Lacosamide

Approved Indications:

• Partial-Onset Seizures:
• As monotherapy or adjunctive therapy in adults and pediatric patients aged ≥1 month with partial-onset seizures.
• Primary Generalized Tonic-Clonic Seizures:
• As adjunctive therapy in adults and pediatric patients aged ≥4 years.
• Status Epilepticus (Off-label, Clinically Accepted Use):
• Intravenous lacosamide is sometimes used off-label in treating refractory status epilepticus, particularly when other agents have failed.

Adults (Oral and IV):

• Partial-Onset Seizures (Monotherapy or Adjunctive):
• Start with 50 mg twice daily
• Increase at weekly intervals by 100 mg/day
• Maintenance dose: 100–200 mg twice daily (max: 400 mg/day)
• Primary Generalized Tonic-Clonic Seizures:
• Same titration as partial seizures

IV Use:

• Used when oral administration is not feasible. IV dosage mirrors oral dosing.
• Administer IV over 15–60 minutes.

Pediatric Dosing:

• 1 Month to <4 Years (Adjunctive Use):
• Oral suspension or IV: 1 mg/kg twice daily, titrated based on weight and response.
• 4 to <17 Years (Monotherapy or Adjunctive):
• Dose based on weight (approx. 1–4 mg/kg twice daily)
• Maximum: Do not exceed 200–400 mg/day depending on weight.

Elderly:

• Use standard adult doses.
• Renal and hepatic function should be considered.

Renal Impairment:

• CrCl <30 mL/min or ESRD: Reduce dose by 25–50%.
• Supplemental doses may be required after dialysis.

Hepatic Impairment:

• Moderate impairment: Reduce max dose to 300 mg/day
• Severe impairment: Use with caution; not studied extensively.

Route of Administration:

• Oral tablets, oral solution, and intravenous injection

Duration:

• Long-term therapy; continue as clinically indicated to control seizures.

Lacosamide selectively enhances the slow inactivation of voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes without affecting fast inactivation. This modulation reduces repetitive firing of neurons involved in seizure propagation. Additionally, it binds to collapsin response mediator protein-2 (CRMP-2), which may influence neuronal differentiation and axonal outgrowth—though the clinical significance of this interaction is not fully established.

• Absorption: Rapid and complete; not significantly affected by food
• Bioavailability: ~100% (oral)
• Peak Plasma Time: ~1–4 hours (oral); immediate (IV)
• Distribution: Low protein binding (~15%), Vd ~0.6 L/kg
• Metabolism: Hepatic via CYP2C19 and non-CYP pathways
• Active Metabolites: One inactive O-desmethyl metabolite
• Elimination: Renal (primarily unchanged)
• Half-life: ~13 hours
• Steady State: Achieved within 2–3 days

• Pregnancy:
  Lacosamide is categorized as Pregnancy Category C (prior FDA classification). Animal studies showed fetal harm at high doses, but no well-controlled human data. Use only if potential benefit justifies potential risk.
• Lactation:
  Lacosamide is excreted in breast milk. Use caution; monitor breastfed infants for sedation, feeding difficulties, or poor weight gain.
• Recommendation:
  Use only when necessary; consider switching to safer alternatives during pregnancy and lactation if appropriate.

• Primary Class: Antiepileptic drug (AED)
• Subclass: Functionalized amino acid
• Generation: Third-generation antiepileptic

• Known hypersensitivity to lacosamide or any of its components
• Second- or third-degree atrioventricular (AV) block without a pacemaker
• Co-administration with drugs that increase PR interval in patients at risk of cardiac conduction disorders

• Cardiac Effects: PR interval prolongation, AV block, bradycardia; use with caution in patients with cardiac conduction abnormalities
• Suicidal Behavior and Ideation: Monitor for mood or behavioral changes
• Dizziness and Ataxia: Caution during activities requiring mental alertness
• Hepatic/Renal Dysfunction: Dose adjustments required
• Withdrawal: Taper gradually over ≥1 week to minimize seizure risk
• Alcohol/CNS Depressants: May enhance sedative effects

Common Side Effects (Dose-Dependent):

• Neurological: Dizziness, headache, fatigue, ataxia, diplopia
• Gastrointestinal: Nausea, vomiting
• Psychiatric: Irritability, depression (less common)
• General: Somnolence

Serious or Rare Side Effects:

• Cardiac arrhythmias (PR prolongation, AV block)
• Syncope
• Hepatotoxicity (rare)
• Suicidal ideation
• Hypersensitivity reactions including angioedema

Onset & Severity:

• Most side effects are dose-related and occur within the first few days to weeks of treatment initiation or dose increase.

• Drugs That Prolong PR Interval (e.g., beta-blockers, calcium channel blockers): Additive effect; risk of AV block
• CYP Enzyme Interactions:
• Metabolized by CYP2C19 (minor pathway)
• No significant inhibition/induction of major CYP enzymes
• CNS Depressants (e.g., alcohol, benzodiazepines): Additive sedation or dizziness
• Strong CYP2C19 inhibitors (e.g., fluconazole): May increase lacosamide levels; monitor for toxicity
• Enzyme-inducing AEDs (e.g., carbamazepine, phenytoin): May slightly reduce lacosamide levels, but not clinically significant

• Drugs That Prolong PR Interval (e.g., beta-blockers, calcium channel blockers): Additive effect; risk of AV block
• CYP Enzyme Interactions:
• Metabolized by CYP2C19 (minor pathway)
• No significant inhibition/induction of major CYP enzymes
• CNS Depressants (e.g., alcohol, benzodiazepines): Additive sedation or dizziness
• Strong CYP2C19 inhibitors (e.g., fluconazole): May increase lacosamide levels; monitor for toxicity
• Enzyme-inducing AEDs (e.g., carbamazepine, phenytoin): May slightly reduce lacosamide levels, but not clinically significant

• Tablets:
• Store below 30°C (86°F)
• Protect from moisture and direct light
• Oral Solution:
• Store at 20–25°C (68–77°F)
• Once opened, use within the recommended period as per packaging
• Injection:
• Store at 15–30°C (59–86°F)
• Do not freeze
• Discard unused portion after opening