Zonisamide

Actions

• Blocks voltage-dependent Na+ channels and T-type Ca++ channels.
• Mildly inhibits carbonic anhydrase.

Metabolism

Hepatic

Enzymes involved

• CYP3A4

Elimination

Renal

Therapeutic serum concentration range

10-40 μg/ml

Half-life

50-80 hours

Plasma protein binding

40-60%

Important side-effects

Serious dermatologic reactions including Stevens-Johnson and TEN.

Aplastic anemia.

Oligohidrosis and hyperthermia in pediatric patients.

Teratogenicity.

Cognitive/Neuropsychiatric adverse events.

Indications

Focal seizures with or without generalization.

Dosing recommendation

Start with 50 mg/day.

Increase to 100 mg/day after 1 week. Further increases by 50 mg/day every 1–2 weeks or by 100 mg/day after 2 weeks.

Target dose: 200–600 mg/day divided in 2 doses.

Renal impairment

Initial and target dose reduction and more frequent serum concentration monitoring might be required in patients with impaired renal function.

Hepatic impairment

Initial and target dose reduction and more frequent serum concentration monitoring might be required in patients with impaired hepatic function.