Posology : מינונים

4.2   Posology and method of administration

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
Starting dose                      100 mg/day or 200 mg/day            100 mg/day 
Single loading dose                200 mg                              200 mg (if applicable)
Titration (incremental steps)      50 mg twice a day (100 mg/day) 50 mg twice a day (100 mg/day) at weekly intervals            at weekly intervals
Maximum recommended dose           up to 600 mg/day               up to 400 mg/day 
Monotherapy
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
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
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. It should be administered under medical supervision with consideration of the potential for increased incidence of serious cardiac arrhythmia and central nervous system adverse reactions (see section 4.8). Administration of a loading dose has not been studied in acute conditions such as status epilepticus.

Discontinuation
In accordance with current clinical practice, if lacosamide has to be discontinued, it is recommended this be done gradually (e.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. Age associated decreased renal clearance with an increase in AUC levels should be considered in elderly patients (see following paragraph ‘renal impairment’ and section 5.2). There is limited clinical data in the elderly patients with epilepsy, particularly at doses greater than 400 mg/day (see sections 4.4, 4.8, and 5.1).

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, in paediatric patients weighing less than 50 kg with mild to moderate hepatic impairment, a reduction of 25 % of the maximum dose should be applied. The pharmacokinetics of lacosamide has not been evaluated in severely hepatic impaired patients (see section 5.2). Lacosamide should be administered to adult and paediatric patients with severe hepatic impairment only when the expected therapeutic benefits are anticipated to outweigh the possible risks. The dose may need to be adjusted while carefully observing disease activity and potential side effects in the patient.

Paediatric population

The physician should prescribe the most appropriate formulation and strength according to weight and dose.

Adolescents and children weighing 50 kg or more
Dosage in adolescents and children weighing 50 kg or more is the same as in adults (see above).

Children (from 4 years of age) and adolescents weighing less than 50 kg The dose is determined based on body weight. The tablets are registered with strengths of 50mg, 100mg, 150mg, 200mg. When there is a need for different strength, the product is also registered in Israel as solution for intravenous injection.

Monotherapy
The recommended starting dose is 2 mg/kg/day which should be increased to an initial therapeutic dose of 4 mg/kg/day after one week.
Depending on response and tolerability, the maintenance dose can be further increased by 2 mg/kg/day every week. The dose should be gradually increased until the optimum response is obtained. In children weighing less than 40 kg, a maximum dose of up to 12 mg/kg/day is recommended. In children weighing from 40 to under 50 kg, a maximum dose of 10 mg/kg/day is recommended.

The following table summarises the recommended posology in monotherapy for children and adolescents weighing less than 50 kg.
Starting dose                                2 mg/kg/day

Single loading dose                                  Not recommended
Titration (incremental steps)                        2 mg/kg/day every week Maximum recommended dose in patients < 40 kg         up to 12 mg/kg/day Maximum recommended dose in patients ≥ 40 kg to      up to 10 mg/kg/day < 50 kg

Adjunctive therapy
The recommended starting dose is 2 mg/kg/day which should be increased to an initial therapeutic dose of 4 mg/kg/day after one week.
Depending on response and tolerability, the maintenance dose can be further increased by 2 mg/kg/day every week. The dose should be gradually adjusted until the optimum response is obtained. In children weighing less than 20 kg, due to an increased clearance compared to adults, a maximum dose of up to 12 mg/kg/day is recommended. In children weighing from 20 to under 30 kg, a maximum dose of 10 mg/kg/day is recommended and in children weighing from 30 to under 50 kg, a maximum dose of 8 mg/kg/day is recommended, although in open-label studies (see sections 4.8 and 5.2), a dose up to 12 mg/kg/day has been used by a small number of these children.

The following table summarises the recommended posology in adjunctive therapy for children and adolescents weighing less than 50 kg.
Starting dose                                           2 mg/kg/day

Single loading dose                                     Not recommended Titration (incremental steps)                           2 mg/kg/day every week Maximum recommended dose in patients < 20 kg            up to 12 mg/kg/day Maximum recommended dose in patients ≥ 20 kg            up to 10 mg/kg/day to < 30 kg
Maximum recommended dose in patients ≥ 30 kg            up to 8 mg/kg/day to < 50 kg

Loading dose
Administration of a loading dose has not been studied in children. Use of a loading dose is not recommended in adolescents and children weighing less than 50 kg.

Children less than 4 years
The safety and efficacy of lacosamide in children aged below 4 years have not yet been established. No data are available.

Method of administration

Lacosamide film-coated tablets are for oral use. Lacosamide may be taken with or without food.
Do not halve the tablets, there is no scoring line, thus the patient cannot ensure the uniformity of both halves. In order to facilitate swallowing, if necessary, the tablet may be crushed and immediately swallowed with water. The crushed tablet may have a bitter taste.