VIMPAT Film-coated tablet Ref.[8018] Active ingredients: Lacosamide

Posology

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

The recommended posology for adults, adolescents and children from 2 years of age is summarised in the following table.

Lacosamide must be taken twice a day, approximately 12 hours apart.

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:

^* 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.

Children from 2 years of age and adolescents weighing less than 50 kg*:

^* Children less than 50 kg should preferably start the treatment with Vimpat 10 mg/ml syrup.

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.

Lacosamide can also be initiated at the dose of 100 mg twice a day (200 mg/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 200 mg twice a day (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 (100 mg/day) which should be increased to an initial therapeutic dose of 100 mg twice a day (200 mg/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 200 mg twice a day (400 mg/day).

Children from 2 years of age and adolescents weighing less than 50 kg

The dose is determined based on body weight. It is therefore recommended to initiate treatment with the syrup and switch to tablets, if desired. When prescribing the syrup, the dose should be expressed in volume (ml) rather than weight (mg).

Monotherapy (in the treatment of partial-onset seizures)

The recommended starting dose is 1 mg/kg twice a day (2 mg/kg/day) which should be increased to an initial therapeutic dose of 2 mg/kg twice a day (4 mg/kg/day) after one week. Depending on response and tolerability, the maintenance dose can be further increased by 1 mg/kg twice a day (2 mg/kg/day) every week. The dose should be gradually increased until the optimum response is obtained. The lowest effective dose should be used. In children weighing from 10 kg to less than 40 kg, a maximum dose of up to 6 mg/kg twice a day (12 mg/kg/day) is recommended. In children weighing from 40 to under 50 kg, a maximum dose of 5 mg/kg twice a day (10 mg/kg/day) is recommended.

Adjunctive therapy (in the treatment of primary generalised tonic-clonic seizures from 4 years of age or in the treatment of partial-onset seizures from 2 years of age)

The recommended starting dose is 1 mg/kg twice a day (2 mg/kg/day) which should be increased to an initial therapeutic dose of 2 mg/kg twice a day (4 mg/kg/day) after one week.

Depending on response and tolerability, the maintenance dose can be further increased by 1 mg/kg twice a day (2 mg/kg/day) every week. The dose should be gradually adjusted until the optimum response is obtained. The lowest effective dose should be used. Due to an increased clearance compared to adults, in children weighing from 10 kg to less than 20 kg, a maximum dose of up to 6 mg/kg twice a day (12 mg/kg/day) is recommended. In children weighing from 20 to under 30 kg, a maximum dose of 5 mg/kg twice a day (10 mg/kg/day) is recommended and in children weighing from 30 to under 50 kg, a maximum dose of 4 mg/kg twice a day (8 mg/kg/day) is recommended, although in open-label studies (see sections 4.8 and 5.2), a dose up to 6 mg/kg twice a day (12 mg/kg/day) has been used by a small number of children from this latter group.

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)

In adolescents and children weighing 50 kg or more, and adults, 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

If lacosamide has to be discontinued, it is recommended that the dose is reduced gradually in weekly decrements of 4 mg/kg/day (for patients with a body weight less than 50 kg) or 200 mg/day (for patients with a body weight of 50 kg or more) for patients who have achieved a dose of lacosamide ≥6 mg/kg/day or ≥300 mg/day, respectively. A slower taper in weekly decrements of 2 mg/kg/day or 100 mg/day can be considered, if medically necessary.

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 (CL_CR >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 (CL_CR ≤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 (CL_CR ≤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

Lacosamide is not recommended for use in children below the age of 4 years in the treatment of primary generalized tonic-clonic seizures and below the age of 2 years in the treatment of partial-onset seizures as there is limited data on safety and efficacy in these age groups, respectively.

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.

Method of administration

Lacosamide film-coated tablets are for oral use.

Lacosamide may be taken with or without food.

Symptoms

Symptoms observed after an accidental or intentional overdose of lacosamide are primarily associated with CNS and gastrointestinal system.

• The types of adverse reactions experienced by patients exposed to doses above 400 mg up to 800 mg were not clinically different from those of patients administered recommended doses of lacosamide.
• Reactions reported after an intake of more than 800 mg are dizziness, nausea, vomiting, seizures (generalised tonic-clonic seizures, status epilepticus). Cardiac conduction disorders, shock and coma have also been observed. Fatalities have been reported in patients following an intake of acute single overdose of several grams of lacosamide.

Management

There is no specific antidote for overdose with lacosamide. Treatment of lacosamide overdose should include general supportive measures and may include haemodialysis if necessary (see section 5.2).

5 years.

This medicinal product does not require any special storage conditions.

Vimpat 50 mg film-coated tablets:

Packs of 14, 28, 56 and 168 film-coated tablets in PVC/PVDC blister sealed with an aluminium foil.

Packs of 14 × 1 and 56 × 1 film-coated tablets in PVC/PVDC perforated unit dose blisters sealed with an aluminium foil.

Packs of 60 film-coated tablets in HDPE bottle with a child-resistant closure.

Vimpat 100 mg film-coated tablets:

Packs of 14, 28, 56 and 168 film-coated tablets in PVC/PVDC blister sealed with an aluminium foil.

Packs of 14 × 1 and 56 × 1 film-coated tablets in PVC/PVDC perforated unit dose blisters sealed with an aluminium foil.

Packs of 60 film-coated tablets in HDPE bottle with a child-resistant closure.

Vimpat 150 mg film-coated tablets:

Packs of 14, 28 and 56 film-coated tablets in PVC/PVDC blister sealed with an aluminium foil.

Multipacks containing 168 (3 packs of 56 tablets) film-coated tablets in PVC/PVDC blister sealed with an aluminium foil.

Packs of 14 × 1 and 56 × 1 film-coated tablets in PVC/PVDC perforated unit dose blisters sealed with an aluminium foil.

Packs of 60 film-coated tablets in HDPE bottle with a child-resistant closure.

Vimpat 200 mg film-coated tablets:

Packs of 14, 28 and 56 film-coated tablets in PVC/PVDC blister sealed with an aluminium foil.

Multipacks containing 168 (3 packs of 56 tablets) film-coated tablets in PVC/PVDC blister sealed with an aluminium foil.

Packs of 14 × 1 and 56 × 1 film-coated tablets in PVC/PVDC perforated unit dose blisters sealed with an aluminium foil.

Packs of 60 film-coated tablets in HDPE bottle with a child-resistant closure.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.