zonisamide
Brand: Zonegran
Prototype: topiramate
Drug Class: antiepileptic drug
Drug Family: antiepileptic
Subclass: sulfonamide-derived AED with multiple mechanisms
Organ Systems: cns
Mechanism of Action
Blocks voltage-gated Na+ and T-type Ca2+ channels, reducing repetitive neuronal firing and absence-type activity. Also inhibits carbonic anhydrase (similar to topiramate). Has unique free radical scavenging activity. Sulfonamide derivative — potential cross-reactivity with sulfonamide allergy.
voltage-gated Na+ channelsT-type Ca2+ channelscarbonic anhydrase
Indications
- adjunctive therapy for partial (focal) seizures in adults
Contraindications
- sulfonamide hypersensitivity
Adverse Effects
Common
- somnolence
- anorexia/weight loss
- dizziness
- cognitive impairment
- ataxia
Serious
- kidney stones (sulfonamide-derived carbonic anhydrase inhibitor)
- oligohidrosis with hyperthermia (rare but potentially fatal)
- metabolic acidosis
- SJS (rare)
- agranulocytosis (rare)
Pharmacokinetics (ADME)
| Absorption | oral; bioavailability ~100% |
| Distribution | 40% protein bound |
| Metabolism | hepatic CYP3A4 |
| Excretion | renal (62% as parent, 35% as SMAP metabolite) |
| Half-life | 63 hours |
| Onset | days to weeks |
| Peak | 2–5 hours |
| Duration | once-daily dosing |
| Protein Binding | 40% |
| Vd | 1.45 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| enzyme inducers (carbamazepine, phenytoin) | reduce zonisamide half-life from 63 to 27 hours; dose adjustments needed | major |
Nursing Considerations
- Hydrate patients well; at least 2 L fluid daily to minimize kidney stone risk (similar concern to topiramate).
- Monitor for oligohidrosis (decreased sweating) and fever in children; educate families to assess sweating in heat.
- Cross-reactivity with sulfonamide allergy requires careful assessment before prescribing.
- Long half-life (63 hours) allows once-daily dosing in most patients; dose adjustments infrequent once therapeutic levels achieved.
Clinical Pearls
- Zonisamide's 63-hour half-life is the longest among common AEDs, allowing true once-daily dosing and providing buffer against occasional missed doses.
- Like topiramate, zonisamide causes significant weight loss (5–7 kg) due to anorexia; this is a notable differentiating feature from weight-gaining AEDs (valproate, carbamazepine, pregabalin).
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.