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 were similar to those seen in adult patients.
VIMPAT is a Schedule V controlled substance.
Adverse Event Profile In Adult Patients2
ADVERSE EVENTS WERE GENERALLY OBSERVED
MILD TO MODERATE IN CLINICAL TRIALS
In placebo-controlled adjunctive trials, the most common adverse reactions were dizziness, headache, nausea, and diplopia. In the historical-control monotherapy trial, adverse reactions were generally similar to those observed in the adjunctive trials, with the exception of insomnia.
The majority of adverse reactions were generally mild to moderate and were generally dose related.
Most common AEs (%) for ≥10% of total VIMPAT-treated patients and greater than placebo*
Most common adverse events in the historical-controlled, conversion-to-monotherapy trial in adult patients
- In the adult monotherapy clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adult adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%)
- Dizziness, headache, nausea, somnolence, and fatigue were all reported at lower incidences during the AED withdrawal phase and monotherapy phase compared with the titration phase
- The discontinuation rate due to AEs was 16% in patients treated with VIMPAT
- The most common AE leading to discontinuation was dizziness
- In adult adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those observed with the oral formulation, with the exception of adverse events 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
- The most common adverse events (≥5%) in the 15-minute infusion 200 mg loading dose study included dizziness, headache, paresthesia, and gait disturbance
Warnings and precautions
Antiepileptic drugs (AEDs), 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, Atrioventricular Block, and Ventricular Tachyarrhythmia
Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in adult patients and in healthy volunteers. When VIMPAT is given with other drugs that prolong the PR interval, further PR prolongation is possible.
In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with VIMPAT, including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole, cardiac arrest, and death. Most, although not all, cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval. These events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose.
VIMPAT should be used with caution in patients with underlying proarrhythmic conditions such as known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome).
VIMPAT should also be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state maintenance dose, is recommended. In addition, these patients should be closely monitored if they are administered VIMPAT through the intravenous route. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away.
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.
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, including VIMPAT. 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.
Please refer to the full Prescribing Information provided by the sales representative, and visit VIMPAThcp.com.
For more information on VIMPAT® contact 844-599-CARE (2273).
VIMPAT® PHARMACOKINETIC (PK) DRUG INTERACTIONS AND
CLINICALLY RELEVANT PK INTERACTIONS WITH OTHER DRUGS ARE UNLIKELY 2
- VIMPAT exhibits low plasma protein binding (<15%)
- Not an enzyme inducer
PK DRUG–DRUG INTERACTIONS WERE IDENTIFIED
No clinically relevant PK drug-drug interactions were observed with the below commonly prescribed antiepileptic drugs (AEDs) and additional medications that are frequently used for conditions such as diabetes and GERD, and for patients at risk for blood clots.*
*Does not rule out the possibility of pharmacodynamic interactions.
†Levetiracetam is a product manufactured by UCB.
CLINICALLY RELEVANT PHARMACODYNAMIC INTERACTIONS
Because of a risk of AV block, bradycardia, or ventricular tachyarrhythmia, VIMPAT should be used with caution in patients on medications that prolong PR interval (including sodium channel blocking AEDs), and concomitant medications that affect cardiac conduction, including:
- sodium channel blockers
- calcium channel blockers
- potassium channel blockers
In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state, is recommended. In addition, these patients should be closely monitored if they are administered VIMPAT through the intravenous route. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away.
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. Dose titration should be performed with caution in all patients with renal and/or hepatic impairment.
Patients with hepatic or renal impairment taking strong inhibitors of CYP3A4 or CYP2C9 may have a significant increase in exposure to VIMPAT. Dose reduction may be necessary in these patients.
Caution should be exercised for dose titration in elderly patients.
- 2.VIMPAT® (lacosamide): US prescribing information. Smyrna (GA): UCB, Inc., January 2019.