100 mg/day) at weekly intervals Maximum recommended dose up to 600 mg/day up to 400 mg/day Monotherapy (in the treatment of partial-onset seizures) The recommended starting dose is 50 mg twice a day which should be increased to an initial therapeutic dose of 100 mg twice a day after one week.

Lacosamide can also be initiated at the dose of 100 mg twice a day based on the physician's assessment of required seizure reduction versus potential side effects. Depending on response and tolerability, the maintenance dose can be further increased at weekly intervals by 50 mg twice a day (100 mg/day), up to a maximum recommended daily dose of 300 mg twice a day (600 mg/day).

In patients having reached a dose greater than 400 mg/day and who need an additional antiepileptic medicinal product, the posology that is recommended for adjunctive therapy below should be followed. Adjunctive therapy (in the treatment of partial-onset seizures or in the treatment of primary generalised tonic-clonic seizures) The recommended starting dose is 50 mg twice a day which should be increased to an initial therapeutic dose of 100 mg twice a day after one week.

Depending on response and tolerability, the maintenance dose can be further increased at weekly intervals by 50 mg twice a day (100 mg/day), up to a maximum recommended daily dose of 400 mg (200 mg twice a day). Initiation of lacosamide treatment with a loading dose (initial monotherapy or conversion to monotherapy in the treatment of partial-onset seizures or adjunctive therapy in the treatment of partial-onset seizures or adjunctive therapy in the treatment of primary generalised tonic-clonic seizures) Lacosamide treatment may also be initiated with a single loading dose of 200 mg, followed approximately 12 hours later by a 100 mg twice a day (200 mg/day) maintenance dose regimen.

Subsequent dose adjustments should be performed according to individual response and tolerability as described above. 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. g. taper the daily dose by 200 mg/week). In patients who develop serious cardiac arrhythmia, clinical benefit/risk assessment should be performed and if needed lacosamide should be discontinued.

Special populations Elderly (over 65 years of age) No dose reduction is necessary in elderly patients. 2). 1). Renal impairment No dose adjustment is necessary in mildly and moderately renally impaired adult and paediatric patients (CLCR > 30 ml/min).

In paediatric patients weighing 50 kg or more and in adult patients with mild or moderate renal impairment a loading dose of 200 mg may be considered, but further dose titration (> 200 mg daily) should be performed with caution. In paediatric patients weighing 50 kg or more and in adult patients with severe renal impairment (CLCR ≤ 30 ml/min) or with end-stage renal disease, a maximum dose of 250 mg/day is recommended and the dose titration should be performed with caution.

If a loading dose is indicated, an initial dose of 100 mg followed by a 50 mg twice daily regimen for the first week should be used. In paediatric patients weighing less than 50 kg with severe renal impairment (CLCR ≤ 30 ml/min) and in those with end-stage renal disease, a reduction of 25 % of the maximum dose is recommended.

For all patients requiring haemodialysis a supplement of up to 50 % of the divided daily dose directly after the end of haemodialysis is recommended. Treatment of patients with end-stage renal disease should be made with caution as there is little clinical experience and accumulation of a metabolite (with no known pharmacological activity).

Hepatic impairment A maximum dose of 300 mg/day is recommended for paediatric patients weighing 50 kg or more and for adult patients with mild to moderate hepatic impairment. The dose titration in these patients should be performed with caution considering co- existing renal impairment.

In adolescents and adults weighing 50 kg or more, a loading dose of 200 mg may be considered, but further dose titration (> 200 mg daily) should be performed with caution. Based on data in adults, […]

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 trial 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 trials 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).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. System organ class Very common Common Uncommon Not known Blood and lymphatic disorders Agranulocytosis(1) Immune system disorders Drug hypersensitivity(1) Drug reaction with eosinophilia and systemic symptoms (DRESS)(1,2) Psychiatric disorders Depression Confusional state Insomnia(1) Aggression Agitation(1) Euphoric mood(1) Psychotic System organ class Very common Common Uncommon Not known disorder(1) Suicide attempt(1) Suicidal ideation Hallucination(1) Nervous system disorders Dizziness Headache Myoclonic seizures(3) Ataxia Balance disorder Memory impairment Cognitive disorder Somnolence Tremor Nystagmus Hypoesthesia Dysarthria Disturbance in attention Paraesthesia Syncope(2) Coordination abnormal Dyskinesia Convulsion(3) Eye disorders Diplopia Vision blurred Ear and labyrinth disorders Vertigo Tinnitus Cardiac disorders Atrioventricular block(1,2) Bradycardia(1,2) Atrial Fibrillation(1,2) Atrial Flutter(1,2) Ventricular tachyarrhythmia(1) Gastrointestinal disorders Nausea Vomiting Constipation Flatulence Dyspepsia Dry mouth Diarrhoea Hepatobiliary disorders Liver function test abnormal(2) Hepatic enzyme increased (> 2x ULN)(1) Skin and subcutaneous Pruritus Angioedema(1) Stevens-Johnson- Syndrome(1) System organ class Very common Common Uncommon Not known tissue disorders Rash(1) Urticaria(1) Toxic epidermal necrolysis(1) Musculoskeletal and connective tissue disorders Muscle spasms General disorders and administration site conditions Gait disturbance Asthenia Fatigue Irritability Feeling drunk Injury, poisoning and procedural complications Fall Skin laceration Contusion (1) Adverse reactions reported in post marketing experience.

(2) See Description of selected adverse reactions. (3) Reported in PGTCS studies. Description of selected adverse reactions The use of lacosamide is associated with dose-related increase in the PR interval. g. atrioventricular block, syncope, bradycardia) may occur.

5 % and 0 % for lacosamide 200 mg, 400 mg, 600 mg or placebo, respectively. No second- or higher degree AV Block was seen in these studies. However, cases with second- and third-degree AV Block associated with lacosamide treatment have been reported in post-marketing experience.

In the monotherapy clinical trial comparing lacosamide to carbamazepine CR, the extent of increase in PR interval was comparable between lacosamide and carbamazepine. 3 %). 2 %) carbamazepine CR patients. Atrial fibrillation or flutter were not reported in short term clinical trials; however, both have been reported in open-label epilepsy trials and in post-marketing experience.

Laboratory abnormalities Abnormalities in liver function tests have been observed in […]

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 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 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 trials of lacosamide in epilepsy patients, atrial fibrillation or flutter were not reported; however, both have been reported in open-label epilepsy trials 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). Potential for new onset or worsening of myoclonic seizures New onset or worsening of myoclonic seizures has been reported in both adult and paediatric patients with PGTCS, in particular during titration.

In patients with more than one seizure type, the observed benefit of control for one seizure type should be weighed against any observed worsening in another seizure type. Potential for electro-clinical worsening in specific paediatric epilepsy syndromes The safety and efficacy of lacosamide in paediatric patients with epilepsy syndromes in which focal and generalised seizures may coexist have not been determined.

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