Vimpat

Adults (17 years and older): Initial dosage for monotherapy for the treatment of partial-onset seizures is 100 mg twice daily (2.1) Initial dosage for adjunctive therapy for the treatment of partial-onset seizures or primary generalized tonic-clonic seizures is 50 mg twice daily (2.1) Maximum recommended dosage for monotherapy and adjunctive therapy is 200 mg twice daily (2.1) Pediatric Patients 1 month to less than 17 years: The recommended dosage is based on body weight and is administered orally twice daily (2.1) Increase dosage based on clinical response and tolerability, no more frequently than once per week (2.1) Injection: for intravenous use only when oral administration is temporarily not feasible; the recommended dosage is based on body weight and is administered two or three times daily over 15 to 60 minutes; obtaining ECG before initiation is recommended in certain patients (2.7, 5.3) Dose adjustment is recommended for severe renal impairment (2.4, 12.3) Dose adjustment is recommended for mild or moderate hepatic impairment; use in patients with severe hepatic impairment is not recommended (2.5, 12.3)

2.1Dosage Information

The recommended dosage for monotherapy and adjunctive therapy for partial-onset seizures in patients 1 month of age and older and for adjunctive therapy for primary generalized tonic-clonic seizures in patients 4 years of age and older is included in Table 1. In pediatric patients, the recommended dosing regimen is dependent upon body weight. Dosage should be increased based on clinical response and tolerability, no more frequently than once per week. Titration increments should not exceed those shown in Table 1. Table 1: Recommended Dosages for Partial-Onset Seizures (Monotherapy or Adjunctive Therapy) in Patients 1 Month and Older, and for Primary Generalized Tonic-Clonic Seizures (Adjunctive Therapy) in Patients 4 Years of Age and Older when not specified, the dosage is the same for monotherapy for partial-onset seizures and adjunctive therapy for partial-onset seizures or primary generalized tonic-clonic seizures. Oral and intravenous dosages are the same unless specified. Age and Body Weight Initial Dosage Titration Regimen Maintenance Dosage Adults (17 years and older) Monotherapy Monotherapy for partial-onset seizures only: 100 mg twice daily (200 mg per day) Adjunctive Therapy: 50 mg twice daily (100 mg per day) Increase by 50 mg twice daily (100 mg per day) every week Monotherapy: 150 mg to 200 mg twice daily (300 mg to 400 mg per day) Adjunctive Therapy: 100 mg to 200 mg twice daily (200 mg to 400 mg per day) Pediatric patients weighing at least 50 kg 50 mg twice daily (100 mg per day) Increase by 50 mg twice daily (100 mg per day) every week Monotherapy: 150 mg to 200 mg twice daily (300 mg to 400 mg per day) Adjunctive Therapy: 100 mg to 200 mg twice daily (200 mg to 400 mg per day) Pediatric patients weighing 30 kg to less than 50 kg 1 mg/kg twice daily (2 mg/kg/day) Increase by 1 mg/kg twice daily (2 mg/kg/day) every week 2 mg/kg to 4 mg/kg twice daily (4 mg/kg/day to 8 mg/kg/day) Pediatric patients weighing 11 kg to less than 30 kg 1 mg/kg twice daily (2 mg/kg/day) Increase by 1 mg/kg twice daily (2 mg/kg/day) every week 3 mg/kg to 6 mg/kg twice daily (6 mg/kg/day to 12 mg/kg/day) Pediatric patients weighing 6 kg to less than 11 kg indicated only for partial-onset seizures Pediatric patients weighing less than 6 kg Intravenous: 0.66 mg/kg three times daily (2 mg/kg/day) Intravenous: Increase by 0.66 mg/kg three times daily (2 mg/kg/day) every week Intravenous: 2.5 mg/kg to 5 mg/kg three times daily (7.5 mg/kg/day to 15 mg/kg/day) Oral: 1 mg/kg twice daily (2 mg/kg/day) Oral: Increase by 1 mg/kg twice daily (2 mg/kg/day) every week Oral: 3.75 mg/kg to 7.5 mg/kg twice daily (7.5 mg/kg/day to 15 mg/kg/day) In adjunctive clinical trials in adult patients with partial-onset seizures, a dosage higher than 200 mg twice daily (400 mg per day) was not more effective and was associated with a substantially higher rate of adverse reactions [see Adverse Reactions (6.1) and Clinical Studies (14.2)]. VIMPAT Injection Dosage VIMPAT injection may be used when oral administration is temporarily not feasible [see Dosage and Administration (2.6) and Warnings and Precautions (5.3)]. VIMPAT injection can be administered intravenously to adult and pediatric patients weighing 6 kg or more with the same dosing regimens described for oral dosing. For pediatric patients weighing less than 6 kg, VIMPAT injection may be initiated with a dose of 0.66 mg/kg three times daily (see Table 1). The clinical study experience of intravenous VIMPAT is limited to 5 days of consecutive treatment. 2.2 Alternate Initial Dosage Information to Achieve the Maintenance Dosage in a Shorter Timeframe For monotherapy and adjunctive therapy for partial-onset seizures in patients 1 month of age and older and for adjunctive therapy for primary generalized tonic-clonic seizures in patients 4 years of age and older, an alternate initial dosing regimen for week 1 (e.g., including a loading dose and/or a higher initial dosage) may be administered in patients for whom achieving the recommended maintenance dosage in a shorter timeframe is clinically indicated (see Table 2). The alternate initial dosage regimen should be continued for one week. VIMPAT may then be titrated based on clinical response and tolerability, no more frequently than once per week, if needed. The loading dose should be administered with medical supervision because of the possibility of increased incidence of adverse reactions, including central nervous system (CNS) and cardiovascular adverse reactions [see Warnings and Precautions (5.2, 5.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.3)]. Titration increments should not exceed those shown in Table 2. Table 2: Alternate Initial Dosing Regimen to Achieve the Maintenance Dosage in a Shorter Timeframe if Clinically Indicated when not specified, the dosage is the same for monotherapy for partial-onset seizures and adjunctive therapy for partial-onset seizures or primary generalized tonic-clonic seizures. Oral and intravenous dosages are the same unless specified. Age and Body Weight Alternate Initial Dosage Titration Regimen Maintenance Dosage Adults (17 years and older) Single loading dose: 200 mg 12 hours later initiate: 100 mg twice daily (200 mg per day) Increase by 50 mg twice daily (100 mg per day) at weekly intervals, if needed Monotherapy Monotherapy for partial-onset seizures only: 150 mg to 200 mg twice daily (300 mg to 400 mg per day) Adjunctive Therapy: 100 mg to 200 mg twice daily (200 mg to 400 mg per day) Pediatric patients weighing at least 50 kg Single loading dose: 200 mg 12 hours later initiate: 100 mg twice daily (200 mg per day) Increase by 50 mg twice daily (100 mg per day) at weekly intervals, if needed Monotherapy: 150 mg to 200 mg twice daily (300 mg to 400 mg per day) Adjunctive Therapy: 100 mg to 200 mg twice daily (200 mg to 400 mg per day) Pediatric patients weighing 30 kg to less than 50 kg Single loading dose: 4 mg/kg 12 hours later initiate: 2 mg/kg twice daily (4 mg/kg/day) Increase by 1 mg/kg twice daily (2 mg/kg/day) at weekly intervals, if needed 2 mg/kg to 4 mg/kg twice daily (4 mg/kg/day to 8 mg/kg/day) Pediatric patients weighing 11 kg to less than 30 kg Single loading dose: 4.5 mg/kg 12 hours later initiate: 3 mg/kg twice daily (6 mg/kg/day) Increase by 1 mg/kg twice daily (2 mg/kg/day) at weekly intervals, if needed 3 mg/kg to 6 mg/kg twice daily (6 mg/kg/day to 12 mg/kg/day) Pediatric patients weighing 6 kg to less than 11 kg indicated only for partial-onset seizures Pediatric patients weighing less than 6 kg Intravenous: No loading dose required 2.5 mg/kg three times daily (7.5 mg/kg/day) Intravenous: Increase by 0.66 mg/kg three times daily (2 mg/kg/day) at weekly intervals, if needed Intravenous: 2.5 mg/kg to 5 mg/kg three times daily (7.5 mg/kg/day to 15 mg/kg/day) Oral: No loading dose required 3.75 mg/kg twice daily (7.5 mg/kg/day) Oral: Increase by 1 mg/kg twice daily (2 mg/kg/day) at weekly intervals, if needed Oral: 3.75 mg/kg to 7.5 mg/kg twice daily (7.5 mg/kg/day to 15 mg/kg/day)

2.3Converting From a Single Antiepileptic

(AED) to VIMPAT Monotherapy for the Treatment of Partial-Onset Seizures For patients who are already on a single AED and will convert to VIMPAT monotherapy, withdrawal of the concomitant AED should not occur until the therapeutic dosage of VIMPAT is achieved and has been administered for at least 3 days. A gradual withdrawal of the concomitant AED over at least 6 weeks is recommended. 2.4 Dosage Information for Patients with Renal Impairment For patients with mild to moderate renal impairment, no dosage adjustment is necessary. For patients with severe renal impairment [creatinine clearance (CL CR) less than 30 mL/min as estimated by the Cockcroft-Gault equation for adults; CL CR less than 30 mL/min/1.73m 2 as estimated by the Schwartz equation for pediatric patients] or end-stage renal disease, a reduction of 25% of the maximum dosage is recommended. In all patients with renal impairment, dose initiation and titration should be based on clinical response and tolerability. Hemodialysis VIMPAT is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, dosage supplementation of up to 50% should be considered. Concomitant Strong CYP3A4 or CYP2C9 Inhibitors Dose reduction may be necessary in patients with renal impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 [see Drug Interactions (7.1), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)]. 2.5 Dosage Information for Patients with Hepatic Impairment For patients with mild or moderate hepatic impairment, a reduction of 25% of the maximum dosage is recommended. The dose initiation and titration should be based on clinical response and tolerability in patients with hepatic impairment. VIMPAT use is not recommended in patients with severe hepatic impairment. Concomitant Strong CYP3A4 and CYP2C9 Inhibitors Dose reduction may be necessary in patients with hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 [see Drug Interactions (7.1), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)]. 2.6 Administration Instructions for VIMPAT Tablets and Oral Solution VIMPAT tablets and oral solution may be taken with or without food. VIMPAT Tablets VIMPAT tablets should be swallowed whole with liquid. Do not divide VIMPAT tablets. VIMPAT Oral Solution A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device. VIMPAT oral solution may also be administered using a nasogastric tube or gastrostomy tube. Discard any unused VIMPAT oral solution remaining after 6 months of first opening the bottle. 2.7 Preparation and Administration Information for VIMPAT Injection Preparation VIMPAT injection can be administered intravenously without further dilution or may be mixed with diluents listed below. The diluted solution should not be stored for more than 4 hours at room temperature. Diluents: Sodium Chloride Injection 0.9% (w/v) Dextrose Injection 5% (w/v) Lactated Ringer's Injection Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Product with particulate matter or discoloration should not be used. VIMPAT injection is for single-dose only. Any unused portion of VIMPAT injection should be discarded. Administration The recommended infusion duration is 30 to 60 minutes; however, infusions as rapid as 15 minutes can be administered in adults if required [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)]. Infusion durations less than 30 minutes are generally not recommended in pediatric patients [see Adverse Reactions (6.1)]. Intravenous infusion of VIMPAT may cause bradycardia, AV blocks, and ventricular tachyarrhythmia [see Warnings and Precautions (5.3)]. Obtaining an ECG before beginning VIMPAT and after VIMPAT is titrated to steady-state maintenance dose is recommended in patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction [see Drug Interactions (7.2)]. Storage and Stability The diluted solution should not be stored for more than 4 hours at room temperature. Any unused portion of VIMPAT injection should be discarded. 2.8 Discontinuation of VIMPAT When discontinuing VIMPAT, a gradual withdrawal over at least 1 week is recommended [see Warnings and Precautions (5.5)].

Monitor patients for suicidal behavior and ideation (5.1) VIMPAT may cause dizziness and ataxia (5.2) Cardiac Rhythm and Conduction Abnormalities: Obtaining ECG before beginning and after titration to steady-state maintenance is recommended in patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction; closely monitor these patients (5.3, 7.2) VIMPAT may cause syncope (5.4) VIMPAT should be gradually withdrawn to minimize the potential of increased seizure frequency (5.5) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/ Multi-Organ Hypersensitivity: Discontinue if no alternate etiology (5.6)

5.1Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated.There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number of events is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs. Table 3: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar. Anyone considering prescribing VIMPAT or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which antiepileptics are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. 5.2 Dizziness and Ataxia VIMPAT may cause dizziness and ataxia in adult and pediatric patients. In adult patients with partial-onset seizures taking 1 to 3 concomitant AEDs, dizziness was experienced by 25% of patients randomized to the recommended doses (200 to 400 mg/day) of VIMPAT (compared with 8% of placebo patients) and was the adverse reaction most frequently leading to discontinuation (3%). Ataxia was experienced by 6% of patients randomized to the recommended doses (200 to 400 mg/day) of VIMPAT (compared to 2% of placebo patients). The onset of dizziness and ataxia was most commonly observed during titration. There was a substantial increase in these adverse reactions at doses higher than 400 mg/day [see Adverse Reactions (6.1)]. If a loading dose is clinically indicated, administer with medical supervision because of the possibility of increased incidence of adverse reactions, including CNS adverse reactions such as dizziness and ataxia. 5.3 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 [see Clinical Pharmacology (12.2)]. In adjunctive clinical trials in adult patients with partial-onset seizures, asymptomatic first-degree atrioventricular (AV) block was observed as an adverse reaction in 0.4% (4/944) of patients randomized to receive VIMPAT and 0% (0/364) of patients randomized to receive placebo. One case of profound bradycardia was observed in a patient during a 15-minute infusion of 150 mg VIMPAT. 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 [see Overdosage (10)]. In all patients for whom a loading dose is clinically indicated, administer the loading dose with medical supervision because of the possibility of increased incidence of adverse reactions, including cardiovascular adverse reactions. 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 [see Drug Interactions (7.2)]. 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 [see Adverse Reactions (6.1) and Drug Interactions (7.2)]. Atrial Fibrillation and Atrial Flutter In the short-term investigational trials of VIMPAT in adult patients with partial-onset seizures there were no cases of atrial fibrillation or flutter. Both atrial fibrillation and atrial flutter have been reported in open label partial-onset seizure trials and in postmarketing experience. In adult patients with diabetic neuropathy, for which VIMPAT is not indicated, 0.5% of patients treated with VIMPAT experienced an adverse reaction of atrial fibrillation or atrial flutter, compared to 0% of placebo-treated patients. VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease. 5.4 Syncope In the short-term controlled trials of VIMPAT in adult patients with partial-onset seizures with no significant system illnesses, there was no increase in syncope compared to placebo. In the short-term controlled trials in adult patients with diabetic neuropathy, for which VIMPAT is not indicated, 1.2% of patients who were treated with VIMPAT reported an adverse reaction of syncope or loss of consciousness, compared with 0% of placebo-treated patients with diabetic neuropathy. Most of the cases of syncope were observed in patients receiving doses above 400 mg/day. The cause of syncope was not determined in most cases. However, several were associated with either changes in orthostatic blood pressure, atrial flutter/fibrillation (and associated tachycardia), or bradycardia. Cases of syncope have also been observed in open-label clinical partial-onset seizure studies in adult and pediatric patients. These cases were associated with a history of risk factors for cardiac disease and the use of drugs that slow AV conduction. 5.5 Withdrawal of Antiepileptic Drugs (AEDs) As with all AEDs, VIMPAT should be withdrawn gradually (over a minimum of 1 week) to minimize the potential of increased seizure frequency in patients with seizure disorders. 5.6 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has been reported in patients taking antiepileptic drugs, including VIMPAT. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. VIMPAT should be discontinued if an alternative etiology for the signs or symptoms cannot be established. 5.7 Risks in Patients with Phenylketonuria Phenylalanine can be harmful in patients with phenylketonuria (PKU). VIMPAT oral solution contains aspartame, a source of phenylalanine. A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine. Before prescribing VIMPAT oral solution to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including VIMPAT oral solution.

The following serious adverse reactions are described below and elsewhere in the labeling: Suicidal Behavior and Ideation [see Warnings and Precautions (5.1)] Dizziness and Ataxia [see Warnings and Precautions (5.2)] Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions (5.3)] Syncope [see Warnings and Precautions (5.4)] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions (5.6)] Adjunctive therapy: Most common adverse reactions in adults (≥10% and greater than placebo) are diplopia, headache, dizziness, nausea, and somnolence (6.1) Monotherapy: Most common adverse reactions are similar to those seen in adjunctive therapy studies (6.1) Pediatric patients: Adverse reactions are similar to those seen in adult patients (6.1) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical 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. VIMPAT Tablet and Oral Solution in Adults In the premarketing development of adjunctive therapy for partial-onset seizures, 1327 adult patients received VIMPAT tablets 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 for partial-onset seizures included 425 adult patients, 310 of whom were treated for longer than 6 months, and 254 for longer than 12 months. Partial-Onset Seizures Monotherapy Historical-Control Trial (Study 1) In the monotherapy trial for partial-onset seizures, 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 [see Adverse Reactions (6.2)]. Because this study did not include a placebo control group, causality could not be established. Dizziness, headache, nausea, somnolence, and fatigue all occurred at lower incidences during the AED Withdrawal Phase and Monotherapy Phase, compared with the Titration Phase [see Clinical Studies (14.1)]. Adjunctive Therapy Controlled Trials (Studies 2, 3, and 4) In adjunctive therapy controlled clinical trials for partial-onset seizures, 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 (1.5 times greater than the maximum recommended dose), 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 4 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 4: Adverse Reactions Incidence in Adjunctive Therapy Pooled, Placebo-Controlled Trials in Adult Patients with Partial-Onset Seizures (Studies 2, 3, and 4) Adverse Reaction Placebo N=364 % VIMPAT 200 mg/day N=270 % VIMPAT 400 mg/day N=471 % VIMPAT 600 mg/day 600 mg dose is 1.5 times greater than the maximum recommended dose. N=203 % VIMPAT Total N=944 % Ear and labyrinth disorder Vertigo 1 5 3 4 4 Eye disorders Diplopia 2 6 10 16 11 Blurred Vision 3 2 9 16 8 Gastrointestinal disorders Nausea 4 7 11 17 11 Vomiting 3 6 9 16 9 Diarrhea 3 3 5 4 4 General disorders and administration site conditions Fatigue 6 7 7 15 9 Gait disturbance <1 <1 2 4 2 Asthenia 1 2 2 4 2 Injury, poisoning and procedural complications Contusion 3 3 4 2 3 Skin laceration 2 2 3 3 3 Nervous system disorders Dizziness 8 16 30 53 31 Headache 9 11 14 12 13 Ataxia 2 4 7 15 8 Somnolence 5 5 8 8 7 Tremor 4 4 6 12 7 Nystagmus 4 2 5 10 5 Balance disorder 0 1 5 6 4 Memory impairment 2 1 2 6 2 Psychiatric disorders Depression 1 2 2 2 2 Skin and subcutaneous disorders Pruritus 1 3 2 3 2 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 reactions compared to Caucasian patients were observed. VIMPAT Tablet and Oral Solution in Pediatric Patients Safety of VIMPAT was evaluated in clinical studies of pediatric patients 1 month to less than 17 years of age for the treatment of partial-onset seizures. Across studies in pediatric patients with partial-onset seizures, 847 patients 1 month to less than 17 years of age received VIMPAT oral solution or tablet, of whom 596 received VIMPAT for at least 1 year. Adverse reactions reported in clinical studies of pediatric patients 1 month to less than 17 years of age were similar to those seen in adult patients. Primary Generalized Tonic-Clonic Seizures in Patients (4 Years of Age and Older) Adjunctive Therapy Trial (Study 5) In the adjunctive therapy placebo-controlled trial for primary generalized tonic-clonic seizures, adverse reactions that occurred in the study were generally similar to those that occurred in partial-onset seizure placebo-controlled studies. The most common adverse reactions (≥ 10% on VIMPAT) reported in patients treated with VIMPAT were dizziness (23%), somnolence (17%), headache (14%), and nausea (10%), compared to 7%, 14%, 10%, and 6%, respectively, of patients who received placebo. Additionally, an adverse reaction not previously reported of myoclonic epilepsy was reported in 3% of patients treated with VIMPAT compared to 1% of patients who received placebo. It is also noted that 2 patients receiving VIMPAT had acute worsening of seizures shortly after drug initiation, including one episode of status epilepticus, compared to no patients receiving placebo. Laboratory Abnormalities 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 >20× 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 adult patients, including controlled trials and long-term open-label extension trials. Adverse reactions addressed in other tables or sections are not listed here. Blood and lymphatic system disorders: neutropenia, anemia Cardiac disorders: palpitations Ear and labyrinth disorders: tinnitus Gastrointestinal disorders: constipation, dyspepsia, dry mouth, oral hypoaesthesia General disorders and administration site conditions: irritability, pyrexia, feeling drunk Injury, poisoning, and procedural complications: fall Musculoskeletal and connective tissue disorders: muscle spasms Nervous system disorders: paresthesia, cognitive disorder, hypoaesthesia, dysarthria, disturbance in attention, cerebellar syndrome Psychiatric disorders: confusional state, mood altered, depressed mood VIMPAT Injection Adult Patients (17 Years and Older) Adverse reactions with intravenous administration to adult patients with partial-onset seizures 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 adult 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 5 gives the incidence of adverse reactions that occurred in ≥5% of adult patients in any VIMPAT dosing group. Table 5: Adverse Reactions in a 15-minute Infusion Study in Adult Patients with Partial-Onset Seizures Adverse Reaction VIMPAT 200 mg N=25 % VIMPAT 300 mg N=50 % VIMPAT 400 mg N=25 % VIMPAT Total N=100 % Eye disorders Diplopia 4 6 20 9 Blurred Vision 0 4 12 5 Gastrointestinal disorders Nausea 0 16 24 14 Dry mouth 0 6 12 6 Vomiting 0 4 12 5 Oral Paresthesia 4 4 8 5 Oral Hypoesthesia 0 6 8 5 Diarrhea 0 8 0 4 General disorders/administration site conditions Fatigue 0 18 12 12 Gait disturbance 8 2 0 3 Chest pain 0 0 12 3 Nervous system disorders Dizziness 20 46 60 43 Somnolence 0 34 36 26 Headache 8 4 16 8 Paresthesia 8 6 4 6 Tremor 0 6 4 4 Abnormal Coordination 0 6 0 3 Skin & subcutaneous tissue disorders Pruritus 0 6 4 4 Hyperhidrosis 0 0 8 2 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 15-minute administration of VIMPAT Injection than with administration over a 30-to 60-minute period. The adverse reactions associated with VIMPAT injection in adult patients with primary generalized tonic-clonic seizures are expected to be similar to those seen in adults with partial-onset seizures. Pediatric Patients (1 Month to less than 17 Years of Age) The safety of VIMPAT injection was evaluated in a multicenter, open-label study of 103 pediatric patients 1 month to less than 17 years of age with epilepsy. Infusions were primarily administered over a 30 to 60 minute time period; infusion times less than 30 minutes were not adequately studied in pediatric patients [see Dosage and Administration (2.7)]. Although no serious or severe adverse reactions were noted at the time of infusion in this small study, the adverse reactions associated with VIMPAT injection in pediatric patients are expected to be similar to those noted in adults. In a retrospective cohort study of electronic healthcare records of 686 pediatric patients who started VIMPAT with intravenous dosing, the incidence of rash within 30 days of discontinuation of intravenous VIMPAT was two-fold higher in the cohort of patients who were initiated with the alternate initial dosing regimen to achieve the maintenance dosage in a shorter timeframe [see Dosage and Administration (2.2)] compared to the cohort of patients who were initiated with a lower initial dosage regimen [see Dosage and Administration (2.1)]. 6.2 Postmarketing Experience 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. Blood and lymphatic system disorders: Agranulocytosis Psychiatric disorders: Aggression, agitation, hallucination, insomnia, psychotic disorder Skin and subcutaneous tissue disorders: Angioedema, rash, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis. Neurologic disorders: Dyskinesia, new or worsening seizures

Pregnancy: Based on animal data, may cause fetal harm (8.1)

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as VIMPAT, during pregnancy. Encourage women who are taking VIMPAT during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series with VIMPAT use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Lacosamide produced developmental toxicity (increased embryofetal and perinatal mortality, growth deficit) in rats following administration during pregnancy. Developmental neurotoxicity was observed in rats following administration during a period of postnatal development corresponding to the third trimester of human pregnancy. These effects were observed at doses associated with clinically relevant plasma exposures (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of lacosamide to pregnant rats (20, 75, or 200 mg/kg/day) and rabbits (6.25, 12.5, or 25 mg/kg/day) during the period of organogenesis did not produce any effects on the incidences of fetal structural abnormalities. However, the maximum doses evaluated were limited by maternal toxicity in both species and embryofetal death in rats. These doses were associated with maternal plasma lacosamide exposures (AUC) approximately 2 and 1 times (rat and rabbit, respectively) that in humans at the maximum recommended human dose (MRHD) of 400 mg/day. In two studies in which lacosamide (25, 70, or 200 mg/kg/day and 50, 100, or 200 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, increased perinatal mortality and decreased body weights in the offspring were observed at the highest dose tested. The no-effect dose for pre- and postnatal developmental toxicity in rats (70 mg/kg/day) was associated with a maternal plasma lacosamide AUC similar to that in humans at the MRHD. Oral administration of lacosamide (30, 90, or 180 mg/kg/day) to rats during the neonatal and juvenile periods of development resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide AUC less than that in humans at the MRHD. In Vitro Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential adverse effects on CNS development related to this activity cannot be ruled out. 8.2 Lactation Risk Summary Data from published literature indicate that lacosamide is present in human milk. There are reports of increased sleepiness in breastfed infants exposed to lacosamide (see Clinical Considerations). There is no information on the effects of lacosamide on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VIMPAT and any potential adverse effects on the breastfed infant from VIMPAT or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to VIMPAT through breastmilk for excess sedation. 8.4 Pediatric Use Partial-Onset Seizures Safety and effectiveness of VIMPAT for the treatment of partial-onset seizures have been established in pediatric patients 1 month to less than 17 years of age. Use of VIMPAT in this age group is supported by evidence from adequate and well-controlled studies of VIMPAT in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 847 pediatric patients 1 month to less than 17 years of age [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2)]. Safety and effectiveness in pediatric patients below 1 month of age have not been established. Primary Generalized Tonic-Clonic Seizures Safety and effectiveness of VIMPAT as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in pediatric patients with idiopathic generalized epilepsy 4 years of age and older was established in a 24-week double-blind, randomized, placebo-controlled, parallel-group, multi-center study (Study 5), which included 37 pediatric patients 4 years to less than 17 years of age [see Adverse Reactions (6.1) and Clinical Studies (14.3)]. Safety and effectiveness in pediatric patients below the age of 4 years have not been established. Animal Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential related adverse effects on CNS development cannot be ruled out. Administration of lacosamide to rats during the neonatal and juvenile periods of postnatal development (approximately equivalent to neonatal through adolescent development in humans) resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide exposure (AUC) less than that in humans at the maximum recommended human dose of 400 mg/day. 8.5 Geriatric Use There were insufficient numbers of elderly patients enrolled in partial-onset seizure trials (n=18) to adequately determine whether they respond differently from younger patients. No VIMPAT dose adjustment based on age is necessary. In elderly patients, dose titration should be performed with caution, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic function, decreased renal function, increased cardiac conduction abnormalities, and polypharmacy [see Dosage and Administration (2.1, 2.4, 2.5) and Clinical Pharmacology (12.3)]. 8.6 Renal Impairment No dose adjustment is necessary in patients with mild to moderate renal impairment (CL CR ≥30 mL/min). In patients with severe renal impairment (CL CR <30 mL/min as estimated by the Cockcroft-Gault equation for adults; CL CR <30 mL/min/1.73m 2 as estimated by the Schwartz equation for pediatric patients) and in those with end-stage renal disease, a reduction of 25% of the maximum dosage is recommended [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. In all patients with renal impairment, dose initiation and titration should be based on clinical response and tolerability. VIMPAT is effectively removed from plasma by hemodialysis. Dosage supplementation of up to 50% following hemodialysis should be considered. 8.7 Hepatic Impairment For adult and pediatric patients with mild to moderate hepatic impairment, a reduction of 25% of the maximum dosage is recommended. Patients with mild to moderate hepatic impairment should be observed closely for adverse reactions, and dose initiation and titration should be based on clinical response and tolerability [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)]. The pharmacokinetics of lacosamide has not been evaluated in severe hepatic impairment. VIMPAT use is not recommended in patients with severe hepatic impairment.

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as VIMPAT, during pregnancy. Encourage women who are taking VIMPAT during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series with VIMPAT use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Lacosamide produced developmental toxicity (increased embryofetal and perinatal mortality, growth deficit) in rats following administration during pregnancy. Developmental neurotoxicity was observed in rats following administration during a period of postnatal development corresponding to the third trimester of human pregnancy. These effects were observed at doses associated with clinically relevant plasma exposures (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of lacosamide to pregnant rats (20, 75, or 200 mg/kg/day) and rabbits (6.25, 12.5, or 25 mg/kg/day) during the period of organogenesis did not produce any effects on the incidences of fetal structural abnormalities. However, the maximum doses evaluated were limited by maternal toxicity in both species and embryofetal death in rats. These doses were associated with maternal plasma lacosamide exposures (AUC) approximately 2 and 1 times (rat and rabbit, respectively) that in humans at the maximum recommended human dose (MRHD) of 400 mg/day. In two studies in which lacosamide (25, 70, or 200 mg/kg/day and 50, 100, or 200 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, increased perinatal mortality and decreased body weights in the offspring were observed at the highest dose tested. The no-effect dose for pre- and postnatal developmental toxicity in rats (70 mg/kg/day) was associated with a maternal plasma lacosamide AUC similar to that in humans at the MRHD. Oral administration of lacosamide (30, 90, or 180 mg/kg/day) to rats during the neonatal and juvenile periods of development resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide AUC less than that in humans at the MRHD. In Vitro Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential adverse effects on CNS development related to this activity cannot be ruled out.

Partial-Onset Seizures Safety and effectiveness of VIMPAT for the treatment of partial-onset seizures have been established in pediatric patients 1 month to less than 17 years of age. Use of VIMPAT in this age group is supported by evidence from adequate and well-controlled studies of VIMPAT in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 847 pediatric patients 1 month to less than 17 years of age [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2)]. Safety and effectiveness in pediatric patients below 1 month of age have not been established. Primary Generalized Tonic-Clonic Seizures Safety and effectiveness of VIMPAT as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in pediatric patients with idiopathic generalized epilepsy 4 years of age and older was established in a 24-week double-blind, randomized, placebo-controlled, parallel-group, multi-center study (Study 5), which included 37 pediatric patients 4 years to less than 17 years of age [see Adverse Reactions (6.1) and Clinical Studies (14.3)]. Safety and effectiveness in pediatric patients below the age of 4 years have not been established. Animal Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential related adverse effects on CNS development cannot be ruled out. Administration of lacosamide to rats during the neonatal and juvenile periods of postnatal development (approximately equivalent to neonatal through adolescent development in humans) resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide exposure (AUC) less than that in humans at the maximum recommended human dose of 400 mg/day.

9.1Controlled Substance

VIMPAT contains lacosamide, a Schedule V controlled substance. 9.2 Abuse Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. In a human abuse potential study, single doses of 200 mg (equal to the maximum single dosage) and 800 mg lacosamide (equal to twice the recommended daily maintenance dosage) 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%. 9.3 Dependence Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. 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.

The chemical name of lacosamide, the single (R)-enantiomer, is (R)-2-acetamido-N-benzyl-3-methoxypropionamide (IUPAC). Lacosamide is a functionalized amino acid. Its molecular formula is C 13 H 18 N 2 O 3 and its molecular weight is 250.30. The chemical structure is: Lacosamide is a white to light yellow powder. It is sparingly soluble in water and slightly soluble in acetonitrile and ethanol. Chemical Structure 11.1 VIMPAT Tablets VIMPAT tablets for oral administration contain lacosamide and the following inactive ingredients: colloidal silicon dioxide, crospovidone, hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and dye pigments as specified below: VIMPAT tablets are supplied as debossed tablets and contain the following coloring agents: 50 mg tablets: red iron oxide, black iron oxide, FD&C Blue #2/indigo carmine aluminum lake 100 mg tablets: yellow iron oxide 150 mg tablets: yellow iron oxide, red iron oxide, black iron oxide 200 mg tablets: FD&C Blue #2/indigo carmine aluminum lake 11.2 VIMPAT Injection VIMPAT injection is a clear, colorless, sterile solution containing 10 mg lacosamide per mL for intravenous infusion. One 20-mL vial contains 200 mg of lacosamide drug substance. The inactive ingredients are sodium chloride (7.62 mg/mL) and water for injection. Hydrochloric acid is used for pH adjustment. VIMPAT injection has a pH of 3.8 to 5.0. 11.3 VIMPAT Oral Solution VIMPAT oral solution contains 10 mg of lacosamide per mL. The inactive ingredients are purified water, sorbitol solution, glycerin, polyethylene glycol, carboxymethylcellulose sodium, acesulfame potassium, methylparaben, flavoring (including natural and artificial flavors, propylene glycol, aspartame, and maltol), anhydrous citric acid and sodium chloride.

16.1How Supplied

VIMPAT (lacosamide) Tablets 50 mg are pink, oval, film-coated tablets debossed with "SP" on one side and "50" on the other. They are supplied as follows: Bottles of 60 NDC 0131-2477-35 Unit Dose Carton of 60 tablets [6 cards, each card contains 10 tablets] NDC 0131-2477-60 100 mg are dark yellow, oval, film-coated tablets debossed with "SP" on one side and "100" on the other. They are supplied as follows: Bottles of 60 NDC 0131-2478-35 Unit Dose Carton of 60 tablets [6 cards, each card contains 10 tablets] NDC 0131-2478-60 150 mg are salmon, oval, film-coated tablets debossed with "SP" on one side and "150" on the other. They are supplied as follows: Bottles of 60 NDC 0131-2479-35 Unit Dose Carton of 60 tablets [6 cards, each card contains 10 tablets] NDC 0131-2479-60 200 mg are blue, oval, film-coated tablets debossed with "SP" on one side and "200" on the other. They are supplied as follows: Bottles of 60 NDC 0131-2480-35 Unit Dose Carton of 60 tablets [6 cards, each card contains 10 tablets] NDC 0131-2480-60 VIMPAT (lacosamide) Injection 200 mg/20 mL is a clear, colorless sterile solution supplied in 20 mL colorless single-dose glass vials. 200 mg/20 mL vial in cartons of 10 vials NDC 0131-1810-67 VIMPAT (lacosamide) Oral Solution 10 mg/mL is a clear, colorless to yellow or yellow-brown, strawberry-flavored liquid. It is supplied as follows: 200 mL in glass bottles NDC 0131-5410-72 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature] Do not freeze VIMPAT injection or oral solution. Discard any unused VIMPAT oral solution remaining after six (6) months of first opening the bottle.