Vigabatrin
Generic: VIGABATRIN
Basic Information
Manufacturer
Amneal Pharmaceuticals NY LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
04fef2ec-c275-405d-91b1-99a74ee8caa2
Indications & Usage
1 INDICATIONS AND USAGE Vigabatrin tablets are indicated for the treatment of: Refractory Complex Partial Seizures as adjunctive therapy in patients 2 years of age and older who have responded inadequately to several alternative treatments; vigabatrin tablets are not indicated as a first line agent (1.1) Infantile Spasms - monotherapy in infants 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss (1.2) 1.1 Refractory Complex Partial Seizures (CPS) Vigabatrin tablets are indicated as adjunctive therapy for adults and pediatric patients 2 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss [see Warnings and Precautions (5.1) ] .
Vigabatrin tablets are not indicated as a first line agent for complex partial seizures.
1.2 Infantile Spasms (IS) Vigabatrin is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see Warnings and Precautions (5.1) ] .
Vigabatrin tablets are not indicated as a first line agent for complex partial seizures.
1.2 Infantile Spasms (IS) Vigabatrin is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see Warnings and Precautions (5.1) ] .
Adverse Reactions
6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are described elsewhere in labeling: Permanent Vision Loss [see BOXED WARNING and Warnings and Precautions (5.1) ] Magnetic Resonance Imaging (MRI) Abnormalities in Infants [see Warnings and Precautions (5.3) ] Neurotoxicity [see Warnings and Precautions (5.4) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.5) ] Withdrawal of Antiepileptic Drugs (AEDs) [see Warnings and Precautions (5.6) ] Anemia [see Warnings and Precautions (5.7) ] Somnolence and Fatigue [see Warnings and Precautions (5.8) ] Peripheral Neuropathy [see Warnings and Precautions (5.9) ] Weight Gain [see Warnings and Precautions (5.10) ] Edema [see Warnings and Precautions (5.11) ] Refractory Complex Partial Seizures Most common adverse reactions in controlled studies include (incidence ≥5% over placebo): Adults: blurred vision, somnolence, dizziness, abnormal coordination, tremor, and fatigue (6.1) Pediatric patients (3 to 16 years of age): weight gain (6.1) Infantile Spasms (incidence >5% and greater than on placebo) Somnolence, bronchitis, ear infection, and acute otitis media (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In U.S.
and primary non-U.S.
clinical studies of 4,079 vigabatrin-treated patients, the most common (≥5%) adverse reactions associated with the use of vigabatrin in combination with other AEDs were headache, somnolence, fatigue, dizziness, convulsion, nasopharyngitis, weight gain, upper respiratory tract infection, visual field defect, depression, tremor, nystagmus, nausea, diarrhea, memory impairment, insomnia, irritability, abnormal coordination, blurred vision, diplopia, vomiting, influenza, pyrexia, and rash.
The adverse reactions most commonly associated with vigabatrin treatment discontinuation in ≥1% of patients were convulsion and depression.
In patients with infantile spasms, the adverse reactions most commonly associated with vigabatrin treatment discontinuation in ≥1% of patients were infections, status epilepticus, developmental coordination disorder, dystonia, hypotonia, hypertonia, weight gain, and insomnia.
Refractory Complex Partial Seizures Adults Table 5 lists the adverse reactions that occurred in ≥2% and more than one patient per vigabatrin-treated group and that occurred more frequently than in placebo patients from 2 U.S.
adjunctive clinical studies of refractory CPS in adults.
Table 5.
Adverse Reactions in Pooled, Adjunctive Trials in Adults with Refractory Complex Partial Seizures Vigabatrin dosage (mg/day) Body System Adverse Reaction 3,000 [N=134] % 6,000 [N=43] % Placebo [N=135] % Ear Disorders Tinnitus Vertigo 2 2 0 5 1 1 Eye Disorders Blurred vision Diplopia Asthenopia Eye pain 13 7 2 0 16 16 2 5 5 3 0 0 Gastrointestinal Disorders Diarrhea Nausea Vomiting Constipation Upper abdominal pain Dyspepsia Stomach discomfort Abdominal pain Toothache Abdominal distension 10 10 7 8 5 4 4 3 2 2 16 2 9 5 5 5 2 2 5 0 7 8 6 3 1 3 1 1 2 1 General Disorders Fatigue Gait disturbance Asthenia Edema peripheral Fever Chest pain Thirst Malaise 23 6 5 5 4 1 2 0 40 12 7 7 7 5 0 5 16 7 1 1 3 1 0 0 Infections Nasopharyngitis Upper respiratory tract infection Influenza Urinary tract infection Bronchitis 14 7 5 4 0 9 9 7 5 5 10 6 4 0 1 Injury Contusion Joint sprain Muscle strain Wound secretion 3 1 1 0 5 2 2 2 2 1 1 0 Metabolism and Nutrition Disorders Increased appetite Weight gain 1 6 5 14 1 3 Musculoskeletal Disorders Arthralgia Back pain Pain in extremity Myalgia Muscle twitching Muscle spasms 10 4 6 3 1 3 5 7 2 5 9 0 3 2 4 1 1 1 Nervous System Disorders Headache Somnolence Dizziness Nystagmus Tremor Memory impairment Abnormal coordination Disturbance in attention Sensory disturbance Hyporeflexia Paraesthesia Lethargy Hyperreflexia Hypoaesthesia Sedation Status epilepticus Dysarthria Postictal state Sensory loss 33 22 24 13 15 7 7 9 4 4 7 4 4 4 4 2 2 2 0 26 26 26 19 16 16 16 0 7 5 2 7 2 5 0 5 2 0 5 31 13 17 9 8 3 2 1 2 1 1 2 3 1 0 0 1 1 0 Psychiatric Disorders Irritability Depression Confusional state Anxiety Depressed mood Abnormal thinking Abnormal behavior Expressive language disorder Nervousness Abnormal dreams 7 6 4 4 5 3 3 1 2 1 23 14 14 0 0 7 5 7 5 5 7 3 1 3 1 0 1 1 2 1 Reproductive System Dysmenorrhea Erectile dysfunction 9 0 5 5 3 0 Respiratory and Thoracic Disorders Pharyngolaryngeal pain Cough Pulmonary congestion Sinus headache 7 2 0 6 14 14 5 2 5 7 1 1 Skin and Subcutaneous Tissue Disorders Rash 4 5 4 Pediatrics 2 to 16 years of age Table 6 lists adverse reactions from controlled clinical studies of pediatric patients receiving vigabatrin or placebo as adjunctive therapy for refractory complex partial seizures.
Adverse reactions that are listed occurred in at least 2% of vigabatrin-treated patients and more frequently than placebo.
The median vigabatrin dose was 49.4 mg/kg (range of 8 to 105.9 mg/kg).
Table 6.
Adverse Reactions in Pooled, Adjunctive Trials in Pediatric Patients 3 to 16 Years of Age with Refractory Complex Partial Seizures Body System Adverse Reaction All Vigabatrin [N=165] % Placebo [N=104] % Eye Disorders Diplopia Blurred vision 3 2 2 0 Gastrointestinal Disorders Upper abdominal pain Constipation 4 2 3 1 General Disorders Fatigue 10 7 Infections and Infestations Upper respiratory tract infection Influenza Otitis media Streptococcal pharyngitis Viral gastroenteritis 15 7 6 4 2 11 3 4 3 0 Investigations Weight gain 15 2 Nervous System Disorders Somnolence Nystagmus Tremor Status epilepticus 6 4 4 2 5 3 2 1 Psychiatric Disorders Abnormal behavior Aggression Disorientation 7 6 3 6 2 0 Safety of vigabatrin for the treatment of refractory CPS in patients 2 years of age is expected to be similar to pediatric patients 3 to 16 years of age.
Infantile Spasms In a randomized, placebo-controlled IS study with a 5 day double-blind treatment phase (n=40), the adverse reactions that occurred in >5% of patients receiving vigabatrin and that occurred more frequently than in placebo patients were somnolence (vigabatrin 45%, placebo 30%), bronchitis (vigabatrin 30%, placebo 15%), ear infection (vigabatrin 10%, placebo 5%), and acute otitis media (vigabatrin 10%, placebo 0%).
In a dose response study of low-dose (18 to 36 mg/kg/day) versus high-dose (100 to 148 mg/kg/day) vigabatrin, no clear correlation between dose and incidence of adverse reactions was observed.
The adverse reactions (≥5% in either dose group) are summarized in Table 7.
Table 7.
Adverse Reactions in a Placebo-Controlled Trial in Patients with Infantile Spasms Body System Adverse Reaction Vigabatrin Low Dose [N=114] % Vigabatrin High Dose [N=108] % Eye Disorders (other than field or acuity changes) Strabismus Conjunctivitis 5 5 5 2 Gastrointestinal Disorders Vomiting Constipation Diarrhea 14 14 13 20 12 12 General Disorders Fever 29 19 Infections Upper respiratory tract infection Otitis media Viral infection Pneumonia Candidiasis Ear infection Gastroenteritis viral Sinusitis Urinary tract infection Influenza Croup infectious 51 44 20 13 8 7 6 5 5 5 5 46 30 19 11 3 14 5 9 6 3 1 Metabolism & Nutrition Disorders Decreased appetite 9 7 Nervous System Disorders Sedation Somnolence Status epilepticus Lethargy Convulsion Hypotonia 19 17 6 5 4 4 17 19 4 7 7 6 Psychiatric Disorders Irritability Insomnia 16 10 23 12 Respiratory Disorders Nasal congestion Cough 13 3 4 8 Skin and Subcutaneous Tissue Disorders Rash 8 11 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of vigabatrin.
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.
Adverse reactions are categorized by system organ class.
Birth Defects: Congenital cardiac defects, congenital external ear anomaly, congenital hemangioma, congenital hydronephrosis, congenital male genital malformation, congenital oral malformation, congenital vesicoureteric reflux, dentofacial anomaly, dysmorphism, fetal anticonvulsant syndrome, hamartomas, hip dysplasia, limb malformation, limb reduction defect, low set ears, renal aplasia, retinitis pigmentosa, supernumerary nipple, talipes Ear Disorders: Deafness Endocrine Disorders: Delayed puberty Gastrointestinal Disorders: Gastrointestinal hemorrhage, esophagitis General Disorders: Developmental delay, facial edema, malignant hyperthermia, multi-organ failure Hepatobiliary Disorders: Cholestasis Nervous System Disorders: Dystonia, encephalopathy, hypertonia, hypotonia, muscle spasticity, myoclonus, optic neuritis, dyskinesia Psychiatric Disorders: Acute psychosis, apathy, delirium, hypomania, neonatal agitation, psychotic disorder Respiratory Disorders: Laryngeal edema, pulmonary embolism, respiratory failure, stridor Skin and Subcutaneous Tissue Disorders: Angioedema, maculo-papular rash, pruritus, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), alopecia
6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In U.S.
and primary non-U.S.
clinical studies of 4,079 vigabatrin-treated patients, the most common (≥5%) adverse reactions associated with the use of vigabatrin in combination with other AEDs were headache, somnolence, fatigue, dizziness, convulsion, nasopharyngitis, weight gain, upper respiratory tract infection, visual field defect, depression, tremor, nystagmus, nausea, diarrhea, memory impairment, insomnia, irritability, abnormal coordination, blurred vision, diplopia, vomiting, influenza, pyrexia, and rash.
The adverse reactions most commonly associated with vigabatrin treatment discontinuation in ≥1% of patients were convulsion and depression.
In patients with infantile spasms, the adverse reactions most commonly associated with vigabatrin treatment discontinuation in ≥1% of patients were infections, status epilepticus, developmental coordination disorder, dystonia, hypotonia, hypertonia, weight gain, and insomnia.
Refractory Complex Partial Seizures Adults Table 5 lists the adverse reactions that occurred in ≥2% and more than one patient per vigabatrin-treated group and that occurred more frequently than in placebo patients from 2 U.S.
adjunctive clinical studies of refractory CPS in adults.
Table 5.
Adverse Reactions in Pooled, Adjunctive Trials in Adults with Refractory Complex Partial Seizures Vigabatrin dosage (mg/day) Body System Adverse Reaction 3,000 [N=134] % 6,000 [N=43] % Placebo [N=135] % Ear Disorders Tinnitus Vertigo 2 2 0 5 1 1 Eye Disorders Blurred vision Diplopia Asthenopia Eye pain 13 7 2 0 16 16 2 5 5 3 0 0 Gastrointestinal Disorders Diarrhea Nausea Vomiting Constipation Upper abdominal pain Dyspepsia Stomach discomfort Abdominal pain Toothache Abdominal distension 10 10 7 8 5 4 4 3 2 2 16 2 9 5 5 5 2 2 5 0 7 8 6 3 1 3 1 1 2 1 General Disorders Fatigue Gait disturbance Asthenia Edema peripheral Fever Chest pain Thirst Malaise 23 6 5 5 4 1 2 0 40 12 7 7 7 5 0 5 16 7 1 1 3 1 0 0 Infections Nasopharyngitis Upper respiratory tract infection Influenza Urinary tract infection Bronchitis 14 7 5 4 0 9 9 7 5 5 10 6 4 0 1 Injury Contusion Joint sprain Muscle strain Wound secretion 3 1 1 0 5 2 2 2 2 1 1 0 Metabolism and Nutrition Disorders Increased appetite Weight gain 1 6 5 14 1 3 Musculoskeletal Disorders Arthralgia Back pain Pain in extremity Myalgia Muscle twitching Muscle spasms 10 4 6 3 1 3 5 7 2 5 9 0 3 2 4 1 1 1 Nervous System Disorders Headache Somnolence Dizziness Nystagmus Tremor Memory impairment Abnormal coordination Disturbance in attention Sensory disturbance Hyporeflexia Paraesthesia Lethargy Hyperreflexia Hypoaesthesia Sedation Status epilepticus Dysarthria Postictal state Sensory loss 33 22 24 13 15 7 7 9 4 4 7 4 4 4 4 2 2 2 0 26 26 26 19 16 16 16 0 7 5 2 7 2 5 0 5 2 0 5 31 13 17 9 8 3 2 1 2 1 1 2 3 1 0 0 1 1 0 Psychiatric Disorders Irritability Depression Confusional state Anxiety Depressed mood Abnormal thinking Abnormal behavior Expressive language disorder Nervousness Abnormal dreams 7 6 4 4 5 3 3 1 2 1 23 14 14 0 0 7 5 7 5 5 7 3 1 3 1 0 1 1 2 1 Reproductive System Dysmenorrhea Erectile dysfunction 9 0 5 5 3 0 Respiratory and Thoracic Disorders Pharyngolaryngeal pain Cough Pulmonary congestion Sinus headache 7 2 0 6 14 14 5 2 5 7 1 1 Skin and Subcutaneous Tissue Disorders Rash 4 5 4 Pediatrics 2 to 16 years of age Table 6 lists adverse reactions from controlled clinical studies of pediatric patients receiving vigabatrin or placebo as adjunctive therapy for refractory complex partial seizures.
Adverse reactions that are listed occurred in at least 2% of vigabatrin-treated patients and more frequently than placebo.
The median vigabatrin dose was 49.4 mg/kg (range of 8 to 105.9 mg/kg).
Table 6.
Adverse Reactions in Pooled, Adjunctive Trials in Pediatric Patients 3 to 16 Years of Age with Refractory Complex Partial Seizures Body System Adverse Reaction All Vigabatrin [N=165] % Placebo [N=104] % Eye Disorders Diplopia Blurred vision 3 2 2 0 Gastrointestinal Disorders Upper abdominal pain Constipation 4 2 3 1 General Disorders Fatigue 10 7 Infections and Infestations Upper respiratory tract infection Influenza Otitis media Streptococcal pharyngitis Viral gastroenteritis 15 7 6 4 2 11 3 4 3 0 Investigations Weight gain 15 2 Nervous System Disorders Somnolence Nystagmus Tremor Status epilepticus 6 4 4 2 5 3 2 1 Psychiatric Disorders Abnormal behavior Aggression Disorientation 7 6 3 6 2 0 Safety of vigabatrin for the treatment of refractory CPS in patients 2 years of age is expected to be similar to pediatric patients 3 to 16 years of age.
Infantile Spasms In a randomized, placebo-controlled IS study with a 5 day double-blind treatment phase (n=40), the adverse reactions that occurred in >5% of patients receiving vigabatrin and that occurred more frequently than in placebo patients were somnolence (vigabatrin 45%, placebo 30%), bronchitis (vigabatrin 30%, placebo 15%), ear infection (vigabatrin 10%, placebo 5%), and acute otitis media (vigabatrin 10%, placebo 0%).
In a dose response study of low-dose (18 to 36 mg/kg/day) versus high-dose (100 to 148 mg/kg/day) vigabatrin, no clear correlation between dose and incidence of adverse reactions was observed.
The adverse reactions (≥5% in either dose group) are summarized in Table 7.
Table 7.
Adverse Reactions in a Placebo-Controlled Trial in Patients with Infantile Spasms Body System Adverse Reaction Vigabatrin Low Dose [N=114] % Vigabatrin High Dose [N=108] % Eye Disorders (other than field or acuity changes) Strabismus Conjunctivitis 5 5 5 2 Gastrointestinal Disorders Vomiting Constipation Diarrhea 14 14 13 20 12 12 General Disorders Fever 29 19 Infections Upper respiratory tract infection Otitis media Viral infection Pneumonia Candidiasis Ear infection Gastroenteritis viral Sinusitis Urinary tract infection Influenza Croup infectious 51 44 20 13 8 7 6 5 5 5 5 46 30 19 11 3 14 5 9 6 3 1 Metabolism & Nutrition Disorders Decreased appetite 9 7 Nervous System Disorders Sedation Somnolence Status epilepticus Lethargy Convulsion Hypotonia 19 17 6 5 4 4 17 19 4 7 7 6 Psychiatric Disorders Irritability Insomnia 16 10 23 12 Respiratory Disorders Nasal congestion Cough 13 3 4 8 Skin and Subcutaneous Tissue Disorders Rash 8 11 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of vigabatrin.
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.
Adverse reactions are categorized by system organ class.
Birth Defects: Congenital cardiac defects, congenital external ear anomaly, congenital hemangioma, congenital hydronephrosis, congenital male genital malformation, congenital oral malformation, congenital vesicoureteric reflux, dentofacial anomaly, dysmorphism, fetal anticonvulsant syndrome, hamartomas, hip dysplasia, limb malformation, limb reduction defect, low set ears, renal aplasia, retinitis pigmentosa, supernumerary nipple, talipes Ear Disorders: Deafness Endocrine Disorders: Delayed puberty Gastrointestinal Disorders: Gastrointestinal hemorrhage, esophagitis General Disorders: Developmental delay, facial edema, malignant hyperthermia, multi-organ failure Hepatobiliary Disorders: Cholestasis Nervous System Disorders: Dystonia, encephalopathy, hypertonia, hypotonia, muscle spasticity, myoclonus, optic neuritis, dyskinesia Psychiatric Disorders: Acute psychosis, apathy, delirium, hypomania, neonatal agitation, psychotic disorder Respiratory Disorders: Laryngeal edema, pulmonary embolism, respiratory failure, stridor Skin and Subcutaneous Tissue Disorders: Angioedema, maculo-papular rash, pruritus, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), alopecia