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Vigabatrin

Vigabatrin is now a second line treatment for patients with partial seizures. It is, however, still a first-line treatment for infantile spasms,1 particularly those associated with tuberous sclerosis. It has no use in primary generalised epilepsy and may worsen myoclonic seizures. Tolerance may develop in up to one-third of initial responders.

Indications
  • Adjunctive treatment in combination with other antiepileptic treatment for partial seizures with or without secondary generalisation not satisfactorily controlled with other antiepileptics. Its use is restricted to patients in whom all other combinations are inadequate or are not tolerated.
  • Monotherapy for management of infantile spasms (West's syndrome).2
Contraindications
Cautions
  • Elderly
  • Closely monitor neurological function
  • Avoid sudden withdrawal (taper off over a 2-4 week period)
  • History of psychosis, depression or behavioural problems
  • Absence seizures (may be exacerbated)
  • Pregnancy (congenital anomalies have been reported)
  • Breast-feeding (present in breast milk and so advice is to avoid)
Important interactions
  • The addition of vigabatrin reduces plasma concentrations of phenytoin. Usually this has no clinical significance, but occasionally an increase in phenytoin dose is necessary.
  • Vigabatrin has no other known interactions
Common problems
  • Sedation, dizziness and headache particularly occur when doses are being increased. The symptoms are usually temporary and self-limiting. These symptoms can usually be prevented by introducing the drug gradually.
  • Up to 10% of patients develop a change in mood, such as agitation, disturbed behaviour or depression. Paranoid and psychotic symptoms occur but only rarely. Treatment is associated with a small increased risk of suicidal thoughts and behaviour. Patients and caregivers should be alert to signs of suicidal thoughts or behaviour throughout treatment.
  • Visual field defects develop in about one-third of patients develop.
    • The CSM has advised that onset of symptoms varies from 1 month to several years after starting
    • In most cases, visual field defects have persisted despite discontinuation
    • Visual fields should be tested before treatment and at 6-month intervals for 5 years. It can then be
      extended to annually in patients who have no defect detected.1
    • Patients should be warned to report any new visual symptoms that develop; those with symptoms should be referred for an urgent ophthalmological opinion and gradual withdrawal of vigabatrin should be considered.
Initiation
  • Treatment should be started with a low dose (250-500 mg/day), and titrated slowly upwards over a period of several weeks until therapeutic response is achieved.
  • Too rapid titration may be associated with an increased incidence of adverse events
  • With current antiepileptic therapy, initially 1 g daily in single or 2 divided doses then increased according to response in steps of 500 mg at weekly intervals.
  • The usual range is 2-3 g daily (maximum 3 g daily)
  • Infantile spasms (West's syndrome): 50 mg/kg daily, adjusted according to response over 7 days up to 150 mg/kg daily
Monitoring
  • Other than checking for compliance, there is no value in measuring the plasma concentration.
  • Patients and caregivers should be alert to signs of suicidal thoughts or behaviour throughout treatment.


Document references
  1. The Ocular Side-Effects of Vigabatrin (Sabril) - Information and Guidance for Screening, Royal College of Ophthalmologists (March 2008)
  2. Summary of Product Characteristics - Sabril Sachets 0.5g and Tablets 500mg (vigabatrin), Sanofi-aventis, electronic Medicines Compendium (updated July 2008)

Internet and further reading AcknowledgementsEMIS is grateful to Dr Colin Tidy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 442
Document Version: 2
DocRef: bgp25131
Last Updated: 1 Oct 2007
Review Date: 30 Sep 2008






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