Vimpat

/ Neopharm

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.
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 maintenance 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 drug, 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 daily (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 central nervous system adverse reactions.
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).
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.
There is limited clinical data in the elderly patients with epilepsy, particularly at doses greater than 400 mg/day.
Renal impairment: No dose adjustment is necessary in mildly and moderately renally impaired patients (CLCR>30 ml/min). In 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 patients with severe renal impairment (CLCR ≤30 ml/min) and in patients with endstage renal disease, a maximum maintenance dose of 250 mg/day is recommended. In these patients, 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. For 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 patients with mild to moderate hepatic impairment.
The dose titration in these patients should be performed with caution considering co-existing renal impairment. A loading dose of 200 mg may be considered, but further dose titration (>200 mg daily) should be performed with caution. The pharmacokinetics of lacosamide has not been evaluated in severely hepatic impaired patients (see section 5.2). Lacosamide should be administered to 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 safety and efficacy of lacosamide in children aged below 16 years have not yet been established. No data are available.

Vimpat is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in adult patients with epilepsy aged 16 years and older.

Hypersensitivity to the active substance or to any of the excipients. Known second- or third-degree atrioventricular (AV) block.      

Suicidal ideation and behaviour: Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptics 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. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Cardiac rhythm and conduction: Dose-related prolongations in PR interval with lacosamide have been observed in clinical studies.
Lacosamide should be used with caution in patients with known conduction problems, severe cardiac disease (e.g. history of myocardial infarction or heart failure), in elderly patients, or when lacosamide is used in combination with products known to be associated with PR prolongation.
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.
Second degree or higher AV block has been reported in post-marketing experience. In the placebocontrolled 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.
Patients should be made aware of the symptoms of second-degree or higher AV block (e.g. slow or irregular pulse, feeling of lightheaded and fainting) and of the symptoms of atrial fibrillation and flutter (e.g. palpitations, rapid or irregular pulse, shortness of breath). Patients should be counselled to seek medical advice should any of these symptoms occur.
Dizziness: Treatment with lacosamide has been associated with dizziness which could increase the occurrence of accidental injury or falls. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicine.

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.
For full details see prescribing information.

Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation (e.g. carbamazepine, lamotrigine, pregabalin) and in patients treated with class I antiarrhythmic drugs. However, subgroup analysis did not identify an increased magnitude of PR prolongation in patients with concomitant administration of carbamazepine or lamotrigine in clinical trials.
Antiepileptic Drugs: In interaction trials lacosamide did not significantly affect the plasma concentrations of carbamazepine and valproic acid. Lacosamide plasma concentrations were not affected by carbamazepine and by valproic acid. A population PK analysis estimated that concomitant treatment with other anti-epileptic drugs known to be enzyme inducers (carbamazepine, phenytoin, phenobarbital, in various doses) decreased the overall systemic exposure of lacosamide by 25%.
Oral Contraceptives: In an interaction trial there was no clinically relevant interaction between lacosamide and the oral contraceptives ethinylestradiol and levonorgestrel. Progesterone concentrations were not affected when the medicinal products were co-administered.
Others: Interaction trials showed that lacosamide had no effect on the pharmacokinetics of digoxin. There was no clinically relevant interaction between lacosamide and metformin. No data on the interaction of lacosamide with alcohol are available. Lacosamide has a low protein binding of less than 15%. Therefore, clinically relevant interactions with other drugs through competition for protein binding sites are considered unlikely.
For full details see prescribing information.

Pregnancy: Lacosamide should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus). If women decide to become pregnant, the use of this product should be carefully re-evaluated.
Breastfeeding: It is unknown whether Lacosamide is excreted in human breast milk. Animal studies have shown excretion of Lacosamide in breast milk. For precautionary measures, breast-feeding should be discontinued during treatment with Lacosamide.
For full details see prescribing information.

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 (generalized 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.