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Sabril

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Sabril

Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the prescribing information:

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.

Adverse Reactions in U.S. and Primary Non-U.S. Clinical Studies

In U.S. and primary non-U.S. clinical studies of 4,079 SABRIL treated patients, the most commonly observed ( ≥ 5%) adverse reactions associated with the use of SABRIL in combination with other AEDs were headache, somnolence, fatigue, dizziness, convulsion, nasopharyngitis, weight increased, upper respiratory tract infection, visual field defect, depression, tremor, nystagmus, nausea, diarrhea, memory impairment, insomnia, irritability, coordination abnormal, vision blurred, diplopia, vomiting, influenza, pyrexia, and rash .

The adverse reactions most commonly associated with SABRIL treatment discontinuation in ≥ 1% of patients were convulsion and depression.

In patients with infantile spasms, the adverse reactions most commonly associated with SABRIL treatment discontinuation in ≥ 1% of patients were infections, status epilepticus, developmental coordination disorder, dystonia, hypotonia, hypertonia, weight increased, and insomnia.

Most Common Adverse Reactions in Controlled Clinical Trials

Refractory Complex Partial Seizures

Adults

Table 5 lists the treatment emergent adverse reactions that occurred in ≥ 2% and more than one patient per SABRIL treated group and that occurred more frequently than in placebo patients from 2 U.S. add-on clinical studies of refractory CPS in adults.

Table 5: Treatment Emergent Adverse Reactions Occurring in ≥ 2% and More than One Patient per SABRIL-Treated Group and More Frequently than in Placebo Patients (Studies 024 and 025)

Body System
Adverse Reaction
SABRIL dosage
(mg/day)
Placebo
[N=135] %
3000
[N=134] %
6000
[N=43] %
Ear Disorders
  Tinnitus 2 0 1
  Vertigo 2 5 1
Eye Disorders
  Vision blurred 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
  Abdominal pain upper 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
  Oedema 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 increased 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
  Coordination abnormal 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
  Thinking abnormal 3 7 0
  Abnormal behaviour 3 5 1
  Expressive language disorder 1 7 1
  Nervousness 2 5 2
  Abnormal dreams 1 5 1
Reproductive System
  Dysmenorrhoea 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 10 to 16 years of age

Table 6 lists adverse reactions from controlled clinical studies of pediatric patients receiving SABRIL or placebo as add-on therapy for refractory complex partial seizures. Adverse reactions that are listed occurred in at least 2% of SABRIL treated patients and more frequently than placebo. The median SABRIL dose was 49.4 mg/kg, (range of 8.0 – 105.9 mg/kg).

Table 6: Treatment-Emergent Adverse Reactions Reported by ≥ 2% of Pediatric CPS Patients (10 to 16 years of age) Treated with SABRIL and Higher than Placebo

Body System
Adverse Reaction
All SABRIL
[N=109] %
Placebo
[N=46] %
Eye Disorders
  Diplopia 5 0
  Vision blurred 3 0
Gastrointestinal Disorders
  Diarrhoea 6 2
  Abdominal pain upper 3 0
  Constipation 3 2
General Disorders
  Fatigue 9 4
Infections and Infestations
  Upper respiratory tract infection 10 4
  Influenza 6 2
  Otitis media 6 2
Investigations
  Weight increased 17 2
Nervous System Disorders
  Somnolence 6 2
  Tremor 6 0
  Nystagmus 5 2
  Psychomotor hyperactivity 4 2
Psychiatric Disorders
  Abnormal behavior 6 2
  Aggression 5 0
  Disorientation 4 0
Reproduction and Breast Disorders
  Dysmenorrhea 3 0
Skin and Subcutaneous Tissue Disorders
  Acne 3 0

Infantile Spasms

In a randomized, placebo-controlled IS study with a 5 day double-blind treatment phase (n=40), the adverse events reported by > 5% of patients receiving SABRIL and that occurred more frequently than in placebo patients, were somnolence (SABRIL 45%, placebo 30%), bronchitis (SABRIL 30%, placebo 15%), ear infection (SABRIL 10%, placebo 5%), and otitis media acute SABRIL 10%, placebo 0%).

In a dose response study of low-dose (18-36 mg/kg/day) versus high-dose (100-148 mg/kg/day) vigabatrin, no clear correlation between dose and incidence of adverse events was observed. The treatment emergent adverse reactions ( ≥ 5% in either dose group) are summarized in Table 7.

Table 7: Treatment Emergent Adverse Reactions Occurring in ≥ 5% of Infantile Spasms Patients

Body System
Adverse Reaction
SABRIL Low Dose
[N=114] %
SABRIL High Dose
[N=108] %
Eye Disorders (other than field or acuitychanges)
  Strabismus 5 5
  Conjunctivitis 5 2
Gastrointestinal Disorders
  Vomiting 14 20
  Constipation 14 12
  Diarrhea 13 12
General Disorders
  Fever 29 19
Infections
  Upper respiratory tract infection 51 46
  Otitis media 44 30
  Viral infection 20 19
  Pneumonia 13 11
  Candidiasis 8 3
  Ear infection 7 14
  Gastroenteritis viral 6 5
  Sinusitis 5 9
  Urinary tract infection 5 6
  Influenza 5 3
  Croup infectious 5 1
Metabolism & Nutrition Disorders
  Decreased appetite 9 7
Nervous System Disorders
  Sedation 19 17
  Somnolence 17 19
  Status epilepticus 6 4
  Lethargy 5 7
  Convulsion 4 7
  Hypotonia 4 6
Psychiatric Disorders
  Irritability 16 23
  Insomnia 10 12
Respiratory Disorders
  Nasal congestion 13 4
  Cough 3 8
Skin and Subcutaneous Tissue Disorders
  Rash 8 11

Post Marketing Experience

The following adverse reactions have been reported during post approval use of SABRIL worldwide. All adverse reactions that are not listed above as adverse reactions reported in clinical trials, that are not relatively common in the population and are not too vague to be useful are listed in this section. These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to 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

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)

Read the Sabril (vigabatrin oral solution) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Antiepileptic Drugs

Phenytoin

Although phenytoin dose adjustments are not routinely required, dose adjustment of phenytoin should be considered if clinically indicated, since SABRIL may cause a moderate reduction in total phenytoin plasma levels [see CLINICAL PHARMACOLOGY].

Clonazepam

SABRIL may moderately increase the Cmax of clonazepam resulting in an increase of clonazepam-associated adverse reactions [see CLINICAL PHARMACOLOGY].

Other AEDs

There are no clinically significant pharmacokinetic interactions between SABRIL and either phenobarbital or sodium valproate. Based on population pharmacokinetics, carbamazepine, clorazepate, primidone, and sodium valproate appear to have no effect on plasma concentrations of vigabatrin [see CLINICAL PHARMACOLOGY].

Oral Contraceptives

SABRIL is unlikely to affect the efficacy of steroid oral contraceptives [see CLINICAL PHARMACOLOGY].

Drug-Laboratory Test Interactions

SABRIL decreases alanine transaminase (ALT) and aspartate transaminase (AST) plasma activity in up to 90% of patients. In some patients, these enzymes become undetectable. The suppression of ALT and AST activity by SABRIL may preclude the use of these markers, especially ALT, to detect early hepatic injury.

SABRIL may increase the amount of amino acids in the urine, possibly leading to a false positive test for certain rare genetic metabolic diseases (e.g., alpha aminoadipic aciduria).

Drug Abuse And Dependence

Controlled Substance

Vigabatrin is not a controlled substance.

Abuse

Vigabatrin did not produce adverse events or overt behaviors associated with abuse when administered to humans or animals. It is not possible to predict the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of vigabatrin (e.g., incrementation of dose, drug-seeking behavior).

Dependence

Following chronic administration of vigabatrin to animals, there were no apparent withdrawal signs upon drug discontinuation. However, as with all AEDs, vigabatrin should be withdrawn gradually to minimize increased seizure frequency [see WARNINGS AND PRECAUTIONS].

Read the Sabril Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 11/18/2013
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
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