- Tablets 50 mg
- Tablets 100 mg
- Tablets 150 mg
- Tablets 200 mg
- Solution, oral 10 mg/mL
- Injection, solution 10 mg/mL
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.
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.
Vd is approximately 0.6 L/kg. Less than 15% is bound to plasma proteins.
Primarily cleared from the systemic circulation by renal excretion and biotransformation. Lacosamide is a CYP2C19 substrate.
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 PopulationsRenal 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 UsageOral
Adjunctive treatment of partial-onset seizures.Parenteral
Adjunctive treatment of partial-onset seizures when oral route is not feasible.
None well documented.
Dosage and AdministrationPartial-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.
- 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.
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 InteractionsAntiepileptic 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.
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).
Contusion (4%); pruritus, skin laceration (3%).
Blurred vision, diplopia (16%); nystagmus (10%).
Nausea (17%); vomiting (16%); diarrhea (5%).
Injection-site pain or discomfort (3%); irritation (1%).
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.
Category C .
Safety and efficacy not established in children younger than 17 y of age.
Titrate dose with caution.
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.
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.
Gradually withdraw treatment over a minimum of 1 wk to minimize the potential of increased seizure frequency.
Has been reported rarely.
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).
The risk of suicidal thoughts and behavior is increased.
Has been reported in patients with diabetic neuropathy who were treated with lacosamide.
Limited experience available. Adverse reactions in patients receiving supratherapeutic doses were not different from those of patients receiving recommended doses.
- 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.
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