What is the recommended dosage and usage of Lacosamide (generic name) for treating focal seizures in adults?

Lacosamide for Focal Seizures in Adults

Lacosamide is approved for adjunctive treatment of focal-onset seizures in adults at a maximum dose of 400 mg/day, initiated at 100 mg/day (50 mg twice daily) and titrated weekly in 100 mg/day increments based on tolerability and seizure control. 1, 2

Dosing and Administration

Initiate lacosamide at 100 mg/day (50 mg twice daily) and increase weekly by 100 mg/day increments to a target maintenance dose of 200-400 mg/day. 1, 3

• The typical titration schedule spans 12 weeks to reach optimal dosing, though flexible titration is acceptable 3
• Intermediate doses may be used for one week at each escalation step in patients particularly sensitive to new antiepileptic drugs 3
• Both oral (tablets, solution) and intravenous formulations are bioequivalent, allowing direct conversion without retitration 2
• IV administration can be given at the same dose as oral formulations when oral intake is not feasible 4, 2

Efficacy Outcomes

Adjunctive lacosamide demonstrates a 69.7% median reduction in focal seizure frequency, with 69.3% of patients achieving ≥50% seizure reduction and 28.4% achieving seizure freedom during maintenance therapy. 3

• Efficacy is sustained over long-term treatment (up to 8 years) 5
• Lacosamide shows noninferiority to carbamazepine controlled-release for monotherapy 5
• Response rates are consistent across diverse patient populations with refractory focal epilepsy 3, 6

Safety and Tolerability Profile

The most common adverse events are dizziness (30.6%), nausea (11.4%), and diplopia (10.5%), which are predominantly dose-related and occur most frequently during titration rather than maintenance. 6

• Other common side effects include headache, back pain, somnolence, and injection site pain (IV formulation) 4
• Most adverse events are mild to moderate in intensity; severe events are predominantly observed at 600 mg/day (above approved dosing) 6
• Discontinuation due to adverse events occurs in 8.1% at 200 mg/day, 17.2% at 400 mg/day, and 28.6% at 600 mg/day 6
• Cardiovascular monitoring is warranted as lacosamide causes small dose-related PR interval prolongation 7

Pharmacokinetic Advantages

Lacosamide has favorable pharmacokinetics including rapid absorption, high oral bioavailability unaffected by food, linear dose-proportional kinetics, low plasma protein binding, and minimal drug-drug interactions. 2

• As a non-enzyme-inducing antiepileptic drug, lacosamide has minimal interactions with other medications, making it safer in polypharmacy 1
• Low inter- and intraindividual variability provides predictable dosing 2
• Renal elimination is the primary route of clearance 2

Critical Clinical Considerations

Never abruptly discontinue lacosamide as this precipitates withdrawal seizures; always taper gradually when discontinuation is necessary. 4, 1, 7

• Lacosamide may impair driving ability, particularly during treatment initiation or dose changes; counsel all patients about this risk 7
• However, epidemiological studies show no increased traffic accident risk compared to other antiepileptic drugs, and arousal-related adverse events are lower than with carbamazepine 4, 7
• In women of childbearing potential, lacosamide is preferred over valproate due to valproate's significant teratogenicity risks 1
• For pregnant women already controlled on lacosamide, continue the medication as seizure control takes priority over theoretical medication risks 8

Role in Status Epilepticus

While lacosamide shows promise for refractory status epilepticus, loading dosages have not been adequately studied, and it requires further investigation before routine recommendation in this setting. 4

• Current evidence for status epilepticus is limited to case series and observational data 4
• Traditional agents (benzodiazepines, phenytoin/fosphenytoin, levetiracetam, valproate) remain first-line for status epilepticus 4

Comparison to Other Antiepileptic Drugs

Lacosamide is favored over older agents due to superior side effect profiles and minimal drug interactions, though valproate remains "probably effective" for partial-onset seizures based on Class II evidence. 1

• Discontinuation rates with lacosamide combined with carbamazepine (15.3%), lamotrigine (19.2%), or levetiracetam (10.1%) are higher than placebo but acceptable in clinical practice 6
• Lacosamide has fewer cognition-related adverse events at doses of 200-400 mg/day compared to higher doses 6