Lacosamide
Third-generation antiepileptic for the treatment of focal seizures
Lacosamide is a third-generation antiepileptic that was approved in the European Union in 2008 under the brand name Vimpat. It belongs to the group of functionalised amino acids and has a unique, dual mechanism of action that distinguishes it from older antiepileptics with sodium channel blockade. Lacosamide is available as a film-coated tablet, oral solution and infusion solution, enabling its use both in outpatient long-term therapy and in the clinical emergency setting.
Lacosamide is used to treat focal (partial) epileptic seizures with and without secondary generalisation, both as monotherapy and as add-on therapy. In adults aged 16 years and over it is approved as monotherapy; in children aged 4 years and older, and in those aged 2 to 4 years (with a body weight of at least 11 kg), it can be used as add-on therapy. In epileptology, lacosamide has taken on an important role due to its favourable tolerability and pharmacokinetic profile.
Mechanism of Action
Lacosamide acts via two complementary mechanisms on voltage-gated sodium channels (Nav). First, it causes slow inactivation of these channels by selectively binding to and stabilising the slow-inactive state of the Nav channel. Conventional sodium channel blockers such as carbamazepine or lamotrigine, by contrast, stabilise the fast-inactivated state. The selective promotion of slow inactivation reduces sustained neuronal firing without significantly impairing normal phasic signal transmission.
Second, an interaction of lacosamide with Collapsin Response Mediator Protein 2 (CRMP-2) has been described. CRMP-2 is a neuronal phosphoprotein that plays a role in axonal outgrowth and channel modulation. The functional significance of this interaction for the antiepileptic effect is still the subject of research, but it is thought to contribute to the inhibition of pathological sustained excitation.
The result of both mechanisms is a stabilisation of hyperexcited neurons and a reduction of ectopic neuronal discharges that underlie epileptic seizures, without significantly impairing normal synaptic transmission.
Indications
- Focal seizures (with or without secondary generalisation): Monotherapy in adults and adolescents aged 16 years and over; add-on therapy in adults and children aged 4 years and over (from 2 years with weight at least 11 kg)
- Status epilepticus (focal seizure): Intravenous administration as an alternative or supplement to benzodiazepines, particularly if they are contraindicated or ineffective
- Off-label: Neuropathic pain (particularly in diabetic neuropathy), painful vasculitides; evidence here is still limited
Dosage and Administration
Adults (mono and add-on therapy): Starting dose 50 mg twice daily; after 1 week increase to 100 mg twice daily (initial therapeutic dose). Further increases in steps of 50 mg per dose weekly up to the maximum daily dose of 300 mg twice daily (600 mg/day). Children aged 4 years and at least 50 kg BW: Dose as for adults. Children with lower body weight: Starting dose 1 mg/kg BW twice daily; increase to 2 to 4 mg/kg BW twice daily (maximum 200 to 300 mg depending on weight category). Intravenous use: Same dosage as oral; infusion duration 15 to 60 minutes.
Lacosamide can be taken independently of meals. With renal insufficiency (GFR below 30 ml/min) and with severe hepatic insufficiency, a dose reduction or special caution is required. Lacosamide should not be discontinued abruptly; gradual tapering over at least 4 weeks is recommended to avoid rebound seizures.
Side Effects
Very common (in more than 10% of patients): Dizziness, headache, nausea, double vision (diplopia). These dose-dependent side effects occur particularly at the start of therapy or when doses are increased and often improve after the initial adjustment period.
Common: Balance disorders, coordination disorders (ataxia), blurred vision, vomiting, fatigue, memory problems, tremor, nystagmus, dry mouth, blocked nose, pruritus.
Cardiac effects: Lacosamide can cause prolongation of the PR interval on the ECG, which can lead to AV block. In patients with known cardiac arrhythmia, existing PR prolongation or use of other PR-prolonging medications (e.g. certain antiarrhythmics), an ECG before starting therapy is recommended. Atrial fibrillation and atrial flutter have been reported as rare side effects.
Rare: Suicidal ideation and suicidal behaviour (class effect of all antiepileptics), agranulocytosis, elevated liver values, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).
Drug Interactions
Lacosamide has a favourable interaction profile since it is only metabolised to a limited extent via CYP2C19 and has little inducing or inhibiting effect on CYP enzymes.
- PR-prolonging substances (beta-blockers, calcium channel blockers, digoxin, antiarrhythmics): Additive risk of AV conduction disturbances; ECG monitoring recommended
- Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampicin): Can reduce lacosamide plasma levels by up to 25%; dose adjustment may be required
- Strong CYP2C19 inhibitors (omeprazole, fluconazole): Can moderately increase lacosamide levels; generally not clinically relevant, but worth noting
- Alcohol: Potentiation of sedative and central nervous system effects possible; should be avoided
- Other antiepileptics: Pharmacodynamic interactions (additive sedation) possible; pharmacokinetic interactions are minimal
Special Notes
Cardiac pre-existing conditions: Lacosamide should only be used with special caution and close cardiac monitoring in patients with known second or third degree AV block. An ECG before starting therapy is recommended in at-risk patients.
Pregnancy: Only limited data on the use of lacosamide in pregnancy are available. Animal studies showed developmental toxic effects at high doses. Since uncontrolled seizures in pregnancy carry significant risks, existing therapy should not be discontinued without medical advice. Lacosamide passes into breast milk; breastfeeding should be decided after medical assessment.
Ability to drive: Lacosamide can cause dizziness, double vision and concentration disorders, which may impair the ability to drive. Particularly at the start of therapy and with dose changes, driving should be avoided.
Alcohol: Concurrent alcohol consumption can intensify central nervous system side effects and should be avoided.
Frequently Asked Questions
What distinguishes lacosamide from other sodium channel blockers?
Classic sodium channel blockers such as carbamazepine or phenytoin bind to the fast-inactivated state of the sodium channel. Lacosamide, by contrast, selectively stabilises the slow-inactivated state, enabling more targeted inhibition of pathologically continuously firing neurons without strongly affecting normal rapid signal transmission. Lacosamide also has linear pharmacokinetics without relevant enzyme induction.
Can lacosamide be taken on an empty stomach?
Yes, lacosamide can be taken independently of meals, as food does not significantly affect absorption. However, patients with gastrointestinal complaints may try taking it with a meal to reduce nausea.
How long must lacosamide be taken?
The duration of therapy depends on the individual course of the epilepsy and is determined by the treating epileptologist or neurologist. With good seizure control over several years, a cautious trial discontinuation may be considered under certain conditions.
References
- Summary of Product Characteristics Vimpat (UCB Pharma), as of 2024
- German Society of Neurology (DGN): S1 Guideline Epilepsy in Adults, 2023
- European Medicines Agency (EMA): Vimpat EPAR
- Errington AC et al.: Lacosamide inhibits neuronal firing by selectively enhancing slow inactivation of voltage-gated sodium channels. Molecular Pharmacology, 2008
- Federal Institute for Drugs and Medical Devices (BfArM): Product monograph lacosamide