Focal (partial) onset seizure:
Monotherapy: Oral, IV:
Initial: 50 to 100 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability (Ref). Alternatively, may give 200 mg loading dose followed 12 hours later by 100 mg twice daily with same titration schedule. Administer loading doses under medical supervision due to increased incidence of CNS adverse reactions (Ref).
Maintenance: 150 to 200 mg twice daily. Doses up to 600 mg/day may provide additional benefit in some patients (Ref).
Adjunctive therapy: Oral, IV:
Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability (Ref). Alternatively, may give 200 mg loading dose followed 12 hours later by 100 mg twice daily with same titration schedule. Administer loading doses under medical supervision due to increased incidence of CNS adverse reactions (Ref).
Maintenance dose: 100 to 200 mg twice daily (Ref). Doses up to 600 mg/day may provide additional benefit in some patients; however, risk of adverse effects may be greater when higher doses of lacosamide are used in combination with other agents (Ref).
Primary generalized tonic-clonic seizures:
Adjunctive therapy: Oral, IV:
Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability. Alternatively, may give 200 mg loading dose followed 12 hours later by 100 mg twice daily with same titration schedule. Administer loading doses under medical supervision due to increased incidence of CNS adverse reactions.
Maintenance dose: 100 to 200 mg twice daily.
Status epilepticus (alternative agent) (off-label use):
IV: Initial: 200 to 400 mg as a single dose followed by a maintenance dose of 200 to 400 mg/day in 2 divided doses (Ref); some patients may require up to 600 mg/day (Ref).
Note: The Neurocritical Care Society recommends an administration rate of 200 mg over 15 minutes; however, some experts administer doses up to 400 mg at a rate of ≤80 mg/minute (eg, 400 mg over 5 minutes) (Ref).
Discontinuation of therapy: Avoid abrupt discontinuation. Lacosamide may be withdrawn in weekly intervals by 200 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
IV, Oral:
Altered kidney function: Note: Renal function may be estimated using the Cockcroft-Gault formula.
CrCl ≥30 mL/minute: Initial and maintenance: No dosage adjustment necessary (Ref).
CrCl <30 mL/minute:
Initial: No dosage adjustment necessary; use caution when titrating to maintenance dose (Ref).
Maintenance: Administer up to 75% of the indication-specific maximum dose (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (50% after a 4-hour hemodialysis session) (Ref):
Initial: No dosage adjustment necessary; administer a supplemental dose (up to 50%) after each hemodialysis session (Ref).
Maintenance: Administer up to 75% of the indication-specific maximum dose; administer a supplemental dose (up to 50%) after each hemodialysis session (Ref).
Peritoneal dialysis:
Initial: No dosage adjustment necessary (Ref).
Maintenance: Administer up to 75% of the indication-specific maximum dose (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement (Ref). Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, seizure control) and consideration of initial loading doses, if applicable. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.
Initial and maintenance: No dosage adjustment is likely necessary (Ref) since lacosamide is significantly removed by CRRT (Ref). However, at higher effluent flow rates (eg, >4,000 mL/hour), some patients may require higher than normal doses (Ref); may consider therapeutic drug monitoring.
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, seizure control) and consideration of initial loading doses, if applicable. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.
Initial: No dosage adjustment necessary; administer a supplemental dose (up to 50%) after each PIRRT session (Ref).
Maintenance: Administer up to 75% of the indication-specific maximum dose; administer a supplemental dose (up to 50%) after each PIRRT session (Ref).
Mild to moderate hepatic impairment: Reduce dose to 75% of the maximum dose.
Severe hepatic impairment: Use is not recommended.
(For additional information see "Lacosamide: Pediatric drug information")
Seizures, focal (partial) onset:
Note: For patients already on a single antiseizure medication and converting to lacosamide monotherapy, maintain the maintenance dose for 3 days before beginning withdrawal of the concomitant antiseizure drug. Gradually taper the concomitant antiseizure drug over ≥6 weeks. When switching from oral to IV formulations in patients weighing ≥6 kg, the total daily dose and frequency should be the same; IV therapy should only be used temporarily. Clinical study experience of IV lacosamide is limited to 5 days of consecutive treatment.
Infants, Children, and Adolescents <17 years:
Monotherapy and adjunctive therapy:
<6 kg: In patients <6 kg, oral and intravenous dosing is different; use caution.
IV:
Initial: IV: 0.66 mg/kg/dose 3 times daily; may be increased at weekly intervals by 0.66 mg/kg/dose 3 times daily based on response and tolerability.
Maintenance: IV: 2.5 to 5 mg/kg/dose 3 times daily.
Oral:
Initial: Oral: 1 mg/kg/dose twice daily; may be increased at weekly intervals by 1 mg/kg/dose twice daily based on response and tolerability.
Maintenance: Oral: 3.75 to 7.5 mg/kg/dose twice daily.
6 to <30 kg:
Initial: Oral, IV: 1 mg/kg/dose twice daily; may be increased at weekly intervals by 1 mg/kg/dose twice daily based on response and tolerability.
Maintenance: Oral, IV: 3 to 6 mg/kg/dose twice daily.
30 to <50 kg:
Initial: Oral, IV: 1 mg/kg/dose twice daily; may be increased at weekly intervals by 1 mg/kg/dose twice daily based on response and tolerability.
Maintenance: Oral, IV: 2 to 4 mg/kg/dose twice daily.
≥50 kg:
Initial (monotherapy and adjunctive therapy): Oral, IV: 50 mg twice daily; may be increased at weekly intervals of 50 mg twice daily based on response and tolerability.
Maintenance:
Monotherapy: Oral, IV: 150 to 200 mg twice daily.
Adjunctive therapy: Oral, IV: 100 to 200 mg twice daily.
Adolescents ≥17 years:
Monotherapy:
Initial: Oral, IV: 100 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability.
Alternate initial dosage: Oral, IV: Loading dose: 200 mg followed approximately 12 hours later by 100 mg twice daily for 1 week; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability. Note: Administer loading doses under medical supervision because of the increased incidence of CNS adverse reactions.
Maintenance: Oral, IV: 150 to 200 mg twice daily. Note: Doses up to 300 mg twice daily may provide additional benefit in some patients (Ref).
Adjunctive therapy:
Initial: Oral, IV: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability.
Alternative initial dosage: Oral, IV: Loading dose of 200 mg followed approximately 12 hours later by 100 mg twice daily for 1 week; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability. Note: Administer loading doses under medical supervision because of the increased incidence of CNS adverse reactions.
Maintenance dose: Oral, IV: 100 to 200 mg twice daily. Note: Doses up to 300 mg twice daily may provide additional benefit in some patients; however, risk of adverse effects may be greater when higher doses of lacosamide are used in combination with other agents (Ref).
Seizures, primary generalized tonic-clonic; adjunctive therapy:
Note: When switching from oral to IV formulations, the total daily dose and frequency should be the same; IV therapy should only be used temporarily. Clinical study experience of IV lacosamide is limited to 5 days of consecutive treatment.
Children ≥4 years and Adolescents <17 years:
11 to <30 kg:
Initial: Oral, IV: 1 mg/kg/dose twice daily; may be increased at weekly intervals by 1 mg/kg/dose twice daily based on response and tolerability.
Maintenance: Oral, IV: 3 to 6 mg/kg/dose twice daily.
30 to <50 kg:
Initial: Oral, IV: 1 mg/kg/dose twice daily; may be increased at weekly intervals by 1 mg/kg/dose twice daily based on response and tolerability.
Maintenance: Oral, IV: 2 to 4 mg/kg/dose twice daily.
≥50 kg:
Initial: Oral, IV: 50 mg twice daily; may be increased at weekly intervals of 50 mg twice daily based on response and tolerability.
Maintenance: Oral, IV: 100 to 200 mg twice daily. Note: In clinical trials of adjunctive therapy in adults, doses higher than 400 mg/day were not more effective and were associated with more adverse reactions.
Adolescents ≥17 years:
Initial: Oral, IV: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability.
Alternative initial dosage: Oral, IV: Loading dose of 200 mg followed approximately 12 hours later by 100 mg twice daily for 1 week; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability. Note: Administer loading doses under medical supervision because of the increased incidence of CNS adverse reactions.
Maintenance dose: Oral, IV: 100 to 200 mg twice daily. Note: In clinical trials of adjunctive therapy in adults, doses higher than 400 mg/day were not more effective and were associated with more adverse reactions.
Seizures, refractory: Limited data available: Infants ≥6 months, Children, and Adolescents: Oral, IV: Initial: 0.5 to 1 mg/kg/dose twice daily (usual maximum initial dose: 50 mg/dose); may titrate by 0.5 to 1 mg/kg/dose weekly based on response and tolerability. Mean maintenance dose: 3.6 mg/kg/dose; reported range: 0.5 to 10 mg/kg/dose twice daily (Ref). Note: Lacosamide may be more effective in refractory focal seizures as compared to generalized seizures, and efficacy may decrease after initial response (Ref).
Status epilepticus, refractory: Limited data available: Note: Optimal place in therapy not defined; variable regimens reported; use is typically reported after failure of ≥2 to 3 agents; dosing based on retrospective case series (Ref).
Infants, Children, and Adolescents:
Loading dose: IV: 5 to 10 mg/kg/dose as a single dose, infused over 15 to 30 minutes; reported range for loading dose: 2 to 11 mg/kg/dose (Ref). Usual maximum loading dose in adults: 400 mg/dose; doses up to 600 mg/dose have been reported (Ref).
Maintenance dose: IV: 6.5 mg/kg/dose twice daily; range of reported maintenance doses: 0.5 to 7 mg/kg/dose twice daily; usual adult maximum dose: 200 mg/dose (Ref).
Discontinuation of therapy: There is currently no standard method for the withdrawal of antiseizure medications in pediatric patients. Successful discontinuation of an antiseizure medication is dependent on several factors including but not limited to: Time of seizure freedom, underlying reason for the seizures, neuroimaging abnormalities, underlying neurodevelopmental status, and medication to be withdrawn (including dose, duration of therapy, and other pharmacokinetic/dynamic considerations) (Ref). Avoid abrupt discontinuation; gradually withdraw over ≥1 week (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: Titrate dose with caution.
Mild to moderate renal impairment (CrCl ≥30 mL/minute/1.73 m2): No dose adjustment necessary.
Severe renal impairment (CrCl <30 mL/minute/1.73 m2): Maximum daily dose: Reduce dose to 75% of maximum dose.
End-stage renal disease (ESRD) requiring hemodialysis: Maximum daily dose: Reduce dose to 75% of maximum dose. Removed by hemodialysis; after 4-hour hemodialysis treatment, a supplemental dose of up to 50% should be considered.
Infants, Children, and Adolescents: Titrate dose with caution.
Mild to moderate hepatic impairment: Maximum daily dose: Reduce dose to 75% of maximum dose.
Severe hepatic impairment: Use is not recommended.
Refer to adult dosing; use caution during dose titration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Generic: 200 mg/20 mL (20 mL)
Solution, Intravenous [preservative free]:
Vimpat: 200 mg/20 mL (20 mL)
Generic: 200 mg/20 mL (20 mL)
Solution, Oral:
Vimpat: 10 mg/mL (200 mL) [contains aspartame, methylparaben, polyethylene glycol (macrogol), propylene glycol]
Vimpat: 10 mg/mL (200 mL [DSC], 465 mL [DSC]) [contains aspartame, methylparaben, polyethylene glycol (macrogol), propylene glycol; strawberry flavor]
Generic: 10 mg/mL (5 mL, 10 mL, 200 mL)
Tablet, Oral:
Vimpat: 50 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Vimpat: 100 mg, 150 mg
Vimpat: 200 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 50 mg, 100 mg, 150 mg, 200 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Vimpat: 200 mg/20 mL (20 mL)
Tablet, Oral:
Vimpat: 50 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Vimpat: 100 mg, 150 mg
Vimpat: 200 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 50 mg, 100 mg, 150 mg, 200 mg
C-V
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
IV:
Infusion: Administer over 15 to 60 minutes; infusions over 30 to 60 minutes are preferred to minimize adverse effects. IV administration has been used for up to 5 days. Can be administered without further dilution or may be mixed with compatible diluents (NS, LR, D5W).
Bolus (off label): Doses up to 400 mg may be administered undiluted at ≤80 mg/minute (eg, 400 mg over 5 minutes) (Ref).
Oral:
Solution, tablets: May be administered with or without food. Oral solution should be administered with a calibrated measuring device (not a household teaspoon or tablespoon). Oral solution may also be administered via a nasogastric or gastrostomy tube. Swallow tablets whole; do not divide.
Oral: May be administered with or without food.
Solution: Should be administered with a calibrated measuring device (not a household teaspoon or tablespoon). May be administered via a nasogastric or gastrostomy tube. Discard any remaining product in bottle after 6 months from first opening.
Tablets: Swallow tablets whole; do not divide.
Parenteral: IV: Administer over 30 to 60 minutes to minimize adverse effects; may be administered undiluted or diluted in compatible diluent. Infusion times <30 minutes are generally not recommended in pediatric patients; in adults, infusions of 15 minutes may be used if necessary. IV infusion may cause bradycardia, AV blocks, and ventricular tachyarrhythmias; monitor closely. Rapid administration has been associated with higher CNS adverse effects (eg, dizziness, somnolence, paresthesia); monitor closely.
Focal (partial) onset seizures: Monotherapy or adjunctive therapy in the treatment of focal (partial) onset seizures in adult and pediatric patients ≥1 month of age.
Primary generalized tonic-clonic seizures: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adult and pediatric patients ≥4 years of age.
Status epilepticus
Lacosamide may be confused with zonisamide
Vimpat may be confused with Venofer, Vfend, Vimovo
Lacosamide may cause cardiac arrhythmias including, but not limited to bradycardia, atrioventricular block, and tachyarrhythmias such as atrial fibrillation, atrial flutter, and ventricular tachycardia (Ref). Cardiovascular (CV) adverse reactions are rare but potentially life-threatening (Ref). Restoration of normal cardiac rhythm has occurred following discontinuation (Ref).
Mechanism: Dose-related; acts predominantly by enhancing the slow inactivation of voltage-dependent sodium channels (Ref). Sodium channel-blocking drugs such as lacosamide cause slowing of conduction velocity in cardiac tissues, predominantly in non-nodal tissues (Ref). Specifically, lacosamide appears to disrupt the SCN5A channel for which mutations have been previously linked to Brugada syndrome (Ref).
Onset: Exact onset is unknown. Some literature suggests onset may occur during IV administration (Ref), but some cases reported abnormal ECG after chronic oral use as well (Ref).
Risk factors:
• Higher doses (Ref)
• CV comorbidities (eg, CV disease, cardiac conduction abnormalities) (Ref)
• Older age (Ref)
• Concurrent use of other proarrhythmic medications (eg, antiarrhythmics, other antiseizure medications) (Ref)
CNS effects, such as dizziness, drowsiness, headache, and ataxia are common and expected adverse reactions that may occur with lacosamide (Ref). Other CNS-related adverse reactions may include confusion, cognitive dysfunction, memory impairment, paresthesia, and sleep disturbance (Ref). CNS effects may be minimized by gradual dose titration, and some may regress spontaneously during continuation of therapy (Ref).
Mechanism: Dose-related; related to the pharmacologic action (Ref).
Onset: Varied; more likely to occur in the early stages of treatment (~3 months). One report showed incidence of dizziness to be 3 to 4 times higher in the titration period than in the maintenance period (Ref).
Risk factors:
• Higher doses (Ref)
• Rapid titration (Ref)
• Older age (Ref)
• Concurrent antiseizure medications or medications that cause sedation (Ref)
A variety of delayed hypersensitivity reactions, ranging from mild with skin rash (Ref) to severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported (Ref).
Mechanism: Non–dose-related; immunologic. Delayed hypersensitivity reactions, including rashes (often maculopapular) and SCARs, are T-cell-mediated (Ref).
Onset: Delayed hypersensitivity reactions: Varied; a diffuse skin rash developed in 1 patient after 8 days of treatment with lacosamide (Ref). SCARs usually occur 1 to 8 weeks after initiation (Ref); reexposure to the same or similar drug may lead to more rapid onset (usually with 1 to 4 days) (Ref).
Risk factors:
• Cross-reactivity: Cross-reactivity has not been well defined. In one report, DRESS developed rapidly after initiation of lacosamide following a previous reaction with phenobarbital. Cross-reactivity with phenobarbital was hypothesized based on the common aromatic ring in phenobarbital and lacosamide (Ref).
Antiseizure medications have been associated with suicidal ideation and suicidal tendencies. However, the FDA meta-analysis has been criticized due to several important limitations (Ref). The risk of suicide is increased in epilepsy (Ref), but the occurrence of suicidal ideation/tendencies in epilepsy is multifactorial. While some antiseizure medications (but not all) have been associated with treatment-emergent psychiatric effects such as anxiety and depression, other factors such as postictal suicidal behavior and pertinent patient history must also be evaluated to provide an accurate assessment of risk for any individual drug (Ref). Suicidal ideation and suicidal tendencies have been reported in association with lacosamide (Ref).
Onset: Varied; peak incidence of suicidality across antiseizure medications (not specific to individual agents) has been noted to occur between 1 and 12 weeks of therapy (Ref). A review of clinical trials noted that risk extended from 1 week to 24 weeks of therapy, corresponding to the duration of most trials.
Risk factors:
• History of depression (Ref)
• Use in conditions other than epilepsy or bipolar disorder (Ref)
• In patients with bipolar disorder, risk for repeat suicide attempt was increased in patients with alcohol/substance abuse disorder, rapid cycling, and earlier age at onset of first manic episode (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with oral formulations, unless otherwise noted.
>10%:
Gastrointestinal: Nausea (7% to 11%)
Nervous system: Dizziness (16% to 30%) (table 1), drowsiness (5% to 17%) (table 2), headache (11% to 14%) (table 3)
|
Drug (Lacosamide) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Lacosamide) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
23% |
7% |
Children and adolescents |
N/A |
Oral solution |
Tonic-clonic seizures |
N/A |
N/A |
|
30% |
8% |
Adults |
400 mg/day |
Oral solution and tablet |
Partial-onset seizures |
471 |
364 |
|
16% |
8% |
Adults |
200 mg/day |
Oral solution and tablet |
Partial-onset seizures |
270 |
364 |
|
Drug (Lacosamide) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Lacosamide) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
17% |
14% |
Children and adolescents |
N/A |
Oral solution |
Tonic-clonic seizures |
N/A |
N/A |
|
8% |
5% |
Adults |
400 mg/day |
Oral solution and tablet |
Partial-onset seizures |
471 |
364 |
|
5% |
5% |
Adults |
200 mg/day |
Oral solution and tablet |
Partial-onset seizures |
270 |
364 |
|
Drug (Lacosamide) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Lacosamide) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
14% |
10% |
Children and adolescents |
N/A |
Oral solution |
Tonic-clonic seizures |
N/A |
N/A |
|
14% |
9% |
Adults |
400 mg/day |
Oral solution and tablet |
Partial-onset seizures |
471 |
364 |
|
11% |
9% |
Adults |
200 mg/day |
Oral solution and tablet |
Partial-onset seizures |
270 |
364 |
1% to 10%:
Dermatologic: Pruritus (2% to 3%)
Gastrointestinal: Diarrhea (5%), vomiting (6% to 9%)
Hematologic & oncologic: Bruise (4%)
Local: Local irritation (IV: 1%), pain at injection site (IV: 3%)
Nervous system: Abnormal gait (2%), ataxia (4% to 7%) (table 4), balance impairment (1% to 5%), depression (2%), fatigue (7%), vertigo (3% to 5%)
|
Drug (Lacosamide) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Lacosamide) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
7% |
2% |
Adults |
400 mg/day |
Oral solution and tablet |
Partial-onset seizures |
471 |
364 |
|
4% |
2% |
Adults |
200 mg/day |
Oral solution and tablet |
Partial-onset seizures |
270 |
364 |
Neuromuscular & skeletal: Asthenia (2%), tremor (6%)
Ophthalmic: Blurred vision (9%), diplopia (6% to 10%), nystagmus disorder (5%)
Miscellaneous: Laceration (3%)
<1%:
Cardiovascular: Bradycardia, first degree atrioventricular block
Hepatic: Abnormal hepatic function tests, hepatitis
Local: Erythema at injection site
Renal: Nephritis
Frequency not defined:
Gastrointestinal: Constipation, dyspepsia, oral hypoesthesia, xerostomia
Hematologic & oncologic: Anemia
Nervous system: Cerebellar syndrome, dysarthria, euphoria, falling, hypoesthesia, intoxicated feeling, irritability, paresthesia
Neuromuscular & skeletal: Muscle spasm
Otic: Tinnitus
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Angina pectoris (Steinhoff 2016), atrial fibrillation (Steinhoff 2016), atrial flutter (Steinhoff 2016), atrioventricular block (Steinhoff 2016), cardiac arrhythmia (Steinhoff 2016), complete atrioventricular block (Steinhoff 2016), palpitations (Steinhoff 2016), prolongation P-R interval on ECG (Steinhoff 2016), prolonged QT interval on ECG (Steinhoff 2016), syncope (Steinhoff 2016), ventricular tachycardia (Steinhoff 2016)
Dermatologic: Skin rash (Kim 2020), Stevens-Johnson syndrome (Kardaun 2016), toxic epidermal necrolysis (Kardaun 2016), urticaria
Endocrine & metabolic: Hyponatremia (Steinhoff 2016)
Hematologic & oncologic: Agranulocytosis (Shibata 2021), neutropenia (Rao 2018)
Hypersensitivity: Angioedema (Goodwin 2011)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Fong 2017)
Nervous system: Acute psychosis, aggressive behavior (Flores 2012), agitation, amnesia (Steinhoff 2016), cognitive dysfunction (Steinhoff 2016), confusion (Steinhoff 2016), depressed mood (Steinhoff 2016), disturbance in attention (Steinhoff 2016), hallucination (Flores 2012), memory impairment (Steinhoff 2016), mood changes (Flores 2012), sleep disturbance (Flores 2012), suicidal ideation (Steinhoff 2016), suicidal tendencies (Steinhoff 2016)
Neuromuscular & skeletal: Dyskinesia (Madani 2020)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Hypersensitivity to lacosamide or any component of the formulation; second- or third-degree atrioventricular (AV) block (current or history of).
Disease-related concerns:
• Hepatic impairment: Not recommended for use in patients with severe hepatic impairment; dosage adjustment required for mild to moderate hepatic impairment.
• Ocular conditions: Blurred vision and diplopia may occur during therapy. Patients with persistent visual disturbances may need further assessment. Consider increased monitoring in patients with preexisting ocular conditions or vision-related issues.
• Renal impairment: Use caution in patients with renal impairment; dosage adjustment required for severe renal impairment (CrCl ≤30 mL/minute) and supplementation may be necessary in hemodialysis.
Dosage form specific issues:
• Phenylalanine: Some products may contain phenylalanine.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007).
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually (≥1 week) to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
In vitro data has shown lacosamide interferes with collapsing response mediator protein-2 (CRMP-2), a protein involved with neuronal differentiation and control of axonal outgrowth; potential effect on CNS development cannot be excluded. Lacosamide administered to neonatal and juvenile rats resulted in decreased brain weights and long-term neurobehavioral changes including learning and memory deficits. Studies of the effects of lacosamide on human CNS development are needed before this medication can be recommended for routine use in pediatric patients <4 years of age.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antiarrhythmic Agents (Class III): May enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Antiseizure Agents (Sodium Channel Blockers): May enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Lidocaine (Systemic): May enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
Mexiletine: May enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Lacosamide crosses the placenta (Ylikotila 2015; Zárubová 2016) and can be detected in the newborn serum at delivery (Landmark 2021).
Outcome data following maternal use of lacosamide during pregnancy are limited (Golembesky 2017; Hoeltzenbein 2011; Lattanzi 2017; Zárubová 2016; Zutshi 2021). In general, maternal polytherapy with antiseizure drugs may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended. Newborns of patients taking antiseizure medications during pregnancy may be at an increased risk of adverse events (Harden 2009).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of lacosamide may be altered (Fukushima 2021; Pennell 2022; Zárubová 2016; Zutshi 2021).
Data collection to monitor pregnancy and infant outcomes following exposure to lacosamide is ongoing. Patients exposed to lacosamide during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at http://www.aedpregnancyregistry.org.
Lacosamide is present in breast milk (Landmark 2021; Ylikotila 2015; Zárubová 2016).
Drowsiness and poor feeding were observed in a breastfeeding newborn following maternal use of lacosamide (in combination with other medications) throughout pregnancy and postpartum (Ylikotila 2015). Monitor infants exposed to lacosamide via breast milk for excess sedation. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of exposure to the infant and the benefits of treatment to the mother.
Some products may contain phenylalanine.
Monitor for signs/symptoms of conduction problems (eg, low or irregular pulse, feeling of lightheadedness and fainting). Patients with conduction problems, sodium channelopathies, severe cardiac disease, or concomitant medications that affect cardiac conduction or prolong PR interval should have ECG tracing prior to start of therapy and when at steady-state. Monitor these patients closely during IV infusions (bradycardia, AV block, or ventricular tachyarrhythmias may occur during infusions). Monitor for suicidality (eg, suicidal thoughts, depression, behavioral changes); mental alertness; signs/symptoms of DRESS (eg, disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems).
Timing of serum samples: Draw trough just before next dose.
Laboratory alert level: 20 mcg/mL (SI: 53.2 micromole/L) (AGNP [Hiemke 2018]).
Therapeutic reference range: Note: There is no clear correlation with therapeutic levels and efficacy or tolerability and suggested therapeutic ranges vary depending on source; base dosing on therapeutic response as opposed to serum concentrations (AGNP [Hiemke 2018]; Patsalos 2018). However, therapeutic drug levels may be useful in children and adolescents, females, and patients on concomitant enzyme-inducing antiseizure drugs due to wide alterations in clearance (Contin 2013; Larsen Burns 2019; May 2018).
Epilepsy: 1 to 10 mcg/mL (SI: 2.66 to 26.6 micromole/L) (AGNP [Hiemke 2018]) or 10 to 20 mcg/mL (SI: 40 to 80 micromole/L) (Patsalos 2018).
In vitro studies have shown that lacosamide stabilizes hyperexcitable neuronal membranes and inhibits repetitive neuronal firing by enhancing the slow inactivation of sodium channels (with no effects on fast inactivation of sodium channels).
Absorption: Oral: Completely
Distribution: Vd: ~0.6 L/kg
Protein binding: <15%
Metabolism: Hepatic via CYP3A4, CYP2C9, and CYP2C19; forms metabolite, O-desmethyl-lacosamide (inactive)
Bioavailability: ~100%
Half-life elimination:
Children ≥4 years and Adolescents:
Mean weight 11 kg: 7.4 hours
Mean weight 28.9 kg: 10.6 hours
Mean weight 70 kg: 14.8 hours
Adults: ~13 hours
Time to peak, plasma: Oral: 1 to 4 hours
Excretion: Urine (95%; 40% as unchanged drug, 30% as inactive metabolite, 20% as uncharacterized metabolite); feces (<0.5%)
Altered kidney function: AUC is increased ~25% in patients with mild or moderate renal impairment (CrCl >30 to 80 mL/minute) and 60% in patients with severe renal impairment (CrCl ≤30 mL/minute). Following a 4-hour hemodialysis treatment, AUC is reduced by ~50%.
Hepatic function impairment: AUC is increased by ~50% to 60% in patients with moderate hepatic impairment (Child-Pugh class B).
Older adult: In patients >65 years of age, AUC and Cmax are increased ~20% compared with younger subjects.
Solution (Lacosamide Intravenous)
200 mg/20 mL (per mL): $2.40 - $4.72
Solution (Lacosamide Oral)
10 mg/mL (per mL): $2.21 - $2.23
Solution (Vimpat Intravenous)
200 mg/20 mL (per mL): $5.24
Solution (Vimpat Oral)
10 mg/mL (per mL): $2.48
Tablets (Lacosamide Oral)
50 mg (per each): $1.48 - $12.63
100 mg (per each): $2.46 - $19.75
150 mg (per each): $2.95 - $20.91
200 mg (per each): $2.95 - $20.92
Tablets (Vimpat Oral)
50 mg (per each): $12.77
100 mg (per each): $19.97
150 mg (per each): $21.15
200 mg (per each): $21.15
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