This page shows what was measured, who it was measured in, and what that does not settle.
What Zonisamide does in the body
Focal (partial-onset) epilepsy, added to other seizure medicines
Zonisamide slows two kinds of electrical gate in nerve membranes: the sodium gates that let a cell fire, and a particular calcium gate that helps groups of cells fire in unison. Damping both makes it harder for a burst of firing to build and to synchronise. It also weakly blocks carbonic anhydrase, an enzyme that handles bicarbonate, and that unrelated action is where the kidney stones, the mild blood acidity and the loss of sweating come from.
What happened in people
Median partial seizure reduction of 40.5% at 400 mg/day against 9% on placebo, with responder rates of 41.8% against 22.2%, in 203 patients
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
It is approved in Japan for Parkinson disease, an indication it does not hold in the United States and which is not covered by any evidence on this page
Where it acts
Cortical neuron membranes for the channel effects; kidney tubule, eye and sweat gland for the carbonic anhydrase effects
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 459384H98V · read 2026-08-29
Its recorded molecular formula is C8H8N2O3S, weighing 212.23.
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 114 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Median percentage reduction from baseline in all partial seizure frequency at 400 mg/day over weeks 8 to 12
✓ The study showed what it set out to show
Who was studied
Adjunctive Study 1 (label Clinical Studies, Tables 1 and 2)
40.5% (n=98) against 9% on placebo (n=72), P<0.05; responders 41.8% against 22.2%, P<0.05; significant differences also at 100 and 200 mg/day
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and oral suspension
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
29.6% (n=69) against -3.2% on placebo (n=72), P<0.05; the responder analysis, 29% against 15%, is reported without the significance marker used elsewhere in the table
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The placebo group had more seizures during treatment than at baseline, so part of the between-group gap is deterioration on placebo rather than improvement on drug.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and oral suspension
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
27.2% (n=67) against -1.1% on placebo (n=66), P<0.05; responders 28% against 12%, P<0.05
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and oral suspension
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
Non-inferiority met in the ITT analysis (HR 1.03, 97.5% CI 0.83 to 1.28) but per-protocol 12-month remission was superior with lamotrigine (HR 1.37, 1.08 to 1.73)
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Adverse reactions were reported by 45% starting zonisamide against 33% starting lamotrigine, and lamotrigine won the cost-utility analysis at 1.403 QALYs against 1.232.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and oral suspension
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Zonisamide
What a person takes: Oral capsule and oral suspension.
The measurement behind this step
There is no intravenous zonisamide and no extended-release form, because the drug half-life already permits once-daily dosing. The oral suspension Zonisade is a separate, later FDA application and is licensed from 16 years of age; the capsule label states that safety and effectiveness in paediatric patients have not been established.
Getting in
Swallowed once a day, and it stays a long time
Absorption is good and the drug persists for days, which is why it can be taken once daily and why a change in dose takes a fortnight to show its full effect.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
A long elimination half-life allows once-daily dosing, and the label reports no apparent difference between once-daily and twice-daily regimens across the registration studies. Metabolism includes reductive opening of the benzisoxazole ring by CYP3A4, so enzyme-inducing anti-seizure drugs shorten the half-life substantially.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
It distributes to the brain, and to the kidney and skin as well
The molecule reaches brain tissue, but carbonic anhydrase, one of the things it blocks, sits in the kidney tubule and the sweat gland. Some of what this drug does never happens in the brain at all.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Distribution is not brain-selective. Inhibition of carbonic anhydrase in the renal tubule accounts for the hyperchloraemic non-anion-gap acidosis, the raised urine pH and the nephrolithiasis; inhibition in the eccrine sweat gland accounts for the oligohidrosis and hyperthermia reported especially in paediatric patients.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
It blocks the sodium gates a nerve cell uses to fire, and a slow calcium gate that helps groups of cells fire together. Both damp the ability of a population of neurons to lock into a rhythm.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
The label states that in vitro pharmacological studies suggest zonisamide blocks sodium channels and reduces voltage-dependent transient inward T-type calcium currents, stabilising neuronal membranes and suppressing neuronal hypersynchronisation, and that the precise mechanisms remain unknown. Binding studies also point to a chloride channel site.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
Synchronisation across a population of cells breaks down
A seizure needs many cells firing in step. Damping both the firing gate and the synchronising gate makes it harder for that lockstep to form or to persist.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
In animal models zonisamide blocked maximal-electroshock tonic extension seizures but not subcutaneous pentylenetetrazol clonic seizures, raised the generalised seizure threshold in kindled rats, shortened cortical focal seizures in cats and suppressed interictal spikes. The label notes that the relevance of these models to human epilepsy is unknown.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
A median 40.5% fall in seizures, against 9% on placebo
In the largest registration trial, the median seizure count fell by 40.5% at 400 mg/day and by 9% on placebo, with 41.8% of patients halving their seizures against 22.2%.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Efficacy is established as adjunctive therapy in refractory partial-onset seizures across three placebo-controlled trials in 499 patients. Efficacy as a first-line monotherapy was tested once, in SANAD II, where zonisamide passed intention-to-treat non-inferiority to lamotrigine and failed the per-protocol comparison.
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with focal epilepsy not controlled on one or two drugs. It is taken once a day, which is unusual in this class and is one of its main practical arguments.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness in pediatric patients below the age of 16 have not been established.”
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
On older people, the label states: “Clinical studies of zonisamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
On people who are pregnant, the label states: “Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs, such as ZONISADE, during pregnancy.”
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Zonisamide is readily transferred to human milk, with a reported milk-to-plasma ratio ranging between 0.7 to 0.9 in the published lactation studies.”
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
On people with reduced kidney function, the label states: “ZONISADE is cleared via renal pathway [see Clinical Pharmacology ( 12.3 )] .”
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
Where the result stopped carrying
Zonisamide was inactive against pentylenetetrazol-induced clonic seizures in animals, one of the two classical screens, and was carried forward on the electroshock and kindling models instead
Serum bicarbonate, the measurement that would have quantified the acidosis, was not collected at all in the adjunctive controlled trials in adults
SANAD II concluded that its findings do not support the use of zonisamide as a first-line treatment for focal epilepsy
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule and oral suspension
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S3.
No source is stored against this line.
What is in the pack
There is no intravenous zonisamide and no extended-release form, because the drug half-life already permits once-daily dosing.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The oral suspension Zonisade is a separate, later FDA application and is licensed from 16 years of age; the capsule label states that safety and effectiveness in paediatric patients have not been established.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
No boxed warning, and a warnings section that opens with the sulfonamide class: Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia and other blood dyscrasias have all proved fatal in this class, and 49 SJS or TEN reports with seven deaths accumulated in eleven years of Japanese marketing. Carbonic anhydrase inhibition drives metabolic acidosis at doses as low as 25 mg daily, kidney stones in 4% of adults, and oligohidrosis with hyperthermia and heat stroke, especially in children. Acute myopia with secondary angle closure glaucoma typically appears within a month. Depression and psychosis led to discontinuation or hospitalisation in 2.2% each against 0.4% and none on placebo. Psychomotor slowing, concentration difficulty and word-finding problems cluster above 300 mg/day. Status epilepticus occurred in 1.1% against none on placebo. The class-wide suicidality warning applies.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Zonisamide United States prescribing information: Clinical Studies Tables 1 and 2, Warnings, Precautions and Mechanism of Action, retrieved from the openFDA … · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule and oral suspension
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: The oral suspension Zonisade is a separate, later FDA application and is licensed from 16 years of age; the capsule label states that safety and effectiveness in paediatric patients have not been established.
No source is stored against this line.
What is recorded as being sold
75 products list this as an active ingredient in the United States drug directory. 75 of them contain it and nothing else.
FDA National Drug Code directory · 13672-001 · read 2026-08-29
They are sold as capsule, powder and suspension, taken oral.
FDA National Drug Code directory · 13672-001 · read 2026-08-29
The regulator's established pharmacologic class for it is anti-epileptic agent [epc], carbonic anhydrase inhibitors [moa] and decreased central nervous system disorganized electrical activity [pe].
FDA National Drug Code directory · 13672-001 · read 2026-08-29
34 published labels name it as an active ingredient. 34 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 467a73f0-1cd1-46bf-83b3-ee38badb761c · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 467a73f0-1cd1-46bf-83b3-ee38badb761c · read 2026-08-29
ZONISADE is oral at 3 DOSAGE FORMS AND STRENGTHS Oral suspension: 100 mg/5 mL of zonisamide as a white to off-white, strawberry flavored liquid., recorded as fda label in effect 2025-09-08 in the United States.
US prescribing information · ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 · read 2026-08-30
Recorded price in US: 0.06202–0.10667 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 26 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Zonisamide studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That a 30-point gap in median seizure reduction means 30% more patients were helped: in Study 2 the responder difference was 14 points and carries no significance marker
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That passing intention-to-treat non-inferiority in SANAD II makes zonisamide equal to lamotrigine, when intention-to-treat analysis biases a non-inferiority trial towards no difference and the per-protocol result went the other way
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the mechanism is established: the label proposes sodium channels, T-type calcium channels and a chloride channel site, and states the precise mechanisms are unknown
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the registration programme characterised the drug rare harms, when no confirmed SJS or TEN case occurred in it and fewer than 100 children took part
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Zonisamide are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Largest registration trial: median seizure reduction 40.5% against 9% on placebo
In plain words
Patients whose seizures continued on one or two drugs added zonisamide or a dummy. Over weeks 8 to 12 the median seizure count fell by 40.5% on the drug and by 9% on placebo, and 41.8% halved their seizures against 22.2%.
What was measured
Median percentage reduction from baseline in all partial seizure frequency, and responder rate at 50% reduction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Three multicentre placebo-controlled double-blind 3-month trials in 499 patients aged 13 to 68 with refractory partial-onset seizures, each with at least four seizures per month despite one or two drugs at therapeutic concentrations, established the adjunctive indication. In Study 1 (n=203), the primary comparison was 400 mg/day against placebo over weeks 8 to 12: median reduction in all partial seizures was 40.5% (n=98) against 9% (n=72), with responders at 41.8% against 22.2%, both p<0.05. Statistically significant treatment differences also appeared at 100 and 200 mg/day. In Study 2 (n=152) the median reduction over weeks 5 to 12 was 29.6% against -3.2%, and in Study 3 (n=138) it was 27.2% against -1.1%, both p<0.05.
Source
Zonisamide United States prescribing information, Clinical Studies, Tables 1 and 2 (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
In two of the three trials the placebo group got worse, and one responder analysis missed
In plain words
The gap between drug and placebo looks larger in Studies 2 and 3 than it is, because the placebo groups deteriorated rather than improved. And in Study 2 the responder analysis, the one that counts people rather than percentages, did not reach significance.
What was measured
Median percentage reduction against responder rate, per study, with the label significance markers
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label reports median percentage reduction in partial seizures of 29.6% against -3.2% in Study 2 and 27.2% against -1.1% in Study 3. A negative value means the placebo group had more seizures during treatment than at baseline, so part of the between-group difference reflects deterioration on placebo rather than improvement on drug, in a population selected for refractory disease and regression away from a high-seizure baseline. In the responder analysis, Study 1 (41.8% against 22.2%) and Study 3 (28% against 12%) reached significance; Study 2 (29% against 15%) is presented without the significance marker that the label applies elsewhere. Median percentage reduction and responder rate can diverge, and where they do, the responder rate is the one that describes patients rather than arithmetic.
Source
Zonisamide United States prescribing information, Clinical Studies, Table 1 (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
SANAD II: passed non-inferiority on one analysis, failed on the other
In plain words
The one large head-to-head trial gave two answers. Counting everyone as randomised, zonisamide was no worse than lamotrigine. Counting only those who took the drug as intended, lamotrigine was clearly better.
What was measured
Time to 12-month remission against lamotrigine, intention-to-treat and per-protocol, plus QALYs
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
SANAD II randomised 990 participants aged 5 and over with newly diagnosed focal epilepsy to lamotrigine (n=330), levetiracetam (n=332) or zonisamide (n=328), with a non-inferiority limit of HR 1.329 for time to 12-month remission. Zonisamide met the non-inferiority criterion in the intention-to-treat analysis (HR 1.03, 97.5% CI 0.83 to 1.28) where levetiracetam did not (1.18, 0.95 to 1.47). The per-protocol analysis showed 12-month remission superior with lamotrigine over both levetiracetam (HR 1.32, 97.5% CI 1.05 to 1.66) and zonisamide (HR 1.37, 1.08 to 1.73). Adverse reactions were reported by 108 (33%) starting lamotrigine, 144 (44%) starting levetiracetam and 146 (45%) starting zonisamide. Lamotrigine was superior in the cost-utility analysis at 1.403 QALYs (97.5% central range 1.319 to 1.458) against 1.232 (1.112 to 1.307) for zonisamide. The authors concluded the findings do not support the use of levetiracetam or zonisamide as first-line treatments for focal epilepsy.
Written into the record, not signed off as a reviewed claim
Fatal skin reactions: 49 cases and 7 deaths across eleven years of Japanese marketing
In plain words
Zonisamide is a sulfonamide, and sulfonamides occasionally cause skin reactions that kill. In the first eleven years of use in Japan, 49 cases of Stevens-Johnson syndrome or toxic epidermal necrolysis were reported and seven people died of severe rash.
What was measured
Post-marketing reporting rate of SJS and TEN per million patient-years, and discontinuation for rash against placebo in randomised trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label reports seven deaths from severe rash, Stevens-Johnson syndrome or toxic epidermal necrolysis, in the first 11 years of marketing in Japan, all in patients also receiving other drugs, and 49 total reported SJS or TEN cases at a reporting rate of 46 per million patient-years, which it states is probably an underestimate because of under-reporting. There were no confirmed SJS or TEN cases in the United States, European or Japanese development programmes. In the United States and European randomised controlled trials, 6 of 269 zonisamide patients (2.2%) discontinued because of rash against none on placebo; across all United States and European development, rash leading to discontinuation was 1.4% (12 events per 1,000 patient-years), and in Japanese development 2% (27.8 per 1,000 patient-years). Rash appeared early: 85% within 16 weeks in the Western studies, 90% within two weeks in the Japanese ones, with no apparent dose relationship. Two confirmed cases of aplastic anaemia and one of agranulocytosis were reported in the same eleven-year Japanese window, at rates above accepted background.
Source
Zonisamide United States prescribing information, Warnings: Potentially Fatal Reactions to Sulfonamides, Serious Skin Reactions and Serious Hematologic Events (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Kidney stones in 4% of adults, and acidosis at doses as low as 25 mg
In plain words
Blocking carbonic anhydrase makes the kidney lose bicarbonate and raises urine pH, which grows stones. Four percent of adults in the development programme formed one, and ultrasound found stones in 8% of children who were scanned.
What was measured
Incidence of nephrolithiasis in adults and children, and the dose threshold at which acidosis is reported
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that zonisamide causes hyperchloraemic non-anion-gap metabolic acidosis through renal bicarbonate loss due to carbonic anhydrase inhibition, that it generally occurs early but can develop at any time, that it appears dose-dependent and can occur at doses as low as 25 mg daily, and that renal disease, severe respiratory disorders, status epilepticus, diarrhoea, a ketogenic diet and specific drugs are additive. Nephrolithiasis occurred in 4% of adults treated in the development programme, was detected by renal ultrasound in 8% of paediatric patients who had at least one prospective ultrasound, and was reported as an adverse event in 3% (4 of 133) of paediatric patients. Chronic untreated acidosis may cause osteomalacia or osteoporosis with increased fracture risk and may reduce growth rates in children; zonisamide treatment was associated with reduced serum phosphorus and raised alkaline phosphatase. The label notes that serum bicarbonate was not measured at all in the adjunctive controlled trials in adults with epilepsy.
Source
Zonisamide United States prescribing information, Warnings: Metabolic Acidosis and Kidney Stones (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Status epilepticus in 1.1% of treated patients and none on placebo
In plain words
A drug given to stop seizures was followed by a continuous, unbroken seizure in about one in ninety patients in the controlled trials. No patient on placebo had one.
What was measured
Proportion of patients with an event labelled status epilepticus, drug against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label states that in controlled trials 1.1% of zonisamide-treated patients had an event labelled as status epilepticus, compared with none of the placebo patients, and that across all epilepsy studies, controlled and uncontrolled, 1% of zonisamide-treated patients had such an event. It notes that incidence estimates are difficult because no standard definition was employed. The comparison against zero on placebo is what makes the signal difficult to dismiss as background rate in a refractory population, and the acknowledged definitional looseness is what stops it being a precise number.
Source
Zonisamide United States prescribing information, Precautions: Status Epilepticus (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Psychiatric discontinuations at five times the placebo rate
In plain words
Depression severe enough to stop the drug or go to hospital happened in 2.2% of trial patients against 0.4% on placebo. Psychosis did the same in 2.2% against nobody on placebo.
What was measured
Discontinuation or hospitalisation for depression and for psychosis, drug against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label groups cognitive and neuropsychiatric events in three categories: psychiatric symptoms including depression and psychosis; psychomotor slowing, difficulty with concentration and speech or language problems, particularly word-finding difficulties; and somnolence or fatigue. In placebo-controlled trials, 2.2% of zonisamide patients discontinued or were hospitalised for depression against 0.4% on placebo, and 2.2% discontinued or were hospitalised for psychosis or psychosis-related symptoms against none on placebo. Across all epilepsy patients treated with zonisamide, 1.4% were discontinued and 1.0% hospitalised for depression or suicide attempts, and 0.9% discontinued and 1.4% hospitalised for psychosis. Psychomotor slowing and concentration difficulty occurred in the first month and were associated with doses above 300 mg/day; speech and language problems tended to appear after 6 to 10 weeks, also above 300 mg/day.
Source
Zonisamide United States prescribing information, Precautions: Cognitive/Neuropsychiatric Adverse Events (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Approved in Japan in 1989 and in the United States in 2000, on largely the same evidence
In plain words
Zonisamide was a routine Japanese epilepsy drug for eleven years before the United States licensed it. Most of what is known about its rarest and worst reactions comes from those eleven years, not from any trial.
What was measured
That a registration trial programme characterises a drug rare harms. For zonisamide it characterised almost none of them; eleven years of use in another country did.
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The drug was approved in Japan in 1989 and in the United States in March 2000 under NDA 020789. The gap is why the safety sections of the United States label read as they do: the fatal skin reactions, the aplastic anaemia and agranulocytosis cases, and the oligohidrosis reports are all drawn from Japanese post-marketing surveillance rather than from the registration trials, in which no confirmed SJS or TEN case occurred and fewer than 100 paediatric patients participated. The label states plainly that oligohidrosis was reported once in 403 Japanese paediatric patients pre-approval, 38 times in the first 11 years of Japanese marketing (about 1 per 10,000 patient-years) and twice in the first year of United States marketing (about 12 per 10,000 patient-years), and that all of these are underestimates. The scientific conclusion did not shift; the evidence base shifted from a trial programme to a surveillance record, and the label was rewritten around it.
Source
Zonisamide United States prescribing information, Warnings: Serious Skin Reactions, Serious Hematologic Events, Oligohidrosis and Hyperthermia in Pediatric Patients (openFDA drug label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
33 documents were read for this substance.
RNAWiki source record
33 of them state the same halfLife, and they agree.
RNAWiki source record
33 of them state the same volumeOfDistribution, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
459384H98V
RxNorm concept
403967
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How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
21 approved applications cover products containing this substance. The earliest was NDA020789, approved 20000327 to ADVANZ PHARMA.
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7 questions this page could not answer
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A once-daily sulfonamide that cut partial seizure frequency by a median of 40.5% against 9% on placebo in its largest registration trial, met non-inferiority to lamotrigine in the intention-to-treat analysis of SANAD II and failed it in the per-protocol analysis, and carries a sulfonamide risk profile that includes 49 reported cases of Stevens-Johnson syndrome or toxic epidermal necrolysis in eleven years of Japanese marketing and kidney stones in 4% of adults in the development programme.
63 hours; The elimination half-life of zonisamide in plasma is approximately 63 hours.
tmaxpharmacokinetics
2-6 hours; Absorption Following a 200-400 mg oral zonisamide dose, peak plasma concentrations (range: 2 mcg/mL to 5 mcg/mL) in normal volunteers occur within 2-6 hours.
metabolismclinical_pharmacology
Metabolism and Elimination Following oral administration of 14 C- zonisamide to healthy volunteers, only zonisamide was detected in plasma.
recorded 2026-08-18 · last checked 2026-09-04
Q7
Which 19 trials of Zonisamide posted no result?
Posted no result
19 of 19 completed trials
Registrations
NCT00055484, NCT00650052, NCT00649714, NCT00056576, NCT01161966 and NCT01161979, and 13 more
Completion dates
oldest 2003-05; newest 2023-06-15
Show the evidence
Trial
NCT00055484
2003-05
NCT00650052
2003-12
NCT00649714
2004-01
NCT00056576
2004-10
NCT01161966
2005-03
NCT01161979
2005-03
13 further recorded trials
NCT00203450
2006-03
NCT00154076
2008-12
NCT00221442
2009-03
NCT00713622
2009-04
NCT00659958
2009-09
NCT00363376
2011-02
NCT01587339
2011-07
NCT01283256
2013-05
NCT01765608
2013-06
NCT01830868
2013-08
NCT01806805
2014-07
NCT04182399
2023-01-01
NCT03196466
2023-06-15
Q8
At the median, Zonisamide's trials enrolled 60 people — anything larger?
Median enrolment
60
Largest enrolment
6498
Registered trials counted
67
Q9
What do 1108 spontaneous reports say about Zonisamide — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Zonisamide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1108 reaction mentions were counted: convulsion 170; seizure 159; somnolence 123; condition aggravated 119. FAERS via Open Targets · CHEMBL750 · 2026-06-24
Show the evidence
convulsion
170
seizure
159
somnolence
123
condition aggravated
119
stevens-johnson syndrome
105
drug interaction
100
4 more recorded rows
drug reaction with eosinophilia and systemic symptoms
92
status epilepticus
83
epilepsy
82
drug rash with eosinophilia and systemic symptoms
75
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Zonisamide's label not list?
Reduction of zonisamide to SMAP is mediated by cytochrome P450 isozyme 3A4 (CYP3A4).
clinical_pharmacology
Effects of Zonisamide on cytochrome P450 enzymes In vitro studies using human liver microsomes show insignificant (<25%) inhibition of cytochrome P450 isozymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, 2B6 or 2C8 at zonisamide levels approximately two-fold or greater than clinically relevant unbound serum concentrations.
clinical_pharmacology
Therefore, zonisamide is not expected to affect the pharmacokinetics of other drugs via cytochrome P450-mediated mechanisms.
clinical_pharmacology
CYP2D6 substrates Coadministration of multiple dosing of zonisamide up to 400 mg/day with single 50 mg doses of desipramine did not significantly affect the pharmacokinetic parameters of desipramine, a probe drug for CYP2D6 activity.
clinical_pharmacology
P-gp substrate An in vitro study showed that zonisamide is a weak inhibitor of P-gp (MDR1) with an IC50 of 267 μmol/L.
clinical_pharmacology
There is a theoretical potential for zonisamide to affect the pharmacokinetics of drugs which are P-gp substrates.
2 more recorded rows
Interaction statementclinical_pharmacology
Caution is advised when starting or stopping zonisamide or changing the zonisamide dose in patients who are also receiving drugs which are P-gp substrates (e.g. digoxin, quinidine).
Interaction statementclinical_pharmacology
Potential for Medicinal Products to Affect Zonisamide Concomitant medications that can induce or inhibit CYP3A4 or N-acetyl-transferases may affect the pharmacokinetics of zonisamide.
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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