INDICATION

VIMPAT® is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. As the safety of VIMPAT injection in pediatric patients has not been established, VIMPAT injection is indicated for the treatment of partial-onset seizures only in adult patients (17 years of age and older).

SELECT IMPORTANT SAFETY INFORMATION

VIMPAT is associated with important warnings and precautions including suicidal behavior and ideation, dizziness and ataxia, cardiac rhythm and conduction abnormalities, syncope, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity.

In the adult monotherapy clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (observed at a higher rate of ≥2%). In the adult adjunctive placebo-controlled trials, the most common adverse reactions (≥10% and greater than placebo) were dizziness, headache, nausea, and diplopia. Pediatric adverse reactions are similar to those seen in adult patients.

VIMPAT is a Schedule V controlled substance.

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Adjunctive therapy in adult patients

VIMPAT DEMONSTRATED SIGNIFICANT CONTROL OF PARTIAL-ONSET SEIZURES
WITH OR WITHOUT SECONDARY GENERALIZATION.3-5*

≥50% RESPONDER RATES FROM BASELINE WITH VIMPAT VS PLACEBO3-5*
VIMPAT® (lacosamide) CV ≥50% Responder Rates From Baseline
VIMPAT® (lacosamide) CV ≥50% Responder Rates From BaselineVIMPAT® (lacosamide) CV ≥50% Responder Rates From BaselineVIMPAT® (lacosamide) CV ≥50% Responder Rates From Baseline

Significantly more adult patients taking VIMPAT experienced a 50% or greater reduction in seizures from baseline compared with placebo.3-5

Trial design

The efficacy of VIMPAT as adjunctive therapy in partial-onset seizures was established in three 12-week, randomized, multicenter, placebo-controlled, double-blind clinical trials in adult patients.3-5

Pooled analysis of the results included 1294 adult patients with partial-onset seizures who were not adequately controlled with 1 to 3 concomitant antiepileptic drugs (AEDs), with or without additional vagus nerve stimulation (VNS).6

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Adverse Reactions

Adjunctive therapy: In adult adjunctive placebo-controlled trials, the most frequently seen adverse reaction with VIMPAT was dizziness (31% vs 8% placebo). Other common adverse reactions occurring in ≥10 percent of VIMPAT-treated patients, and greater than placebo, were headache, nausea, and diplopia.

IN THE ADULT PLACEBO-CONTROLLED ADJUNCTIVE THERAPY CLINICAL TRIALS,
VIMPAT DEMONSTRATED EFFICACY WHEN ADDED TO A BROAD RANGE OF AEDs.6

Pooled baseline demographics and characteristics across 3 pivotal adult adjunctive therapy trials (N=1294)

  • Age (mean): 38.6 years
  • Female 51.1%, male 48.9%
  • Patients averaged 23 years since diagnosis of epilepsy
  • 45% of patients had tried 7 or more AEDs in his or her lifetime
  • 84% of patients were on 2 or 3 concomitant AEDs when VIMPAT or placebo was added
  • Average seizure frequency was 11.5 seizures every 28 days
  • History of, or presently having: simple partial seizures, 32% (n=416); complex partial seizures, 84% (n=1087); partial seizures with secondary generalization, 42% (n=540)2‡

Some patients experienced more than 1 seizure type at baseline and, therefore, were represented in more than 1 group.

 

VIMPAT was added to 1 to 3 concomitant AEDs in placebo-controlled adjunctive therapy pivotal trials in adult patients.6

  • Carbamazepine
  • Lamotrigine
  • Levetiracetam§
  • Oxcarbazepine
  • Phenobarbital
  • Phenytoin
  • Topiramate
  • Valproate
  • Zonisamide

§Levetiracetam is a product manufactured by UCB.

Download Complimentary Adjunctive Therapy Adult Pivotal Trial Publications

Study 2

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.

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Study 3

Chung S, Sperling MR, Biton V, et al; on behalf of the SP754 Study Group. Lacosamide as adjunctive therapy for partial-onset seizures: A randomized controlled trial.
Epilepsia. 2010;51(6):958-967.

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Study 4

Halász P, Kälviäinen R, Mazurkiewicz-Bełdzińska M, et al. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial.
Epilepsia. 2009;50(3):443-453.

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Monotherapy in adult patients

VIMPAT ESTABLISHED EFFICACY IN MONOTHERAPY.2

VIMPAT MET THE PRE-SPECIFIED CRITERIA FOR EFFICACY IN ADULTS WITH PARTIAL-ONSET SEIZURES.2

Separation of the VIMPAT 95% confidence interval upper limit from the
historical control's 95% prediction interval lower limit established the
efficacy of VIMPAT as monotherapy2,7
VIMPAT® (lacosamide) CV Monotherapy Clinical Trials Chart

Trial demonstrated the efficacy of VIMPAT for conversion to monotherapy in adult patients with partial-onset seizures, with statistical superiority to the historical control.2

For the VIMPAT 400 mg/day (200 mg twice-daily) group, the estimate of the percentage of patients meeting at least 1 exit criterion was 30% (95% confidence interval: 25%, 36%). The upper limit of the 2-sided 95% confidence interval (36%) was below 65%, the lower limit of the historical control 95% prediction interval derived from the historical control data, meeting the pre-specified criteria for efficacy.2

The VIMPAT 300 mg/day (150 mg twice-daily) group also met the pre-specified criteria for efficacy.2
 


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Adverse Reactions

Monotherapy: In the adult clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).

VIMPAT USE AS MONOTHERAPY IN ADULTS WITH PARTIAL-ONSET SEIZURES WAS EVALUATED WITH HISTORICAL CONTROL.2

THE VIMPAT HISTORICAL CONTROL STUDY WAS DESIGNED TO EVALUATE EFFICACY WITHOUT
THE EXPOSURE OF SUBJECTS TO SUBOPTIMAL AED DOSING.2,8

VIMPAT was tested in a conversion-to-monotherapy trial using a historical control group derived from a meta-analysis of data from 8 previous AED monotherapy trials of similar design, which utilized a subtherapeutic dose of an AED as a control.2,8

VIMPAT® (lacosamide) CV Monotherapy Historical Control Chart

Trial design: Using a historical control to evaluate efficacy and safety in monotherapy2

  • A historical control, multicenter, randomized trial* was conducted to assess the efficacy and safety of conversion to monotherapy with VIMPAT in adult epilepsy patients with partial-onset seizures (POS) on a stable regimen of 1 or 2 AEDs. Patients taking 2 AEDs must have been taking ≤50% of the minimum FDA-recommended maintenance dose of 1 of the 2 AEDs
  • The primary efficacy variable was the percentage of patients taking VIMPAT 400 mg/day meeting 1 or more predefined exit criteria of clinically relevant worsening of seizures8 by Day 112 of the maintenance phase compared to the percentage of patients exiting in the historical control group
  • A lower exit percentage indicates superior outcome to historical control

Baseline demographics and characteristics (N=425)

  • The study population profile appeared comparable to the historical control population.2 Patients averaged 17.2 years since diagnosis of epilepsy, with a median baseline seizure frequency of 6.6 per 28 days7
  • History of, or presently having: baseline simple partial seizures, 47.3% (n=201); complex partial seizures, 85.4% (n=363); partial seizures with secondary generalization, 67.5% (n=287)
  • 73.4% taking 1 background AED; 26.6% taking 2 background AEDs. Most common primary background AEDs: carbamazepine, lamotrigine, and levetiracetam§

*Patients were randomized 3 to 1 to receive either VIMPAT 400 mg/day or 300 mg/day.

The exit criteria were 1 or more of the following: (1) doubling of average monthly seizure frequency during any 28 consecutive days, (2) doubling of highest consecutive 2-day seizure frequency, (3) occurrence of a single generalized tonic-clonic seizure, (4) clinically significant prolongation or worsening of overall seizure duration, frequency, type, or pattern considered by the investigator to require trial discontinuation, (5) status epilepticus or new onset serial/cluster seizures.

Some patients experienced more than 1 seizure type at baseline and, therefore, were represented in more than 1 group.

§Levetiracetam is a product manufactured by UCB.

Download Complimentary adult Monotherapy Pivotal Trial Publication

Study 1

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.

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200 mg Loading Dose in Adult Patients

USE THE VIMPAT LOADING DOSE WHEN YOUR ADULT PATIENTS NEED TO GET TO A THERAPEUTIC DOSE MORE RAPIDLY THAN STANDARD TITRATION ALLOWS. THE USE OF A LOADING DOSE IN PEDIATRIC PATIENTS HAS NOT BEEN STUDIED.

Trial design2,9

  • The safety and tolerability of an adjunctive VIMPAT loading dose was evaluated in a Phase IIIb, multicenter, open-label, sequential cohort trial with a single, intravenous loading dose, followed by oral administration of an equivalent dose divided twice-daily for 6.5 days in adult epilepsy patients with partial-onset seizures who were naive to VIMPAT and on a stable dose of 1 or 2 concomitant AEDs
  • VIMPAT IV loading dose (10 mg/mL) administered undiluted via a 15-minute infusion
  • Efficacy was not evaluated in this trial

Safety and tolerability of loading dose infusion2,9

  • The most common 200 mg loading dose AEs ≥5% in the 15-minute infusion loading dose study included dizziness, headache, paresthesia, and gait disturbance
  • A VIMPAT loading dose is only approved for use at 200 mg
Overall incidence of treatment-emergent adverse events (AEs)
in 15-minute infusion loading dose study (AEs ≥5% of subjects in any VIMPAT dose group)
VIMPAT® (lacosamide) CV Overall Adverse Events for Loading Dose

Special considerations when using injection2

  • Infusion over 30 to 60 minutes is preferable and should be used when a 15-minute administration is not required
  • Closely monitor patients with known cardiac conduction problems, on concomitant medications that prolong PR interval, or with severe cardiac disease, as intravenous infusion of VIMPAT may cause bradycardia or AV blocks in these patients

Download Complimentary 200 mg LOADING DOSE IN ADULT PATIENTS Trial Publication

Loading Dose Study

Fountain NB, Krauss G, Isojarvi J, et al. Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures. Epilepsia. 2013;54(1):58-65.

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References

  1. Data on file. UCB, Inc.
  2. VIMPAT® (lacosamide): US prescribing information. Smyrna (GA): UCB, Inc., November 2017.
  3. 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.
  4. Chung S, Sperling MR, Biton V, et al; on behalf of the SP754 Study Group. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51(6):958-967.
  5. Halász P, Kälviäinen R, Mazurkiewicz-Bełdzińska M, et al. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50(3):443-453.
  6. Chung S, Ben-Menachem E, Sperling MR, et al. Examining the clinical utility of lacosamide: pooled analyses of three phase II/III clinical trials. CNS Drugs. 2010;24(12):1041-1054.
  7. 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.
  8. French JA, Wang S, Warnock B, Temkin N. Historical control monotherapy design in the treatment of epilepsy. Epilepsia. 2010;51(10):1936-1943.
  9. Fountain NB, Krauss G, Isojarvi J, et al. Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures. Epilepsia. 2013;54(1):58-65.

Important Safety Information

Warnings and Precautions

  • Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal behavior and ideation. Monitor patients taking VIMPAT for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.

  • Dizziness and Ataxia: VIMPAT may cause dizziness and ataxia. In adult clinical trials, the onset of dizziness and ataxia was most commonly observed during titration. Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they are familiar with the effects of VIMPAT on their ability to perform such activities. Dizziness and ataxia were also observed in pediatric clinical trials.

  • Cardiac Rhythm and Conduction Abnormalities:

    PR interval prolongation

    Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in adult patients and in healthy volunteers. Second-degree and complete AV block have been reported in patients with seizures. When VIMPAT is given with other drugs that prolong the PR interval, further PR prolongation is possible.

    Use VIMPAT with caution in patients with known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), sodium channelopathies (e.g., Brugada Syndrome), or with severe cardiac disease such as myocardial ischemia or heart failure, or structural heart disease. Also, use VIMPAT with caution in patients on concomitant medications that prolong PR interval (e.g., beta-blockers and calcium channel blockers) because of a risk of AV block or bradycardia. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state maintenance dose, is recommended. In addition, closely monitor these patients if they are administered VIMPAT through the intravenous route.

    Atrial fibrillation and Atrial flutter

    VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease.

  • Syncope: VIMPAT may cause syncope in adult and pediatric patients.

  • Withdrawal of Antiepileptic Drugs: Gradually withdraw VIMPAT (over a minimum of 1 week) to minimize the potential of increased seizure frequency.

  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as multi-organ hypersensitivity, has been reported with antiepileptic drugs. Some of these events have been fatal or life-threatening. If signs or symptoms are present, immediately evaluate the patient. Discontinue VIMPAT if an alternative etiology for the signs and symptoms cannot be established.

  • Risks in Patients with Phenylketonuria: VIMPAT oral solution contains aspartame, a source of phenylalanine which can be harmful in patients with phenylketonuria (PKU). A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine.

Adverse Reactions

  • Adjunctive therapy: In the adult placebo-controlled clinical trials, the most frequently seen adverse reaction with VIMPAT was dizziness (31% vs 8% placebo). Other common adverse reactions occurring in ≥10 percent of VIMPAT-treated patients, and greater than placebo, were headache, nausea, and diplopia.

  • Monotherapy: In the adult clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).

  • Pediatric patients: Adverse reactions reported in clinical studies of pediatric patients 4 to less than 17 years of age were similar to those seen in adult patients.

  • Injection: In adult adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those that occurred with the oral formulation, although intravenous administration was associated with local adverse reactions such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%). When administering a loading dose, the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia may be higher with 15-minute administration than over a 30- to 60-minute period.

Dosing Considerations

VIMPAT injection is for intravenous and adult use only when oral administration is temporarily not feasible. The loading dose for adult patients should be administered with medical supervision considering the VIMPAT pharmacokinetics and increased incidence of CNS adverse reactions. The safety of VIMPAT injection and the use of a loading dose in pediatric patients have not been studied. Dosage adjustments are recommended for patients with mild or moderate hepatic impairment or severe renal impairment. Use in patients with severe hepatic impairment is not recommended. Perform dose titration with caution in all patients with renal and/or hepatic impairment.

VIMPAT is a Schedule V controlled substance.

Please see full Prescribing Information.

For more information on VIMPAT® contact 844-599-CARE (2273).