What is the recommended dosing for Lacosamide (antiepileptic drug)?

Lacosamide Dosing for Epilepsy

For adults with partial-onset seizures, initiate lacosamide at 100 mg twice daily (200 mg/day), then increase weekly by 100 mg/day increments to the recommended maintenance dose of 200-400 mg/day (100 mg twice daily to 200 mg twice daily), with a maximum dose of 400 mg/day for most patients. 1, 2

Standard Oral Dosing Protocol

Initial Titration:

• Start at 100 mg twice daily (200 mg/day total) 1
• Increase by 100 mg/day each week until reaching target maintenance dose 1
• Target maintenance: 200-400 mg/day (divided into twice-daily dosing) 1, 2
• Maximum recommended dose: 400 mg/day for optimal efficacy-tolerability balance 1

Higher Dose Considerations:

• Lacosamide 600 mg/day may provide additional benefit for some patients, particularly those with secondarily generalized tonic-clonic seizures, but is associated with significantly more adverse events 1
• The 600 mg/day dose showed 93% median reduction in secondarily generalized seizures versus 59.4% at 400 mg/day 1
• However, discontinuation rates increase substantially: 8.1% at 200 mg/day, 17.2% at 400 mg/day, and 28.6% at 600 mg/day 2

Rapid Titration Options

When faster seizure control is needed:

• Rapid titration to 400 mg/day within one week is feasible and does not increase adverse events compared to conventional weekly titration 3
• Most adverse events (74%) occur after reaching the target dose of 400 mg/day, demonstrating dose-dependency rather than titration-speed dependency 3

Intravenous Loading Dose Protocol

For lacosamide-naive patients requiring rapid initiation:

• Recommended IV loading dose: 200-300 mg over 15 minutes 4
• Follow 12 hours later with oral maintenance dosing at one-half the loading dose, given twice daily 4
• The 200 mg and 300 mg loading doses are well tolerated 4
• The 400 mg loading dose is less well tolerated due to higher frequency of dose-related adverse events (16% discontinuation rate) 4
• IV and oral formulations have equivalent tolerability profiles when not using loading doses 5

Pediatric Dosing (Off-Label, <16 Years)

For children with refractory epilepsy:

• Initial dose: 1-2 mg/kg/day 6
• Uptitrate over 4-6 weeks to target dose of 6-9 mg/kg/day 6
• Mean effective dose in clinical practice: 6.80 ± 2.39 mg/kg/day 6
• Administer twice daily as oral solution or tablets 6
• This achieved >50% seizure reduction in 62.3% of pediatric patients 6

Critical Safety Considerations

Most Common Adverse Events (dose-related):

• Dizziness (30.6% vs 8.2% placebo) 2
• Nausea (11.4% vs 4.4% placebo) 2
• Diplopia (10.5% vs 1.9% placebo) 2
• These predominantly occur during titration phase and decrease during maintenance 2

Drug Interaction Alert:

• Concomitant sodium channel blockers significantly increase adverse event risk 3
• Discontinuation rates with common AEDs: carbamazepine 15.3%, lamotrigine 19.2%, levetiracetam 10.1% 2
• Most patients (82-84%) in clinical trials were taking 2-3 concomitant AEDs 1, 2

Timing of Adverse Events:

• With IV loading: most adverse events occur within first 4 hours post-infusion 4
• With oral titration: adverse events are more common during titration than maintenance phase 2

Available Formulations

Tablet strengths: 50 mg, 100 mg, 150 mg, 200 mg 7

Clinical Pearls

• The 400 mg/day dose provides the best balance of efficacy and tolerability for most patients 1
• Near steady-state plasma concentrations are achieved with a single IV loading dose 4
• Cognitive-related adverse events at 200-400 mg/day are similar to placebo (odds ratio 1.3) 2
• Few adverse events related to rash, weight changes, or psychiatric disturbances 2