Lacosamide

INDICATIONS: monotherapy is for partial-onset seizures; adjunctive therapy is for partial-onset seizures or for primary generalised tonic-clonic seizures. In patients on monotherapy who have reached a dose greater than 200 mg twice a day (400 mg/day) and who need an additional antiepileptic medicinal product, the adjunctive-therapy posology should be followed. LOADING DOSE (alternate initial dosage, adults and patients 50 kg or more): a single 200 mg loading dose followed approximately 12 hours later by a 100 mg twice a day (200 mg/day) maintenance regimen; a loading dose may be used when the physician determines that rapid attainment of steady-state plasma concentration and therapeutic effect is warranted, and must be given under medical supervision because of the potential for increased serious cardiac arrhythmia and CNS adverse reactions. Administration of a loading dose has NOT been studied in acute conditions such as status epilepticus, has not been studied in children, and is not recommended in adolescents and children weighing less than 50 kg. MISSED DOSE: take the missed dose immediately and then take the next dose at the regularly scheduled time; if the missed dose is noticed within 6 hours of the next one, wait and take the next dose at the regularly scheduled time. Patients should not take a double dose. DISCONTINUATION: reduce gradually in weekly decrements of 200 mg/day (patients 50 kg or more) or 4 mg/kg/day (patients under 50 kg) for those who have reached 300 mg/day or 6 mg/kg/day respectively; a slower taper of 100 mg/day or 2 mg/kg/day weekly can be considered if medically necessary. If serious cardiac arrhythmia develops, perform a clinical benefit/risk assessment and discontinue if needed. ELDERLY (over 65 years): no dose reduction is necessary, but age-associated decreased renal clearance with increased AUC should be considered; clinical data in elderly patients with epilepsy are limited, particularly above 400 mg/day. HEPATIC IMPAIRMENT: maximum 300 mg/day for adults and paediatric patients weighing 50 kg or more with mild to moderate hepatic impairment, titrating with caution and considering co-existing renal impairment; a 200 mg loading dose may be considered in adolescents and adults 50 kg or more but titration above 200 mg daily should be cautious; in paediatric patients under 50 kg with mild to moderate hepatic impairment apply a 25% reduction of the maximum dose; pharmacokinetics have not been evaluated in severe hepatic impairment — use only when expected benefits outweigh the risks. CARDIAC MONITORING: dose-related PR interval prolongation has been observed; consider an ECG before increasing above 400 mg/day and after titration to steady state in patients with proarrhythmic conditions, on medicinal products affecting cardiac conduction, or elderly. INTRAVENOUS ROUTE: not covered by this oral-syrup SPC — the IV solution for infusion is a separate SPC that was NOT fetched in this bundle, and its posology has not been reproduced here.

Applies to children from 2 years of age and adolescents weighing LESS THAN 50 kg; adolescents and children weighing 50 kg or more use the adult dosing. The dose should be gradually increased until the optimum response is obtained and the lowest effective dose used. In the adjunctive 30 kg to under 50 kg band the SPC notes that a dose up to 6 mg/kg twice a day (12 mg/kg/day) has been used by a small number of children in open-label studies, although 4 mg/kg twice a day is the recommended maximum. AGE LIMITS: lacosamide is not recommended below 4 years of age for primary generalised tonic-clonic seizures and below 2 years of age for partial-onset seizures, as safety and efficacy data are limited. A LOADING DOSE IS NOT RECOMMENDED in adolescents and children weighing less than 50 kg and has not been studied in children. RENAL: no dose adjustment in mild or moderate renal impairment (creatinine clearance above 30 ml/min); in paediatric patients under 50 kg with severe renal impairment (creatinine clearance 30 ml/min or less) or end-stage renal disease, reduce the maximum dose by 25%; for all patients on haemodialysis a supplement of up to 50% of the divided daily dose is recommended directly after dialysis. HEPATIC: in paediatric patients under 50 kg with mild to moderate hepatic impairment apply a 25% reduction of the maximum dose. DISCONTINUATION: taper in weekly decrements of 4 mg/kg/day (or 2 mg/kg/day if a slower taper is medically necessary). Verify all paediatric dosing against a children's formulary and specialist paediatric neurology advice before prescribing.