LACOSAMIDE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Selectively enhances slow inactivation of voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes and inhibiting repetitive neuronal firing.
| Metabolism | Approximately 40% of dose excreted unchanged in urine. Major metabolic pathway is O-desmethylation via CYP2C19, CYP3A4, and CYP2C9 to inactive metabolite. Minor pathways include glucuronidation and hydroxylation. |
| Excretion | Renal: approximately 95% (40% unchanged, remainder as O-desmethyl metabolite). Fecal: <5%. |
| Half-life | Terminal elimination half-life is approximately 13 hours (range 12–16 hours) in adults. Steady state achieved after 3 days with BID dosing. |
| Protein binding | Less than 15% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 0.6 L/kg (range 0.5–0.8 L/kg), suggesting distribution into total body water. |
| Bioavailability | Oral: approximately 100% (highly absorbed). IV: 100%. |
| Onset of Action | Oral: approximately 1–2 hours post-dose (peak concentrations at 1–4 hours). IV: immediate (administered as infusion, onset within minutes). |
| Duration of Action | Approximately 12 hours, consistent with twice-daily dosing. Clinical effect persists throughout dosing interval. |
| Molecular Weight | 250.29 |
Oral or IV: 50 mg twice daily initially; increase by 50 mg twice daily weekly to maintenance 100-200 mg twice daily. Maximum 200 mg twice daily.
| Dosage form | SOLUTION |
| Renal impairment | CrCl >30 mL/min: No adjustment. CrCl ≤30 mL/min: Max 300 mg/day (150 mg twice daily). Hemodialysis: Max 300 mg/day, supplement 50% of dose after dialysis. |
| Liver impairment | Mild to moderate (Child-Pugh A or B): Max 300 mg/day (150 mg twice daily). Severe (Child-Pugh C): Not recommended. |
| Pediatric use | Weight ≥50 kg: 50 mg orally twice daily; titrate by 50 mg twice daily weekly to 100-200 mg twice daily. Weight 30-49 kg: 1 mg/kg twice daily initial; titrate by 1 mg/kg twice daily weekly to 2-4 mg/kg twice daily (max 200 mg twice daily). Weight 11-29 kg: 1 mg/kg twice daily initial; titrate by 1 mg/kg twice daily weekly to 2-4 mg/kg twice daily (max 100 mg twice daily). |
| Geriatric use | Start at 25-50 mg twice daily based on creatinine clearance; titrate slowly. Monitor for CNS effects, hyponatremia, and arrhythmias. |
| 1st trimester | Limited human data; animal studies show increased fetal malformations; use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal harm; consider alternative if possible; monitor fetal growth. |
| 3rd trimester | Risk of neonatal withdrawal syndrome; discontinue gradually if possible prior to delivery. |
Clinical note
No significant drug interactions May cause dizziness and PR interval prolongation.
| Placental transfer | Crosses placenta; fetal serum levels approximately 50-80% of maternal levels. |
| Breastfeeding | Lacosamide is excreted in human breast milk in low concentrations; monitor infant for drowsiness, poor feeding. Consider benefit of breastfeeding vs risk of infant exposure. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Dizziness Headache Nausea Sleepiness Vomiting Visual disturbance Dryness in mouth Muscle spasm |
| Serious Effects |
Hypersensitivity to lacosamide or any componentSecond- or third-degree AV block without pacemakerConcurrent use with strong CYP3A4 inhibitors/inducers without dose adjustmentSevere hepatic impairment (Child-Pugh C)
| Precautions | Cardiac conduction abnormalities (PR interval prolongation, risk of second/third degree AV block), especially in patients with known conduction problems or on sodium channel blockers, Suicidal behavior and ideation (antiepileptic drugs class warning), Dizziness, ataxia, and syncope with rapid dose titration, Risk of antiepileptic drug hypersensitivity syndrome (rare), Monitor electrocardiogram (ECG) in patients with cardiac risk factors |
| Food/Dietary |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations (neural tube defects, cleft palate, cardiac defects) based on animal studies and limited human data. Second and third trimesters: Potential for fetal growth restriction, neurodevelopmental effects, and neonatal withdrawal syndrome. Late third trimester: Risk of neonatal hemorrhage due to vitamin K depletion. |
| Fetal Monitoring | Maternal: Serum lacosamide levels, liver and renal function, complete blood count, ECG for PR interval prolongation. Fetal: Ultrasound for anatomy at 18-20 weeks, serial growth scans in third trimester, fetal heart rate monitoring during labor. |
| Fertility Effects | In animal studies, no adverse effects on fertility or reproductive performance were observed. Human data are insufficient to exclude a risk of reduced fertility. |
| No significant food interactions. Grapefruit does not affect lacosamide. Alcohol may worsen CNS side effects (dizziness, sedation). Maintain a balanced diet as seizures can be triggered by extreme hunger or dehydration. |
| Clinical Pearls | Lacosamide is a sodium channel slow inactivation enhancer used for focal-onset seizures. Titrate slowly (50 mg BID increase weekly) to reduce CNS side effects like dizziness and diplopia. Dose adjustment needed in renal impairment (CrCl <30 mL/min: max 300 mg/day). Monitor for PR interval prolongation on ECG, especially in patients with conduction disorders. Use with caution in patients with cardiac disease or on drugs that prolong PR interval. |
| Patient Advice | Take lacosamide exactly as prescribed, with or without food. · Do not stop suddenly; taper to avoid withdrawal seizures. · May cause dizziness, ataxia, or blurred vision; avoid driving until effects are known. · Report any irregular heartbeat, fainting, or prolonged dizziness to your doctor. · Use effective contraception if applicable; discuss pregnancy plans with your doctor. |