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.
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).
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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