lacosamide

la-KOSE-a-mide

Therapeutic Classification: anticonvulsants

REMS

Partial-onset seizures (as either monotherapy or adjunctive therapy).
Primary generalized tonic-clonic seizures (as adjunctive therapy).

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 generalized tonic-clonic seizures.

Absorption: 100% absorbed following oral administration; IV administration results in complete bioavailability.

Distribution: Unknown.

Protein Binding: <15%.

Metabolism/Excretion: Partially metabolized by the liver; 40% excreted in urine as unchanged drug; 30% as a metabolite.

Half-Life: 13 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO-IR	unknown	1–4 hr	12 hr
PO-XR	unknown	7 hr	24 hr
IV	unknown	end of infusion	12 hr

Contraindicated in:

Hypersensitivity;
Severe hepatic impairment.

Use Cautiously in:

CCr <30 mL/min (use lower daily dose);
All patients (may ↑ risk of suicidal thoughts/behaviors);
Mild to moderate hepatic impairment;
Severe renal impairment;
Known cardiac conduction problems (heart block or sick sinus syndrome without a pacemaker), severe cardiac disease (MI or HF), Brugada syndrome, or taking medications that affect cardiac conduction;
Diabetic neuropathy or cardiac disease (↑ risk for atrial fibrillation/flutter);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children 1 mo (safety and effectiveness not established);
Geri: Titrate dose carefully in older adults.

CV: atrial fibrillation/flutter, bradycardia, heart block, syncope, VENTRICULAR ARRHYTHMIAS

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

EENT: diplopia

GI: nausea, vomiting

Hemat: AGRANULOCYTOSIS

Neuro: dizziness, headache, ataxia, hallucinations, SUICIDAL THOUGHTS, syncope, vertigo

Misc: physical dependence, psychological dependence

Drug-drug:

Use cautiously with other drugs that affect cardiac conduction, including sodium channel blockers, beta blockers, diltiazem, verapamil, potassium channel blockers, and PR-interval prolonging medications.

Partial-Onset Seizures

PO IV (Adults ): Monotherapy (immediate-release PO or IV): 100 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 150–200 mg twice daily; may also initiate therapy with 200-mg single loading dose followed 12 hr later by 100 mg twice daily for 1 wk; may then ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 150–200 mg twice daily. Monotherapy (extended-release PO)200 mg once daily; may ↑ weekly by 100 mg once daily up to a maintenance dose of 300–400 mg once daily; Adjunctive therapy (immediate-release PO or IV): 50 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily; may also initiate therapy with 200-mg single loading dose followed 12 hr later by 100 mg twice daily for 1 wk; may then ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily. Adjunctive therapy (extended-release PO): 100 mg once daily; may ↑ weekly by 100 mg once daily up to a maintenance dose of 200–400 mg once daily.
PO IV (Children ≥1 mo and ≥50 kg): Monotherapy (immediate-release PO or IV): 50 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 150–200 mg twice daily; may also initiate therapy with 200-mg single loading dose followed 12 hr later by 100 mg twice daily for 1 wk; may then ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 150–200 mg twice daily. Monotherapy (extended-release PO): 100 mg once daily; may ↑ weekly by 100 mg once daily up to a maintenance dose of 300–400 mg once daily. Adjunctive therapy (immediate-release PO or IV): 50 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily; may also initiate therapy with 200-mg single loading dose followed 12 hr later by 100 mg twice daily for 1 wk; may then ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily. Adjunctive therapy (extended-release PO): 100 mg once daily; may ↑ weekly by 100 mg once daily up to a maintenance dose of 200–400 mg once daily.
PO IV (Children ≥1 mo and 30–<50 kg): Monotherapy or adjunctive therapy (immediate-release PO or IV): 1 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 2–4 mg/kg twice daily; may also initiate therapy with 4 mg/kg single loading dose followed 12 hr later by 2 mg/kg twice daily for 1 wk; may then ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 2–4 mg/kg twice daily.
PO IV (Children ≥1 mo and 6–<30 kg): Monotherapy or adjunctive therapy (immediate-release PO or IV): 1 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 3–6 mg/kg twice daily; may also initiate therapy with 4.5 mg/kg single loading dose followed 12 hr later by 3 mg/kg twice daily for 1 wk; may then ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 3–6 mg/kg twice daily.
PO (Children ≥1 mo and <6 kg): Monotherapy or adjunctive therapy (immediate-release PO or IV): 1 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 3.75–7.5 mg/kg twice daily; may also initiate therapy with 3.75 mg/kg twice daily for 1 wk; may then ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 3.75–7.5 mg/kg twice daily.
IV (Children ≥1 mo and <6 kg): Monotherapy or adjunctive therapy (immediate-release PO or IV): 0.66 mg/kg 3 times daily; may ↑ weekly by 2 mg/kg/day in 3 divided doses up to a maintenance dose of 2.5–5 mg/kg 3 times daily; may also initiate therapy with 2.5 mg/kg 3 times daily for 1 wk; may then ↑ weekly by 2 mg/kg/day in 3 divided doses up to a maintenance dose of 2.5–5 mg/kg 3 times daily.

Renal Impairment

PO IV (Adults and Children ≥1 mo): CCr ≤30 mL: Monotherapy or adjunctive therapy (immediate-release PO or IV): ↓ maximum dose by 25%. Monotherapy or adjunctive therapy (extended-release PO): Not to exceed maximum dose of 300 mg once daily.

Hepatic Impairment

PO IV (Adults and Children ≥1 mo): Mild or moderate hepatic impairment: Monotherapy or adjunctive therapy (immediate-release PO or IV): ↓ maximum dose by 25%. Monotherapy or adjunctive therapy (extended-release PO): Not to exceed dose of 300 mg once daily.

Primary Generalized Tonic-Clonic Seizures

PO IV (Adults ): Adjunctive therapy (immediate-release PO or IV): 50 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily; may also initiate therapy with 200-mg single loading dose followed 12 hr later by 100 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily.Adjunctive therapy (extended-release PO): 100 mg once daily; may ↑ weekly by 100 mg once daily up to a maintenance dose of 200–400 mg once daily.
PO IV (Children ≥4 yr and ≥50 kg): Adjunctive therapy (immediate-release PO or IV): 50 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily; may also initiate therapy with 200-mg single loading dose followed 12 hr later by 100 mg twice daily; may ↑ weekly by 100 mg/day in 2 divided doses up to a maintenance dose of 100–200 mg twice daily. Adjunctive therapy (extended-release PO): 100 mg once daily; may ↑ weekly by 100 mg once daily up to a maintenance dose of 200–400 mg once daily.
PO IV (Children ≥4 yr and 30–<50 kg): Adjunctive therapy (immediate-release PO or IV): 1 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 2–4 mg/kg twice daily; may also initiate therapy with 4 mg/kg single loading dose followed 12 hr later by 2 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 2–4 mg/kg twice daily.
PO IV (Children ≥4 yr and 11–<30 kg): Adjunctive therapy (immediate-release PO or IV): 1 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 3–6 mg/kg twice daily; may also initiate therapy with 4.5 mg/kg single loading dose followed 12 hr later by 3 mg/kg twice daily; may ↑ weekly by 2 mg/kg/day in 2 divided doses up to a maintenance dose of 3–6 mg/kg twice daily.

Renal Impairment

PO IV (Adults and Children ≥4 yr): CCr ≤30 mL/min: Adjunctive therapy (immediate-release PO or IV): ↓ maximum dose by 25%. Adjunctive therapy (extended-release PO): Not to exceed dose of 300 mg once daily.

Hepatic Impairment

PO IV (Adults and Children ≥4 yr): Mild or moderate hepatic impairment: Adjunctive therapy (immediate-release PO or IV): ↓ maximum dose by 25%. Adjunctive therapy (extended-release PO): Not to exceed dose of 300 mg once daily.

(Generic available)

Immediate-release tablets: 50 mg; 100 mg; 150 mg; 200 mg
Extended-release capsules: 100 mg; 150 mg; 200 mg
Oral solution: 10 mg/mL
Solution for injection: 10 mg/mL

Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
Monitor for changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. SJS may develop. Treat symptomatically; may recur once treatment is stopped.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis), during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
IV: Assess ECG prior to therapy in patients with pre-existing cardiac disease before starting and after titration to steady-state maintenance. Closely monitor patients with cardiac conduction problems or on medications that affect conduction. IV lacosamide may cause bradycardia or AV block.

Lab Test Considerations:

May cause ↑ ALT, which may return to normal without treatment.
- Monitor CBC and platelets periodically during therapy.

Do not confuse Vimpat with Venofer or Vfend.
IV: IV administration is indicated for short term replacement (up to 5 days) when PO 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 .
When switching from another antiepileptic drug to lacosamide, administer 150–200 mg twice daily for at least 3 days before beginning withdrawal of other antiepileptic drug. Gradually ↓ other antiepileptic drug over 6 wk.
When administering loading dose, closely monitor for CNS and cardiovascular adverse reactions.
When discontinuing lacosamide, gradually ↓ dose over 1 wk.
PO: May be administered with or without food. DNC: Swallow tablets whole with liquid; do not crush, break, or chew.
- Use a calibrated measuring device for accurate dosing of oral solution; household measures are not accurate. Discard any unused solution 6 mo after opening bottle.
- Oral solution may also be given via nasogastric tube or gastrostomy tube.

IV 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 if cloudy, discolored, or contains precipitates. Solution is stable for 4 hr at room temperature. Discard unused portion.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Instruct patient to take lacosamide around the clock, as directed. Medication should be gradually discontinued over >1 wk to prevent seizures.
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 health care professional gives clearance based on control of seizure disorder. If syncope occurs, advise patient to lie down with legs raised until recovered and notify health care professional.
Inform patients and families of risk of suicidal thoughts and behavior. Advise that behavior or mood changes; worsening or emergent symptoms of depression, suicidal or self-harm thoughts or behavior; or rash 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.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor infants exposed to lacosamide through breast milk for excess sedation. Encourage pregnant patients to enroll in the North American Antiepileptic Drug registry by calling 1-888-233-2334; call must be made by patient. Information on registry can be found at http://www.aedpregnancyregistry.org/.

Decreased seizure activity.

Motpoly XR, Vimpat

Schedule V (C-V)

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Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Contr. Subst. Schedule ⬆