Lacosamide
Generic: LACOSAMIDE
Basic Information
Manufacturer
Indoco Remedies Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
ba337b2c-7c1f-4f7b-ba93-054f502400f3
Indications & Usage
1 INDICATIONS AND USAGE Lacosamide Injection is indicated for: Treatment of partial-onset seizures in patients 4 years 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 Lacosamide injection is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.
1.2 Primary Generalized Tonic-Clonic Seizures Lacosamide injection is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older.
Additional pediatric use information is approved for UCB, Inc.’s VIMPAT® (lacosamide) injection.
However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
1.2 Primary Generalized Tonic-Clonic Seizures Lacosamide injection is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older.
Additional pediatric use information is approved for UCB, Inc.’s VIMPAT® (lacosamide) injection.
However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
Adverse Reactions
6 ADVERSE REACTIONS 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 ) To report SUSPECTED ADVERSE REACTIONS, contact Indoco Remedies Limited at +1-855-642-2594 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.
Laboratory Abnormalities Abnormalities in liver function tests have occurred in controlled trials with lacosamide in adult patients with partial-onset seizures who were taking 1 to 3 concomitant anti-epileptic drugs.
Elevations of ALT to ≥3x ULN occurred in 0.7% (7/935) of lacosamide patients and 0% (0/356) of placebo patients.
One case of hepatitis with transaminases >20x ULN occurred in one healthy subject 10 days after lacosamide 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 lacosamide.
Other Adverse Reactions The following is a list of adverse reactions reported by patients treated with lacosamide 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 Lacosamide 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 lacosamide.
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 lacosamide Injection 200 mg to 400 mg followed by oral administration of lacosamide 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 lacosamide injection 200 mg followed by oral lacosamide 200 mg/day (100 mg every 12 hours) Single dose of intravenous lacosamide injection 300 mg followed by oral lacosamide 300 mg/day (150 mg every 12 hours) Single dose of intravenous lacosamide Injection 400 mg followed by oral lacosamide 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 lacosamide dosing group.
Table 5: Adverse Reactions in a 15-minute Infusion Study in Adult Patients with Partial-Onset Seizures Adverse Reaction Lacosamide 200 mg N=25 % Lacosamide 300 mg N=50 % Lacosamide 400 mg N=25 % Lacosamide 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 Lacosamide 200 mg over 15-minutes followed by Lacosamide 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 lacosamide Injection than with administration over a 30-to 60-minute period.
The adverse reactions associated with lacosamide 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 (4 Years to less than 17 Years of Age) The safety of lacosamide injection was evaluated in a multicenter, open-label study of 77 pediatric patients 4 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 lacosamide injection in pediatric patients are expected to be similar to those noted in adults.
Additional pediatric use information is approved for UCB, Inc.’s VIMPAT® (lacosamide) injection.
However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lacosamide.
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
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.
Laboratory Abnormalities Abnormalities in liver function tests have occurred in controlled trials with lacosamide in adult patients with partial-onset seizures who were taking 1 to 3 concomitant anti-epileptic drugs.
Elevations of ALT to ≥3x ULN occurred in 0.7% (7/935) of lacosamide patients and 0% (0/356) of placebo patients.
One case of hepatitis with transaminases >20x ULN occurred in one healthy subject 10 days after lacosamide 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 lacosamide.
Other Adverse Reactions The following is a list of adverse reactions reported by patients treated with lacosamide 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 Lacosamide 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 lacosamide.
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 lacosamide Injection 200 mg to 400 mg followed by oral administration of lacosamide 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 lacosamide injection 200 mg followed by oral lacosamide 200 mg/day (100 mg every 12 hours) Single dose of intravenous lacosamide injection 300 mg followed by oral lacosamide 300 mg/day (150 mg every 12 hours) Single dose of intravenous lacosamide Injection 400 mg followed by oral lacosamide 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 lacosamide dosing group.
Table 5: Adverse Reactions in a 15-minute Infusion Study in Adult Patients with Partial-Onset Seizures Adverse Reaction Lacosamide 200 mg N=25 % Lacosamide 300 mg N=50 % Lacosamide 400 mg N=25 % Lacosamide 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 Lacosamide 200 mg over 15-minutes followed by Lacosamide 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 lacosamide Injection than with administration over a 30-to 60-minute period.
The adverse reactions associated with lacosamide 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 (4 Years to less than 17 Years of Age) The safety of lacosamide injection was evaluated in a multicenter, open-label study of 77 pediatric patients 4 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 lacosamide injection in pediatric patients are expected to be similar to those noted in adults.
Additional pediatric use information is approved for UCB, Inc.’s VIMPAT® (lacosamide) injection.
However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lacosamide.
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