"The U.S. Food and Drug Administration today approved a device to help reduce the frequency of seizures in epilepsy patients who have not responded well to medications.
The RNS Stimulator consists of a small neurostimulator implanted within "...
The following serious adverse reactions are described below and elsewhere in the labeling:
- Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
- Dizziness and Ataxia [see WARNINGS AND PRECAUTIONS]
- Cardiac Rhythm and Conduction Abnormalities [see WARNINGS AND PRECAUTIONS]
- Syncope [see WARNINGS AND PRECAUTIONS]
- Multiorgan Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the premarketing development of adjunctive therapy for partial-onset seizures, 1327 patients received VIMPAT in controlled and uncontrolled trials, of whom 1000 were treated for longer than 6 months, and 852 for longer than 12 months. The monotherapy development program included 425 patients, 310 of whom were treated for longer than 6 months, and 254 for longer than 12 months.
VIMPAT Tablet and Oral Solution
Monotherapy Historical-Control Trial (Study 1)
In the monotherapy trial, 16% of patients randomized to receive VIMPAT at the recommended doses of 300 and 400 mg/day discontinued from the trial as a result of an adverse reaction. The adverse reaction most commonly ( ≥ 1% on VIMPAT) leading to discontinuation was dizziness.
Adverse reactions that occurred in this study were generally similar to those that occurred in adjunctive placebo-controlled studies. One adverse reaction, insomnia, occurred at a rate of ≥ 2% and was not reported at a similar rate in previous studies. This adverse reaction has also been observed in postmarketing experience. Because this study did not include a placebo control group, causality could not be established.
Adjunctive Therapy Controlled Trials (Studies 2, 3, and 4)
In adjunctive therapy controlled clinical trials, the rate of discontinuation as a result of an adverse reaction was 8% and 17% in patients randomized to receive VIMPAT at the recommended doses of 200 and 400 mg/day, respectively, 29% at 600 mg/day, and 5% in patients randomized to receive placebo. The adverse reactions most commonly ( > 1% on VIMPAT and greater than placebo) leading to discontinuation were dizziness, ataxia, vomiting, diplopia, nausea, vertigo, and blurred vision.
Table 2 gives the incidence of adverse reactions that occurred in ≥ 2% of adult patients with partial-onset seizures in the VIMPAT total group and for which the incidence was greater than placebo.
Table 2: Adverse Reactions Incidence in Adjunctive
Therapy Pooled, Placebo-Controlled Trials in Patients with Partial-Onset
Seizures (Studies 2, 3, and 4)
|System Organ Class/ Preferred Term||Placebo
|VIMPAT 200 mg/day
|VIMPAT 400 mg/day
|VIMPAT 600 mg/day
|Ear and labyrinth disorder|
|General disorders and administration site conditions|
|Gait disturbance||< 1||< 1||2||4||2|
|Injury, poisoning and procedural complications|
|Nervous system disorders|
|Skin and subcutaneous disorders|
The overall adverse reaction rate was similar in male and female patients. Although there were few non-Caucasian patients, no differences in the incidences of adverse events compared to Caucasian patients were observed.
Abnormalities in liver function tests have occurred in controlled trials with VIMPAT in adult patients with partial-onset seizures who were taking 1 to 3 concomitant anti-epileptic drugs. Elevations of ALT to ≥ 3× ULN occurred in 0.7% (7/935) of VIMPAT patients and 0% (0/356) of placebo patients. One case of hepatitis with transaminases > 20x ULN occurred in one healthy subject 10 days after VIMPAT treatment completion, along with nephritis (proteinuria and urine casts). Serologic studies were negative for viral hepatitis. Transaminases returned to normal within one month without specific treatment. At the time of this event, bilirubin was normal. The hepatitis/nephritis was interpreted as a delayed hypersensitivity reaction to VIMPAT.
Other Adverse Reactions
The following is a list of adverse reactions reported by patients treated with VIMPAT in all clinical trials in patients with partial-onset seizures, including controlled trials and long-term open-label extension trials. Adverse reactions addressed in other tables or sections are not listed here.
Cardiac disorders: palpitations
Ear and labyrinth disorders: tinnitus
General disorders and administration site conditions: irritability, pyrexia, feeling drunk
Injury, poisoning, and procedural complications: fall
Musculoskeletal and connective tissue disorders: muscle spasms
Psychiatric disorders: confusional state, mood altered, depressed mood
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%). One case of profound bradycardia (26 bpm: BP 100/60 mmHg) occurred in a patient during a 15-minute infusion of 150 mg VIMPAT. This patient was on a beta-blocker. Infusion was discontinued and the patient experienced a rapid recovery.
The safety of a 15-minute loading dose administration of VIMPAT Injection 200 mg to 400 mg followed by oral administration of VIMPAT given twice daily at the same total daily dose as the initial intravenous infusion was assessed in an open-label study in patients with partial-onset seizures. Patients had to have been maintained on a stable dose regimen of 1 to 2 marketed antiepileptics for at least 28 days prior to treatment assignment. Treatment groups were as follows:
- Single dose of intravenous VIMPAT Injection 200 mg followed by oral VIMPAT 200 mg/day (100 mg every 12 hours)
- Single dose of intravenous VIMPAT Injection 300 mg followed by oral VIMPAT 300 mg/day (150 mg every 12 hours)
- Single dose of intravenous VIMPAT Injection 400 mg followed by oral VIMPAT 400 mg/day (200 mg every 12 hours).
Table 3 gives the incidence of adverse reactions that occurred in ≥ 5% of adult patients in any VIMPAT dosing group.
Table 3: Adverse Reactions
in a 15-minute Infusion Study in Patients with Partial-Onset Seizures
|System Organ Class/Preferred Term||VIMPAT 200 mg
|VIMPAT 300 mg
|VIMPAT 400 mg
|General disorders/administration site conditions|
|Nervous system disorders|
|Skin & subcutaneous tissue disorders|
Adverse reactions that occurred with infusion of VIMPAT 200 mg over 15-minutes followed by VIMPAT 100 mg administered orally twice per day were similar in frequency to those that occurred in 3-month adjunctive therapy controlled trials. Considering the difference in period of observations (1 week vs. 3 months), the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia may be higher with 15minute administration of VIMPAT Injection than with administration over a 30-to 60-minute period.
The following adverse reactions have been identified during post-approval use of VIMPAT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Psychiatric disorders: Aggression, agitation, hallucination, insomnia, psychotic disorder
Read the Vimpat (lacosamide tablet and injection) Side Effects Center for a complete guide to possible side effects
Strong CYP3A4 Or CYP2C9 Inhibitors
Patients with renal or hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to VIMPAT. Dose reduction may be necessary in these patients.
Concomitant Medications That Prolong PR Interval
VIMPAT should be used with caution in patients on concomitant medications that prolong PR interval, because of a risk of AV block or bradycardia, e.g., beta-blockers and calcium 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 [see WARNINGS AND PRECAUTIONS].
Drug Abuse And Dependence
VIMPAT is a Schedule V controlled substance.
In a human abuse potential study, single doses of 200 mg and 800 mg lacosamide produced euphoria-type subjective responses that differentiated statistically from placebo; at 800 mg, these euphoria-type responses were statistically indistinguishable from those produced by alprazolam, a Schedule IV drug. The duration of the euphoria-type responses following lacosamide was less than that following alprazolam. A high rate of euphoria was also reported as an adverse event in the human abuse potential study following single doses of 800 mg lacosamide (15% [5/34]) compared to placebo (0%) and in two pharmacokinetic studies following single and multiple doses of 300-800 mg lacosamide (ranging from 6% [2/33] to 25% [3/12]) compared to placebo (0%). However, the rate of euphoria reported as an adverse event in the VIMPAT development program at therapeutic doses was less than 1%.
Abrupt termination of lacosamide in clinical trials with diabetic neuropathic pain patients produced no signs or symptoms that are associated with a withdrawal syndrome indicative of physical dependence. However, psychological dependence cannot be excluded due to the ability of lacosamide to produce euphoria-type adverse events in humans.
Read the Vimpat Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 8/27/2015
This monograph has been modified to include the generic and brand name in many instances.
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