lacosamide

lacosamide

(la-kose-a-mide) ,

Vimpat

(trade name)

Classification

Therapeutic: anticonvulsants
Pregnancy Category: C

Indications

Adjunctive therapy of partial-onset seizures.

Action

Mechanism is not known, but may involve enhancement of slow inactivation of sodium channels with resultant membrane stabilization

Therapeutic effects

Decreased incidence and severity of partial-onset seizures.

Pharmacokinetics

Absorption: 100% absorbed following oral administration; IV administration results in complete bioavailability.
Distribution: Unknown.
Protein Binding: <15%.
Metabolism and Excretion: Partially metabolized by the liver; 40% excreted in urine as unchanged drug, 30% as a metabolite.
Half-life: 13 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown1–4 hr 12 hr
IVunknownend of infusion12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Severe hepatic impairment; Lactation: Lactation.
Use Cautiously in: CCr <30 mL/min (use lower daily dose);All patients (may ↑ risk of suicidal thoughts/behaviors);Hepatic or renal impairment and taking strong inhibitor of CYP3A4 or CYP2C9 (dose ↓ may be needed)Mild to moderate hepatic impairment; titrate dose carefully, use lower daily dose;Known cardiac conduction problems or severe cardiac disease (heart block or sick sinus syndrome without a pacemaker, Brugada syndrome, MI or HF);Diabetic neuropathy or cardiac disease (↑ risk for atrial fibrillation/flutter) Obstetric: Use only if potential benefit justifies risk to the fetus; Pediatric: Children <17 yr (limited data available); Geriatric: Titrate dose carefully.

Adverse Reactions/Side Effects

Central nervous system

  • suicidal thoughts (life-threatening)
  • dizziness (most frequent)
  • headache (most frequent)
  • hallucinations
  • syncope
  • vertigo

Ear, Eye, Nose, Throat

  • diplopia (most frequent)

Cardiovascular

  • atrial fibrillation/flutter
  • bradycardia
  • PR interval prolongation

Dermatologic

  • drug reaction with eosinophilia and systemic symptoms (life-threatening)
  • stevens-johnson syndrome (life-threatening)
  • toxic epidermal necrolysis (life-threatening)
  • rash

Gastrointestinal

  • nausea (most frequent)
  • vomiting

Hematologic

  • agranulocytosis (life-threatening)

Neurologic

  • ataxia

Miscellaneous

  • physical dependence
  • psychological dependence
  • multiorgan hypersensitivity reactions (Drug Reaction with Eosinophilia and Systemic Symptoms—DRESS)

Interactions

Drug-Drug interaction

Use cautiously with other drugs that affect cardiac conduction.

Route/Dosage

Oral Intravenous (Adults) 50 mg twice daily; may be ↑ weekly by 100 mg/day in two divided doses up to a maintenance dose of 200–400 mg/day given in two divided doses.
Oral (Children 3–16 yr) 1 mg/kg/day divided BID initially (maximum dose: 50 mg); may be ↑ weekly by 1 mg/kg/day up to a maintenance dose of 10 mg/kg/day (maximum dose: 400 mg/day).

Hepatic/Renal Impairment

Oral Intravenous (Adults) CCr ≤30 mL/min or mild to moderate hepatic impairment—daily dose should not exceed 300 mg.

Availability

Tablets: 50 mg, 100 mg, 150 mg, 200 mg
Solution for injection: 10 mg/mL
Oral solution: 10 mg/mL

Nursing implications

Nursing assessment

  • Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
  • Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Assess ECG prior to therapy in patients with pre-existing cardiac disease.
  • Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.
  • Lab Test Considerations: May cause ↑ALT, which may return to normal without treatment.
    • Monitor CBC and platelets periodically during therapy.

Potential Nursing Diagnoses

Risk for injury (Indications)

Implementation

  • IV administration is indicated for short term replacement when PO administration is not feasible. When switching from PO to IV, initial total daily dose should be equivalent to total daily dose and frequency of PO therapy. At end of IV period, may switch to PO at equivalent daily dose and frequency of IV therapy.
  • Oral: May be administered with or without food.
    • Use a calibrated measuring device for accurate dosing of oral solution; household measures are not accurate.
  • Intravenous Administration
  • Intermittent Infusion: Diluent: May be administered undiluted or diluted with 0.9% NaCl, D5W, or LR.Concentration: 10 mg/mL. Solution is clear and colorless; do not administer solutions that are discolored or contain a precipitate. Solution is stable for 24 hr at room temperature. Discard unused portion.
  • Rate: Infuse over 30–60 min.

Patient/Family Teaching

  • Instruct patient to take lacosamide around the clock, as directed. Medication should be gradually discontinued over at least 1 wk to prevent seizures. Advise patient to read the Medication Guide before starting therapy and with each Rx refill.
  • May cause dizziness, ataxia, and syncope. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Tell patient not to resume driving until physician gives clearance based on control of seizure disorder. If syncope occurs, advise patient to lay down with legs raised until recovered and notify health care professional.
  • Inform patients and families of risk of suicidal thoughts and behavior and advise that behavioral changes, emergency or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm should be reported to health care professional immediately.
  • Instruct patient to notify health care professional if signs of multiorgan hypersensitivity reactions (fever, rash, fatigue, jaundice, dark urine) occur.
  • Advise patient to consult health care professional before taking other Rx, OTC, or herbal preparation and to avoid taking alcohol or other CNS depressants concurrently with lacosamide.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage pregnant patients to enroll in the pregnancy registry by calling 1-888-537-7734.

Evaluation/Desired Outcomes

  • Decreased seizure activity.
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References in periodicals archive ?
Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide.
He eventually became seizure free, and his antiseizure medications were tapered to monotherapy lacosamide.
High Predictability of Plasma Lacosamide and No Relevant Differences by Age and Gender Following Normalization
By the pharmaceutical company for all medicines called Vimpat with lacosamide (discount drugs) for the period 1.
The trialAamet its primary endpoint showing that the predicted exit rate for patients on lacosamide was significantly lower than the historical control exit rate.
Unlike other sodium channel-targeting AEDs, Lacosamide is the only drug that reduces voltage-gated sodium channel availability by selective enhancement of slow inactivation, but without apparent interaction with fast-inactivation gating.
Turning to emerging agents for migraine prophylaxis, she highlighted several novel drugs now in phase II studies: DP-VPA, a valproic acid prodrug being developed by the Israeli company D-Pharm; a botanically sourced compound, MGX-008, that comes from the bark of the Monterey pine and is under development by Migco; an oral leukotriene D, receptor antagonist backed by Lilly; and lacosamide, also known as BGG492, an AMPA/kainate glutamate receptor antagonist under development by Novartis.
This edition has 200 new monographs, new and updated interactions advice, and the addition of drugs like febuxostat, ivabradine, lacosamide, pitavastatin, retigabine (ezogabine), rufinamide, and ulipristal.
Release date- 22072011 - The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has agreed to a recall of Vimpat 15 mg/ml syrup because of a quality defect in some batches leading to uneven distribution of the active substance lacosamide in the syrup.
The key ingredient - lacosamide - has been found to be distributed unevenly
But these studies were conducted before the widespread use of the "second wave" of new-generation AEDs, including levetiracetam, oxcarbazepine, zonisamide, pregabalin, and lacosamide.
These newer agents include gabapentin, felbamate, oxcarbazepine, topiramate, tiagabine, vigabatrin, levetiracetam, lamotrigine, pregabalin, zonisamide, rufinamide, and lacosamide.