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Antiepileptic — Multiple Mechanisms Pregnancy: Avoid — teratogenic in animals; use effective contraception

Zonisamide

Brand names: Zonegran

Adult dose

Dose: 100 mg once daily initially; increase by 100 mg every 2 weeks; maintenance 300–500 mg/day
Route: Oral
Frequency: Once or twice daily
Max: 500 mg/day
Broad-spectrum AED — blocks Na+ and T-type Ca2+ channels, inhibits carbonic anhydrase. Adjunctive treatment for focal seizures. Also studied in Parkinson's disease (off-label). Long half-life (63 hours) allows once-daily dosing.

Paediatric dose

Dose: 1 mg/day/kg
Route: Oral
Frequency: Once daily
Max: 12 mg/kg/day (max 500 mg/day)
Children ≥6 years: 1 mg/kg/day increasing to 6–8 mg/kg/day.

Dose adjustments

Renal

Caution — avoid if eGFR <50 mL/min (insufficient data). Withdraw gradually.

Hepatic

Caution in hepatic impairment — slower titration required.

Paediatric weight-based calculator

Children ≥6 years: 1 mg/kg/day increasing to 6–8 mg/kg/day.

Clinical pearls

  • Renal stones: adequate hydration (>2L/day) is mandatory — carbonic anhydrase inhibition raises urinary pH, promoting stone formation
  • Oligohydrosis and hyperthermia: particularly in children — counsel caregivers to monitor for reduced sweating and fever. Withdraw drug and seek medical attention.
  • Weight loss effect sometimes exploited therapeutically in overweight patients with epilepsy

Contraindications

  • Sulfonamide hypersensitivity (zonisamide is a sulfonamide derivative)
  • Severe hepatic impairment

Side effects

  • Anorexia and weight loss
  • Renal stones (carbonic anhydrase inhibition — hydration essential)
  • Cognitive impairment
  • Metabolic acidosis
  • Oligohydrosis and hyperthermia (especially in children)
  • Depression and suicidal ideation

Interactions

  • CYP3A4 inducers — carbamazepine/phenytoin (reduce zonisamide levels)
  • CYP3A4 inhibitors — fluconazole (increase levels)
  • Carbonic anhydrase inhibitors — topiramate (additive stone risk and metabolic acidosis)

Monitoring

  • Serum bicarbonate (metabolic acidosis)
  • Renal function and urine for haematuria (stones)
  • Weight
  • Cognitive function assessment

Reference: BNFc; BNF 90; NICE NG217; BNFc; EMA Zonegran SPC. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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