Vigabatrin

Usage

  • Vigabatrin is a potential treatment for epileptic spasms.
  • It is a first line therapy for the treatment of epileptic spasms due to Tuberous Sclerosis.
  • It is also a potential treatment for focal seizures or secondarily generalised seizures that have not responded to other medication including in patients with Tuberous Sclerosis.

Resources

Side effects

Common side effects

  • Somnolence/sedation (rarely Vigabatrin may cause encephalopathic symptoms)
  • Weight gain
  • Dizziness
  • Double vision
  • Fatigue
  • Headaches
  • Nausea and abdominal pain
  • Behavioural disturbance (excitation/agitation/irritability)
  • Cognitive change (thought disturbance/psychosis)

Other notable side effects

  • Peripheral visual field loss: Vigabatrin is associated with a significant incidence of visual field constriction on testing, though the clinical significance in all patients is often not stated in the literature1. Some patients are, however, at risk of significant visual compromise that is irreversible2. Licensing of Vigabatrin in the USA was delayed until 2009 and mandatory baseline testing and serial data entry was conducted through to 2016. Across all 9423 patients enrolled for serial testing, the risk of clinical vision impact appears low (no patient had documented visual loss). 37% had clinically significant pathology affecting their visual system before vigabatrin was commenced. Test results of 1509 patients (OCT, ERG, VF) was available. The risk of change on tests was low - 2%3.

    However, regular monitoring is strongly recommended (see MIMS: Precautions in usage and USA FDA advice). It is critical to do baseline testing, collaborate with an ophthalmologist and discuss monitoring in the very young with a paediatric neurologist, where perimetry is not possible and ERG utilized. Decisions are based on risk-benefit ratio noting the significant impact of drug resistant epilepsy and epileptic encephalopathy. Further data is required, particularly in patients with infantile spasms, determining pre vigabatrin retinal function, optimal monitoring and longitudinal follow-up on visual function. 

  • MRI abnormality: Vigabatrin may cause prominent signal abnormality in basal ganglia and upper brain stem, especially in infants. These abnormalities are usually reversible and may even remit with continued drug usage.They are known as VABAM (vigabatrin associated brain abnormalities on magnetic resonance imaging). In the majority of circumstances, the patient is asymptomatic. In 2020, attention was drawn to movement disorder, encephalopathy and dysautonomia in 3 patients where combined hormonal and vigabatrin treatment was used, with Down Syndrome patients at particular risk4. Again further data is required particularly to determine causation.
  • Rarely: Optic neuritis, rash, urticaria and angioedema.

For a complete list of adverse effects, appropriate formularies should be consulted.

  • 1. Epilepsia: 48 (7) 2007; 1318-27
  • 2. The Neurologist: 16 (2) 2010; 69-75
  • 3. Neuro-Opthalmol: 2018; 38;442-450
  • 4. Epilepsia: 61, 2020: e159-164

Dosing

The initiation and escalation dose depends upon age, weight, syndrome, seizure frequency and intensity, and side effect profile.
Unfortunately, a one dose regime does not fit all. A Paediatric Neurologist should be consulted if there is uncertainty.

Commonly used regime

  • Initial dose (Infantile spasms): 25mg/kg bd. The dose may be increased by 25-50mg/kg/day at intervals (for example, every 2-3 days depending upon response). In the UKISS study, dosage was increased up to 150mg/kg/day.
  • Initial dose (Adjunctive treatment for focal seizures): 10-20mg/kg/day given in two divided doses, then increase over 2-3 weeks to maintenance dose.
  • Gradual escalation to maintenance dose depends on efficacy and tolerance. Aim is to achieve the lowest possible efficacious dose, particularly to avoid side-effect of peripheral field restriction. Discussion with a neurologist is suggested in usage for focal seizures, particularly above dosages of 30-40mg/kg/day in children less than 40kg. Regular visual field surveillance is mandatory.
  • If the patient does not respond to Vigabatrin after a period of, for example, 3 months, withdrawal is suggested to avoid visual field abnormality.
  • Vigabatrin can be taken with or without food
  • Dosages per kilogram can only be used in children of weight approximately up to 30-40kgs.
  • Consult appropriate formularies for children with higher weights and in the adult range.
  • These dosages are only a guide and appropriate formularies should be consulted as needed and tailored to the patient by the primary physician.

These dosages are only a guideline and appropriate formularies should be consulted as needed.

Weaning

  • When ceasing Vigabatrin it is recommended to reduce gradually (over a minimum of 2-4 weeks) to minimise the risk of increased seizure frequency or status epilepticus.

Preparations

  • 500mg tablets
  • 500mg sachets – dissolve in 10mL water.

Interactions | Precautions

Precautions

  • Use with caution in patients with a history of behavioural problems, depression or psychosis.
  • Vigabatrin may worsen absence and myoclonic seizures.
  • Renal impairment: As Vigabatrin is renally excreted, consult formularies and neurology.

Pregnancy

  • Usage in pregnancy needs to be discussed with a neurologist.
  • There is limited data on the safety of Vigabatrin in pregnancy.
  • All anticonvulsants are potentially teratogenic and this is often dose related (see section: AED Prescribing - Pregnancy)