Version July 2025
Seizures, partial (focal) 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 (immediate release): 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 (immediate release): 3.75 to 7.5 mg/kg/dose twice daily.
6 to <30 kg:
Initial: Oral (immediate release), 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 (immediate release), IV: 3 to 6 mg/kg/dose twice daily.
30 to <50 kg:
Initial: Oral (immediate release), 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 (immediate release), IV: 2 to 4 mg/kg/dose twice daily.
≥50 kg:
Immediate-release preparations:
Initial (monotherapy and adjunctive therapy): Oral (immediate release), IV: 50 mg twice daily; may be increased at weekly intervals of 50 mg twice daily based on response and tolerability.
Maintenance:
Monotherapy maintenance: Oral (immediate release), IV: 150 to 200 mg twice daily.
Adjunctive therapy maintenance: Oral (immediate release), IV: 100 to 200 mg twice daily.
Extended-release preparations:
Initial (monotherapy and adjunctive therapy): Oral (extended release [eg, Motpoly XR]): 100 mg once daily; may be increased at weekly intervals in 100 mg/day increments based on response and tolerability.
Maintenance:
Monotherapy maintenance: Oral (extended release [eg, Motpoly XR]): 300 to 400 mg once daily.
Adjunctive therapy maintenance: Oral (extended release [eg, Motpoly XR]): 200 to 400 mg once daily.
Adolescents ≥17 years:
Immediate-release preparations:
Monotherapy:
Initial: Oral (immediate release), 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 (immediate release), 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 (immediate release), 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 (immediate release), 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 (immediate release), 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 (immediate release), 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).
Extended-release preparations :
Monotherapy:
Initial: Oral (extended release [Motpoly XR]): 200 mg once daily; may be increased at weekly intervals in 100 mg/day increments based on response and tolerability.
Maintenance: Oral (extended release [Motpoly XR]): 300 to 400 mg once daily.
Adjunctive therapy:
Initial: Oral (extended release [Motpoly XR]): 100 mg once daily; may be increased at weekly intervals in 100 mg/day increments based on response and tolerability.
Maintenance: Oral (extended release [Motpoly XR]): 200 to 400 mg once daily.
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:
Immediate-release preparations:
Initial: Oral (immediate release), 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 (immediate release), IV: 3 to 6 mg/kg/dose twice daily.
30 to <50 kg:
Immediate-release preparations:
Initial: Oral (immediate release), 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 (immediate release), IV: 2 to 4 mg/kg/dose twice daily.
≥50 kg:
Immediate-release preparations:
Initial: Oral (immediate release), IV: 50 mg twice daily; may be increased at weekly intervals of 50 mg twice daily based on response and tolerability.
Maintenance: Oral (immediate release), 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.
Extended-release preparations:
Initial: Oral (extended release): 100 mg once daily; may be increased at weekly intervals in 100 mg/day increments based on response and tolerability.
Maintenance: Oral (extended release): 200 to 400 mg once daily.
Adolescents ≥17 years:
Immediate-release preparations:
Initial: Oral (immediate release), 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 (immediate release), 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 (immediate release), 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.
Extended-release preparations:
Initial: Oral (extended release): 100 mg once daily; may be increased at weekly intervals in 100 mg/day increments based on response and tolerability.
Maintenance: Oral (extended release): 200 to 400 mg once daily.
Seizures, refractory: Limited data available: Infants ≥6 months, Children, and Adolescents: Oral (immediate release), 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: Immediate release, extended release:
Note: Titrate dose with caution; use the Schwartz equation for calculation in pediatric patients.
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, not to exceed 300 mg/day.
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.
(For additional information see "Lacosamide: Drug information")
Focal (partial) onset seizures:
Monotherapy:
Oral:
Immediate release (tablets, oral solution): Initial: 50 to 100 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability to a maintenance dose of 150 to 200 mg twice daily. Doses up to 600 mg/day may provide additional benefit in some patients (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).
Extended release (capsules): Initial: 200 mg once daily; may be increased at weekly intervals by 100 mg once daily based on response and tolerability to a maintenance dose of 300 to 400 mg once daily.
IV: Initial: 50 to 100 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability to a maintenance dose of 150 to 200 mg twice daily (Ref). Doses up to 600 mg/day may provide additional benefit in some patients based on data with the oral formulation (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).
Adjunctive therapy:
Oral:
Immediate release (tablets, oral solution): Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability to a maintenance dose of 100 to 200 mg twice daily (Ref). Alternatively, may give 200 mg loading dose followed 12 hours later by 100 mg twice daily with same titration schedule. 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). Administer loading doses under medical supervision due to increased incidence of CNS adverse reactions (Ref).
Extended release (capsules): Initial: 100 mg once daily; may be increased at weekly intervals by 100 mg once daily up to a maintenance dose of 200 to 400 mg once daily.
IV: Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability to a maintenance dose of 100 to 200 mg twice daily (Ref). Alternatively, may give 200 mg loading dose followed 12 hours later by 100 mg twice daily with same titration schedule. Doses up to 600 mg/day may provide additional benefit in some patients based on data with the oral formulation; however, risk of adverse effects may be greater when higher doses of lacosamide are used in combination with other agents (Ref). Administer loading doses under medical supervision due to increased incidence of CNS adverse reactions (Ref).
Primary generalized tonic-clonic seizures:
Adjunctive therapy:
Oral:
Immediate release (tablets, oral solution): Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability to a maintenance dose of 100 to 200 mg twice daily. 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.
Extended release (capsules): 100 mg once daily; may be increased at weekly intervals by 100 mg once daily up to a maintenance dose of 200 to 400 mg once daily.
IV: Initial: 50 mg twice daily; may be increased at weekly intervals by 50 mg twice daily based on response and tolerability to a maintenance dose of 100 to 200 mg twice daily. 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.
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.
Immediate release (tablets, oral solution), IV: Withdraw gradually in weekly intervals by 200 mg/day (Ref).
Extended release (capsules): Withdraw gradually over ≥1 week.
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 (IR tablets, oral solution; ER capsules) :
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; base initiation and titration schedule on clinical response and tolerability (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).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: ~40% of unchanged lacosamide is excreted in the urine and ~30% of lacosamide is metabolized in the liver to inactive metabolites (Ref). An increase in exposure (AUC increased by ~50%) was observed in patients with moderate liver impairment (Child-Turcotte-Pugh class B) versus healthy controls (manufacturer's labeling). Dosing recommendations are applicable to all oral formulations (IR tablets, oral solution, and ER capsules) in addition to the IV formulation.
Liver impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A: IV, Oral: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B: IV, Oral: Initial: No dosage adjustment necessary; may titrate up to 75% of the usual indication-specific maintenance dose based on response and tolerability, not to exceed a maximum dose of 300 mg/day (Ref).
Child-Turcotte-Pugh class C: IV, Oral: Avoid use (Ref). Note: There is a single case report of lacosamide (200 mg/day) use in Child-Turcotte-Pugh class C as add-on therapy for refractory seizures (Ref).
Liver impairment developing in patient already receiving lacosamide:
Chronic disease progression (eg, outpatient):
Progression from baseline to Child-Turcotte-Pugh class A: IV, Oral: No dosage adjustment necessary (Ref).
Progression to Child-Turcotte-Pugh class B: IV, Oral: Consider reducing dose to 75% of the usual indication-specific maintenance dose; maximum dose: 300 mg/day (Ref).
Progression to Child-Turcotte-Pugh class C: IV, Oral: Although use is generally not recommended in patients with severe impairment, continued use in select patients with refractory seizures may be considered; use with caution. Consider reducing dose to 75% of the usual indication-specific maintenance dose (Ref). Note: There is a single case report of lacosamide (200 mg/day) use in Child-Turcotte-Pugh class C as add-on therapy for refractory seizures (Ref).
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 immediate-release 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: Irritation at injection site (IV: 1%), pain at injection site (IV: 3%)
Nervous system: Abnormal gait (2%), asthenia (2%), ataxia (4% to 7%) (table 4), balance impairment (1% to 5%), depression (2%), fatigue (7%), myoclonic seizure (3%), tremor (6%), 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 |
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 (IV)
Renal: Nephritis
Frequency not defined:
Gastrointestinal: Constipation, oral hypoesthesia, xerostomia
Hematologic & oncologic: Anemia
Nervous system: Cerebellar syndrome, dysarthria, euphoria, exacerbation of epilepsy (including status epilepticus), falling, hypoesthesia, intoxicated feeling
Neuromuscular & skeletal: Muscle spasm
Otic: Tinnitus
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Angina pectoris (Ref), atrial fibrillation (Ref), atrial flutter (Ref), atrioventricular block (Ref), cardiac arrhythmia (Ref), complete atrioventricular block (Ref), palpitations (Ref), prolongation P-R interval on ECG (Ref), prolonged QT interval on ECG (Ref), syncope (Ref), ventricular tachycardia (Ref)
Dermatologic: Skin rash (Ref), Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref), urticaria
Endocrine & metabolic: Hyponatremia (Ref)
Gastrointestinal: Dyspepsia (Ref)
Hematologic & oncologic: Agranulocytosis (Ref), neutropenia (Ref)
Hypersensitivity: Angioedema (Ref), drug reaction with eosinophilia and systemic symptoms (Ref)
Nervous system: Aggressive behavior (Ref), agitation, amnesia (Ref), cognitive dysfunction (Ref), confusion (Ref), depressed mood (Ref), disturbance in attention (Ref), hallucination (Ref), irritability (Ref), memory impairment (Ref), mood changes (Ref), paresthesia (Ref), psychosis, sleep disturbance (Ref), suicidal ideation (Ref), suicidal tendencies (Ref)
Neuromuscular & skeletal: Dyskinesia (Ref), panniculitis (Ref)
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:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. May consider performing pre- and postsurgical therapeutic drug monitoring to evaluate exposure (Hiemke 2018). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• Hepatic impairment: Not recommended for use in patients with severe hepatic impairment, although rare use reported (Romigi 2014); dosage adjustment required for 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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 24 Hour, Oral:
Motpoly XR: 100 mg, 150 mg
Motpoly XR: 200 mg [contains fd&c blue #1 (brilliant blue)]
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]
Generic: 10 mg/mL (5 mL, 10 mL, 15 mL, 20 mL, 200 mL, 465 mL); 50 mg/5 mL (5 mL); 100 mg/10 mL (10 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
May be product dependent
Capsule ER 24 Hour Therapy Pack (Motpoly XR Oral)
100 mg (per each): $25.50
150 mg (per each): $25.50
200 mg (per each): $25.50
Solution (Lacosamide Intravenous)
200 mg/20 mL (per mL): $1.98 - $5.80
Solution (Lacosamide Oral)
10 mg/mL (per mL): $0.44 - $2.23
Solution (Vimpat Intravenous)
200 mg/20 mL (per mL): $5.95
Solution (Vimpat Oral)
10 mg/mL (per mL): $2.81
Tablets (Lacosamide Oral)
50 mg (per each): $1.48 - $12.63
100 mg (per each): $2.46 - $18.75
150 mg (per each): $2.95 - $19.82
200 mg (per each): $2.95 - $20.92
Tablets (Vimpat Oral)
50 mg (per each): $14.49
100 mg (per each): $22.65
150 mg (per each): $23.99
200 mg (per each): $23.99
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Vimpat: 200 mg/20 mL (20 mL)
Generic: 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
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN; Lucas E. Orth, PharmD, BCPPS; Russel J. Roberts, PharmD, BCCCP, FCCM.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: May be administered with or without food.
Immediate release:
Oral solution (commercially available): Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon (overdosage may occur). Discard any remaining product in bottle after 6 months from first opening.
Administration via feeding tube: Note: Lacosamide absorption following post-pyloric administration is unknown. If post-pyloric administration is deemed necessary, consider the risks vs benefits and monitor closely for efficacy (Ref).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Dilute dose with at least an equivalent volume of purified water immediately prior to administration to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is 3 times the lacosamide solution volume (eg, 10 mL lacosamide solution diluted in 30 mL purified water) for post-pyloric administration. Draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Although there is no information available on the osmolality of lacosamide oral solution, this product may have elevated osmolality which could impact tolerance; consider the potential risks versus benefits prior to use (Ref).
General guidance: Hold enteral nutrition during lacosamide administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Tablets: Swallow tablets whole; do not divide.
Administration via feeding tube: Note: Lacosamide absorption following post-pyloric administration is unknown. If post-pyloric administration is deemed necessary, consider the risks vs benefits and monitor closely for efficacy (Ref).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Crush tablet(s) into a fine powder and disperse in 10 to 30 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated lacosamide tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed prior to administration (Ref).
General guidance: Hold enteral nutrition during lacosamide administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Extended-release capsules (eg, Motpoly XR): Swallow capsules whole; do not open, chew, or crush.
Administration via feeding tube: NOT recommended: Crushing modified-release dosage forms (eg, extended-release capsules) may result in release of excessive doses, variable serum concentrations, and increased risk of severe adverse effects (Ref).
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.
IV:
Infusion: According to the manufacturer, administer over 30 to 60 minutes to minimize adverse effects; infusions of 15 minutes may be used if needed. IV administration has been used for up to 5 days. Administer loading doses under medical supervision due to increased risk of adverse reactions, including cardiovascular and CNS. 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:
Capsules, 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). Swallow tablets whole; do not divide. Swallow capsules whole; do not open, chew, or crush.
Bariatric surgery: Lacosamide is available in an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery; providers should determine if the condition being treated can be safely monitored or if a switch to an alternate formulation is necessary (Ref). Lacosamide is also available in an IR formulation. Oral solutions may contain nonabsorbable sugars (eg, mannitol, sorbitol, xylitol) that can cause dumping syndrome after bariatric surgery; refer to manufacturer labeling and monitor for tolerability with use (Ref).
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN; Lucas E. Orth, PharmD, BCPPS; Russel J. Roberts, PharmD, BCCCP, FCCM.
Note: Lacosamide absorption following post-pyloric administration is unknown. If post-pyloric administration is deemed necessary, consider the risks vs benefits and closely monitor for efficacy (Ref).
Oral capsule, extended release:
Enteral feeding tube administration utilizing lacosamide ER capsules is not recommended. Crushing modified-release dosage forms (eg, ER capsules) may result in release of excessive doses, variable serum concentrations, and increased risk of severe adverse effects (Ref).
Oral solution (commercially available):
Gastric (eg, NG, G-tube ) or post-pyloric tubes (eg, J-tube): Dilute dose with at least an equivalent volume of purified water immediately prior to administration to reduce osmolality and viscosity; some experts recommend diluting in a volume of purified water that is 3 times the lacosamide solution volume (eg, 10 mL lacosamide solution diluted in 30 mL purified water). Draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Although there is no information available on the osmolality of lacosamide oral solution, this product may have elevated osmolality, which could impact tolerance; consider the potential risks vs benefits prior to use (Ref).
General guidance: Hold enteral nutrition (EN) during lacosamide administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart EN (Ref).
Oral tablet:
Gastric (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube): Crush tablet(s) into a fine powder and disperse in 10 to 30 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated lacosamide tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold EN during lacosamide administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart EN (Ref).
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Injection: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Do not freeze. Stable when mixed with compatible diluents (NS, LR, D5W) for up to 4 hours at room temperature; extended storage information for prepared solution at room temperature may be available; contact product manufacturer to obtain current recommendations. Discard any unused portion.
Oral solution, tablets, capsule: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Do not freeze oral solution. Discard any unused portion of oral solution after 6 months.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Motpoly XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216185s000lbl.pdf#page=22
Oral:
Immediate release (eg, Vimpat): Treatment (monotherapy or adjunctive) of partial-onset seizures (FDA approved in ages ≥1 month and adults); adjunctive treatment of primary generalized tonic-clonic seizures (All indications: FDA approved in ages ≥4 years and adults); has also been used for treatment of refractory seizures.
Extended release (eg, Motpoly XR): Treatment (monotherapy or adjunctive) of partial-onset seizures; adjunctive treatment of primary generalized tonic-clonic seizures (All indications: FDA approved in pediatric patients weighing ≥50 kg and adults).
Parenteral: Injection (eg, Vimpat): Treatment (monotherapy or adjunctive) of partial-onset seizures (FDA approved in ages ≥1 month and adults); adjunctive treatment of primary generalized tonic-clonic seizures (All indications: FDA approved in ages ≥4 years and adults); has also been used for treatment of refractory seizures and refractory status epilepticus.
Lacosamide may be confused with zonisamide
Vimpat may be confused with Venofer, Vfend, Vimovo
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Antiarrhythmic Agents (Class III): May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Antiseizure Agents (Sodium Channel Blockers): May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Bradycardia-Causing Agents: May increase AV-blocking effects of Lacosamide. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cenobamate: May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lidocaine (Systemic): May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease 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
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mexiletine: May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
PHENobarbital: Lacosamide may increase CNS depressant effects of PHENobarbital. PHENobarbital may decrease serum concentration of Lacosamide. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Some products may contain phenylalanine.
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.
Seizure frequency, duration, and severity; patients with conduction problems, sodium channelopathies, severe cardiac disease, or concomitant medications that affect cardiac conduction or prolong the PR interval should have ECG tracing prior to start of therapy and when at steady-state; monitor heart rate and blood pressure during IV administration (bradycardia, atrioventricular block, or ventricular tachyarrhythmias may occur during infusions); monitor hepatic and renal function; suicidality (eg, suicidal thoughts, depression, behavioral changes).
Therapeutic reference range: Note: There is no clear correlation with therapeutic concentrations 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 monitoring may be useful in pediatric patients, females, and patients receiving drugs that may interact with lacosamide (Contin 2013; Larsen Burns 2019; May 2018).
Seizures: 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).
Timing of serum samples: Draw trough at steady-state, at the end of the scheduled dosing interval (just before the next dose).
In vitro studies have shown that lacosamide stabilizes hyperexcitable neuronal membranes and inhibits repetitive neuronal firing by enhancing the slow inactivation of sodium channels.
Absorption: Oral: Complete.
Distribution: Vd: ~0.6 to 0.67 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: Immediate release (tablets, oral solution): 1 to 4 hours; extended release (capsules): 7 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.
