ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Lacosamide: Drug information

Lacosamide: Drug information
(For additional information see "Lacosamide: Patient drug information" and see "Lacosamide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Vimpat
Brand Names: Canada
  • ACH-Lacosamide;
  • AG-Lacosamide;
  • APO-Lacosamide;
  • Auro-Lacosamide;
  • JAMP-Lacosamide;
  • MAR-Lacosamide;
  • MINT-Lacosamide;
  • NRA-Lacosamide;
  • Pharma-Lacosamide;
  • SANDOZ Lacosamide;
  • TEVA-Lacosamide;
  • Vimpat
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous
Dosing: Adult
Focal onset seizure

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 (Baulac 2017; Wechsler 2014). 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 (Fountain 2013; manufacturer's labeling).

Maintenance: 150 to 200 mg twice daily. Doses up to 600 mg/day may provide additional benefit in some patients (Baulac 2017).

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 (Halász 2009). 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 (Fountain 2013; manufacturer's labeling).

Maintenance dose: 100 to 200 mg twice daily (Halász 2009). 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 (Ben-Menachem 2007; Chung 2010; Weston 2015).

Primary generalized tonic-clonic seizures

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

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 (Jirsch 2020; Misra 2017; NCS [Brophy 2012]; Sutter 2013); some patients may require up to 600 mg/day (Strzelczyk 2017).

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) (Davidson 2018; Kellinghaus 2011; NCS [Brophy 2012]).

Discontinuation of therapy: Avoid abrupt discontinuation. Lacosamide may be withdrawn in weekly intervals by 200 mg/day (Ben-Menachem 2007; Chung 2010; Halász 2009).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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 (manufacturer’s labeling).

CrCl <30 mL/minute:

Initial: No dosage adjustment necessary; use caution when titrating to maintenance dose (manufacturer’s labeling).

Maintenance: Administer up to 75% of the indication-specific maximum dose (manufacturer’s labeling).

Hemodialysis, intermittent (thrice weekly): Dialyzable (50% after a 4-hour hemodialysis session) (Cawello 2013):

Initial: No dosage adjustment necessary; administer a supplemental dose (up to 50%) after each hemodialysis session (manufacturer’s labeling).

Maintenance: Administer up to 75% of the indication-specific maximum dose; administer a supplemental dose (up to 50%) after each hemodialysis session (manufacturer’s labeling).

Peritoneal dialysis:

Initial: No dosage adjustment necessary (expert opinion).

Maintenance: Administer up to 75% of the indication-specific maximum dose (expert opinion).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement (Kalaria 2021). 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 (expert opinion) since lacosamide is significantly removed by CRRT (Franquiz 2018; Kalaria 2021). However, at higher effluent flow rates (eg, >4,000 mL/hour), some patients may require higher than normal doses (Kalaria 2021; expert opinion); 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 (expert opinion).

Maintenance: Administer up to 75% of the indication-specific maximum dose; administer a supplemental dose (up to 50%) after each PIRRT session (expert opinion).

Dosing: Hepatic Impairment: Adult

Mild to moderate hepatic impairment: Reduce dose to 75% of the maximum dose.

Severe hepatic impairment: Use is not recommended.

Dosing: Pediatric

(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 (Baulac 2017).

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 (Chung 2010; McGinnis 2016; Weston 2015).

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 (Casas-Fernández 2012; Farkas 2019; Gavatha 2011; Grosso 2014a; Grosso 2014b; Ortiz de la Rosa 2018; Verrotti 2013). Note: Lacosamide may be more effective in refractory focal seizures as compared to generalized seizures, and efficacy may decrease after initial response (McGinnis 2016; Ortiz de la Rosa 2018).

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 (Arkilo 2016; Grosso 2014c; Poddar 2016; Welsh 2017).

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 (Arkilo 2016; Grosso 2014c; Poddar 2016; Vossler 2020; Welsh 2017). Usual maximum loading dose in adults: 400 mg/dose; doses up to 600 mg/dose have been reported (NCS [Brophy 2012]; Strzelczyk 2017).

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 (Grosso 2014c; Vossler 2020; Welsh 2017).

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) (Ayuga Loro 2020). Avoid abrupt discontinuation; gradually withdraw over ≥1 week (manufacturer's labeling).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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.

Dosing: Older Adult

Refer to adult dosing; use caution during dose titration.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

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, propylene glycol]

Vimpat: 10 mg/mL (200 mL [DSC], 465 mL [DSC]) [contains aspartame, methylparaben, polyethylene glycol, propylene glycol; strawberry flavor]

Generic: 10 mg/mL (200 mL)

Tablet, Oral:

Vimpat: 50 mg [contains fd&c blue #2 aluminum lake]

Vimpat: 100 mg, 150 mg

Vimpat: 200 mg [contains fd&c blue #2 aluminum lake]

Generic: 50 mg, 100 mg, 150 mg, 200 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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 aluminum lake]

Vimpat: 100 mg, 150 mg

Vimpat: 200 mg [contains fd&c blue #2 aluminum lake]

Generic: 50 mg, 100 mg, 150 mg, 200 mg

Controlled Substance

C-V

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Vimpat: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022253s049,022254s039,022255s031lbl.pdf#page=31

Administration: Adult

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) (Davidson 2018; Kellinghaus 2011).

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.

Administration: Pediatric

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.

Use: Labeled Indications

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.

Use: Off-Label: Adult

Status epilepticus

Medication Safety Issues
Sound-alike/look-alike issues:

Lacosamide may be confused with zonisamide

Vimpat may be confused with Venofer, Vfend, Vimovo

Adverse Reactions (Significant): Considerations
Cardiovascular effects

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

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)

Hypersensitivity reactions (delayed)

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).

Suicidal ideation/tendencies

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)

Adverse Reactions

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)

Lacosamide: Adverse Reaction: Dizziness

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

Lacosamide: Adverse Reaction: Drowsiness

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

Lacosamide: Adverse Reaction: Headache

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%)

Lacosamide: Adverse Reaction: Ataxia

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)

Contraindications

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).

Warnings/Precautions

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.

Warnings: Additional Pediatric Considerations

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).

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

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

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

Pregnancy Considerations

Lacosamide crosses the placenta (Ylikotila 2015; Zárubová 2016).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of lacosamide may be altered (Zárubová 2016). Information related to pregnancy outcomes following maternal use of lacosamide is limited (Hoeltzenbein 2011; Lattanzi 2017; Zárubová 2016). In general, maternal polytherapy with antiseizure drugs may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended. Newborns of women taking antiseizure medications may be at an increased risk of adverse events (Harden 2009).

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.

Breastfeeding Considerations

Lacosamide is present in breast milk (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). According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Dietary Considerations

Some products may contain phenylalanine.

Monitoring Parameters

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).

Reference Range

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).

Mechanism of Action

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).

Pharmacokinetics

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%)

Pharmacokinetics: Additional Considerations

Renal function impairment: 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).

Geriatric: In patients >65 years of age, AUC and Cmax are increased ~20% compared with younger subjects.

Pricing: US

Solution (Lacosamide Intravenous)

200 mg/20 mL (per mL): $3.93

Solution (Lacosamide Oral)

10 mg/mL (per mL): $2.21

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): $10.75 - $12.63

100 mg (per each): $16.81 - $19.75

150 mg (per each): $17.80 - $20.91

200 mg (per each): $17.81 - $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

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.

Brand Names: International
  • Aldinam (CL);
  • Andovimpamide (EG);
  • Copinate (CR, DO, GT, HN, NI, PA, SV);
  • Cosamide (ZW);
  • Fedolacosa (EG);
  • Lacosam (BD);
  • Lacosamet (EG);
  • Lacotem (AR);
  • Lacovimp (EG);
  • Vimpat (AR, AT, AU, BB, BE, BH, CH, CO, CR, CY, CZ, DE, DK, DO, EE, ES, FR, GB, GR, GT, HK, HN, HR, HU, IE, IL, IS, JP, KR, LB, LT, LU, MT, MY, NI, NL, NO, NZ, PA, PH, PL, PT, RO, RU, SE, SI, SK, SV, TH, TR, TW)


For country abbreviations used in Lexicomp (show table)
  1. Albers JM, Möddel G, Dittrich R, et al. Intravenous lacosamide—an effective add-on treatment of refractory status epilepticus. Seizure. 2011;20(5):428-430. [PubMed 21354831]
  2. Arana A, Wentworth CE, Ayuso-Mateos JL, Arellano FM. Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med. 2010 5;363(6):542-551. doi:10.1056/NEJMoa0909801 [PubMed 20818889]
  3. Arkilo D, Gustafson M, Ritter FJ. Clinical experience of intravenous lacosamide in infants and young children. Eur J Paediatr Neurol. 2016;20(2):212-217. doi:10.1016/j.ejpn.2015.12.013 [PubMed 26810009]
  4. Ayuga Loro F, Gisbert Tijeras E, Brigo F. Rapid versus slow withdrawal of antiepileptic drugs. Cochrane Database Syst Rev. 2020;1(1):CD005003. doi:10.1002/14651858.CD005003.pub3 [PubMed 31990368]
  5. Baulac M, Rosenow F, Toledo M, et al. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial [published correction appears in Lancet Neurol. 2017;16(2):102]. Lancet Neurol. 2017;16(1):43-54. doi:10.1016/S1474-4422(16)30292-7 [PubMed 27889312]
  6. Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander JW. Suicide in people with epilepsy: how great is the risk? Epilepsia. 2009;50(8):1933-1942. doi:10.1111/j.1528-1167.2009.02106.x [PubMed 19453718]
  7. Bellivier F, Belzeaux R, Scott J, Courtet P, Golmard JL, Azorin JM. Anticonvulsants and suicide attempts in bipolar I disorders. Acta Psychiatr Scand. 2017;135(5):470-478. doi:10.1111/acps.12709 [PubMed 28190254]
  8. Bellón T. Mechanisms of severe cutaneous adverse reactions: Recent advances. Drug Saf. 2019;42(8):973-992. doi: 10.1007/s40264-019-00825-2 [PubMed 31020549]
  9. Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48(7):1308-1317. [PubMed 17635557]
  10. Berei TJ, Lillyblad MP, Almquist AK. Lacosamide-induced recurrent ventricular tachycardia in the acute care setting. J Pharm Pract. 2018;31(2):222-226. doi:10.1177/0897190017700557 [PubMed 28343443]
  11. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  12. Brophy GM, Bell R, Claassen J, et al; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-23. [PubMed 22528274]
  13. Casas-Fernández C, Martínez-Bermejo A, Rufo-Campos M, et al. Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain. Drugs R D. 2012;12(4):187-197. [PubMed 23193979]
  14. Cawello W, Fuhr U, Hering U, Maatouk H, Halabi A. Impact of impaired renal function on the pharmacokinetics of the antiepileptic drug lacosamide. Clin Pharmacokinet. 2013;52(10):897-906. doi:10.1007/s40262-013-0080-7 [PubMed 23737404]
  15. Chinnasami S, Rathore C, Duncan JS. Sinus node dysfunction: an adverse effect of lacosamide. Epilepsia. 2013;54(6):e90-e93. doi:10.1111/epi.12108 [PubMed 23360388]
  16. Chung S, Sperling MR, Biton V, et al; SP754 Study Group. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51(6):958-967. doi:10.1111/j.1528-1167.2009.02496.x [PubMed 20132285]
  17. Contin M, Albani F, Riva R, Candela C, Mohamed S, Baruzzi A. Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013;35(6):849-852. doi:10.1097/FTD.0b013e318290eacc [PubMed 23942540]
  18. Davidson KE, Newell J, Alsherbini K, Krushinski J, Jones GM. Safety and efficiency of intravenous push lacosamide administration. Neurocrit Care. 2018;29(3):491-495. doi:10.1007/s12028-018-0560-6 [PubMed 29949010]
  19. DeGiorgio AC, Desso TE, Lee L, DeGiorgio CM. Ventricular tachycardia associated with lacosamide co-medication in drug-resistant epilepsy. Epilepsy Behav Case Rep. 2012;1:26-28. doi:10.1016/j.ebcr.2012.10.001 [PubMed 25688050]
  20. Farkas V, Steinborn B, Flamini JR, et al. Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures. Neurology. 2019;93(12):e1212-e1226. doi:10.1212/WNL.0000000000008126 [PubMed 31462582]
  21. Farrokh S, Bon J, Erdman M, Tesoro E. Use of newer anticonvulsants for the treatment of status epilepticus. Pharmacotherapy. 2019;39(3):297-316. doi:10.1002/phar.2229 [PubMed 30723940]
  22. Flores L, Kemp S, Colbeck K, et al. Clinical experience with oral lacosamide as adjunctive therapy in adult patients with uncontrolled epilepsy: a multicentre study in epilepsy clinics in the United Kingdom (UK). Seizure. 2012;21(7):512-517. doi:10.1016/j.seizure.2012.05.005 [PubMed 22698379]
  23. Fong MK, Sheng B. DRESS syndrome: A case of cross-reactivity with lacosamide? Epilepsia Open. 2017;2(2):273-275. doi:10.1002/epi4.12053 [PubMed 29588957]
  24. Fountain NB, Krauss G, Isojarvi J, Dilley D, Doty P, Rudd GD. Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures. Epilepsia. 2013;54(1):58‐65. doi:10.1111/j.1528-1167.2012.03543.x [PubMed 22708895]
  25. Franquiz MJ, Kalaria SN, Armahizer MJ, Gopalakrishnan M, McCarthy PJ, Badjatia N. Lacosamide pharmacokinetics in a critically ill patient receiving continuous venovenous hemofiltration. Pharmacotherapy. 2018;38(2):e17-e21. doi:10.1002/phar.2063 [PubMed 29160945]
  26. Gavatha M, Ioannou I, Papavasiliou AS. Efficacy and Tolerability of Oral Lacosamide as Adjunctive Therapy in Pediatric Patients With Pharmacoresistant Focal Epilepsy. Epilepsy Behav. 2011;20(4):691-693. [PubMed 21406334]
  27. Goodwin H, Hinson HE, Shermock KM, Karanjia N, Lewin JJ 3rd. The use of lacosamide in refractory status epilepticus. Neurocrit Care. 2011;14(3):348-353. doi:10.1007/s12028-010-9501-8 [PubMed 21249530]
  28. Grosso S, Coppola G, Cusmai R, et al. Efficacy and tolerability of add-on lacosamide in children with Lennox-Gastaut syndrome. Acta Neurol Scand. 2014a;129(6):420-424. [PubMed 24479878]
  29. Grosso S, Parisi P, Spalice A, Verrotti A, Balestri P. Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy. Eur J Paediatr Neurol. 2014b;18(1):55-59. [PubMed 24129195]
  30. Grosso S, Zamponi N, Bartocci A, et al. Lacosamide in children with refractory status epilepticus. A multicenter Italian experience. Eur J Paediatr Neurol. 2014c;18(5):604-608. doi:10.1016/j.ejpn.2014.04.013 [PubMed 24836405]
  31. Halász P, Kälviäinen R, Mazurkiewicz-Beldzińska M, et al; SP755 Study Group. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50(3):443‐453. doi:10.1111/j.1528-1167.2008.01951.x [PubMed 19183227]
  32. Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73(2):133-141. [PubMed 19398681]
  33. Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm? Epilepsia. 2009;50(5):978-986. doi:10.1111/j.1528-1167.2009.02012.x [PubMed 19496806]
  34. Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017 [published correction appears in Pharmacopsychiatry. 2018;51(1-02):e1]. Pharmacopsychiatry. 2018;51(1-02):9-62. doi:10.1055/s-0043-116492 [PubMed 28910830]
  35. Hoeltzenbein M, Supcun-Ritzler S, Langthaler M, et al. Lacosamide During pregnancy: Experience of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy. Reprod Toxicol. 2011;31(2):259.
  36. Höfler J, Trinka E. Lacosamide as a new treatment option in status epilepticus. Epilepsia. 2013;54(3):393-404. doi:10.1111/epi.12058 [PubMed 23293881]
  37. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  38. Jirsch J, Hirsch LJ. Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 18, 2020.
  39. Kalaria SN, Armahizer M, McCarthy P, Badjatia N, Gobburu JV, Gopalakrishnan M. A prospective, real-world, clinical pharmacokinetic study to inform lacosamide dosing in critically ill patients undergoing continuous venovenous haemofiltration (PADRE-02). Br J Clin Pharmacol. 2021;87(11):4375-4385. doi:10.1111/bcp.14858 [PubMed 33855736]
  40. Kardaun SH, Vos BJ, Chandran NS. Stevens Johnson syndrome/toxic epidermal necrolysis-overlap, induced by lacosamide. Eur J Dermatol. 2016;26(2):185-186. doi:10.1684/ejd.2015.2674 [PubMed 27017922]
  41. Kellinghaus C. Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety. Ther Clin Risk Manag. 2009;5:757-766. doi:10.2147/tcrm.s5189 [PubMed 19816574]
  42. Kellinghaus C, Berning S, Immisch I, et al. Intravenous lacosamide for treatment of status epilepticus. Acta Neurol Scand. 2011;123(2):137-141. doi:10.1111/j.1600-0404.2010.01423.x [PubMed 20868429]
  43. Kennedy GM, Lhatoo SD. CNS adverse events associated with antiepileptic drugs. CNS Drugs. 2008;22(9):739-760. doi:10.2165/00023210-200822090-00003 [PubMed 18698874]
  44. Kim HK, Kim DY, Bae EK, Kim DW. Adverse skin reactions with antiepileptic drugs using Korea adverse event reporting system database, 2008-2017. J Korean Med Sci. 2020;35(4):e17. doi:10.3346/jkms.2020.35.e17 [PubMed 31997613]
  45. Koubeissi MZ, Vismer M, Ehrlich A. Lacosamide-induced rash. Epileptic Disord. 2014;16(3):380-383. doi:10.1684/epd.2014.0667 [PubMed 25035958]
  46. Larsen Burns M, Nikanorova M, Baftiu A, et al. Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway. Ther Drug Monit. 2019;41(3):340-347. doi:10.1097/FTD.0000000000000599 [PubMed 30688870]
  47. Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Lacosamide during pregnancy and breastfeeding. Neurol Neurochir Pol. 2017;51(3):266-269. doi:10.1016/j.pjnns.2017.03.003 [PubMed 28385340]
  48. Li J, Sun M, Wang X. The adverse-effect profile of lacosamide. Expert Opin Drug Saf. 2020;19(2):131-138. doi:10.1080/14740338.2020.1713089 [PubMed 31914330]
  49. Madani N, O'Malley JA, Porter BE, Baumer FM. Lacosamide-induced dyskinesia in children with intractable epilepsy. J Child Neurol. 2020;35(10):662-666. doi:10.1177/0883073820926634 [PubMed 32524876]
  50. May TW, Helmer R, Bien CG, Brandt C. Influence of dose and antiepileptic comedication on lacosamide serum concentrations in patients with epilepsy of different ages. Ther Drug Monit. 2018;40(5):620-627. doi:10.1097/FTD.0000000000000538 [PubMed 30086089]
  51. McGinnis E, Kessler SK. Lacosamide use in children with epilepsy: Retention rate and effect of concomitant sodium channel blockers in a large cohort. Epilepsia. 2016;57(9):1416-1425. doi:10.1111/epi.13466 [PubMed 27430392]
  52. Miliszewski MA, Kirchhof MG, Sikora S, Papp A, Dutz JP. Stevens-johnson syndrome and toxic epidermal necrolysis: An analysis of triggers and implications for improving prevention. Am J Med. 2016;129(11):1221-1225. doi:10.1016/j.amjmed.2016.03.022 [PubMed 27086495]
  53. Misra UK, Dubey D, Kalita J. Comparison of lacosamide versus sodium valproate in status epilepticus: a pilot study. Epilepsy Behav. 2017;76:110. doi:10.1016/j.yebeh.2017.07.005 [PubMed 28919386]
  54. Mula M, Hesdorffer DC. Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence. Drug Healthc Patient Saf. 2011;3:15-20. doi:10.2147/DHPS.S13070 [PubMed 21753899]
  55. Newey CR, Le NM, Ahrens C, Sahota P, Hantus S. The safety and efficacy of intravenous lacosamide for refractory status epilepticus in the critically ill. Neurocrit Care. 2017;26(2):273-279. doi:10.1007/s12028-016-0322-2 [PubMed 27844464]
  56. National Institute for Health and Care Excellence (NICE). Drug allergy: diagnosis and management of drug allergy in adults, children and young people. Published September 2014. Accessed November 11, 2021. https://www.nice.org.uk/guidance/cg183 [PubMed 27844464]
  57. Ortiz de la Rosa JS, Ladino LD, Rodríguez PJ, Rueda MC, Polanía JP, Castañeda AC. Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory status epilepticus: a systematic review. Seizure. 2018;56:34-40. doi:10.1016/j.seizure.2018.01.014 [PubMed 29428899]
  58. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40(5):526-548. doi:10.1097/FTD.0000000000000546 [PubMed 29957667]
  59. Patorno E, Bohn RL, Wahl PM, et al. Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA. 2010;303(14):1401-1409. doi:10.1001/jama.2010.410. Erratum in: JAMA. 2010;303(22):2252. Dosage error in article text. [PubMed 20388896]
  60. Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol. 2012;11(9):792-802. doi:10.1016/S1474-4422(12)70153-9. Erratum in: Lancet Neurol. 2012;11(9):746. [PubMed 22832500]
  61. Poddar K, Sharma R, Ng YT. Intravenous lacosamide in pediatric status epilepticus: an open-label efficacy and safety study. Pediatr Neurol. 2016;61:83-86. doi:10.1016/j.pediatrneurol.2016.03.021 [PubMed 27241232]
  62. Rao NP, Sheth S, Varambally S. Lacosamide precipitated neutropenia in a patient with bipolar disorder and comorbid epilepsy. Indian J Psychol Med. 2018;40(5):496-497. doi:10.4103/IJPSYM.IJPSYM_16_18 [PubMed 30275630]
  63. Rudd GD, Haverkamp W, Mason JW, et al. Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures. Acta Neurol Scand. 2015;132(5):355-363. doi:10.1111/ane.12414 [PubMed 25933358]
  64. Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]
  65. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  66. Shibata M, Hoshino R, Shimizu C, Sato M, Furuta N, Ikeda Y. Lacosamide-induced sinus node dysfunction followed by severe agranulocytosis. BMC Neurol. 2021;21(1):217. doi:10.1186/s12883-021-02253-1 [PubMed 34102997]
  67. Steinhoff BJ, Eckhardt K, Doty P, De Backer M, Brunnert M, Schulze-Bonhage A. A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures. Epilepsy Behav. 2016;58:35-43. doi:10.1016/j.yebeh.2016.02.041 [PubMed 27054272]
  68. Strzelczyk A, Zöllner JP, Willems LM, et al. Lacosamide in status epilepticus: systematic review of current evidence. Epilepsia. 2017;58(6):933-950. doi:10.1111/epi.13716 [PubMed 28295226]
  69. Sutter R, Marsch S, Rüegg S. Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: a comparative cohort study. CNS Drugs. 2013;27(4):321-329. doi:10.1007/s40263-013-0049-y [PubMed 23533010]
  70. Verrotti A, Loiacono G, Pizzolorusso A, et al. Lacosamide in pediatric and adult patients: comparison of efficacy and safety. Seizure. 2013;22(3):210-216. [PubMed 23298605]
  71. Vimpat (lacosamide) injection, oral solution, tablet [prescribing information]. Smyrna, GA: UCB Inc; October 2021.
  72. Vimpat (lacosamide) [product monograph]. Oakville, Ontario, Canada: UCB Canada Inc; July 2021.
  73. Vossler DG, Bainbridge JL, Boggs JG, et al. Treatment of refractory convulsive status epilepticus: a comprehensive review by the American Epilepsy Society Treatments Committee. Epilepsy Curr. 2020;20(5):245-264. doi:10.1177/1535759720928269 [PubMed 32822230]
  74. Wechsler RT, Li G, French J, et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results from a historical-controlled, multicenter, double-blind study. Epilepsia. 2014;55(7):1088‐1098. doi:10.1111/epi.12681 [PubMed 24915838]
  75. Welsh SS, Lin N, Topjian AA, Abend NS. Safety of intravenous lacosamide in critically ill children. Seizure. 2017;52:76-80. doi:10.1016/j.seizure.2017.09.019 [PubMed 29017081]
  76. Weston J, Shukralla A, McKay AJ, Marson AG. Lacosamide add-on therapy for partial epilepsy. Cochrane Database Syst Rev. 2015;(6):CD008841. doi:10.1002/14651858.CD008841.pub2 [PubMed 26077821]
  77. Ylikotila P, Ketola RA, Timonen S, Malm H, Ruuskanen JO. Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy. Reprod Toxicol. 2015;57:204-206. doi:10.1016/j.reprotox.2015.07.068 [PubMed 26187779]
  78. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
  79. Zárubová J, Kremlackova V, Borecka K, et al. Plasma and breast milk levels of lacosamide before, during and post pregnancy. Epilepsia. 2016;57:69. Abstract. doi:10.1111/epi.13609.
Topic 10268 Version 281.0