Zonisamide | Epilepsy clinician handbook

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

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
  • Gastrointestinal 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

All anti-seizure medications are potentially teratogenic and this is often dose related. For a complete list of adverse effects, appropriate formularies should be consulted.

Interactions and 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.
  • Lower maintenance doses may be needed in some children, especially those not taking enzyme inducing drugs.

Weaning

  • If there is an indication of hypersensitivity or a skin reaction, zonisamide should be ceased immediately.
  • For other indications, when ceasing Zonisamide it is important to withdraw slowly to minimize the potential of increased seizure frequency. 

Pregnancy

  • All anti-seizure medications are potentially teratogenic and this is often dose related.
  • Usage in pregnancy needs to be discussed with a neurologist.
  • There is limited data of the safety of Zonisamide in pregnancy.

Resources

Dosing