Zonisamide
Pronunciation: pronunciation varies by local usage.
- Generic name
- zonisamide
- Brand names
- Epizon, Zonisep, Ospolot, Zonegran
- Drug class
- Antiepileptic (Anticonvulsant)
- Form
- Capsules (25 mg, 50 mg, 100 mg) and orodispersible tablets (25 mg, 50 mg, 100 mg, 300 mg)
- Route
- Oral
- Legal status
- Prescription-only medicine
Supply Rules Vary
Trade names by country: United States · United Kingdom · Australia · New Zealand
Australia: Zonegran · Full directory
What zonisamide is and how it works
Zonisamide is an antiepileptic medicine with a sulfonamide-related chemical structure. It blocks sodium and calcium channels on nerve cells and enhances GABA activity to prevent abnormal electrical discharges that cause seizures. Approved uses include partial seizures (with or without secondary generalisation) as monotherapy or adjunctive therapy in adults, and as adjunctive therapy in children aged 6 years and older. Country-specific indications and age limits apply; the U.S. label restricts use to adjunctive therapy in adults only. (1) (2) (3) (4) (6)
Treatment is started and supervised by a specialist. Dose and titration depend on indication, age, body weight, kidney/liver function, and other antiepileptic medicines. Gradual dose reduction is required when stopping to avoid seizure recurrence. Zonisamide is a long-term preventive treatment, not a rescue medicine for acute seizures.
Mechanism of action: how zonisamide works
Zonisamide is a benzisoxazole derivative with a sulfonamide group. It blocks voltage-sensitive sodium and T-type calcium channels, reduces repetitive neuronal firing, and modulates GABA-mediated inhibition. It also weakly inhibits carbonic anhydrase, which is responsible for metabolic acidosis and increased kidney stone risk. (1) (2) (6)
What zonisamide is used for
Partial seizures – adjunctive therapy
Zonisamide may be added to existing antiepileptic treatment for partial seizures with or without secondary generalisation. In the U.S., it is approved for adjunctive therapy in adults (16 years and older). In the EU, UK, Australia, and New Zealand, it is also approved as add-on therapy in children aged 6 years and above. Dose, titration, and monitoring must follow local prescribing information. (1) (2) (3) (4) (6)
Partial seizures – monotherapy
In the EU, UK, Australia, and New Zealand, zonisamide is also licensed as a sole agent for newly diagnosed partial seizures in adults. The U.S. label does not include a monotherapy indication. Eligibility criteria and starting regimens differ between regions. (2) (3) (4) (6)
Before taking zonisamide
Do not take / not appropriate for
- Do not take zonisamide if you have a known hypersensitivity to zonisamide, sulfonamides (e.g., certain antibiotics, diuretics), or any excipient in the product. Some products contain hydrogenated soya oil; if you have peanut or soya allergy, check with your specialist. (all products) (1) (2) (6)
Tell your clinician about
- Any history of allergic reactions to sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, or other medicines.
- History of kidney stones, kidney disease, or metabolic acidosis.
- Liver problems.
- Mental health conditions, including depression, suicidal thoughts, or psychosis.
- Pregnancy, plans for pregnancy, or breastfeeding.
- If you are taking other antiepileptic medicines, especially valproate or topiramate.
- Any tendency to overheat easily or reduced sweating, particularly important in children.
- Eye problems such as glaucoma or sudden vision changes.
How to take zonisamide
- Zonisamide is taken by mouth once or twice daily, with or without food. Swallow capsules whole with water. Orodispersible tablets can be placed on the tongue and swallowed with saliva; they do not need to be taken with water.
- The starting dose and titration schedule are determined by the prescriber based on indication, age, weight, kidney/liver function, and interaction with other medicines. Increases are typically made every 1–2 weeks to a target maintenance dose; do not alter the dose or stop treatment without specialist advice.
- Abrupt withdrawal may cause a sudden increase in seizure frequency; dose reduction must be gradual, normally over weeks to months, under medical supervision.
- If you have trouble swallowing capsules, talk to your pharmacist about available alternative formulations (e.g., orodispersible tablets).
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (6)
Missed dose
Specific missed-dose guidance is not provided in the reviewed product information. Contact your prescriber for rescheduling advice. Do not take a double dose to make up for a forgotten dose.
Overdose
If too much zonisamide is taken, seek immediate medical attention. Symptoms may include drowsiness, slow heart rate, low blood pressure, and breathing difficulties. There is no specific antidote; treatment is supportive. Activated charcoal may be considered if given soon after ingestion. Hemodialysis may be effective but has not been formally studied in overdose. (1)
Side effects
Zonisamide can cause a range of side effects. The risk and severity vary with dose, age, and other medications. Some effects, such as metabolic acidosis or oligohidrosis, may be more frequent and severe in children.
Somnolence (sleepiness) and dizziness
What to notice: Feeling unusually tired, drowsy, or unsteady; these are among the most common side effects, especially at higher doses or during dose increases.
What to do: Avoid driving or operating machinery until you know how zonisamide affects you. Tell your prescriber if severe or persistent. (1) (2) (6)
Anorexia, decreased appetite, and weight loss
What to notice: Loss of appetite, food tasting different, or unintended weight loss; these are frequent and may be more noticeable in children.
What to do: Discuss with your specialist, especially if weight loss is rapid or concerning. Do not stop treatment without advice. (1) (2) (6)
Agitation, irritability, or mood changes
What to notice: Feeling restless, easily annoyed, or emotional; sometimes confused or depressed.
What to do: Report any significant changes in mood or behaviour to your prescriber promptly. (1) (2) (6)
Memory and concentration difficulty
What to notice: Trouble remembering things, thinking slowly, or finding words; more common at doses above 300 mg/day.
What to do: Inform your doctor if this interferes with daily life; dose adjustment may be considered. (1) (2)
Ataxia (unsteadiness) and coordination problems
What to notice: Clumsiness, difficulty walking, or poor balance.
What to do: Report to your prescriber; may improve with dose adjustment. (1) (2) (6)
Rash
What to notice: Skin redness, itching, or hives; although many rashes are mild, some can be the first sign of a serious reaction.
What to do: Always inform your doctor promptly about any rash. Do not ignore a rash. (1) (2) (6)
Decreased blood bicarbonate (metabolic acidosis)
What to notice: Often symptomless; sometimes rapid breathing, fatigue, loss of appetite, or confusion.
What to do: Your doctor will monitor bicarbonate levels. Do not adjust your dose yourself. Seek advice if you notice new symptoms. (1) (2) (3) (6)
Serious skin reactions (Stevens-Johnson syndrome / toxic epidermal necrolysis)
What to notice: Widespread rash, blistering, peeling skin, sores in the mouth or around the eyes, fever.
What to do: Seek emergency medical care immediately. The clinical team will assess and decide on stopping the medicine. (1) (2) (6)
Decreased sweating and hyperthermia (heatstroke)
What to notice: Inability to sweat in warm conditions, hot dry skin, high body temperature, confusion, fainting. This is especially dangerous in children.
What to do: Cool the person down rapidly and get emergency medical help. This can be life-threatening. (1) (2) (3) (6)
Acute myopia and secondary angle-closure glaucoma
What to notice: Sudden blurry vision, eye pain, headache, nausea or vomiting; usually within the first month of treatment.
What to do: Seek urgent eye examination. Permanent vision loss can occur if untreated. (1) (2)
Suicidal ideation and behaviour
What to notice: New or worsening depression, thoughts of harming yourself, unusual behaviour or extreme mood swings.
What to do: Contact your prescriber or a mental health crisis service immediately. Do not stop zonisamide abruptly without guidance. (1) (2)
Blood disorders (aplastic anaemia, agranulocytosis, thrombocytopenia)
What to notice: Unexplained bruising, bleeding, persistent sore throat, fever, or signs of infection.
What to do: Seek medical attention urgently for blood tests. (1) (2)
DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)
What to notice: Fever, rash, swollen lymph glands, facial swelling, and possible organ involvement (e.g., hepatitis, nephritis).
What to do: Seek medical help immediately; this can be life-threatening. The clinical team will decide whether to stop the medicine. (1)
Hyperammonaemia and encephalopathy
What to notice: Confusion, lethargy, vomiting, especially in patients also taking valproate or topiramate; may be asymptomatic.
What to do: Contact your prescriber for assessment; blood test can confirm. (1) (2)
Kidney stones
What to notice: Severe pain in the side or back, blood in urine, pain when urinating.
What to do: Notify your prescriber; increased fluid intake may help reduce risk. (1) (2)
Serious warnings
Life-threatening skin reactions (Stevens-Johnson syndrome / toxic epidermal necrolysis) — emergency
Symptoms: Rapidly spreading rash, blistering, skin peeling, painful mouth sores, fever, and flu-like symptoms; most cases occur within the first 16 weeks of treatment.
Action: Go to the emergency department immediately. Do not delay. The clinical team will assess and decide whether zonisamide needs to be stopped. (1) (2) (6)
Oligohidrosis and hyperthermia (heatstroke) — emergency
Symptoms: Decreased sweating even in hot weather, hot dry skin, high body temperature (above 39°C), confusion, loss of consciousness. Children are at highest risk; the UK product information warns of potential brain damage or death if untreated.
Action: Get emergency medical help. Move to a cool place, remove excess clothing, and cool the skin with water while waiting. The clinical team will decide on further dosing. (1) (2) (3) (6)
Severe metabolic acidosis — urgent
Symptoms: Rapid breathing, severe tiredness, loss of appetite, vomiting, confusion, or irregular heartbeat; may occur even at low doses. Children and those with kidney disease are at higher risk.
Action: Contact your prescriber or seek urgent medical assessment. Do not increase the dose or self-medicate. (1) (2) (3) (6)
Suicidal thoughts and behaviour — urgent
Symptoms: New or worsening depression, anxiety, panic attacks, thoughts of self-harm, or acting on dangerous impulses; risk may appear within one week of starting.
Action: Contact your specialist, mental health crisis line, or go to the emergency department immediately. Do not change your dose yourself. (1) (2)
Acute myopia and secondary angle-closure glaucoma — urgent
Symptoms: Sudden blurry vision, eye pain, headache, nausea or vomiting; typically within the first month of treatment. Can lead to permanent vision loss if untreated.
Action: Go to an eye emergency department or general hospital immediately. Do not wait for an outpatient appointment. (1) (2)
Abrupt withdrawal resulting in increased seizures — warning
Symptoms: Seizure frequency may increase significantly if zonisamide is stopped suddenly.
Action: Never stop zonisamide abruptly without prescriber guidance. Gradual dose reduction over weeks to months is required. (2) (3)
Interactions
| Medicine or test | Effect | Action |
|---|---|---|
| Other carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide) | Increased risk of metabolic acidosis, kidney stone formation, and hyperammonaemia. The combination is contraindicated in children in some regions. | Inform your prescriber of all medicines you take. Additional monitoring of bicarbonate levels and kidney function is required. (1) (2) (3) |
| CYP3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital) | These medicines can reduce zonisamide blood levels, potentially lowering its effectiveness. Zonisamide dose may need to be higher or increased more rapidly. | Tell your specialist if you are taking or starting any of these medicines; dose adjustments are often needed and differ by region. (1) (2) |
| Valproate (valproic acid) | Combined use may increase the risk of hyperammonaemia and encephalopathy, even without liver dysfunction. | Report symptoms such as confusion, lethargy, or vomiting. Monitoring of blood ammonia may be advised. (1) (2) |
| CNS depressants, including alcohol and sedating medicines | Additive drowsiness and coordination problems may occur; formal study data are lacking but caution is advised. | Avoid or limit alcohol and drugs that cause drowsiness until you know how zonisamide affects you. (1) |
| P-glycoprotein (P-gp) substrates (e.g., digoxin, quinidine) | Zonisamide is a weak P-gp inhibitor in vitro; the clinical significance is unknown, but plasma levels of some substrates could theoretically increase. | Mention all your medicines to your specialist; monitoring may be considered. (1) (2) |
Pregnancy, breastfeeding, kidney/liver function, age
Children (aged 6 years and above)
Safety and efficacy have not been established for children younger than 6 years or for monotherapy in children. In children aged 6 years and above, zonisamide is used only as adjunctive therapy for partial seizures. Dosing is weight‑based. Children are at higher risk of oligohidrosis, hyperthermia, metabolic acidosis, reduced growth rate, and bone effects. Close monitoring is required. The U.S. label does not approve use below 16 years. (1) (2) (3) (6)
Patients with kidney impairment
Zonisamide is contraindicated in patients with an estimated GFR <50 mL/min according to U.S. labeling. Slower titration and more frequent monitoring are required in any degree of renal impairment. Acute renal failure or a clinically significant creatinine rise warrants immediate review and possible discontinuation. The Australian PI notes similar caution; the UK SmPC advises increased monitoring. (1) (2) (4)
Patients with liver impairment
Avoid in severe hepatic impairment. Use with caution in mild to moderate impairment and titrate more slowly. No specific dose adjustment tables exist; specialist judgement is required. (2)
Elderly patients
Limited safety data are available. Elderly patients may have reduced kidney or liver function; start at the lower end of the dosing range. A higher frequency of Stevens‑Johnson syndrome and drug-induced hypersensitivity syndrome has been reported in this age group, necessitating vigilance at treatment initiation. (1) (2)
Pregnancy and breastfeeding
Zonisamide was teratogenic and embryolethal in animal studies at clinically relevant exposures. Women of childbearing potential must use effective contraception during treatment and for at least one month after discontinuation. If you become pregnant while taking zonisamide, contact your specialist immediately. Zonisamide passes into breast milk; breastfeeding is not recommended during treatment and for one month after discontinuation. Enrollment in the North American Antiepileptic Drug Pregnancy Registry is encouraged. (1) (2)
People with sulfonamide or soy/peanut allergy
Zonisamide is a sulfonamide, and cross‑hypersensitivity with sulfonamide antibiotics and diuretics is possible. Fatal hypersensitivity reactions have occurred. Some products contain hydrogenated soya oil; if you have peanut or soya allergy, check the excipient list before use. (1) (2)
Monitoring
Before starting
- Confirm the diagnosis of epilepsy and suitability for zonisamide (partial seizures with or without secondary generalisation).
- Assess age: pediatric use is only from 6 years and only as add‑on; U.S. use is restricted to adults ≥16 years.
- Check renal function (eGFR/creatinine); zonisamide is contraindicated if eGFR <50 mL/min (U.S.).
- Record baseline serum bicarbonate and consider ongoing monitoring, especially in children or those with risk factors for acidosis.
- Review all concurrent medications, particularly other carbonic anhydrase inhibitors, valproate, and CYP3A4 inducers.
- Evaluate for any history of sulfonamide hypersensitivity, psychiatric illness, kidney stones, or glaucoma.
- Perform pregnancy testing in women of childbearing age and confirm adequate contraception.
- Document baseline weight, especially in children.
During treatment
- Watch for any rash, especially in the first 4 months, and report it to the prescriber immediately; the prescriber will decide whether zonisamide needs to be discontinued and whether specialist referral is needed.
- Periodically measure serum bicarbonate; a clinically significant drop may require dose reduction or discontinuation.
- Monitor for signs of decreased sweating or hyperthermia in children, particularly in warm environments.
- Assess for new or worsening depression, suicidal ideation, or psychosis at every visit.
- Promptly evaluate any blurring of vision, eye pain, or headache for acute myopia/glaucoma.
- Monitor renal function periodically and increase fluid intake to reduce kidney stone risk; perform urinalysis or imaging if symptoms suggest stones.
- In children, monitor growth and weight regularly, and check blood ammonia if taking valproate or topiramate.
- Re‑assess the need for continued treatment at regular intervals; withdrawal should be gradual.
Storage
Specific storage instructions are not provided in the reviewed notes; refer to the product packaging or local prescribing information. Generally, store at room temperature away from light and moisture.
Professional information
Clinician-facing summary. Always consult the full local prescribing information for your region, as dosing algorithms, indications, and safety updates may differ.
United States
Indication: Adjunctive therapy for partial seizures in adults (16+ years)
Dose summary: Start 100 mg once daily; increase by 100 mg every 2 weeks. Typical target dose 400 mg/day (range 100–600 mg/day). Slow titration in renal or hepatic impairment. No pediatric indication below 16 years.
Renal context: Contraindicated if eGFR <50 mL/min. Caution and slower titration in all degrees of renal impairment. (1)
United Kingdom / EU
Indication: Monotherapy in newly diagnosed adult partial seizures; adjunctive therapy in adults and children ≥6 years
Dose summary: Monotherapy: Week 1–2 100 mg once daily, week 3–4 200 mg once daily, week 5–6 300 mg once daily (usual maintenance). Max 500 mg daily. Adjunctive adults (without CYP3A4 inducers): start 25 mg twice daily, increase by 100 mg every 2 weeks to 300–500 mg/day. Adjunctive with CYP3A4 inducers: increase weekly. Pediatric: 1–8 mg/kg/day, max 500 mg/day. Withdraw gradually.
Renal context: Caution; AUC increased 35% if CrCl <20 mL/min. The prescriber will decide whether zonisamide needs to be discontinued if acute renal failure develops. (2) (6)
Australia
Indication: Monotherapy for partial seizures in adults where other agents are intolerant or contraindicated
Dose summary: Initiate 100 mg once daily, titrate by 100 mg every 2 weeks to max 500 mg once daily.
Renal context: Use with caution in renal impairment; slower titration recommended. (4)
New Zealand
Indication: Monotherapy or add-on therapy in adults; add-on therapy in children ≥6 years
Dose summary: Titrate on clinical effect. Limited data below 20 kg body weight. Gradual withdrawal.
Renal context: As with other regions, caution in renal impairment. (3)
Hepatic guidance
Avoid in severe hepatic impairment. Caution in mild to moderate impairment; slower titration recommended.
Overdose note
Overdose may cause coma, bradycardia, hypotension, and respiratory depression. No specific antidote; supportive care, including possible gastric lavage or activated charcoal. Hemodialysis may be effective but has not been studied prospectively. (1) (2) (6)
Frequently asked questions
Can zonisamide cause heatstroke, and what should I do?
Yes. Zonisamide can reduce sweating, leading to dangerously high body temperature, especially in children. Signs include hot dry skin, confusion, and fainting. Move to a cool place, remove excess clothing, apply cool water, and get emergency medical help immediately. (2) (6)
I developed a rash while taking zonisamide. Is it serious?
Any rash should be reported to your prescriber straightaway because zonisamide can cause severe, life‑threatening skin reactions (Stevens‑Johnson syndrome / toxic epidermal necrolysis). Most cases occur in the first few months. Do not wait or dismiss a rash. (1) (2)
Why does my doctor do blood tests while I’m on zonisamide?
Blood tests measure bicarbonate to check for metabolic acidosis, a common side effect that can weaken bones and increase kidney stone risk. Other tests may monitor kidney function, ammonia levels, or blood cell counts. (1) (2)
Can I take zonisamide if I am allergic to sulfa drugs?
If you have had a serious allergic reaction to a sulfonamide (certain antibiotics or diuretics), you should not take zonisamide. Always tell your doctor about any drug allergies before starting. (1) (2)
Is zonisamide safe in pregnancy?
Zonisamide may harm an unborn baby. Women must use effective contraception during treatment and for one month after stopping. If you become or plan to become pregnant, contact your specialist immediately; do not stop the medicine suddenly. (1) (2)
What is the mechanism of action of zonisamide?
Zonisamide is a benzisoxazole derivative with a sulfonamide group. It blocks voltage-sensitive sodium and T-type calcium channels, reduces repetitive neuronal firing, and modulates GABA-mediated inhibition. It also weakly inhibits carbonic anhydrase, which is responsible for metabolic acidosis and increased kidney stone risk. (1) (2) (6)
References
- ZONEGRAN (zonisamide) capsules — prescribing informationU.S. National Library of Medicine, DailyMed · United States · dated 2025-09-12 · accessed 2026-07-22 · source 1
- Zonegran 100 mg hard capsules — Summary of Product Characteristicselectronic Medicines Compendium (UK) · United Kingdom · accessed 2026-07-22 · source 2
- Zonisamide Te Arai capsules — Data SheetNew Zealand Medicines and Medical Devices Safety Authority (Medsafe) · New Zealand · accessed 2026-07-22 · source 3
- ZONEGRAN zonisamide capsule entries (25 mg, 50 mg, 100 mg) — ARTG 125869, 125870, 125871Therapeutic Goods Administration · Australia · dated 2007-07-31 · accessed 2026-07-22 · source 4
- Australian Public Assessment Report for zonisamide (Zonegran) — Product InformationTherapeutic Goods Administration · Australia · dated 2022-07-13 · accessed 2026-07-22 · source 5
- Zonegran (zonisamide) — EPAR summary for the public (EMA/477663/2013)European Medicines Agency · European Union · dated 2013 · accessed 2026-07-22 · source 6
Brand names by country
Single-ingredient zonisamide names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.
Priority countries
United States
- Zonegran100 mg, 25 mg · advanz pharma (us) corp.
- ZONISADE100 mg/5mL · azurity pharmaceuticals, inc.
United Kingdom
- Zonegrancurrent licensed product · 100 mg product example · ADVANZ Pharma
Australia
- Zonegrancurrent register product example · 25 mg, 50 mg, 100 mg · Amdipharm Mercury Australia Pty Ltd
New Zealand
- Zonisamide Te Araicurrent registered product · 25 mg, 50 mg, 100 mg · See current Medsafe data sheet
View brands in additional countries.
European Union
Zonegran