Lacosamide
Generic: LACOSAMIDE
Basic Information
Manufacturer
Unichem Pharmaceuticals (USA), Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
7ed5cebe-470e-48a4-86ec-2ce79cc32688
Indications & Usage
1 INDICATIONS AND USAGE Lacosamide tablet 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 tablets are indicated for the treatment of partial-onset seizures in patients 4 years of age and older.
Additional pediatric use information is approved for UCB, Inc.'s VIMPAT ® (lacosamide) tablets.
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 tablets are 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) tablets.
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 tablets are indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older.
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 ) Pediatric patients: Adverse reactions are similar to those seen in adult patients ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Unichem Pharmaceuticals (USA) Inc.
at 1-866-562-4616 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.
Lacosamide Tablet and Oral Solution in Adults In the premarketing development of adjunctive therapy for partial-onset seizures, 1327 adult patients received Lacosamide 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 lacosamide 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 lacosamide) 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 lacosamide 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 lacosamide 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 lacosamide 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 % Lacosamide 200 mg/day N=270 % Lacosamide 400 mg/day N=471 % Lacosamide 600 mg/day* N=203 % Lacosamide 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 *600 mg dose is 1.5 times greater than the maximum recommended dose.
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.
Lacosamide Tablet and Oral Solution in Pediatric Patients Safety of lacosamide was evaluated in clinical studies of pediatric patients 4 years to less than 17 years of age for the treatment of partial-onset seizures.
Across studies in pediatric patients with partial-onset seizures, 328 patients 4 years to less than 17 years of age received lacosamide oral solution or tablet, of whom 148 received lacosamide for at least 1 year.
Adverse reactions reported in clinical studies of pediatric patients 4 years 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 lacosamide) reported in patients treated with lacosamide 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 lacosamide compared to 1% of patients who received placebo.
It is also noted that 2 patients receiving lacosamide 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 lacosamide 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 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 Additional pediatric use information is approved for UCB, Inc.'s VIMPAT ® (lacosamide) tablets.
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
at 1-866-562-4616 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.
Lacosamide Tablet and Oral Solution in Adults In the premarketing development of adjunctive therapy for partial-onset seizures, 1327 adult patients received Lacosamide 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 lacosamide 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 lacosamide) 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 lacosamide 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 lacosamide 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 lacosamide 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 % Lacosamide 200 mg/day N=270 % Lacosamide 400 mg/day N=471 % Lacosamide 600 mg/day* N=203 % Lacosamide 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 *600 mg dose is 1.5 times greater than the maximum recommended dose.
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.
Lacosamide Tablet and Oral Solution in Pediatric Patients Safety of lacosamide was evaluated in clinical studies of pediatric patients 4 years to less than 17 years of age for the treatment of partial-onset seizures.
Across studies in pediatric patients with partial-onset seizures, 328 patients 4 years to less than 17 years of age received lacosamide oral solution or tablet, of whom 148 received lacosamide for at least 1 year.
Adverse reactions reported in clinical studies of pediatric patients 4 years 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 lacosamide) reported in patients treated with lacosamide 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 lacosamide compared to 1% of patients who received placebo.
It is also noted that 2 patients receiving lacosamide 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 lacosamide 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 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 Additional pediatric use information is approved for UCB, Inc.'s VIMPAT ® (lacosamide) tablets.
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