Zonisamide

ZONEGRAN

Open Zonisamide in the interactive console ↗

Pronunciation: zoe-NIS-a-mide (ZOE-ne-gran)

Zonisamide ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Zonisamide ballicule

Zonisamide ZONEGRAN mascot mnemonic cartoon — Visual mnemonic: Zonisamide mascot
**“Zone is mighty, Zone is grand”**
seismic hazard ZONes → anti-seizure med
angry face → may cause irritability

What it isSodium- and T-type calcium-channel blocker with weak carbonic anhydrase inhibition; focal seizures, broad-spectrum off-label.

Why this oneOnce-daily use and frequent weight loss distinguish it from many antiseizure drugs.

What limits itKidney stones and metabolic acidosis require attention; cognitive slowing, reduced sweating, and sulfonamide reactions can occur.

Pearls

Oligohidrosis can cause heat stroke in children
Titrate slowly and dose with meals to improve tolerance
Depression and psychosis reported; watch mood
Off-label for migraine prevention

Zonisamide molecular structure (skeletal formula) — Molecular structure: Zonisamide

Zonisamide prescription history

Animated chart of estimated U.S. prescriptions per year, Antiseizure meds (1869–2026). Zonisamide enters in 2000 (estimated).

FDA-approved for

seizures (2000)

Off-label

migraine prophylaxis
binge-eating disorder

Principal riskKidney stones; sulfonamide cross-reactivity

Sulfonamide

Sulfonamide-derived drug (non-antibacterial) — label warns

An aliphatic (methane)sulfonamide on a benzisoxazole — no N4 aromatic amine, no N1 heterocycle on the sulfonamide nitrogen; the label contraindicates it in sulfonamide hypersensitivity. Not named by Khan; the evidence for the non-antimicrobials as a group says cross-reactivity is unlikely.

Open the sulfonamide hypersensitivity presentation → · sources [n] are on its References slide.

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability1 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityMetabolic acidosis, kidney stones, serious rash and reduced sweating/heat injury.

FDA label

Read the full label on DailyMed ↗

NO BOXED WARNINGS

FDA dosing	Population	Start	Target	Max
Partial seizures (adjunctive)	Adults ≥16 yr	100 mg QD	100-400 mg/day (QD or BID)	600 mg/day

Titration Increase no sooner than every 2 weeks (long half-life; up to 2 weeks to reach steady state)

Renal Use caution; may require slower titration and more frequent monitoring in renal disease

Hepatic Use caution; may require slower titration and more frequent monitoring in hepatic disease

Long half-life — allow ≥2 weeks at each dose level to reach steady state

Instructions

Swallow capsules whole; take once or twice daily with or without food

Available strengths

cap 25, 50, 100 mg
susp 100 mg/5 mL

Contraindications

Hypersensitivity to sulfonamides

Cautions

DRESS and serious skin reactions
Metabolic acidosis (monitor, including in pregnancy)
Acute myopia and secondary angle-closure glaucoma
Hyperammonemia and encephalopathy
Acute pancreatitis and rhabdomyolysis (postmarketing)
CNS effects: somnolence, cognitive/memory difficulty, ataxia
Suicidal behavior/ideation (antiepileptic class effect)

Adverse reactions

Somnolence
Anorexia
Dizziness
Ataxia
Agitation/irritability
Difficulty with memory/concentration
Nausea
Headache

Pregnancy May cause fetal harm — teratogenic in animals (cardiovascular malformations, embryolethality); can cause metabolic acidosis; monitor mother and neonate.

Lactation Undefined