Lacosamide: Mechanism of Action, Side Effects, and Dosing
Lacosamide works through a unique mechanism of selectively enhancing slow inactivation of voltage-gated sodium channels, with a recommended dosage of 200-400 mg/day administered twice daily for partial-onset seizures. 1
Mechanism of Action
Lacosamide has a distinctive mechanism of action compared to other antiepileptic drugs:
- Selectively enhances slow inactivation of voltage-gated sodium channels
- Stabilizes hyperexcitable neuronal membranes
- Inhibits neuronal firing
- Potentially interacts with collapsin-response mediator protein 2 (CRMP-2) 1, 2
This unique mechanism contributes to its efficacy in controlling partial-onset seizures, particularly as an adjunctive therapy.
Dosing Recommendations
Lacosamide dosing follows a specific protocol:
- Recommended dose range: 200-400 mg/day divided into twice-daily administration 1
- Titration: Begin at 100 mg/day and increase by 100 mg/day weekly until reaching target dose 3
- Formulations: Available as oral tablets, oral solution, and solution for intravenous infusion, with bioequivalence established between formulations 1, 4
- Administration: Can be taken with or without food (does not affect bioavailability) 4
Pharmacokinetic Profile
Lacosamide demonstrates favorable pharmacokinetic characteristics:
- Rapid absorption with high oral bioavailability
- Linear and dose-proportional pharmacokinetics
- Low inter- and intraindividual variability
- Low plasma protein binding
- Primarily renal elimination
- Low potential for clinically relevant drug-drug interactions 4
These properties make lacosamide relatively predictable in its effects and easy to use in clinical practice.
Efficacy
Clinical trials have demonstrated significant efficacy as adjunctive therapy:
- 34% of patients achieve ≥50% reduction in seizure frequency at 200 mg/day
- 40% of patients achieve ≥50% reduction in seizure frequency at 400 mg/day
- Compared to 23% with placebo 1
- Particularly effective for secondarily generalized tonic-clonic seizures, with median percent reductions in seizure frequency of 59.4% for 400 mg/day and 93.0% for 600 mg/day 3
Side Effects
The most common adverse effects include:
- Central nervous system effects: Dizziness (30.6% vs 8.2% for placebo) 5
- Visual disturbances: Diplopia (10.5% vs 1.9% for placebo) 5
- Gastrointestinal effects: Nausea (11.4% vs 4.4% for placebo), vomiting 5
- Cardiac effects: Dose-dependent PR interval prolongation and risk of atrioventricular block 1
Most side effects are dose-related and more common during the titration phase than during maintenance therapy. Side effects are generally mild to moderate in intensity, with severe adverse events predominantly observed at higher doses (600 mg/day) 5.
Special Considerations and Monitoring
Important monitoring parameters include:
Cardiac monitoring: Baseline ECG and periodic cardiac assessment, especially in:
- Elderly patients
- Patients with pre-existing cardiac conduction disorders
- Patients taking other medications affecting cardiac conduction
- Patients with renal impairment 1
Mental health monitoring: For signs of depression or suicidal ideation 1
Driving performance: Patients should be counseled on potential effects on driving ability 1
Clinical Advantages
Lacosamide offers several clinical advantages:
- Lower incidence of arousal-related adverse events compared to carbamazepine
- Does not induce or inhibit cytochrome P450 enzymes
- Fewer drug-drug interactions than older antiseizure medications 1
- Can be directly converted between oral and IV formulations without titration 4
Regulatory Status
Lacosamide is classified as a Schedule V controlled substance in the United States and is FDA-approved for adjunctive therapy for partial-onset seizures in adults with epilepsy, with or without secondary generalization 1.