Lacosamide

Pronunciation

Pronunciation: la-KOE-sa-mide
Class: Anticonvulsant

Trade Names

Vimpat
- Tablets 50 mg
- Tablets 100 mg
- Tablets 150 mg
- Tablets 200 mg
- Solution, oral 10 mg/mL
- Injection, solution 10 mg/mL

Pharmacology

Precise mechanism of action is unknown; however, lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Completely absorbed following oral administration with negligible first-pass effect and an absolute bioavailability of approximately 100%. Food does not affect the rate or extent of absorption. Following IV administration, C max is reached at the end of the infusion.

Distribution

Vd is approximately 0.6 L/kg. Less than 15% is bound to plasma proteins.

Metabolism

Primarily cleared from the systemic circulation by renal excretion and biotransformation. Lacosamide is a CYP2C19 substrate.

Elimination

Approximately 95% is eliminated in the urine and less than 0.5% in the feces, mainly as unchanged drug (40%), 30% as the O-desmethyl metabolite, and approximately 20% as a structurally unknown inactive polar metabolite. Elimination half-life is approximately 13 h.

Special Populations

Renal Function Impairment

AUC is increased approximately 25% in patients with mild or moderate renal impairment and 60% in patients with severe renal impairment. No dosage adjustment is needed in patients with mild or moderate renal impairment.

Hepatic Function Impairment

AUC is increased by approximately 50% to 60% in patients with moderate hepatic impairment.

Elderly

In patients older than 65 y of age, AUC and C max are increased approximately 20% compared with younger subjects.

Children

Pharmacokinetics have not been studied.

Gender

Pharmacokinetics not affected by gender.

Race

No differences in pharmacokinetics among Asian, black, and white subjects.

Indications and Usage

Oral

Adjunctive treatment of partial-onset seizures.

Parenteral

Adjunctive treatment of partial-onset seizures when oral route is not feasible.

Contraindications

None well documented.

Dosage and Administration

Partial-Onset Seizures
Adults and Children 17 y of age and older

PO/IV Start with 50 mg twice daily. The dosage may be increased by 50 mg twice daily at weekly intervals up to the recommended maintenance dosage of 200 to 400 mg/day, based on response and tolerability.

Hepatic Function Impairment
Adults and Children 17 y of age and older

PO/IV Titrate the dose with caution. Max dosage of 300 mg/day is recommended in patients with mild or moderate hepatic impairment. Not recommended in patients with severe hepatic impairment.

Renal Function Impairment
Adults and Children 17 y of age and older Mild or moderate renal function impairment

PO/IV No dosage adjustment is needed.

Severe renal function impairment (CrCl less than 30 mL/min) and ESRD

PO/IV Max dosage is 300 mg/day. Following a 4-hour hemodialysis treatment, consider supplementation with up to 50% of the dose.

General Advice

  • When switching between the oral and IV route, administer the equivalent daily dose and frequency. Infuse the drug IV over a 30- to 60-min period.
  • May be taken without regard to meals.
  • Use of a calibrated measuring device is recommended when using the oral solution.
  • Injection may be administered IV without further dilution or may be further diluted with sodium chloride 0.9% injection, dextrose 5% injection, or Ringer's lactate injection. Do not administer if particulate matter, cloudiness, or discoloration is noted.
  • When discontinuing therapy, gradually withdraw over a minimum of 1 wk.

Storage/Stability

Store between 59° and 86°F. Do not freeze. Following dilution, store IV form for up to 24 h at 59° to 86°F in glass or PVC bags. Discard any unused portion of the injection. Discard any unused oral solution remaining after 7 wk of first opening the bottle.

Drug Interactions

Antiepileptic drugs (ie, carbamazepine, phenobarbital, phenytoin)

Small reductions (15% to 20%) in lacosamide plasma concentrations resulted with coadministration. A clinically important pharmacokinetic interaction is unlikely.

Hormonal contraceptives

A 20% increase in ethinyl estradiol C max has been observed. A clinically important pharmacokinetic interaction is unlikely.

Omeprazole

Plasma levels of the O-desmethyl-lacosamide metabolite were reduced approximately 60% in the presence of omeprazole. A clinically important pharmacokinetic interaction is unlikely.

Adverse Reactions

CNS

Dizziness (53%); ataxia, fatigue (15%); headache (14%); tremor (12%); somnolence (8%); balance disorder, memory impairment (6%); vertigo (5%); asthenia, gait disturbance (4%); depression (2%); bradycardia (postmarketing).

Dermatologic

Contusion (4%); pruritus, skin laceration (3%).

EENT

Blurred vision, diplopia (16%); nystagmus (10%).

GI

Nausea (17%); vomiting (16%); diarrhea (5%).

Local

Injection-site pain or discomfort (3%); irritation (1%).

Precautions

Monitor

In patients with known conduction problems or severe cardiac disease, obtain ECG before starting treatment and after titrating to steady state. Monitor patients for emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior. Closely monitor patients with coexisting hepatic and renal impairment during dose titration.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 17 y of age.

Elderly

Titrate dose with caution.

Renal Function

Titrate dose with caution in patients with any degree of renal impairment. A max dosage of 300 mg/day is recommended for patients with severe renal impairment or ESRD.

Hepatic Function

Titrate dose with caution in patients with mild or moderate hepatic impairment. A max dosage of 300 mg/day is recommended for patients with mild or moderate hepatic impairment. Not recommended in patients with severe hepatic impairment.

Ataxia and dizziness

May occur. Advise patients not to drive or operate complex machinery until they are familiar with the drug's effects on their ability to perform.

Atrial fibrillation and atrial flutter

Has been reported in patients with diabetic neuropathy who received treatment with lacosamide.

Discontinuation

Gradually withdraw treatment over a minimum of 1 wk to minimize the potential of increased seizure frequency.

Multiorgan hypersensitivity

Has been reported rarely.

Phenylketonurics

Oral solution contains aspartame, a source of phenylalanine. A 200 mg dose contains phenylalanine 0.32 mg.

PR interval prolongation

Dose-related PR interval prolongation may occur. Use with caution in patients with known conduction problems (eg, marked first-degree AV block, second-degree or higher AV block, sick sinus syndrome without a pacemaker) or with severe cardiac disease (eg, myocardial ischemia, heart failure).

Suicide

The risk of suicidal thoughts and behavior is increased.

Syncope

Has been reported in patients with diabetic neuropathy who were treated with lacosamide.

Overdosage

Symptoms

Limited experience available. Adverse reactions in patients receiving supratherapeutic doses were not different from those of patients receiving recommended doses.

Patient Information

  • Instruct patient to contact health care provider if palpitation, rapid pulse, or shortness of breath occurs.
  • Advise patient or caregivers to be alert for emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior, or thoughts about self-harm, and to immediately report any behaviors of concern to health care provider.
  • Advise patients that serious hypersensitivity reactions affecting multiple organs may occur. Instruct patients to promptly report symptoms, including dark urine, fatigue, and jaundice, to their health care provider.
  • Advise patient not to drive, operate complex machinery, or engage in other hazardous activities until accustomed to any dizziness, blurred vision, abnormal coordination and balance, and somnolence caused by taking lacosamide.
  • Advise patient that syncope can occur, and to lie down with raised legs until they recover and to contact health care provider.

Copyright © 2009 Wolters Kluwer Health.

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