Usage
- Lacosamide is an anticonvulsant medication prescribed for the adjunctive treatment of partial-onset seizures in individuals with epilepsy aged 4 years and older. In some regions, it’s approved as monotherapy in adults (16 years and older). It is also approved for adjunctive treatment of primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy aged 4 years and older.
- Pharmacological Classification: Anticonvulsant
- Mechanism of Action: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, reducing neuronal hyperexcitability. It has a dual mode of action, also binding to the collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and axonal outgrowth.
Alternate Names
- (R)-2-acetamido-N-benzyl-3-methoxypropionamide
- Brand Names: Vimpat
How It Works
- Pharmacodynamics: Lacosamide stabilizes neuronal membranes by selectively enhancing slow inactivation of voltage-gated sodium channels, decreasing the repetitive firing of neurons and reducing seizure activity. Its action on CRMP-2 may contribute to its antiepileptic effects, but the exact mechanism is not fully elucidated.
- Pharmacokinetics:
- Absorption: Lacosamide is rapidly and almost completely absorbed after oral administration, with bioavailability approaching 100%. Food does not affect the extent of absorption.
- Metabolism: Primarily hepatic, mainly through CYP2C19 and to a lesser extent, CYP2C9 and CYP3A4. Forms inactive metabolites.
- Elimination: Primarily renal excretion (approximately 40% as unchanged drug and 30% as O-desmethyl metabolite).
- Mode of Action: Lacosamide’s primary mechanism involves slowing the inactivation of voltage-gated sodium channels, thereby reducing sustained repetitive neuronal firing. This action is state-dependent, preferentially targeting rapidly firing neurons, as seen in seizure activity.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Primarily interacts with voltage-gated sodium channels, enhancing their slow inactivation. Also binds to CRMP-2.
- Elimination Pathways: Primarily renal excretion (around 70%, including unchanged drug and metabolites). Minor hepatic elimination.
Dosage
Standard Dosage
Adults:
- Adjunctive Therapy: Initial dose: 50 mg twice daily. Increase weekly by 50 mg twice daily up to a maintenance dose of 100-200 mg twice daily (200-400 mg/day).
- Monotherapy: Initial dose: 100mg twice daily. Can be increased to 150-200mg twice daily.
- Loading Dose (Optional): 200 mg single dose, followed by 100 mg twice daily.
- Maximum Dose (Adjunctive): 400 mg/day
Children (4-16 years):
- Initial dose: 1 mg/kg twice daily. Titrate weekly by 1 mg/kg twice daily.
- Maintenance dose:
- 11 kg to <30 kg: 3-6 mg/kg twice daily.
- 30 kg to <50 kg: 2-4 mg/kg twice daily.
- ≥50 kg: Same as adult dosing.
Special Cases:
- Elderly Patients: Caution advised; start at lower end of dosing range due to potential age-related decrease in renal and hepatic function.
- Patients with Renal Impairment:
- Mild/Moderate: No adjustment required.
- Severe/ESRD: Maximum dose of 300 mg/day. Supplemental dose (up to 50%) after dialysis may be needed.
- Patients with Hepatic Dysfunction:
- Mild/Moderate: Maximum dose of 300 mg/day.
- Severe: Not recommended.
- Patients with Comorbid Conditions: Adjust dose based on drug interactions and individual patient considerations.
Clinical Use Cases
- Lacosamide’s primary indication is the adjunctive treatment of partial-onset seizures. Clinical use cases include:
- Management of focal seizures originating in a specific brain area, both with and without secondary generalization
- Reduction of tonic-clonic seizures in idiopathic generalized epilepsy
Dosages in specialized settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not specifically defined for lacosamide and would follow general epilepsy management principles within the approved dosing guidelines.
Dosage Adjustments
- Based on patient response, tolerability, and comorbidities (renal/hepatic dysfunction). Monitor for drug interactions, especially with strong CYP inhibitors (e.g., some azole antifungals, macrolides) which may necessitate dose reduction.
Side Effects
Common Side Effects:
- Dizziness, headache, nausea, vomiting, diplopia, blurred vision, ataxia, somnolence, fatigue, tremor.
Rare but Serious Side Effects:
- Suicidal ideation, cardiac conduction abnormalities (PR interval prolongation), atrioventricular block, severe allergic reactions (e.g., angioedema, Stevens-Johnson syndrome), multi-organ hypersensitivity.
Long-Term Effects:
- Potential for cognitive impairment and mood disturbances with prolonged use.
Adverse Drug Reactions (ADR):
- Severe skin reactions, cardiac arrhythmias, suicidal thoughts, neuropsychiatric symptoms.
Contraindications
- Second- or third-degree atrioventricular block.
- Hypersensitivity to lacosamide or any component of the formulation.
Drug Interactions
- CYP450 Interactions:
- Lacosamide is primarily metabolized by CYP2C19 and to a lesser extent by CYP2C9 and CYP3A4.
- Strong inhibitors of these enzymes (e.g., some azole antifungals, macrolides) may increase lacosamide levels.
- Inducers (e.g., rifampin, St. John’s Wort) may decrease lacosamide levels.
- Other Interactions:
- Drugs that prolong the PR interval (e.g., certain antiarrhythmics, some antidepressants) may increase the risk of cardiac conduction delays.
- Concomitant use with other CNS depressants (e.g., alcohol, benzodiazepines) can increase the risk of sedation and dizziness.
- There are known interactions between lacosamide and other antiepileptic drugs which should be monitored.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (FDA). Lacosamide should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
- Fetal Risks: Limited human data available. Animal studies show adverse effects.
- Breastfeeding: Lacosamide is excreted in breast milk. Monitor infants for drowsiness and poor feeding. Decision to breastfeed should be individualized, weighing the benefits and potential risks.
Drug Profile Summary
- Mechanism of Action: Selectively enhances slow inactivation of voltage-gated sodium channels and binds to CRMP-2, thereby reducing neuronal hyperexcitability and decreasing seizure activity.
- Side Effects: Dizziness, headache, nausea, diplopia, blurred vision, ataxia, somnolence, fatigue, tremor. Rarely, suicidal ideation, cardiac conduction abnormalities.
- Contraindications: Second- or third-degree AV block, hypersensitivity.
- Drug Interactions: CYP2C19, 2C9, and 3A4 inhibitors/inducers; drugs prolonging PR interval; CNS depressants.
- Pregnancy & Breastfeeding: Category C; excreted in breast milk; use with caution.
- Dosage: Adults: 200-400 mg/day divided twice daily. Children: weight-based dosing.
- Monitoring Parameters: Seizure frequency, ECG (for PR interval), adverse events, liver function tests, complete blood count (periodically).
Popular Combinations
- Lacosamide is often used in combination with other antiepileptic drugs (AEDs) such as levetiracetam, valproic acid, lamotrigine, and topiramate, when monotherapy is insufficient for seizure control. The specific combinations are tailored based on the individual patient’s seizure type, other medical conditions, and response to treatment.
Precautions
- General Precautions: Assess baseline cardiac function (ECG) in patients with cardiac disease or conduction abnormalities. Screen for suicidality, mood disorders, and drug interactions. Monitor for rash.
- Specific Populations:
- Pregnant Women: Counsel about risks and benefits.
- Breastfeeding Mothers: Monitor infant for drowsiness and weight gain.
- Children & Elderly: Age-specific dosing. Monitor closely.
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. Caution with activities requiring alertness (e.g., driving).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lacosamide?
A: Adults: The standard starting dose is 50 mg twice daily, increasing weekly to a maintenance dose of 200-400 mg/day, divided twice daily. A loading dose of 200 mg can be given, followed by 100 mg twice daily. Children: weight-based dosing (see dosage section).
Q2: What are the common side effects of Lacosamide?
A: Dizziness, headache, nausea, diplopia, blurred vision, ataxia, somnolence, fatigue, and tremor are common.
Q3: How does Lacosamide work?
A: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, reducing neuronal hyperexcitability, and also binds to CRMP-2.
Q4: Is Lacosamide safe during pregnancy?
A: Lacosamide is Pregnancy Category C. Use only if the benefit outweighs the risk. Limited human data and animal studies suggest potential adverse effects. Discuss risks with patients.
Q5: Can Lacosamide be used in children?
A: Yes, lacosamide is approved for adjunctive treatment of partial-onset seizures in children aged 4 years and older. Dosage is weight-based.
Q6: What are the serious side effects of Lacosamide?
A: Rare but serious side effects include suicidal thoughts, cardiac conduction abnormalities, severe allergic reactions. Seek immediate medical attention if these occur.
Q7: Does Lacosamide interact with other medications?
A: Yes. It can interact with CYP2C19, 2C9, and 3A4 inhibitors and inducers, drugs that prolong the PR interval, and CNS depressants. A thorough medication review is essential.
Q8: How should Lacosamide be discontinued?
A: Gradual withdrawal over at least one week is recommended to minimize the risk of seizure recurrence.
Q9: Can Lacosamide be used as monotherapy?
A: Yes, lacosamide is approved as monotherapy for partial-onset seizures in adults in some regions.
Q10: What should patients be monitored for while taking Lacosamide?
A: Monitor for seizure frequency, adverse events (including suicidal thoughts, cardiac symptoms, skin rash), ECG changes, and periodically check liver function tests and complete blood count.
