Capsule (Zonegran)
- Strengths
- 25, 100 mg
- Product note
- Brand-specific strengths in the linked label. Adjunctive treatment of partial seizures in adults; swallow whole.
Zonisamide
Zonegran · Zonisade
DailyMed-verified antiseizure indications
Indication / use
- Label / evidence summary
- Zonegran capsules: adjunctive treatment of partial (focal) seizures in adults. Zonisade oral suspension: adjunctive treatment of partial-onset seizures from age 16 years.
- Role
- Maintenance
- Class
- Proposed sodium- and T-type calcium-channel effects; carbonic anhydrase inhibition
Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.
- Representative source · Zonegran capsules — DailyMed label (PDF) ↗
- Zonisade suspension — DailyMed label (PDF) ↗
- Zonegran capsules U.S. label
Focal seizures · Adults · MaintenanceAdjunctive treatment of partial (focal) seizures in adults. The Zonegran indication specifies adults; Zonisade has a separate indication from age 16 years.
- Zonisade suspension U.S. label
Focal seizures · 16 years and older · MaintenanceAdjunctive only.
Formulations & strengths
U.S. products unless another country is named. Strengths are per unit or stated volume.
Generic zonisamide capsule
- Strengths
- 25, 50, 100 mg
- Product note
- Swallow whole.
Oral suspension (Zonisade)
- Strengths
- 100 mg/5 mL (20 mg/mL)
- Product note
- Shake well; U.S. adjunctive focal-seizure label ages ≥16 years.
Brand & formulation labels
Each link names the product and formulation it covers. Archived labels do not establish current availability.
Dosing & administration
- Adult / product-specific schedule
- Zonisade: start 100 mg/day; increase by 100 mg/day every 2 weeks to 400 mg/day. If tolerated and further control needed, maximum 600 mg/day.
- Pediatric
- Zonisade: labeled from age 16, same schedule. Below 16: safety/effectiveness not established in this label.
- Titration / repeat dosing
- 100 mg/day increments every 2 weeks according to response/tolerability; Zonisade ceiling 600 mg/day.
Dose adjustment & concentrations
- Renal impairment
- Avoid when estimated GFR <50 mL/min because dosing/toxicity experience is insufficient.
- Hepatic impairment
- Use caution and slower titration because pharmacokinetics have not been studied adequately.
- Serum reference information
- 10–40 mcg/mL
Safety
- Boxed warning
- No boxed warning.
- Contraindications
- Hypersensitivity to sulfonamides or zonisamide.
- Serious precautions & monitoring
- Baseline/periodic bicarbonate; monitor renal function, stones, oligohidrosis/hyperthermia, cognition and serious sulfonamide reactions.
Common / selected adverse effects
- Somnolence
- Anorexia
- Dizziness
- Ataxia
- Agitation/irritability
- Difficulty with memory
Drug interactions: toxicity & clinical action
| Partner / combination | Clinical effect | Clinical action |
|---|---|---|
| Topiramate, sulthiame or acetazolamide | Additive metabolic acidosis and kidney-stone risk. | Monitor bicarbonate, hydration and renal symptoms; avoid unnecessary combined CA inhibition. |
| CYP3A4-inducing ASMs | Lower zonisamide exposure; stopping an inducer may raise exposure. | Monitor seizure control and adverse effects after co-medication changes. |
| Valproate / topiramate / other CNS depressants | Hyperammonemia/encephalopathy risk may increase with ammonia-raising drugs; sedatives add impairment. | Check ammonia with unexplained altered mental status; review cumulative CNS effects. |
Pregnancy & contraception
- Fetal / neonatal risk
- Zonisamide may cause fetal harm. Human data are limited and conflicting for malformations; small-for-gestational-age birth has been reported. Maternal metabolic acidosis is an additional concern.
- Contraception
- Use effective contraception during zonisamide treatment and for one month after stopping, per the Zonisade label. Zonisamide did not alter the studied ethinylestradiol/norethisterone contraceptive concentrations.
- Pregnancy / postpartum monitoring
- Monitor maternal bicarbonate for metabolic acidosis and observe exposed newborns for acidosis.
Clinical evidence
Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.
Direct pivotal trial Guideline-supported off-label use
Trial summary
- Study design / duration
- Three multicenter, randomized, double-blind, placebo-controlled adjunctive focal-seizure trials used baseline observation and fixed-dose maintenance; seizure-frequency reduction and responder rate were assessed.
- Primary endpoint
- No single pivotal endpoint is identified in the cited source.
- Results
- Pivotal adjunctive focal-seizure trials showed median reductions of approximately 27–41% at studied doses versus roughly 8–10% with placebo; ≥50% responder rates were approximately 30–42% versus 10–22%.
Trial publications
- PubMed · Focal seizures (2001) ↗
- PubMed · Focal seizures · dose response (2005) ↗
- PubMed · Focal seizures · European trial (1993) ↗
Comparative evidence
- Findings
- SANAD II: open-label randomized initial treatment of newly diagnosed focal epilepsy, age ≥5. For time to 12-month remission, levetiracetam did not meet noninferiority versus lamotrigine; zonisamide did in the intention-to-treat analysis.
Mechanism of action
- In-vitro studies suggest sodium-channel blockade and reduction of T-type calcium currents. The precise antiseizure mechanism in humans remains unknown.
- Carbonic anhydrase inhibition is established pharmacology, but its contribution to efficacy is unknown; it helps explain metabolic acidosis and stone risk.
- The label does not support describing zonisamide as a direct enhancer of synaptic GABA activity.
Pharmacology
Adult values unless specified. Vd/F denotes apparent oral distribution volume.
Pharmacokinetics
- Bioavailability
- Well absorbed orally; food delays the peak but does not change overall exposure. A numeric absolute bioavailability is not specified in the cited U.S. label.
- Elimination half-life
- Plasma approximately 63 hours; red blood cells approximately 105 hours. Plasma half-life is shorter (approximately 27–38 hours) with enzyme-inducing ASMs.
- Volume of distribution
- Apparent oral V/F approximately 1.45 L/kg after a 400 mg dose.
- Active metabolite(s)
- No clinically established active metabolite contribution; N-acetyl-zonisamide and SMAP-related products are described.
- Active-metabolite half-life
- Not applicable — no clinically established active metabolite.
- Protein binding
- ~40%
- Metabolism / elimination
- CYP3A4 reduction plus acetylation; renal excretion
Strong red-cell binding produces different plasma and erythrocyte half-lives.
Molecular structure
NIH PubChem structure and record ↗
Product history
- Initial U.S. approval
- 2000
- Market / formulation history
- 2000 in the U.S.
- Brands
- Zonegran · Zonisade
- Manufacturer / marketer
- Azurity (Zonisade); Zonegran brand ownership varies by market
- Generic availability
- Yes (capsules)
- Related drugs
- Sulfonamide ASM; shares weak carbonic-anhydrase inhibition with topiramate.
Sources & review status
Representative sources are selected product labels, not an exhaustive list of generic manufacturers. Consult the exact product and formulation prescribed. Brand-name package inserts are linked separately.
Brand reference: Zonegran capsules ↗
Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 5/2025. This is a draft reference; final review is pending.