Lacosamide
Lacosamide
Generic Name
Lacosamide
Brand Names
*Vimpat*)** is an anticonvulsant approved for the adjunctive treatment of partial‑onset seizures in adults and adolescents.
Mechanism
- Selective enhancement of slow inactivation of voltage‑gated sodium channels
- Preserves the resting Na⁺ channel in the inactivated state, decreasing neuronal hyperexcitability without affecting peak inactivation.
- Minimal interaction with other sodium‑channel or GABA‑ergic pathways
- Results in a favorable side‑effect profile compared with classic sodium‑channel blockers (e.g., phenytoin).
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Pharmacokinetics
| Parameter | Value (Adults) |
| Absorption | Oral BID; peak plasma 2–3 h; ~95 % bioavailability (food increases Cmax by >2 h, no dose adjustment needed). |
| Distribution | Vd ≈ 17 L; highly soluble in water; negligible protein binding (~40 %). |
| Metabolism | Primarily glucuronidation via UGT2B7; minor CYP3A4 oxidation. |
| Elimination | 30–40 % renal, 35–36 % biliary; half‑life 12–13 h (10 h in severe renal impairment). |
| Drug‑Drug Interactions | Weak inducer/inhibitor of CYP3A4; can reduce levels of carbamazepine, phenytoin, valproate (reverse‑directional). |
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Indications
- Adjunctive therapy for partial‑onset (complex partial) seizures in adults and adolescents (≥12 yrs).
- Proven efficacy in randomized, double‑blind, placebo–controlled trials (e.g., LATE, LEST series).
- FDA‑approved use: *partial seizures in adults and adolescents.*
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Contraindications
- Contraindications
- Known hypersensitivity to lacosamide or any excipient.
- Severe cardiac conduction disorders (e.g., QRS >120 ms, prolonged QTc, known AV block).
- Warnings
- Cardiac effects: Dose‑dependent QRS widening (max 2–3 ms at 400 mg).
- Pregnancy: Category B; limited data—use if benefit outweighs risk.
- Surgery: Avoid in patients undergoing procedures that can alter drug metabolism (e.g., hepatic resection).
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Dosing
Adult & Adolescent (≥12 yrs)
| Setting | Typical Dose | Titration Regimen | Max Daily Dose |
| Start | 50 mg BID | +50 mg BID every 2 weeks until ≥200 mg BID tolerated | 400 mg BID |
• Initiation: 50 mg BID for 2 weeks → 100 mg BID × 2 weeks → 200 mg BID.
• Therapeutic target: 200–400 mg BID; adjust for seizure control and adverse events.
• Renal impairment: Reduce dose proportionally; 200 mg BID → 100 mg BID if CrCl < 30 mL/min.
• Drug interactions: When concomitant on carbamazepine/phenytoin, start at 25 mg BID and titrate slowly to avoid tachycardia.
Administration tips
• Take with or without food; fat increases absorption but not dose‑requiring adjustment.
• Avoid abrupt dose withdrawal – taper over ≥4 weeks to mitigate rebound seizures.
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Adverse Effects
| Class | Common (≤10 %) | Serious (≤1 %) |
| Neurologic | Dizziness, paresthesia, ataxia, diplopia | CNS depression, seizures (rebound) |
| Cardiovascular | Palpitations, bradycardia, mild QTc prolongation | Transient tachycardia, QRS widening |
| Gastrointestinal | Nausea, vomiting, constipation | Severe GI upset (rare) |
| Respiratory | Rare cough | Hypoventilation (very rare) |
| Other | Vertigo, fatigue, anxiety | Dermatologic rash, hypersensitivity reactions |
• Key safety signal: QRS widening up to 3 ms at the highest dose; monitor ECG if conduction abnormalities present.
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Monitoring
| Parameter | Frequency | Rationale |
| ECG | Baseline; at 2 weeks; every 6–8 weeks if dose ↑ | Detect QRS/QT changes; avoid cardiac toxicity |
| Serum electrolytes | Baseline; annually | Electrolyte disturbances may exacerbate arrhythmias |
| Hepatic function | Baseline; every 3 months | Hepatic impairment can increase exposure |
| Renal function | Baseline; every 6 months | Adjust dose for CrCl < 30 mL/min |
| CNS symptoms | Every visit | Identify early signs of ataxia, dizziness |
| Seizure log | Continuously | Evaluate efficacy and dose adjustments |
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Clinical Pearls
- Dual‑drug synergy: Lacosamide can be combined with levetiracetam or topiramate, but avoid high‑dose carbamazepine or phenytoin due to enzyme induction and potential cardiac conduction slowing; start at the lowest dose and titrate slowly.
- QRS monitoring: A ≥2 ms increase in QRS on routine ECG often correlates with dose‑related toxicity; maintain QRS <120 ms to reduce risk of arrhythmia.
- Renal dose adjustment: Since ~40 % is renally eliminated, patients with CrCl 10–30 mL/min should receive no more than 150 mg BID (total 300 mg daily).
- Pregnancy counseling: Though data are limited, lacosamide has a better safety profile than older sodium‑channel blockers; discuss with obstetrician if seizure control is critical.
- Drug–Drug Interaction caution: Lacosamide’s weak CYP3A4 inhibition can increase plasma levels of concomitant drugs like clobazam or mirtazapine. Check levels or consider dose adjustments.
- Adjunctive role: Use as add‑on rather than monotherapy; most evidence supports adjunctive use in partial‑onset seizures.
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