Vigabatrin (Page 4 of 9)

5.11 Edema

Vigabatrin causes edema in adults. Pediatric clinical trials were not designed to assess edema, but observed incidence of edema-based pooled data from controlled pediatric studies appeared similar for pediatric patients on vigabatrin and placebo.

Pooled data from controlled trials demonstrated increased risk among vigabatrin patients compared to placebo patients for peripheral edema (vigabatrin 2%, placebo 1%), and edema (vigabatrin 1%, placebo 0%). In these studies, one vigabatrin and no placebo patients discontinued for an edema related AE. In adults, there was no apparent association between edema and cardiovascular adverse events such as hypertension or congestive heart failure. Edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function.

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)]

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.

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 2 0 1
Vertigo 2 5 1
Eye Disorders
Blurred vision 13 16 5
Diplopia 7 16 3
Asthenopia 2 2 0
Eye pain 0 5 0
Gastrointestinal Disorders
Diarrhea 10 16 7
Nausea 10 2 8
Vomiting 7 9 6
Constipation 8 5 3
Upper abdominal pain 5 5 1
Dyspepsia 4 5 3
Stomach discomfort 4 2 1
Abdominal pain 3 2 1
Toothache 2 5 2
Abdominal distension 2 0 1
General Disorders
Fatigue 23 40 16
Gait disturbance 6 12 7
Asthenia 5 7 1
Edema peripheral 5 7 1
Fever 4 7 3
Chest pain 1 5 1
Thirst 2 0 0
Malaise 0 5 0
Infections
Nasopharyngitis 14 9 10
Upper respiratory tract infection 7 9 6
Influenza 5 7 4
Urinary tract infection 4 5 0
Bronchitis 0 5 1
Injury
Contusion 3 5 2
Joint sprain 1 2 1
Muscle strain 1 2 1
Wound secretion 0 2 0
Metabolism and Nutrition Disorders
Increased appetite 1 5 1
Weight gain 6 14 3
Musculoskeletal Disorders
Arthralgia 10 5 3
Back pain 4 7 2
Pain in extremity 6 2 4
Myalgia 3 5 1
Muscle twitching 1 9 1
Muscle spasms 3 0 1
Nervous System Disorders
Headache 33 26 31
Somnolence 22 26 13
Dizziness 24 26 17
Nystagmus 13 19 9
Tremor 15 16 8
Memory impairment 7 16 3
Abnormal coordination 7 16 2
Disturbance in attention 9 0 1
Sensory disturbance 4 7 2
Hyporeflexia 4 5 1
Paraesthesia 7 2 1
Lethargy 4 7 2
Hyperreflexia 4 2 3
Hypoaesthesia 4 5 1
Sedation 4 0 0
Status epilepticus 2 5 0
Dysarthria 2 2 1
Postictal state 2 0 1
Sensory loss 0 5 0
Psychiatric Disorders
Irritability 7 23 7
Depression 6 14 3
Confusional state 4 14 1
Anxiety 4 0 3
Depressed mood 5 0 1
Abnormal thinking 3 7 0
Abnormal behavior 3 5 1
Expressive language disorder 1 7 1
Nervousness 2 5 2
Abnormal dreams 1 5 1
Reproductive System
Dysmenorrhea 9 5 3
Erectile dysfunction 0 5 0
Respiratory and Thoracic Disorders
Pharyngolaryngeal pain 7 14 5
Cough 2 14 7
Pulmonary congestion 0 5 1
Sinus headache 6 2 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
All Vigabatrin Placebo
Body System Adverse Reaction [N=165] % [N=104] %
Eye Disorders
Diplopia 3 2
Blurred vision 2 0
Gastrointestinal Disorders
Upper abdominal pain 4 3
Constipation 2 1
General Disorders
Fatigue 10 7
Infections and Infestations
Upper respiratory tract infection 15 11
Influenza 7 3
Otitis media 6 4
Streptococcal pharyngitis 4 3
Viral gastroenteritis 2 0
Investigations
Weight gain 15 2
Nervous System Disorders
Somnolence 6 5
Nystagmus 4 3
Tremor 4 2
Status epilepticus 2 1
Psychiatric Disorders
Abnormal behavior 7 6
Aggression 6 2
Disorientation 3 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.

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