Vigabatrin

Registered South African indications:

• Resistant partial epilepsy with or without secondary generalisation 
  - In combination with other anti-epileptic medicines where all other appropriate medicine combinations have proved inadequate or have not been tolerated

• Visual field defects (VFDs) have been observed in patients receiving vigabatrin, with about one third of patients being affected
• Males may be at a higher risk of these defects than females
• Most patients with confirmed VFDs through perimetry were asymptomatic
• Available evidence indicates that VFDs are irreversible, even after discontinuation of vigabatrin
• The possibility of VFD deterioration after treatment discontinuation cannot be ruled out
• All patients should have an ophthalmological consultation, including a visual field examination, before the initiation of vigabatrin treatment and at six-month intervals thereafter
• It is recommended for prescribers to ensure that the patient consent form has been signed before issuing a prescription for vigabatrin

Contraindications

South African registered contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Renal impairment with CrCl<60ml/min

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment (CrCl≥60ml/min) (South African recommendations)
• Renal impairment (Recommendations in other jurisdictions)
• Elderly
• Children
• Monotherapy
• Pre-existing clinically significant visual field defect
• Abrupt withdrawal
• History of psychosis, depression or behavioural problems

Forms avail. in SA and covered in this monograph: fct

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Vigabatrin treatment should only be initiated by a specialist in neurology, who treats patients with epilepsy for which vigabatrin is indicated

Resistant partial epilepsy with or without secondary generalisation (Additional agent(s) required)
- In combination with other anti-epileptic medicines where all other appropriate medicine combinations have proved inadequate or have not been tolerated

• Oral (fct): Initial: 1g daily, in 1 or 2 divided doses added to the patient's current anti-epileptic medicine regimen; Max: 3g/24hrs

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Follow-up should be arranged under supervision of a specialist in neurology

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The maximum recommended dose should not be exceeded

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Doses may be taken before or after meals

Paed. forms avail. in SA and covered in this monograph: fct

Paed. dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Vigabatrin treatment should only be initiated by a specialist in neurology, paediatric neurology or paediatricians who treat patients with epilepsy for which vigabatrin is indicated

Resistant partial epilepsy with or without secondary generalisation (Additional agent(s) required)
- In combination with other anti-epileptic medicines where all other appropriate medicine combinations have proved inadequate or have not been tolerated

• Oral (fct): Initial: 40mg/kg/day; Maintenance: See table below; Max: 3g/24hrs

Body Mass (kg)	Maintenance dose
10-15	0.5-1g/day
15-30	1-1.5g/day
30-50	1.5-3g/day
>50	2-3g/day

Follow-up should be arranged under supervision of a specialist in one of the above-mentioned fields

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Clinical experience suggests a relatively higher vigabatrin dose in children

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The maximum recommended dose should not be exceeded

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Doses may be taken before or after meals

Pregnancy

South African recommendations

• Contraindicated
• Vigabatrin is contraindicated in pregnant women as teratogenicity has been seen in animals
• The risk of congenital defects is increased from 2 to 3-fold in children born from mothers treated with an anti-epileptic; those more frequently reported are cleft lip, cardiovascular defects, and neural tube defects
• Polytherapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is important that monotherapy is practised whenever possible
• Abnormal outcomes (congenital anomalies or spontaneous abortion) were reported in the offspring of mothers taking vigabatrin
• Specialist advice should be provided to all patients who could begin a pregnancy or who are in the fertile age. The need for antiepileptic treatment must be re-evaluated when a patient plans a pregnancy
• If a patient is already pregnant, anti-epileptic therapy should not be suddenly interrupted due to the hazard of epileptic attack relapse that might have serious outcomes both for the mother and the child

Recommendations in other jurisdictions

• Caution; not recommended
• Risk related to epilepsy and antiepileptic medicinal products in general
  • In the offspring of women treated with antiepileptic medication, the prevalence of malformations is two to three times greater than in the general population. Most frequently reported are cleft lip, cardiovascular malformations, and neural tube defects
  • Polytherapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is important that monotherapy is practised whenever possible
  • Specialist advice should be provided to all patients who could begin a pregnancy or who are in the fertile age. The need for antiepileptic treatment must be re-evaluated when a patient plans a pregnancy
  • If a patient becomes pregnant, effective antiepileptic therapy should not be suddenly interrupted, since the aggravation of the illness may be detrimental to both the mother and the foetus
• Risk related to vigabatrin
  • Based on data on pregnancies exposed to vigabatrin, available from spontaneous reports, abnormal outcomes (congenital anomalies or spontaneous abortion) were reported in the offspring of mothers taking vigabatrin. No definite conclusion can be drawn as to whether vigabatrin produces an increased risk of malformation when taken during pregnancy because of limited data and the presence of concomitant antiepileptics
  • Studies in animals have shown reproductive toxicity
  • Vigabatrin should not be used during pregnancy unless the clinical condition of the woman requires treatment with vigabatrin
  • There is a limited amount of information on the possible occurrence of visual field defect in children who have been exposed to vigabatrin in utero

Breastfeeding

South African recommendations

• Contraindicated
• Vigabatrin is contraindicated in lactating women as teratogenicity has been seen in animals
• Vigabatrin is excreted into breast milk in low concentrations and is contraindicated in women breastfeeding their infants

Recommendations in other jurisdictions

• Caution; not recommended
• Vigabatrin is excreted into human milk. There is insufficient information on the effects of vigabatrin in newborns/infants
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from vigabatrin therapy taking into account the benefit to breastfeeding for the child and the benefit therapy for the woman

Renal Impairment

South African recommendations

• CrCl≥60ml/min: Caution; no dose adjustment recommended
• CrCl<60ml/min: Contraindicated

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Since vigabatrin is eliminated via the kidney, caution should be exercised when administering the drug particularly in patients with creatinine CrCl<60ml/min
  Adjustment of dose or frequency of administration should be considered. Such patients may respond to a lower maintenance dose
  Patients should be monitored for undesirable effects such as sedation or confusion

Hepatic Impairment

South African recommendations & Recommendations in other jurisdictions

• Caution; no information available

Elderly

South African recommendations & Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Since vigabatrin is eliminated via the kidney, caution should be exercised in older people
  These patients should be monitored closely for undesirable effects such as sedation and confusion

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Agitation
• Aggression
• Nervousness
• Depression
• Paranoid reaction
• Hypomania
• Mania
• Psychotic disorders
• Suicide attempts
• Hallucinations
• Somnolence
• Speech disorder
• Headache
• Dizziness
• Paraesthesia
• Disturbance in attention
• Impaired memory 
• Disturbed thoughts 
• Tremor
• Abnormal coordination
• Encephalopathy
• Optic neuritis
• Brain magnetic resonance imaging abnormalities 
• Dystonia
• Dyskinesia
• Hypertonia
• Fatigue
• Irritability

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain

Hepatobiliary Disorders

• Hepatitis

Endocrine and Metabolic Disorders

• Increased weight

Musculoskeletal Disorders

• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Rash
• Angioedema
• Urticaria
• Oedema

Immune, Blood and Lymphatic System Disorders

• Anaemia

Sensory Disorders

• Visual field defect
• Blurred vision 
• Diplopia
• Nystagmus
• Retinal disorder
• Optic atrophy

Phenytoin

• Ophthalmic examination
• Full blood count
• Weight
• Mental status

Vigabatrin is a selective irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase, the enzyme responsible for the breakdown of GABA. Thus, treatment with vigabatrin leads to an increase in the concentration of GABA, the major inhibitory neurotransmitter in the brain.

Film-coated tablet 500mg

• Sabril (Sanofi) Originator