Adults Children

VIMPAT® SAFETY AND
TOLERABILITY IN CHILDREN

(4 YEARS OF AGE AND OLDER)

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Adverse Event Profile

Warnings and Precautions

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.

View full Prescribing Information

TREATMENT-EMERGENT ADVERSE EVENTS

VIMPAT ADVERSE EVENTS ACROSS ADULT AND PEDIATRIC TRIALS WERE CONSISTENT.2

The safety profile of VIMPAT in pediatric patients with partial-onset seizures is based on open-label trials, which was similar to the safety profile in adult patients with partial-onset seizures.1,2

In adult adjunctive placebo-controlled trials, the most common adverse reactions (≥10% and greater than placebo) were dizziness, headache, nausea, and diplopia. 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%).2

ADULT TRIAL DATA

 

The safety profile of VIMPAT as adjunctive therapy in pediatric patients was further confirmed in a placebo-controlled trial.1

Trial enrolled 343 pediatric patients ≥4 to <17 years of age with partial-onset seizures taking 1 to ≤3 concomitant AEDs.

The most common adverse events (≥10% and greater than placebo) were dizziness and somnolence.1

Discontinuation rates due to adverse events

  • Discontinuation rates were 5.8% for placebo and 4.1% for the VIMPAT group1
  • Reasons for discontinuation in the VIMPAT arm ≥1% were vertigo and diplopia1

Warnings and precautions

Antiepileptic drugs, including VIMPAT, increase the risk of suicidal behavior and ideation

Pooled analyses of 199 placebo-controlled clinical trials of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients randomized to placebo.

Monitor patients for the emergence or worsening of depression; unusual changes in mood or behavior; or suicidal thoughts, behavior, or self-harm.

Advise patients, their caregivers, and/or families to be alert for these changes and report them immediately to a healthcare provider.

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.

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 adult patients and in healthy volunteers.

Second-degree and complete AV block have been reported in pain studies and 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 (eg, marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), sodium channelopathies (eg, Brugada syndrome), or with severe cardiac disease such as myocardial ischemia or heart failure, or structural heart disease
  • On concomitant medications that prolong PR interval (eg, 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.

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.

VIMPAT is a Schedule V controlled substance.

DRUG–DRUG INTERACTIONS

IN VIMPAT STUDIES, NO CLINICALLY RELEVANT
DRUG–DRUG INTERACTIONS WERE OBSERVED.2

  • No evidence of any clinically relevant drug–drug interactions with AEDs most commonly used
  • No clinically relevant non-AED interactions with:
    • Digoxin, metformin, omeprazole, midazolam, oral contraceptives containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel, or warfarin. This does not rule out the possibility of pharmacodynamic interactions

ADULT DRUG–DRUG DATA

References

  1. 1.Data on file. UCB, Inc.
  2. 2.VIMPAT® (lacosamide): US prescribing information. Smyrna (GA): UCB, Inc., November 2017.

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).