Zonisamide

Usage

  • The usual indication for Zonisamide is focal seizures and secondarily generalised seizures that have not been satisfactorily controlled by other anti-epileptic drugs.
  • There is evidence that Zonisamide is an effective broad spectrum antiepileptic drug and has been used in myoclonic seizures, generalised seizures, and syndromes such as Lennox-Gastaut and Myoclonic-astatic epilepsy.

Resources

Side effects

Possible side effects:

  • Dizziness
  • Drowsiness/fatigue
  • Psychomotor slowing
  • Behavioural changes (aggression/agitation/irritability or psychiatric adverse effects)
  • Insomnia
  • Double vision
  • Weight/appetite loss
  • GI disturbance
  • Ataxia

Other notable side effects:

  • Hypersensitivity reaction (fever, rash, lymphadenopathy, haematuria, deranged liver function tests)
  • Reduced sweating and heat tolerance
  • Metabolic acidosis
  • Increased incidence of kidney stones (1-2%)
  • Paraesthesia
  • Rarely: blood dyscrasia, oligohidrosis, hyperthermia
  • 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 below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

  • Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

Commonly used regime

  • Initial dose: 1mg/kg once daily for 2 weeks, then increase as needed and tolerated in steps of 1-2mg/kg/day as tolerated every 2 weeks.
  • A reasonable maintenance dose is 6-8mg/kg/day.
  • Dosages per kilogram can only be used up to weights of 30-40kgs.  
  • Zonisamide can be taken with food.
  • Capsules can be opened and sprinkled onto food or mixed with juice.
  • In view of its long half-life, Zonisamide can be administered once or twice daily.

Preparations

  • Capsules: 25mg, 50mg, 100mg

Interactions | Precautions

Precautions

  • With increased incidence of renal stones, patients are encouraged to drink liberally.
  • If possible, Zonisamide should not be used with Acetazolamide, Topiramate, the Ketogenic Diet, or treatments that may also lead to metabolic acidosis or increased incidence of kidney stones.
  • Hepatic impairment: No data. Advised not to use in severe hepatic impairment and use with caution in mild-moderate impairment.
  • Renal impairment: Limited data. Slower dose titration may be required.
  • Enzyme inducing drugs can increase the clearance of Zonisamide and decrease plasma levels.

Weaning

When ceasing Zonisamide it is important to withdraw slowly (over a minimum of several weeks, recommended rate of reduction of 1mg/kg/week) to minimize the potential of increased seizure frequency.
 

Pregnancy

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