This page shows what was measured, who it was measured in, and what that does not settle.
What Levetiracetam does in the body
Epilepsy, including focal seizures and generalised seizures
Nerve endings store their chemical messengers in tiny bubbles and release them when the cell fires. Levetiracetam gets inside those bubbles and sticks to a protein in their wall called SV2A. When firing is normal, little changes. When firing becomes rapid and repetitive, as it does in a seizure, the drug damps down how much is released, so the burst is less able to build and spread.
What happened in people
Responder rates of 33.0% and 39.8% against 10.8% on placebo as adjunctive therapy in 294 patients with refractory partial seizures
✎ 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.
That levetiracetam is a first-line drug equal to lamotrigine in focal epilepsy: SANAD II tested exactly that and non-inferiority failed
Where it acts
Presynaptic nerve terminal, inside the synaptic vesicle membrane (cortex and hippocampus)
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 44YRR34555 · read 2026-08-29
Its recorded molecular formula is C8H14N2O2, weighing 170.21.
US prescribing information · 5e5b0ed3-b104-45a7-bb3e-ee56febb46e8 · read 2026-08-30
Where each sentence above came from
The recorded explanation is written in label language rather than for a beginner. 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 99 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.
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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
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.
Partial seizure frequency over the 18-week evaluation period, with responder rate as a key secondary
✓ The study showed what it set out to show
Who was studied
Cereghino pivotal add-on trial (levetiracetam 1000 and 3000 mg/day)
47% (95% credible interval 39 to 55) on levetiracetam against 45% fosphenytoin and 46% valproate; posterior probability of being most effective 0.41
Repeated elsewhere
Unreplicated
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. Numerically more deaths occurred in the levetiracetam group and more hypotension and intubation with fosphenytoin, neither difference significant. The trial stopped early for futility of separating the drugs.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and solution, extended-release tablet, orally disintegrating printed tablet, and intravenous infusion
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 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.
Where a source records it acting
Brain: A saturable and stereoselective neuronal binding site described in brain tissue is the synaptic vesicle protein SV2A, thought to be involved in the regulation of vesicle exocytosis
US prescribing information · 01aef7f7-6092-4e39-8451-dc02d8db9254 · read 2026-08-27
Start
Levetiracetam
What a person takes: Oral tablet and solution, extended-release tablet, orally disintegrating printed tablet, and intravenous infusion.
The measurement behind this step
The intravenous form matters more than the formulation list suggests: it can be given quickly, needs no cardiac monitoring, and is why levetiracetam entered emergency departments so widely before any head-to-head evidence existed. Renal clearance means exposure rises when kidney function falls.
Getting in
Swallowed, absorbed almost completely, barely metabolised
The tablet is absorbed rapidly and nearly all of it reaches the blood. The liver does very little to it, which is why it rarely interferes with other medicines.
──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
Oral bioavailability approaches 100% and is unaffected by food. Roughly two-thirds is excreted unchanged in the urine; the remainder is hydrolysed by a non-hepatic amidase to the inactive carboxylic acid metabolite ucb L057. No cytochrome P450 involvement and minimal plasma protein binding, so renal function rather than liver enzymes governs exposure.
It crosses into the brain and enters nerve endings
The molecule is small and passes into brain tissue, where it collects in the endings of nerve cells: the part that releases chemical messages to the next cell.
──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
Rapid blood-brain barrier penetration with brain concentrations tracking plasma. The relevant compartment is the presynaptic terminal, where SV2A sits in the membrane of synaptic vesicles at roughly the same copy number as synaptophysin.
Its target sits on the inner face of the storage bubble, so the drug can only reach it when a bubble opens to release its contents and then closes again. Nerve endings that fire more often expose the target more often.
╌╌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
The levetiracetam binding site is on the luminal side of SV2A, requiring vesicle exocytosis and endocytosis for access. Binding is saturable and stereoselective; the inactive (R) enantiomer ucb L060 does not bind, and SV2A-knockout brain tissue shows no specific binding at all.
When a nerve ending fires slowly, almost nothing changes. When it fires in a fast burst, the amount of messenger released falls off faster than it normally would, so the burst does not build.
╌╌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
SV2A binding reduces vesicle release probability during sustained high-frequency trains, with little effect on single evoked responses. Proposed downstream effects include altered vesicle priming and reduced presynaptic calcium-dependent release; the exact step SV2A controls remains contested in the literature.
Fewer seizures, in about a third to two-fifths of people who add it
The measured result is a lower seizure count. In the pivotal add-on trial, 33 to 40% of patients halved their seizures against 11% on placebo, and 11 of 199 became seizure-free.
╌╌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
Efficacy is established against placebo as adjunctive therapy in focal, myoclonic and primary generalised tonic-clonic seizures. Superiority to older first-line drugs has been tested three times (SANAD II focal, SANAD II generalised, KOMET) and shown in none of them.
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.
One of the two or three most-prescribed anti-seizure medicines in the world, used from the neonatal unit to old age, and the usual first choice in hospital when someone needs an intravenous drug quickly.
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 of levetiracetam injection in patients below the age of 16 years have not been established.”
US prescribing information · 5e5b0ed3-b104-45a7-bb3e-ee56febb46e8 · read 2026-08-30
On older people, the label states: “There were 347 subjects in clinical studies of levetiracetam that were 65 years old and over.”
US prescribing information · 5e5b0ed3-b104-45a7-bb3e-ee56febb46e8 · read 2026-08-30
On people who are pregnant, the label states: “Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including levetiracetam, during pregnancy.”
US prescribing information · 5e5b0ed3-b104-45a7-bb3e-ee56febb46e8 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Levetiracetam is excreted in human milk.”
US prescribing information · 5e5b0ed3-b104-45a7-bb3e-ee56febb46e8 · read 2026-08-30
On people with reduced kidney function, the label states: “Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [see Clinical Pharmacology (12.3) ] .”
US prescribing information · 5e5b0ed3-b104-45a7-bb3e-ee56febb46e8 · read 2026-08-30
Where the result stopped carrying
The two classical screening tests, maximal electroshock and maximal pentylenetetrazol, both showed no activity at doses up to 540 mg/kg; the drug survived because it was tested in kindling models as well
KOMET, a 1,688-patient superiority trial against carbamazepine and valproate, showed no advantage on treatment withdrawal and a disadvantage on time to first seizure
Both arms of SANAD II failed their pre-specified non-inferiority margins
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
Given by a clinician
❝ 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 tablet and solution, extended-release tablet, orally disintegrating printed tablet, and intravenous infusion
✎ 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
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
The intravenous form matters more than the formulation list suggests: it can be given quickly, needs no cardiac monitoring, and is why levetiracetam entered emergency departments so widely before any head-to-head evidence existed.
✎ 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: Renal clearance means exposure rises when kidney function falls.
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
The commonest problems are somnolence, asthenia, dizziness and infection. The distinctive one is behavioural: irritability, aggression and mood change at rates of 13% in adults and 38% in children in the registration trials. Psychotic symptoms occurred in 1% of adults. The class-wide suicidality warning applies. Rare but serious reactions include DRESS and anaphylaxis. There is no interaction burden with hormonal contraception or with warfarin.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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 tablet and solution, extended-release tablet, orally disintegrating printed tablet, and intravenous infusion
✎ 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
Renal clearance means exposure rises when kidney function falls.
✎ 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 which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
350 products list this as an active ingredient in the United States drug directory. 350 of them contain it and nothing else.
FDA National Drug Code directory · 72865-189 · read 2026-08-29
They are sold as injection, injection, solution, injection, solution, concentrate, powder, solution and tablet, taken intravenous and oral.
FDA National Drug Code directory · 72865-189 · read 2026-08-29
The regulator's established pharmacologic class for it is decreased central nervous system disorganized electrical activity [pe].
FDA National Drug Code directory · 72865-189 · read 2026-08-29
169 published labels name it as an active ingredient. 169 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 0a688786-879b-4e27-a46a-5c86bbfa1292 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 0a688786-879b-4e27-a46a-5c86bbfa1292 · read 2026-08-29
Levetiracetam is film-coated, scored tablets at 250 mg, 500 mg, 750 mg, and 1000 mg, recorded as prescription product; fda label in effect 2025-11-21 in the United States.
US prescribing information · 01aef7f7-6092-4e39-8451-dc02d8db9254 · read 2026-08-27
Recorded price in US: 0.03013 USD per one millilitre, across 11 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
Recorded price in US: 0.05838–0.15657 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 108 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.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Levetiracetam 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 levetiracetam is a first-line drug equal to lamotrigine in focal epilepsy: SANAD II tested exactly that and non-inferiority failed
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 it is an adequate replacement for valproate in generalised epilepsy on seizure control, rather than a safer drug that controls seizures less well
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 SV2A binding story explains the clinical effect quantitatively, rather than correlating with it across a compound series
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 a low structural malformation rate in a registry implies normal neurodevelopment, which is a separate endpoint measured at a later age
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 Levetiracetam 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.
Add-on trial: 40% of patients halved their seizures, against 11% on placebo
In plain words
In the pivotal United States trial, patients whose seizures were not controlled by their existing drugs added levetiracetam or a dummy tablet. About four in ten on the higher dose halved their seizure count, against about one in ten on the dummy.
What was measured
Proportion of patients with at least 50% reduction in partial seizure frequency over the 18-week evaluation period
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Cereghino and colleagues randomised 294 patients with uncontrolled partial seizures (at least 12 per 12 weeks) to placebo (n=95), levetiracetam 1000 mg/day (n=98) or levetiracetam 3000 mg/day (n=101), after a 12-week baseline, with a 4-week titration and 14 weeks at fixed dose. Partial seizure frequency across the whole evaluation period was lower on both doses than on placebo (p<=0.001). Responder rates, defined as at least a 50% reduction, were 33.0% at 1000 mg/day and 39.8% at 3000 mg/day against 10.8% on placebo (p<0.001). Of 199 patients on levetiracetam, 11 became seizure-free; none did on placebo. Treatment-emergent adverse events above 10% and above placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis and somnolence.
Written into the record, not signed off as a reviewed claim
SANAD II: levetiracetam failed non-inferiority to lamotrigine in focal epilepsy
In plain words
A trial of 990 newly diagnosed patients set out to show that levetiracetam was no worse than lamotrigine as a first drug. It did not show that. On the stricter analysis, lamotrigine was better.
What was measured
Time to 12-month remission, intention-to-treat and per-protocol
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 1:1:1 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. Levetiracetam did not meet non-inferiority in the intention-to-treat analysis (HR 1.18, 97.5% CI 0.95 to 1.47). The per-protocol analysis showed 12-month remission superior with lamotrigine over levetiracetam (HR 1.32, 97.5% CI 1.05 to 1.66). Adverse reactions were reported by 108 (33%) starting lamotrigine and 144 (44%) starting levetiracetam. Lamotrigine also won the cost-utility analysis, at 1.403 QALYs against 1.222. The authors concluded the findings do not support levetiracetam as a first-line treatment for focal epilepsy.
Written into the record, not signed off as a reviewed claim
SANAD II: levetiracetam also failed non-inferiority to valproate in generalised epilepsy
In plain words
Levetiracetam is widely prescribed to women who would otherwise take valproate, because valproate harms a developing fetus. The trial designed to check whether it controls generalised seizures as well as valproate found that it did not.
What was measured
Time to 12-month remission against a pre-specified non-inferiority margin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The companion SANAD II arm randomised 520 participants with newly diagnosed generalised or unclassifiable epilepsy 1:1 to levetiracetam (n=260) or valproate (n=260), non-inferiority limit HR 1.314. Levetiracetam did not meet non-inferiority for time to 12-month remission (HR 1.19, 95% CI 0.96 to 1.47), and the per-protocol analysis showed 12-month remission superior with valproate. Levetiracetam was dominated in the cost-utility analysis, with an incremental net health benefit of -0.040 (95% central range -0.175 to 0.037) and a 0.17 probability of being cost-effective at 20,000 pounds per QALY. The authors framed the result as informing, rather than settling, the benefit-and-harm discussion for girls and women of child-bearing potential.
Written into the record, not signed off as a reviewed claim
ESETT: no better and no worse than fosphenytoin or valproate in status epilepticus
In plain words
When a seizure will not stop after a benzodiazepine, three drugs are commonly given next. A blinded trial compared them head to head and found all three worked in about half of patients, with no winner.
What was measured
Seizure cessation with improved level of consciousness at 60 minutes, without additional anticonvulsant
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ESETT randomised 384 children and adults with benzodiazepine-refractory convulsive status epilepticus to levetiracetam (145), fosphenytoin (118) or valproate (121), in a blinded, response-adaptive design. The primary outcome, absence of clinically evident seizures with improved consciousness at 60 minutes without further anticonvulsant, occurred in 47% on levetiracetam (95% credible interval 39 to 55), 45% on fosphenytoin (36 to 54) and 46% on valproate (38 to 55). Posterior probabilities of being the most effective drug were 0.41, 0.24 and 0.35. The trial was stopped at a planned interim analysis for futility of finding any drug superior or inferior. Numerically more hypotension and intubation occurred with fosphenytoin and more deaths with levetiracetam, neither significantly.
Written into the record, not signed off as a reviewed claim
The drug was approved in 1999; its target was identified in 2004
In plain words
Levetiracetam was licensed for five years before anyone knew what it binds to. It was also inactive in the two animal tests that most anti-seizure drugs are discovered with, and would have been discarded if those tests had been the only filter.
What was measured
That an anti-seizure drug inactive in the classical screening models cannot work in people, an inference the standard discovery pipeline encoded and this drug falsified
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Klitgaard and colleagues reported in 1998 that levetiracetam had no anticonvulsant activity in the acute maximal electroshock test or the maximal pentylenetetrazol test in mice up to 540 mg/kg, the two screens through which most established anti-seizure drugs were found, while protecting potently in electrically and pentylenetetrazol-kindled mice (ED50 7 and 36 mg/kg). The safety margin between rotarod impairment and seizure suppression was 148 in corneally kindled mice, against 2 to 17 for existing drugs. Six years later Lynch and colleagues identified the brain binding site as the synaptic vesicle protein SV2A, showing that binding affinity across a series of analogues correlated with anti-seizure potency and that SV2A-knockout brain tissue showed no binding. The label still opens by stating the precise mechanism is unknown.
Written into the record, not signed off as a reviewed claim
Behavioural effects are common, quantified on the label, and dose-limiting
In plain words
Irritability, anger and mood change are the signature problem with this drug. The label puts them at 13% of adults and 38% of children, against 6% and 19% on placebo.
What was measured
Incidence of non-psychotic behavioural symptoms and psychotic symptoms against placebo in the registration trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The United States prescribing information reports that 13% of adults and 38% of paediatric patients aged 4 to 16 treated with immediate-release levetiracetam experienced non-psychotic behavioural symptoms (aggression, agitation, anger, anxiety, apathy, depersonalisation, depression, emotional lability, hostility, hyperkinesia, irritability, nervousness, neurosis, personality disorder) against 6% and 19% on placebo. Psychotic symptoms occurred in 1% of adults against 0.2% on placebo. In the extended-release trials, 7% of treated patients had irritability or aggression against 0% on placebo. Separately, the FDA pooled analysis of 199 placebo-controlled trials across the anti-seizure class found suicidal thinking or behaviour in 0.43% of 27,863 drug-treated patients against 0.24% of 16,029 on placebo, about one additional case per 530 patients treated.
Source
KEPPRA and KEPPRA XR United States prescribing information, Warnings and Precautions 5.1 and 5.2 (Drugs@FDA NDA 021035 and NDA 022285)
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
Lowest malformation rate in the EURAP registry, tied with lamotrigine
In plain words
Across 7,355 pregnancies in 42 countries, babies exposed to levetiracetam alone had a birth-defect rate of 2.8%, the lowest of the eight drugs studied, and inside the range reported for unexposed pregnancies.
What was measured
Prevalence of major congenital malformations at 1 year, by drug and dose
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The EURAP prospective registry followed pregnancies on anti-epileptic monotherapy at conception from 42 countries between 1999 and 2016. Major congenital malformation prevalence at one year was 17 of 599 (2.8%) for levetiracetam, 74 of 2,514 (2.9%) for lamotrigine, 10 of 333 (3.0%) for oxcarbazepine, 6 of 152 (3.9%) for topiramate, 107 of 1,957 (5.5%) for carbamazepine, 8 of 125 (6.4%) for phenytoin, 19 of 294 (6.5%) for phenobarbital and 142 of 1,381 (10.3%) for valproate. Valproate at 650 mg/day or less still carried an increased risk against levetiracetam at 250 to 4000 mg/day (OR 2.43, 95% CI 1.30 to 4.55, p=0.0069). The authors placed lamotrigine, levetiracetam and oxcarbazepine within the background range for unexposed offspring. This is a registry, not a randomised comparison, and it measures structural malformation at one year, not cognition at six.
Written into the record, not signed off as a reviewed claim
KOMET: not superior to carbamazepine or valproate, and slower to first seizure
In plain words
A 1,688-patient trial run to show levetiracetam was better than the older standards as a first drug did not show it. On time to the first seizure the older drugs did better.
What was measured
Time to treatment withdrawal and time to first seizure over 52 weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
KOMET was an unblinded, randomised, 52-week superiority trial in 1,688 patients aged 16 and over with newly diagnosed epilepsy, randomised to levetiracetam (n=841) or a physician-chosen standard (extended-release valproate or controlled-release carbamazepine, n=847). Time to treatment withdrawal, the primary outcome, did not differ (HR 0.90, 95% CI 0.74 to 1.08). Time to first seizure was significantly longer on the standard drugs (HR 1.20, 95% CI 1.03 to 1.39). Estimated 12-month seizure freedom was 58.7% on levetiracetam against 64.5% on extended-release valproate, and 50.5% against 56.7% on controlled-release carbamazepine. The authors concluded levetiracetam was not superior for the global outcome.
Written into the record, not signed off as a reviewed claim
How many documents were read
165 documents were read for this substance.
RNAWiki source record
114 of them state the same bioavailability, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
44YRR34555
CAS registry number
102767-28-2
PubChem compound
5284583
RxNorm concept
114477
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What is missing or unclear◇Read from sources, not yet reviewed
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.
Withdrawn in United States, 2025, for "LABELING: LABEL MIX-UP: The infusion bag is incorrectly labeled as Levetiracetam in 0.82% Sodium Chloride Injection 500 mg/100 mL, while the aluminum overwrap packaging correctly identifies the…" (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2018, for "Labeling: Label Error on Declared Strength; the pre-printed text on the primary infusion bag and the NDC incorrectly identifies the product as Levetiracetam in 0.75% Sodium Chloride (1000 mg/100 mL)…" (openFDA drug enforcement Class I recall)
What the approval register records
113 approved applications cover products containing this substance. The earliest was NDA021035, approved 19991130 to UCB INC.
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What is not here
7 questions this page could not answer
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What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
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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 drug that binds the synaptic vesicle protein SV2A to blunt neurotransmitter release during high-frequency firing, with a replicated add-on effect (33 to 40% of patients halved their seizures against 11% on placebo) and two large randomised trials in which it failed to match older, cheaper drugs as a first-line treatment.
Recorded evidence blocks (10)
Q1
On the Levetiracetam label: indicated for what?
"Levetiracetam is indicated for the treatment of partial-onset seizures in patients 1 month of age and older ( 1.1 ) Levetiracetam is indicated for adjunctive therapy for the treatment of: • Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy ( 1.2 ) • Primary generalized…": indications and usage on Levetiracetam's label. DailyMed label · e1b14939-7262-40dc-a334-2b3b72c88d47 · 2026-08-10
Q2
226 registered trials of Levetiracetam — at which phases?
Registered studies posting no result
150 of 226
226 registered studies of Levetiracetam: 67 phase2, 57 phase3, 46 phase4, 30 na, 27 phase1, 12 na or unstated. CLINICALTRIALS_SNAPSHOT · 2026-09-01
terminated; "Initiation of CMS BMT study for sickle-cell disease operating under NCT01166009 made further accrual to this study impossible."
NCT00563459
terminated; "Carisbamate partial onset seizures studies lacked consistent efficacy data so trials in this indication were terminated."
NCT00566046
terminated; "Sponsor decision because of to small enrollment"
14 further recorded trials
NCT00584025
withdrawn; "Study withdrawn due to personnel limitations."
NCT00760318
terminated; "Sponsor decided to stop enrollment to review data."
NCT00774306
terminated; "study no longer consistent with current clinical practice"
NCT00862563
terminated; "Recruitment goals could not be met before ending of funding for this project."
NCT01375374
terminated; "Slow progress despite recruitment boosting efforts e.g., expert advice obtained from leading study center Investigators; decision thus made to terminate."
NCT01464359
terminated; "Slow accrual"
NCT01475656
terminated; "difficulty with recruitment"
NCT01891890
terminated; "Poor recruitment"
NCT01935908
withdrawn; "no funding"
NCT01974700
terminated; "Lack of enrollment - since the start of the study in 2013, only 17 subjects have consented. Of those, only 8 completed the study."
NCT02550028
terminated; "The study was concluded as planned upon reaching its predetermined endpoint, which included the completion of data collection and achievement of the necessary sample size for statistical significance."
NCT02726867
withdrawn; "No participants enrolled"
NCT03436433
terminated; "Did not enroll as planned"
NCT04277936
terminated; "Study was redesigned and submitted as a new protocol (NCT04559529)."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Levetiracetam used Levetiracetam 166 mg — over how long?
Human studies of Levetiracetam used "Levetiracetam 166 mg". ClinicalTrials.gov · 2026-09-01
19 recorded entries; human; also "Levetiracetam 250 mg", "Levetiracetam 500 mg", "Keppra 1500 mg BID"
7 ± 1 hour; Elimination Levetiracetam plasma half-life in adults is 7 ± 1 hour and is unaffected by either dose or repeated administration.
tmaxpharmacokinetics
1.5 hours; Food does not affect the extent of absorption of levetiracetam but it decreases C max by 20% and delays T max by 1.5 hours.
bioavailabilitypharmacokinetics
100 %; The oral bioavailability of levetiracetam tablets is 100% and the tablets and oral solution are bioequivalent in rate and extent of absorption.
metabolismpharmacokinetics
Metabolism Levetiracetam is not extensively metabolized in humans.
recorded 2026-08-10 · last checked 2026-09-04
Q6
Which running trial of Levetiracetam could settle lifespan?
NCT06442748 measures 2-year seizure free survival, reading out 2031-06-01.
1 open trial; n 604; "Short Versus Long-term Levetiracetam in Brain Tumors"
Show the evidence
TrialNCT06442748
"Short Versus Long-term Levetiracetam in Brain Tumors"; n 604; "2-year seizure free survival"; 2031-06-01
Q7
Which 77 trials of Levetiracetam posted no result?
Posted no result
77 of 77 completed trials
Registrations
NCT00615615, NCT00015769, NCT00544050, NCT00545012, NCT00643500 and NCT00600509, and 71 more
Completion dates
oldest 2003-03; newest 2024-03-19
Show the evidence
Trial
NCT00615615
2003-03
NCT00015769
2003-04
NCT00544050
2003-05
NCT00545012
2003-05
NCT00643500
2003-05
NCT00600509
2003-07
14 further recorded trials
NCT00630630
2003-11
NCT01131897
2003-11
NCT01132352
2003-11
NCT00630968
2004-02
NCT00946751
2004-03
NCT00612859
2004-06
NCT00630357
2004-07
NCT00631150
2004-07
NCT00610454
2004-08
NCT00160628
2004-10
NCT00160576
2004-11
NCT00245713
2004-11
NCT00150774
2004-12
NCT00254657
2005-04
Q8
At the median, Levetiracetam's trials enrolled 52 people — anything larger?
Median enrolment
52
Largest enrolment
2423
Registered trials counted
226
Q9
What do 11001 spontaneous reports say about Levetiracetam — 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.
Levetiracetam appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 11001 reaction mentions were counted: seizure 2804; abortion spontaneous 1295; convulsion 1133; epilepsy 1026. FAERS via Open Targets · CHEMBL1286 · 2026-06-24
Show the evidence
seizure
2804
abortion spontaneous
1295
convulsion
1133
epilepsy
1026
status epilepticus
1012
somnolence
896
4 more recorded rows
pregnancy
862
generalised tonic-clonic seizure
706
aggression
675
rhabdomyolysis
592
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Levetiracetam's label not list?
2 label terms; 10 reported and unlisted; e1b14939-7262-40dc-a334-2b3b72c88d47
Show the evidence
abortion spontaneous
count not stated
aggression
count not stated
convulsion
count not stated
epilepsy
count not stated
generalised tonic-clonic seizure
count not stated
pregnancy
count not stated
4 more recorded rows
rhabdomyolysis
count not stated
seizure
count not stated
somnolence
count not stated
status epilepticus
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Where it is registered
Where it’s registered
Withdrawn in United States, 2025, for "LABELING: LABEL MIX-UP: The infusion bag is incorrectly labeled as Levetiracetam in 0.82% Sodium Chloride Injection 500 mg/100 mL, while the aluminum overwrap packaging correctly identifies the…" (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2018, for "Labeling: Label Error on Declared Strength; the pre-printed text on the primary infusion bag and the NDC incorrectly identifies the product as Levetiracetam in 0.75% Sodium Chloride (1000 mg/100 mL)…" (openFDA drug enforcement Class I recall)
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 · openFDA enforcement — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
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