Normal Therapeutic Level of Lacosamide
The therapeutic reference range for lacosamide in adults with epilepsy is typically between 2.2 to 20 mg/L, though there is currently no well-established consensus reference range for this antiepileptic medication 1.
Pharmacokinetic Properties
Lacosamide has several favorable pharmacokinetic characteristics that distinguish it from many other antiepileptic drugs:
- Linear pharmacokinetics with predictable blood concentrations
- High oral bioavailability (100%)
- Low protein binding
- Primarily metabolized by CYP2C19 into inactive metabolites
- Elimination half-life of approximately 13 hours
- Primarily renal excretion
Therapeutic Drug Monitoring Considerations
Unlike some older antiepileptic drugs (such as phenytoin and carbamazepine), routine therapeutic drug monitoring for lacosamide is generally considered "probably of no use" for most patients 2. This is due to:
- Linear dose-concentration relationship
- Minimal inter-individual variability
- Low potential for drug-drug interactions
- No clear established relationship between concentration and efficacy
However, therapeutic drug monitoring may be beneficial in certain populations where lacosamide pharmacokinetics may be altered:
- Patients taking enzyme-inducing antiepileptic drugs
- Patients with severe renal dysfunction or on dialysis
- Older adults
- Patients experiencing unexpected toxicity or lack of efficacy
Dosing Considerations
When administering lacosamide, clinicians should consider:
- For partial-onset seizures, doses of 400 mg/day have shown good balance of efficacy and tolerability 3
- Higher doses (600 mg/day) may provide additional benefit for some patients, particularly those with secondarily generalized tonic-clonic seizures 3
- For intravenous administration in status epilepticus, a loading dose of 400 mg has been associated with higher early response rates compared to 200 mg 4
- In pediatric status epilepticus, a loading dose of approximately 10 mg/kg has shown efficacy 5
Adverse Effects
Dose-related adverse effects may include:
- Dizziness
- Nausea
- Vomiting
- PR interval prolongation (requiring caution in patients with cardiac conduction disorders)
Clinical Pearls
- While the therapeutic range is generally cited as 2.2-20 mg/L, the relationship between lacosamide concentration and efficacy is not as clearly established as it is with some other antiepileptic drugs
- Adverse effects appear to be concentration-dependent, making monitoring potentially useful when toxicity is suspected
- Unlike many other antiepileptic drugs, lacosamide has few clinically significant drug interactions, though enzyme-inducing antiepileptic drugs may affect its metabolism
In clinical practice, lacosamide dosing is typically guided by clinical response and tolerability rather than serum concentrations for most patients, with therapeutic drug monitoring reserved for special populations or clinical scenarios where altered pharmacokinetics are suspected.