Topiramate

Usage

  • Topiramate has a broad range of seizure efficacy and on the Australian PBS can be considered in treatment for partial epileptic seizures, primary generalised tonic-clonic seizures and seizure of Lennox Gastaut Syndrome not controlled satisfactorily by other antiepileptic drugs. Irritability, anorexia, sedation should be considered before prescribing. It has been used in neonates and infants.

Resources

 

Side effects

Notable side effects

  • Irritability, anorexia, sedation should be considered before prescribing.
  • Marked loss of appetite/loss of weight may require cessation of drug.
  • Metabolic acidosis (topiramate is a carbonic anhydrase inhibitor) is a common finding in young infants. Blood bicarbonate levels around 16-18mmol/L are to be expected and usually cause no significant problems. Lower levels may require treatment.
  • Nephrocalcinosis can occur and patients on long term treatment or who have other risk factors can be monitored with urine studies and renal ultrasound.
  • Reduced sweating may cause heat intolerance which is manageable with simple measures. Care must be taken in warm climates. In the very young heat intolerance can be a more serious side effect and overheating must be avoided.
  • Word finding difficulty and language impairment may be pronounced and are more of a risk with higher doses.
  • Sedation can occur but is more common with higher doses.
  • Mood disturbance (irritability, crankiness, depression) can occur.
  • Glaucoma is a contraindication. Advise urgent review if painful eyes develop.
  • Rarely, visual field defect is described.
  • Paraesthesia’s and hand tingling can occur but are uncommon.
  • All anticonvulsants are potentially teratogenic and this is often dose related (see section: AED Prescribing - Pregnancy)

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

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

  • Typical dosage is approximately 5mg/kg/day in two divided doses.  Some patients may respond to 2mg/kg/day.  Dose can be increased to 8-9mg/kg/day in refractory cases (a patient is probably failing the drug if there is no significant effect on seizures above 7mg/kg/day). Advice from a Paediatric Neurologist may be helpful.
  • Starting dose 0.5-1mg/kg/day in two divided doses increasing either weekly or fortnightly by 0.5mg/kg/day to target.  In certain acute situations such as an epileptic encephalopathy or status, initiating dose can be higher (e.g. 2mg/kg/day) and rate of escalation faster. Consultation with Paediatric Neurology may be helpful.
  • Dosages per kilogram can only be used in children of weight approximately up to 30-40kgs. Consult appropriate formularies for higher weights and in the adult range.

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

  • Tablets 25mg, 50mg, 100mg, 200mg  
  • Topamax Sprinkle Capsule 15mg, 25mg, 50mg 
  • Tablets or capsule contents can be dissolved to make a liquid form.
  • It can be given rectally if a patient is fasting.

Monitoring

  • Drug level monitoring is not routinely utilized or readily available.
  • Blood bicarbonate should be checked within a month as a guide and then at intervals with escalation. This is particularly important in the infant.
  • Renal ultrasound and urine testing are considered as necessary, particularly if back pain or haematuria

Interactions | Precautions

  • Topiramate may decrease serum concentrations of oestrogens.
  • Topiramate may increase toxicity of sodium valproate.
  • Topiramate concentration may be decreased by carbamazepine.