Drug Detail:Lacosamide (monograph) (Vimpat)
Drug Class:
Usual Adult Dose for Epilepsy
MONOTHERAPY FOR PARTIAL-ONSET SEIZURES:
Initial dose: 100 mg orally twice a day
- Titrate in increments of 100 mg (50 mg twice a day) no more frequently than once a week based on clinical response and tolerability
ADJUNCTIVE THERAPY FOR PARTIAL-ONSET SEIZURES OR GENERALIZED TONIC-CLONIC SEIZURES: :
Initial dose: 50 mg orally twice a day
- Titrate in increments of 100 mg (50 mg twice a day) no more frequently than once a week based on clinical response and tolerability
Alternatively, may initiate therapy with a loading dose:
LOADING DOSE: 200 mg oral/IV once, followed in 12 hours with 100 mg oral/IV every 12 hours for at least 1 week; subsequent dose titrations should be performed as described above
- Due to increased incidence of CNS adverse reactions, the loading dose should be administered under medical supervision
Comments:
- Therapy may be administered either orally or via IV infusion using the same dosing regimen; IV infusion should preferably be over 30 to 60 minutes, although may be infused over 15 minutes if needed; experience with IV therapy is limited to 5 days of consecutive treatment.
- In adult clinical trials, adjunctive doses higher than 200 mg twice a day were not more effective and were associated with a substantially higher rate of adverse reactions.
- If converting from a single antiepileptic drug (AED) to lacosamide monotherapy, withdrawal of concomitant AED should not occur until a therapeutic dose of lacosamide has been achieved and administered for 3 days, then the concomitant AED may be gradually withdrawn over 6 weeks.
Use: As monotherapy for partial-onset seizures or adjunctive therapy for partial-onset seizures or primary generalized tonic-clonic seizures in patients 17 years and older
Usual Adult Dose for Seizures
MONOTHERAPY FOR PARTIAL-ONSET SEIZURES:
Initial dose: 100 mg orally twice a day
- Titrate in increments of 100 mg (50 mg twice a day) no more frequently than once a week based on clinical response and tolerability
ADJUNCTIVE THERAPY FOR PARTIAL-ONSET SEIZURES OR GENERALIZED TONIC-CLONIC SEIZURES: :
Initial dose: 50 mg orally twice a day
- Titrate in increments of 100 mg (50 mg twice a day) no more frequently than once a week based on clinical response and tolerability
Alternatively, may initiate therapy with a loading dose:
LOADING DOSE: 200 mg oral/IV once, followed in 12 hours with 100 mg oral/IV every 12 hours for at least 1 week; subsequent dose titrations should be performed as described above
- Due to increased incidence of CNS adverse reactions, the loading dose should be administered under medical supervision
Comments:
- Therapy may be administered either orally or via IV infusion using the same dosing regimen; IV infusion should preferably be over 30 to 60 minutes, although may be infused over 15 minutes if needed; experience with IV therapy is limited to 5 days of consecutive treatment.
- In adult clinical trials, adjunctive doses higher than 200 mg twice a day were not more effective and were associated with a substantially higher rate of adverse reactions.
- If converting from a single antiepileptic drug (AED) to lacosamide monotherapy, withdrawal of concomitant AED should not occur until a therapeutic dose of lacosamide has been achieved and administered for 3 days, then the concomitant AED may be gradually withdrawn over 6 weeks.
Use: As monotherapy for partial-onset seizures or adjunctive therapy for partial-onset seizures or primary generalized tonic-clonic seizures in patients 17 years and older
Usual Pediatric Dose for Epilepsy
AGE: 1 month or older:
WEIGHT: Less than 6 kg: Monotherapy Only
- Initial dose: 2 mg/kg/day as 0.66 mg/kg IV 3 times a day OR 1 mg/kg orally 2 times a day
- Titrate by 2 mg/kg/day no more frequently than once a week based on response and tolerability
- Maintenance dose: 7.5 to 15 mg/kg/day as 2.5 to 5 mg/kg IV 3 times a day OR 3.75 to 7.5 mg/kg orally 2 times a day
- Initial dose: 1 mg/kg oral/IV 2 times a day
- Titrate by 1 mg/kg twice a day no more frequently than once a week based on response and tolerability
- Maintenance dose: 3 to 6 mg/kg oral/IV twice a day
AGE: 4 to less than 17 years:
WEIGHT: 11 to less than 30 kg:
- Initial dose: 1 mg/kg oral/IV 2 times a day
- Titrate by 1 mg/kg oral/IV twice a day no more frequently than once a week based on response and tolerability
- Maintenance dose: 3 to 6 mg/kg oral/IV twice a day
- Initial dose: 1 mg/kg oral/IV twice a day
- Titrate by 1 mg/kg twice a day no more frequently than once a week based on clinical response and tolerability
- Maintenance dose: 2 to 4 mg/kg oral/IV twice a day
- Initial dose: 50 mg oral/IV twice a day
- Titrate by 50 mg twice a day no more frequently than once a week based on clinical response and tolerability
- MONOTHERAPY: Maintenance dose: 150 to 200 mg oral/IV twice a day
- ADJUNCTIVE THERAPY: Maintenance dose: 100 to 200 mg oral/IV twice a day
17 years and older: See Adult Dosing
Comments:
- The use of loading dose in pediatric patients has not been established.
- Oral and IV doses are the same unless specified; IV doses should be administered as an IV infusion over 30 to 60 minutes; experience with IV therapy is limited to 5 days of consecutive treatment.
- In adult clinical trials, adjunctive doses higher than 200 mg twice a day were not more effective and were associated with a substantially higher rate of adverse reactions.
- If converting from a from a single antiepileptic drug (AED) to lacosamide monotherapy, withdrawal of concomitant AED should not occur until a therapeutic dose of lacosamide has been achieved and administered for 3 days, then the concomitant AED may be gradually withdrawn over 6 weeks.
Uses: For the treatment of partial onset seizures in patients 1 month or older and as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years or older.
Usual Pediatric Dose for Seizures
AGE: 1 month or older:
WEIGHT: Less than 6 kg: Monotherapy Only
- Initial dose: 2 mg/kg/day as 0.66 mg/kg IV 3 times a day OR 1 mg/kg orally 2 times a day
- Titrate by 2 mg/kg/day no more frequently than once a week based on response and tolerability
- Maintenance dose: 7.5 to 15 mg/kg/day as 2.5 to 5 mg/kg IV 3 times a day OR 3.75 to 7.5 mg/kg orally 2 times a day
- Initial dose: 1 mg/kg oral/IV 2 times a day
- Titrate by 1 mg/kg twice a day no more frequently than once a week based on response and tolerability
- Maintenance dose: 3 to 6 mg/kg oral/IV twice a day
AGE: 4 to less than 17 years:
WEIGHT: 11 to less than 30 kg:
- Initial dose: 1 mg/kg oral/IV 2 times a day
- Titrate by 1 mg/kg oral/IV twice a day no more frequently than once a week based on response and tolerability
- Maintenance dose: 3 to 6 mg/kg oral/IV twice a day
- Initial dose: 1 mg/kg oral/IV twice a day
- Titrate by 1 mg/kg twice a day no more frequently than once a week based on clinical response and tolerability
- Maintenance dose: 2 to 4 mg/kg oral/IV twice a day
- Initial dose: 50 mg oral/IV twice a day
- Titrate by 50 mg twice a day no more frequently than once a week based on clinical response and tolerability
- MONOTHERAPY: Maintenance dose: 150 to 200 mg oral/IV twice a day
- ADJUNCTIVE THERAPY: Maintenance dose: 100 to 200 mg oral/IV twice a day
17 years and older: See Adult Dosing
Comments:
- The use of loading dose in pediatric patients has not been established.
- Oral and IV doses are the same unless specified; IV doses should be administered as an IV infusion over 30 to 60 minutes; experience with IV therapy is limited to 5 days of consecutive treatment.
- In adult clinical trials, adjunctive doses higher than 200 mg twice a day were not more effective and were associated with a substantially higher rate of adverse reactions.
- If converting from a from a single antiepileptic drug (AED) to lacosamide monotherapy, withdrawal of concomitant AED should not occur until a therapeutic dose of lacosamide has been achieved and administered for 3 days, then the concomitant AED may be gradually withdrawn over 6 weeks.
Uses: For the treatment of partial onset seizures in patients 1 month or older and as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years or older.
Renal Dose Adjustments
Mild to moderate renal dysfunction (CrCl greater than 30 mL/min): No adjustment recommended
Severe renal dysfunction (CrCl less than 30 mL/min [adults] or CrCl less than 30 mL/min/1.73 m2 [pediatrics]) and ESRD: Maximum dose should be reduced by 25%
Dose titration should be performed with caution in patients with renal impairment
Liver Dose Adjustments
Mild to moderate hepatic impairment: Maximum dose should be reduced by 25%
Severe hepatic impairment: Not recommended
Dose titration should be performed with caution in patients with hepatic impairment
Dose Adjustments
Elderly: Dose titration should be cautious, usually starting at the lower end of the dosing ranges
Concomitant Use with Strong CYP450 3A4 or CYP450 2C9 Inhibitors:
- Lacosamide dose reduction may be necessary in patients with renal impairment or hepatic impairment
Therapy Discontinuation:
- Upon discontinuation, this drug should be withdrawn gradually over at least 1 week
Precautions
CONTRAINDICATIONS:
- None
Safety and efficacy have not been established in treating partial onset seizures in patients younger than 1 month
Safety and efficacy have not been established in treating primary generalized tonic-clonic seizures in patients younger than 4 years
Consult WARNINGS section for additional precautions.
US Controlled Substance: Schedule V
Dialysis
Following a 4-hour hemodialysis treatment, dosage supplementation of up to 50% should be considered as this drug is effectively removed by hemodialysis
Other Comments
Administration advice:
Oral Tablets:
- May be taken with or without food
- Swallow whole with liquid; do not divide tablets
Oral Solution:
- May be taken with or without food
- Use provided calibrated measuring device; do not use a household teaspoon or tablespoon as it is not an adequate measuring device
- May be administered using a nasogastric tube or gastrostomy tube
- Discard unused oral solution 6 months after first opening bottle
- Note: Oral solution contains aspartame, a source of phenylalanine (200 mg dose contains 0.32 mg of phenylalanine)
IV formulation
- Administer as IV infusion preferably over 30 to 60 minutes; if necessary, may infuse over 15 minutes in adults.
- May be administered without further dilution or may be diluted with normal saline, D5W, or lactated ringers; diluted solution should not be stored for more than 4 hours at room temperature
Storage requirements:
- IV injection: Store at 20C to 25C (68F to 77F); Do not freeze
- Diluted IV solution should not be stored for more than 4 hours at room temperature
- Oral solution: Store at 20C to 25C (68F to 77F); do not freeze; discard unused oral solution 6 months after first opening bottle
General:
- This drug is associated with ECG changes that can cause irregular heart beats and syncope; use cautiously in patients with underlying proarrhythmic conditions, severe cardiac disease, cardiac sodium channelopathies, or those receiving concomitant medications that affect cardiac conduction; if used in these patients, obtain an ECG prior to initiation and after titrated to steady-state maintenance dose. If the IV route is used, increased monitoring is recommended.
- Patients with phenylketonuria (PKU) should be aware that the oral solution contains aspartame, a source of phenylalanine.
Monitoring:
- Cardiac: Obtain ECG before initiation and after titration to steady-state maintenance dose in patients with underlying proarrhythmic conditions, severe cardiac disease, cardiac sodium channelopathies, or those receiving concomitant medications that affect cardiac conduction
- Closely monitor patients receiving IV therapy
- Psychiatric: Monitor for unusual changes in mood or behavior, especially the emergence of suicidal thoughts or behaviors
Patient Advice:
- Read the US FDA-approved patient labeling (Medication Guide).
- Patients should be aware that this drug is associated with ECG changes that may predispose them to irregular heart beat and syncope; patients should be aware of the cardiac symptoms that should be reported promptly to their healthcare provider.
- Patients should be aware that this drug may increase the risk of suicidal thoughts and behaviors; unusual changes in mood or behaviors should be reported immediately to their healthcare provider.
- Patients should be aware that this drug may cause dizziness, double vision, abnormal coordination and balance, and somnolence; patients should be counseled on the risks of driving and engaging in other hazardous activities.
- Patients should be instructed to speak with their healthcare provider if they are pregnant, intending to become pregnant or breastfeeding.
- Patients should be instructed to promptly report signs or symptoms of hepatotoxicity or early manifestation of hypersensitivity (e.g., fever, lymphadenopathy).
