Vimpat
lacosamide · Tablet, Film Coated · Oral, Intravenous
Uses
1 INDICATIONS AND USAGE VIMPAT is indicated for: Treatment of partial-onset seizures in patients 1 month of age and older ( 1.1 ) Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older ( 1.2 ) 1.1 Partial-Onset Seizures VIMPAT is indicated for the treatment of partial-onset seizures in patients 1 month of age and older. 1.2 Primary Generalized Tonic-Clonic Seizures VIMPAT is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older.
Dosage and administration
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 ) 2.1 Dosage 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.
Dosage forms and strengths
50 mg, 100 mg, 150 mg, 200 mg tablets ( 3 ) 200 mg/20 mL single-dose vial for intravenous use ( 3 ) 10 mg/mL oral solution ( 3 ) VIMPAT Tablets 50 mg: pink, oval, film-coated, debossed with "SP" on one side and "50" on the other 100 mg: dark yellow, oval, film-coated, debossed with "SP" on one side and "100" on the other 150 mg: salmon, oval, film-coated, debossed with "SP" on one side and "150" on the other 200 mg: blue, oval, film-coated, debossed with "SP" on one side and "200" on the other VIMPAT Injection 200 mg/20 mL: clear, colorless sterile solution in single-dose vials VIMPAT Oral Solution 10 mg/mL: clear, colorless to yellow or yellow-brown, strawberry-flavored liquid
Contraindications
None . None ( 4 )
Warnings and precautions
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 ) 5.1 Suicidal 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.
Side effects
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 6.1 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. 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.
Drug interactions
7.1 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. 7.2 Concomitant Medications that Affect Cardiac Conduction VIMPAT should be used with caution in patients on concomitant medications that affect cardiac conduction (sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers) including those that prolong PR interval (including sodium channel blocking AEDs), because of a risk of AV block, bradycardia, or ventricular tachyarrhythmia. 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 (5.3) ] .
Use in specific populations
Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) 8.1 Pregnancy 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).
Pregnancy
8.1 Pregnancy 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.
Pediatric use
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.
Geriatric use
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) ] .
Overdosage
Events reported after an intake of more than 800 mg (twice the maximum recommended daily dosage) of VIMPAT include dizziness, nausea, and seizures (generalized tonic-clonic seizures, status epilepticus). Cardiac conduction disorders, confusion, decreased level of consciousness, cardiogenic shock, cardiac arrest, and coma have also been observed. Fatalities have occurred following lacosamide overdoses of several grams. There is no specific antidote for overdose with VIMPAT. Standard decontamination procedures should be followed. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of patient. A Certified Poison Control Center should be contacted for up to date information on the management of overdose with VIMPAT. Standard hemodialysis procedures result in significant clearance of VIMPAT (reduction of systemic exposure by 50% in 4 hours). Hemodialysis may be indicated based on the patient's clinical state or in patients with significant renal impairment.
Description
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.
Mechanism of action
12.1 Mechanism of Action The precise mechanism by which VIMPAT exerts its antiepileptic effects in humans remains to be fully elucidated. In vitro electrophysiological studies have shown that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing.
How supplied
16.1 How 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.
Storage
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.
Patient information
Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide). The Medication Guide accompanies the product and can also be accessed on www.vimpat.com or by calling 1-844-599-2273. Suicidal Thinking and Behavior Patients, their caregivers, and families should be counseled that AEDs, including VIMPAT, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions (5.1) ] . Dizziness and Ataxia Patients should be counseled that VIMPAT use may cause dizziness, double vision, abnormal coordination and balance, and somnolence. Patients taking VIMPAT should be advised not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects associated with VIMPAT [see Warnings and Precautions (5.2) ] . Cardiac Rhythm and Conduction Abnormalities Patients should be counseled that VIMPAT is associated with electrocardiographic changes that may predispose to irregular heart beat and syncope. Cardiac arrest has been reported. This risk is increased in patients with underlying cardiovascular disease, with heart conduction problems, or who are taking other medications that affect the heart. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away. Patients who develop syncope should lay down with raised legs and contact their health care provider [see Warnings and Precautions (5.3) ] . Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity Patients should be aware that VIMPAT may cause serious hypersensitivity reactions affecting multiple organs such as the liver and kidney. VIMPAT should be discontinued if a serious hypersensitivity reaction is suspected. Patients should also be instructed to report promptly to their physicians any symptoms of liver toxicity (e.g., fatigue, jaundice, dark urine) [see Warnings and Precautions (5.6) ] . Pregnancy Registry Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during VIMPAT therapy. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry if they become pregnant. This registry is collecting information about the safety of AEDs during pregnancy [see Use in Specific Populations (8.1) ] . Lactation Advise breastfeeding women using VIMPAT to monitor infants for excess sleepiness and to seek medical care if they notice this sign [see Use in Specific Populations (8.2) ].
Label text from the FDA structured product label by UCB, Inc. (revised May 12, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Lacosamide in 6 products
Vimpat NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0131-1810 | Lacosamide 10 mg/mL Injection | UCB, Inc. | NDA · DEA CV |
| 0131-2477 | Lacosamide 50 mg/1 Tablet, Film Coated | UCB, Inc. | NDA · DEA CV |
| 0131-2478 | Lacosamide 100 mg/1 Tablet, Film Coated | UCB, Inc. | NDA · DEA CV |
| 0131-2479 | Lacosamide 150 mg/1 Tablet, Film Coated | UCB, Inc. | NDA · DEA CV |
| 0131-2480 | Lacosamide 200 mg/1 Tablet, Film Coated | UCB, Inc. | NDA · DEA CV |
| 0131-5410 | Lacosamide 10 mg/mL Solution | UCB, Inc. | NDA · DEA CV |
Vimpat recalls
- D-0590-2021 Jun 2, 2021 · Class II · Terminated
CGMP Deviations: Intermittent exposure to temperature excursion during storage.
Frequently asked questions
What is Vimpat used for?
1 INDICATIONS AND USAGE VIMPAT is indicated for: Treatment of partial-onset seizures in patients 1 month of age and older ( 1.1 ) Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older ( 1.2 ) 1.1 Partial-Onset Seizures VIMPAT is indicated for the treatment of partial-onset seizures in patients 1 month of age and older. 1.2 Primary…
What are the side effects of Vimpat?
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… See the full label for the complete list.
Who makes Vimpat?
Vimpat is listed by 1 labeler in the FDA NDC directory, including UCB, Inc..
Has Vimpat been recalled?
The FDA enforcement database lists 1 recall for Vimpat, most recently D-0590-2021 (class ii): CGMP Deviations: Intermittent exposure to temperature excursion during storage.