Vimpat (UCB Pharma)
50 mg, 100 mg, 150 mg and 200 mg tablets
Approved indication: partial seizures
Australian Medicines Handbook section 16.1.3
Many patients with epilepsy have partial seizures and these can become generalised. Carbamazepine or valproate are often used, but some patients require more than one drug to keep them free of seizures. Drugs which can be added on include gabapentin, lamotrigine, levetiracetam and now lacosamide.
The exact mechanism of action of lacosamide is uncertain. It is thought to stabilise neuronal membranes by enhancing the slow inactivation of voltage-gated sodium channels.
Oral doses of lacosamide are completely absorbed. Twice-daily doses produce steady-state concentrations after three days. Metabolism of the drug includes cytochrome P450 2C19, but 40% of the dose is excreted unchanged. As most of the drug and its metabolites are excreted in the urine, doses may need to be limited in patients with severe renal or liver impairment. The elimination half-life of lacosamide is approximately 13 hours.
The safety and efficacy of lacosamide was assessed in a trial which randomised 421 adults with simple or complex partial-onset seizures, with or without generalisation. These patients were having seizures despite having taken at least two anticonvulsants. They were randomised to add a placebo or lacosamide 200 mg, 400 mg or 600 mg daily. After dose titration, the patients were maintained on these doses for 12 weeks. The median reduction in seizure frequency was 39% with 400 mg and 40% with 600 mg. While lacosamide 200 mg reduced seizure frequency by 26% this was not significantly different from the 10% reduction in the placebo group.1
The 200 mg and 400 mg doses were studied in a similar placebo-controlled trial involving 485 adults. During 12 weeks of maintenance treatment, the median reduction in seizure frequency per 28 days was 35% with 200 mg and 36% with 400 mg daily. These reductions were significantly greater than the 21% reduction in the group who added placebo.2Another study of 421 patients also found a 21% reduction in the placebo group, while lacosamide 400 mg and 600 mg reduced seizure frequency by 37% and 38%.
The intravenous formulation of lacosamide can be used when patients are unable to take their tablets, for example because of surgery. As the tablets have very high bioavailability the intravenous dose is the same as the oral dose.3
In the clinical trials the most frequent adverse reactions were dizziness, altered vision, headache, nausea and vomiting. As the adverse effects were more frequent with lacosamide 600 mg, the maximum total daily dose for patients with normal renal function is 400 mg. There is also a dose-dependent prolongation of the PR interval on the ECG. Second or third degree heart block is therefore a contraindication to lacosamide.
The efficacy and safety of lacosamide in children and pregnant or lactating women is unknown. There was an increase in stillbirths in studies of pregnant animals.
While lacosamide adds to the choice of adjunctive anticonvulsants for partial seizures, not many patients became seizure free in the trials. Approximately 34% of patients taking lacosamide 200 mg daily will have a greater than 50% reduction in seizure frequency, but this is not always statistically different from placebo.1,2Some patients may have an increased number of seizures.1As the trials were relatively short for a chronic condition, there is a possibility that serious adverse reactions could emerge. One healthy volunteer developed hepatitis and nephritis after taking lacosamide. There may also be an increase in suicidal thoughts.
The Transparency Score is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007;48:1308-17.
- Halsz P, Klviinen R, Mazurkiewicz-Beldzinska M, Rosenow F, Doty P, Hebert D, et al; SP755 Study Group. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia 2009;50:443-53.
- Biton V, Rosenfeld WE, Whitesides J, Fountain NB, Vaiciene N, Rudd GD. Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. Epilepsia 2008;49:418-24.
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