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.
Adverse Event Profile In Adult Patients
MOST COMMON ADVERSE EVENTS IN ADULT CLINICAL TRIALS.2
ADJUNCTIVE THERAPY |
Most common adverse events in adult patients in placebo-controlled trials2
- The majority of AEs were generally mild to moderate and were generally dose related
- The onset of dizziness was most commonly observed during titration
- The discontinuation rates due to AEs were 8% and 17% in patients treated with VIMPAT at the recommended doses of 200 mg/day and 400 mg/day, respectively
- The most common AEs leading to discontinuation were dizziness, ataxia, vomiting, diplopia, nausea, vertigo, and blurred vision
Most common Adverse Reactions (≥10% in the VIMPAT total group 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, 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.
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.
IN VIMPAT® STUDIES, NO CLINICALLY RELEVANT
DRUG–DRUG INTERACTIONS WERE OBSERVED.2
CLINICALLY RELEVANT INTERACTIONS WITH OTHER DRUGS ARE UNLIKELY |
No drug–drug interactions were observed with the below commonly prescribed AEDs and additional medications (Tables 1 and 2) that are frequently used for conditions such as diabetes and GERD, and for patients at risk for blood clots.
- Use VIMPAT with caution in patients on concomitant medications that prolong PR interval because of a risk of AV block or bradycardia. Also, use VIMPAT with caution in patients with known cardiac conduction problems, sodium channelopathies, severe cardiac disease, or structural heart disease. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state, is recommended. In addition, closely monitor these patients if they are administered VIMPAT through the intravenous route
- 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
*Levetiracetam is a product manufactured by UCB.
†Does not rule out the possibility of pharmacodynamic interactions.
- 2.VIMPAT® (lacosamide): US prescribing information. Smyrna (GA): UCB, Inc., November 2017.