This page shows what was measured, who it was measured in, and what that does not settle.
What Perampanel does in the body
Focal epilepsy, and added-on treatment for generalised tonic-clonic seizures
Glutamate is the signal nerve cells use to excite each other, and it acts on a receptor called AMPA that opens a channel and passes the message on. Most seizure drugs work indirectly, by damping the electrical machinery around that process. Perampanel blocks the receptor itself, and it does so at a site away from where glutamate binds, so the block cannot be overcome by more glutamate arriving. That is why it works where other things have failed, and it is also why the same molecule that quietens a seizure can change how a person behaves.
What happened in people
Median 76% reduction in primary generalised tonic-clonic seizure frequency against 38% on placebo in 162 patients (P<0.0001)
✎ 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.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
The limit that matters most
The only AMPA receptor antagonist licensed anywhere, and therefore the only option of its kind for someone who has failed everything else
Where it acts
Postsynaptic membrane of cortical neurons, at the AMPA-type glutamate receptor
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 · H821664NPK · read 2026-08-29
Its recorded molecular formula is C23H15N3O, weighing 362.90.
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · 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 126 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.
Percent change from baseline in primary generalised tonic-clonic seizure frequency per 28 days during the treatment period
✓ The study showed what it set out to show
Who was studied
Perampanel PGTC Study 4 (label Clinical Studies 14.2)
How many people
162
Study design
Phase 3 multicentre randomised double-blind placebo-controlled trial, 17 weeks, 78 sites in 16 countries
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Median reduction 76% on perampanel 8 mg against 38% on placebo, P<0.0001
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. The placebo group achieved a 38% median reduction on its own, so more than a third of the improvement seen on the drug was matched by patients whose treatment did not change.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral suspension, once daily at bedtime
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
Three Phase 3 randomised double-blind placebo-controlled multicentre trials, 19 weeks each
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Significant reduction at 4 mg to 12 mg/day; pooled responder rates 19% placebo, 29% at 4 mg, 35% at 8 mg, 35% at 12 mg
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. Approximately 50% of patients were on a CYP3A4-inducing anti-seizure drug, and the label reports a substantially reduced treatment effect in that group. The inducer-stratified tables exclude all Latin American patients post hoc because of a high placebo response.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral suspension, once daily at bedtime
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
RNAWiki holds 2 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
Perampanel
What a person takes: Oral tablet and oral suspension, once daily at bedtime.
The measurement behind this step
Once-daily bedtime dosing is not a convenience feature but a tolerability one: dizziness and somnolence peak after the dose, and taking it before sleep moves the worst of that into the night. There is no intravenous form. Titration is mandatory and slow, in 2 mg weekly increments, because the label ties the highest risk of both psychiatric reactions and falls to the titration period.
Getting in
Swallowed once a day at bedtime, and cleared by an enzyme other seizure drugs speed up
Absorption is complete and the drug lasts long enough for once-daily dosing. It is broken down by a liver enzyme that carbamazepine, oxcarbazepine and phenytoin all switch on, so taking any of those alongside it substantially lowers the amount that reaches the brain.
──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
Perampanel is metabolised primarily by CYP3A4. The label states that approximately 50% of patients in the pivotal trials were on a CYP3A4-inducing anti-seizure drug, resulting in a significant reduction in serum concentration, and reports a substantially reduced treatment effect in that group. Bedtime dosing is standard because dizziness and somnolence peak after the dose.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
Reaching the cell
It reaches the receiving side of the synapse
Most seizure drugs act on the sending nerve cell or on its electrical machinery. This one acts on the receiving cell, at the point where the excitatory message is picked up.
╌╌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 relevant compartment is the postsynaptic membrane of cortical neurons, where AMPA-type ionotropic glutamate receptors mediate the fast excitatory postsynaptic current. This is a different physical location from the presynaptic vesicle target of levetiracetam and brivaracetam and from the axonal sodium channels of the older drugs.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
What it acts on
It blocks the AMPA receptor away from where glutamate binds
Rather than competing with glutamate for the same slot, it attaches elsewhere on the receptor and stops it working. That matters, because during a seizure there is a great deal of glutamate about, and a competing blocker would simply be outnumbered.
╌╌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 label describes perampanel as a non-competitive antagonist of the ionotropic AMPA glutamate receptor on post-synaptic neurons, and states that the precise mechanism by which it exerts its antiepileptic effects in humans is unknown. Non-competitive block is insurmountable by rising agonist concentration, which is the property that distinguishes it from the competitive AMPA antagonists that failed in development.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
The change it makes
Fast excitatory transmission is turned down across the cortex
The main excitatory signal between nerve cells weakens everywhere it is blocked. That prevents a seizure from recruiting neighbouring tissue, and it also changes the ordinary excitatory traffic that mood and behaviour run on.
──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
Reduced AMPA-mediated postsynaptic current lowers the probability that an excitatory input triggers firing in the receiving neuron. Nothing in the pharmacology confines that effect to epileptic tissue, which is the most parsimonious explanation for a boxed warning describing aggression, hostility and homicidal ideation in patients with no psychiatric history.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · a recorded source, not a stored snapshot
What that does for a person
A 76% median fall in convulsive seizures, and a responder rate that stops rising at 8 mg
In generalised epilepsy, convulsive seizures fell by a median of 76% against 38% on placebo. In focal epilepsy, 35% of patients halved their seizures at 8 mg against 19% on placebo, and 12 mg added nothing.
╌╌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 in three placebo-controlled adjunctive trials in refractory focal epilepsy and one in primary generalised tonic-clonic seizures. Dose response is apparent from 4 mg to 8 mg with little additional reduction at 12 mg, while hostility, falls and dizziness all continue to rise across that step. No active-comparator trial exists.
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · 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.
People with focal epilepsy from age 4 and generalised tonic-clonic seizures from age 12, almost always after several other drugs have failed. It is taken once daily at bedtime.
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 FYCOMPA for the treatment of partial-onset seizures have been established in pediatric patients 4 years of age and older.”
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-30
On older people, the label states: “Clinical studies of FYCOMPA did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of FYCOMPA in the elderly population.”
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · 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 (AEDs), such as FYCOMPA, during pregnancy.”
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-30
On people with reduced liver function, the label states: “Use of FYCOMPA in patients with severe hepatic impairment is not recommended, and dosage adjustments are recommended in patients with mild or moderate hepatic impairment [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ] .”
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-30
On people with reduced kidney function, the label states: “Dose adjustment is not required in patients with mild renal impairment.”
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-30
Where the result stopped carrying
AMPA receptor antagonism was pursued for decades and the competitive antagonists that reached development did not reach the market, on sedation and psychiatric effects
Half the pivotal trial population was taking a drug that substantially lowered perampanel exposure, and the label reports the resulting loss of effect rather than the trial having been designed to avoid it
The dose-response flattens above 8 mg while every dose-related harm continues to climb
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 tablet and oral suspension, once daily at bedtime
✎ 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
Once-daily bedtime dosing is not a convenience feature but a tolerability one: dizziness and somnolence peak after the dose, and taking it before sleep moves the worst of that into the night.
✎ 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: There is no intravenous form. Titration is mandatory and slow, in 2 mg weekly increments, because the label ties the highest risk of both psychiatric reactions and falls to the titration period.
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
A boxed warning for serious or life-threatening psychiatric and behavioural reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats, occurring in patients with and without any prior psychiatric history. Hostility-related reactions ran at 12% and 20% at 8 and 12 mg against 6% on placebo. Dizziness and vertigo reached 47% at 12 mg against 10%; falls 10% against 3%, some causing head injuries and fractures; gait disturbance 16% against 2%; somnolence 18% against 7%. Elderly patients are at higher risk of falls and unsteadiness. DRESS and multi-organ hypersensitivity are labelled. Withdrawal must be gradual. It is a Schedule III controlled substance. 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
Perampanel United States prescribing information: boxed warning, Clinical Studies 14.1 and 14.2 with Tables 4, 5 and 6, Warnings and Precautions 5.1 to 5.6, … · a recorded source, not a stored snapshot
Drugs@FDA: FYCOMPA (perampanel), NDA 202834, original approval 22 October 2012; primary generalised tonic-clonic indication added 2015 (https://www.accessdat… · 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 tablet and oral suspension, once daily at bedtime
✎ 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
There is no intravenous form. Titration is mandatory and slow, in 2 mg weekly increments, because the label ties the highest risk of both psychiatric reactions and falls to the titration period.
✎ 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
53 products list this as an active ingredient in the United States drug directory. 53 of them contain it and nothing else.
FDA National Drug Code directory · 72205-223 · read 2026-08-29
They are sold as powder, suspension, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 72205-223 · read 2026-08-29
The regulator's established pharmacologic class for it is ampa receptor antagonists [moa], cytochrome p450 2c8 inhibitors [moa] and cytochrome p450 3a4 inhibitors [moa].
FDA National Drug Code directory · 72205-223 · read 2026-08-29
7 published labels name it as an active ingredient. 7 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-29
Fycompa is oral at 3 DOSAGE FORMS AND STRENGTHS Tablets 2 mg tablets: orange, round, debossed with “2” on one side and “Є 275” on the other. 4 mg tablets: red, round, debossed with “4” on one side and “Є 277” on the other. 6 mg tablets: p…, recorded as fda label in effect 2022-12-28 in the United States.
US prescribing information · 71cf3309-e182-473c-8b0b-280cabd0e122 · read 2026-08-30
Recorded price in US: 3.96309 USD per one millilitre, across 2 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: 6.62272–19.33055 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 18 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 Perampanel 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 the pooled efficacy figures describe a typical patient, when the effect roughly halves in the 50% of patients taking carbamazepine, oxcarbazepine or phenytoin
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 inducer-stratified tables describe the whole trial population, when they exclude one entire region on the basis of its placebo response
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 12 mg is a stronger dose worth reaching for, when it matched 8 mg on responder rate while doubling falls and hostility
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 seventy-fold price difference over lacosamide or levetiracetam reflects a difference in benefit, when no head-to-head trial exists
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 Perampanel 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.
Generalised tonic-clonic seizures fell by a median of 76% against 38% on placebo
In plain words
In 162 patients with generalised epilepsy having convulsive seizures, adding perampanel cut those seizures by a median of 76%. On placebo the median fall was 38%.
What was measured
Median percent change from baseline in primary generalised tonic-clonic seizure frequency per 28 days
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study 4 was a multicentre randomised double-blind placebo-controlled trial at 78 sites in 16 countries, enrolling patients aged 12 and over with idiopathic generalised epilepsy on a stable dose of 1 to 3 anti-seizure drugs and at least 3 primary generalised tonic-clonic seizures in an 8-week baseline. Efficacy was analysed in 162 patients (81 perampanel, 81 placebo) who received medication and at least one post-treatment assessment. Titration ran 4 weeks to 8 mg/day or the highest tolerated dose, followed by 13 weeks of treatment, 17 weeks in total, dosed once daily. Median percent reduction from baseline in PGTC seizure frequency during treatment was 76% on perampanel against 38% on placebo, p<0.0001. The 38% placebo figure is worth holding onto: more than a third of the reduction seen on the drug was matched by patients whose treatment did not change.
Source
Perampanel United States prescribing information, Clinical Studies 14.2, Study 4, Table 6 (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
Boxed warning: hostility and aggression in 20% of patients at the top dose
In plain words
The boxed warning names aggression, hostility, irritability, anger and homicidal ideation and threats. In the trials, hostility-related reactions occurred in 12% of patients at 8 mg and 20% at 12 mg, against 6% on placebo.
What was measured
Incidence of hostility- and aggression-related adverse reactions by dose, against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Warnings and Precautions 5.1 reports that in the controlled partial-onset seizure trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomised to 8 mg and 12 mg per day against 6% on placebo. The effects were dose-related and generally appeared within the first 6 weeks, though new events continued to be observed beyond 37 weeks. Perampanel-treated patients had more such reactions that were serious, severe, and led to dose reduction, interruption and discontinuation. Irritability, aggression, anger and anxiety each occurred in 2% or more of treated patients and at twice the placebo rate, alongside belligerence, affect lability, agitation and physical assault. Homicidal ideation or threat was exhibited in 0.1% of 4,368 perampanel-treated patients across controlled and open-label trials including non-epilepsy trials. The boxed warning states plainly that these reactions occurred in patients with and without prior psychiatric history, prior aggressive behaviour or concomitant medications associated with hostility.
Source
Perampanel United States prescribing information, boxed warning and Warnings and Precautions 5.1 (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
Half the pivotal population was on a drug that halves perampanel levels
In plain words
About half the patients in the three focal-epilepsy trials were taking carbamazepine, oxcarbazepine or phenytoin, all of which speed up perampanel removal. In that half the drug worked far less well, and the label shows the two sets of numbers side by side.
What was measured
Median percent seizure reduction and responder rate, stratified by presence of a concomitant CYP3A4-inducing anti-seizure drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label states that approximately 50% of patients in Studies 1, 2 and 3 were on at least one anti-seizure drug known to induce CYP3A4, specifically carbamazepine, oxcarbazepine or phenytoin, resulting in a significant reduction in perampanel serum concentration, and that a combined analysis revealed a substantially reduced effect in the presence of inducers. Without inducers, median percent reduction was 22% at 4 mg, 45% at 8 mg and 54% at 12 mg against placebo values of 16%, 16% and 19%. With inducers it was 33%, 24% and 22% against placebo values of 14%, 12% and 9%. Responder rates without inducers were 35%, 45% and 54% against placebo 19%, 17% and 15%; with inducers, 26%, 32% and 33% against placebo 18%, 19% and 21%. In the induced group, the 12 mg dose barely separates from placebo on the responder endpoint. The headline efficacy figures for this drug are therefore an average across two populations in which it behaves very differently, and the interaction is with the three commonest older anti-seizure drugs in the world.
Source
Perampanel United States prescribing information, Clinical Studies 14.1, Tables 4 and 5 (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
One whole region was removed from the efficacy analysis after the fact
In plain words
The tables that show perampanel working best exclude every patient from Latin America. The stated reason is that those sites had an unusually high placebo response, which is a decision made after seeing the data.
What was measured
Size of the excluded regional subgroup, 162 of 1,480 treated patients (10.9%), on a treatment-by-region interaction at P=0.042
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both Table 4 and Table 5 of the label carry the same footnote: patients from the Latin American region are excluded because of a significant treatment-by-region interaction due to high placebo response. That is a post hoc exclusion of a geographic subgroup from the efficacy analysis, justified by an outcome observed in the data rather than by a pre-specified rule. A high placebo response is a real phenomenon and a recognised problem in add-on epilepsy trials, and excluding the affected sites can be defensible. The published pooled analysis puts a size on it: 162 of 1,480 treated patients, 10.9% of the cohort, excluded on a treatment-by-region interaction significant at p=0.042. It is also, mechanically, the removal of the patients among whom the drug looked least effective, and the label reports the exclusion without reporting what the numbers look like with those patients included. The primary endpoint analyses in Figure 1 are separate from these tables, but Tables 4 and 5 are where the largest effect sizes on the label appear.
Written into the record, not signed off as a reviewed claim
Dizziness in nearly half of patients, and falls in one in ten at the top dose
In plain words
At 12 mg a day, 47% of patients reported dizziness or vertigo and 10% fell, some suffering head injuries and fractures. On placebo those rates were 10% and 3%.
What was measured
Incidence of dizziness, gait disturbance, somnolence and falls by dose, against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Warnings and Precautions 5.3 reports dizziness and vertigo in 35% and 47% of patients at 8 mg and 12 mg per day against 10% on placebo, and gait disturbance events, grouping ataxia, gait disturbance, balance disorder and abnormal coordination, in 12% and 16% against 2%. Somnolence occurred in 16% and 18% against 7%. These reactions occurred mostly during titration and led to discontinuation in 3% of treated patients against 1% on placebo. Warnings and Precautions 5.4 reports falls in 5% and 10% at those doses against 3% on placebo, in some cases causing serious injuries including head injuries and bone fracture, occurring both with and without concurrent seizures. Elderly patients had increased risk of both unsteadiness and falls compared with younger adults and children. In a drug whose purpose is to prevent injury from falling during a seizure, a fall rate that rises from 3% to 10% is a direct offset against the benefit.
Source
Perampanel United States prescribing information, Warnings and Precautions 5.3 and 5.4 (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
The dose-response stops at 8 mg while the harm curve keeps climbing
In plain words
Going from 8 mg to 12 mg produced no extra seizure reduction. It roughly doubled the rate of falls and hostility and lifted dizziness from 35% to 47%.
What was measured
Responder rate at 8 mg against 12 mg, set beside the dose-related adverse reaction rates over the same interval
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that a statistically significant decrease in seizure rate was observed at doses of 4 mg to 12 mg per day, and that dose response was apparent at 4 mg to 8 mg with little additional reduction in frequency at 12 mg per day. The pooled responder rates were 19% on placebo, 29% at 4 mg, 35% at 8 mg and 35% at 12 mg, identical at the top two doses. Across the same step from 8 mg to 12 mg, hostility- and aggression-related reactions rose from 12% to 20%, falls from 5% to 10%, dizziness and vertigo from 35% to 47%, gait disturbance from 12% to 16% and somnolence from 16% to 18%. A flat efficacy curve above 8 mg with a steeply rising harm curve is one of the clearest risk-benefit statements available on any label on these pages, and it is assembled from three separate sections rather than stated in one place.
Source
Perampanel United States prescribing information, Clinical Studies 14.1 and Warnings and Precautions 5.1, 5.3 and 5.4 (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
The obvious target in epilepsy took forty years to become a drug, and the reason is on the label
In plain words
Blocking glutamate receptors is the most direct way to stop a seizure, and it was tried for decades. The compounds that reached people caused sedation and psychiatric effects that ended their development. Perampanel is what happened when one was pushed through anyway.
What was measured
That psychiatric toxicity at the AMPA receptor was a property of particular molecules that a better one would avoid. It appears instead to be a property of the target.
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Glutamate is the primary excitatory neurotransmitter and the AMPA receptor carries most fast excitatory transmission, so antagonising it has been an obvious anti-seizure strategy since the receptor was characterised. Competitive AMPA antagonists reached clinical development and did not reach the market. Perampanel, a non-competitive antagonist acting away from the glutamate binding site, was approved in 2012 as the first AMPA receptor antagonist licensed for any indication, and it arrived with a boxed warning describing serious or life-threatening psychiatric and behavioural reactions including homicidal ideation and threats. It is a Schedule III controlled substance, the most restrictive scheduling of any drug on these pages. The conclusion that shifted is not about the biology, which was always correct. It is about what a therapeutic window looks like at this target: the psychiatric effects were treated for decades as a development failure to be engineered away, and were ultimately accepted as an intrinsic consequence of blocking the brain main excitatory receptor, to be managed by monitoring rather than removed by chemistry.
Source
Perampanel United States prescribing information, boxed warning, Mechanism of Action 12.1 and Drug Abuse and Dependence 9.1 (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
Seventy times the price of its alternatives, with no head-to-head evidence supporting it
In plain words
A perampanel tablet costs a United States pharmacy about $17.50 to buy. The equivalent unit of lacosamide costs about 17 cents and of levetiracetam about 11 cents. No trial has compared perampanel with either.
What was measured
That a seventy-fold price difference reflects a corresponding difference in clinical benefit. No trial compares perampanel with any alternative, so no such comparison exists to support or refute it.
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The CMS National Average Drug Acquisition Cost file, effective 19 August 2026, gives a median of US$17.50 per unit across 34 listed perampanel products, against US$0.1676 across 94 lacosamide products, US$0.2634 across 35 brivaracetam products and US$0.1105 across 134 levetiracetam products. The efficacy record supporting that difference is three placebo-controlled adjunctive trials in refractory focal epilepsy and one in generalised tonic-clonic seizures. There is no randomised comparison of perampanel with any other anti-seizure drug. The defensible arguments for the price are that the synthesis is genuinely more complex, involving sequential metal-catalysed couplings rather than a single condensation, and that the mechanism is unique so nothing else substitutes for it in a patient who has failed everything else. Neither argument is an efficacy argument, and the label contains no data that would support one.
Source
CMS National Average Drug Acquisition Cost 2026 file, prices effective 19 August 2026, compared across perampanel, lacosamide, brivaracetam and levetiracetam
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
How many documents were read
7 documents were read for this substance.
RNAWiki source record
7 of them state the same halfLife, and they agree.
RNAWiki source record
7 of them state the same tMax, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
H821664NPK
RxNorm concept
1356557
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✗ Not passed
Safety mode resolved
No register row and no identity class settled the question.
✓ Passed
Canonical metadata present
slug and display name present
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.
What the approval register records
8 approved applications cover products containing this substance. The earliest was NDA202834, approved 20121022 to CATALYST PHARMS.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
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.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
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.
The first licensed AMPA receptor antagonist, which cut generalised tonic-clonic seizures by a median of 76% against 38% on placebo and raised focal-seizure responder rates from 19% to 35%, but which carries a boxed warning for aggression, hostility and homicidal ideation, produced hostility-related reactions in 20% of patients at 12 mg against 6% on placebo, and cost about US$17.50 per unit at pharmacy acquisition price, roughly seventy times the other drugs on these pages.
Recorded evidence blocks (10)
Q1
On the Perampanel label: indicated for what?
"Perampanel, a non-competitive AMPA glutamate receptor antagonist, is indicated for: Treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and older ( 1.1 ) Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in…": indications and usage on Perampanel's label. DailyMed label · 3c72a5f7-bb22-4c48-942a-543ca84ed5a9 · 2026-06-02
Q2
98 registered trials of Perampanel — at which phases?
Registered studies posting no result
57 of 98
98 registered studies of Perampanel: 31 phase2, 19 na or unstated, 18 phase3, 17 phase1, 14 phase4, 3 na, 2 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
105 hours; The half-life of perampanel is about 105 hours, so that steady state is reached in about 2 to 3 weeks.
tmaxpharmacokinetics
0.5 to 2.5 hours; Median time to reach peak concentration (t max ) ranged from 0.5 to 2.5 hours under fasted condition.
metabolismpharmacokinetics
Absorption Perampanel is rapidly and completely absorbed after oral administration with negligible first-pass metabolism.
recorded 2026-06-02 · last checked 2026-09-04
Q6
Which 31 trials of Perampanel posted no result?
Posted no result
31 of 31 completed trials
Registrations
NCT03780907, NCT00144690, NCT00286897, NCT01240187, NCT01396590 and NCT01396577, and 25 more
Completion dates
oldest 2003-08-06; newest 2024-02-06
Show the evidence
Trial
NCT03780907
2003-08-06
NCT00144690
2007-02
NCT00286897
2007-08
NCT01240187
2010-09
NCT01396590
2011-03
NCT01396577
2011-04
14 further recorded trials
NCT02020486
2014-03
NCT02116907
2014-09
NCT02279485
2015-01
NCT02876289
2015-09
NCT04230044
2017-07-03
NCT02033902
2018-01-31
NCT03376997
2018-02-16
NCT03399734
2018-03-09
NCT03424564
2018-05-25
NCT03208660
2019-03-15
NCT04257604
2019-04-30
NCT03059329
2019-09-13
NCT02131467
2020-02-28
NCT03836924
2020-03-01
Q7
At the median, Perampanel's trials enrolled 54 people — anything larger?
Median enrolment
54
Largest enrolment
3809
Registered trials counted
95
Q8
What do 1230 spontaneous reports say about Perampanel — 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.
Perampanel appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1230 reaction mentions were counted: aggression 265; seizure 149; irritability 135; dizziness 125. FAERS via Open Targets · CHEMBL1214124 · 2026-06-24
Show the evidence
aggression
265
seizure
149
irritability
135
dizziness
125
suicide attempt
119
somnolence
111
4 more recorded rows
suicidal ideation
103
agitation
83
status epilepticus
76
drug interaction
64
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Perampanel's label not list?
Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations.
drug_interactions
When moderate or strong CYP3A4 inducers are introduced or withdrawn, monitor patients closely.
drug_interactions
7.2 Moderate and Strong CYP3A4 Inducers The concomitant use of known moderate and strong CYP3A4 inducers including carbamazepine, phenytoin, or oxcarbazepine with perampanel decreased the plasma levels of perampanel by approximately 50-67% [see Clinical Pharmacology (12.3) ] .
drug_interactions
The starting doses for perampanel should be increased in the presence of moderate or strong CYP3A4 inducers [see Dosage and Administration (2.3) ] .
drug_interactions
When these moderate or strong CYP3A4 inducers are introduced or withdrawn from a patient's treatment regimen, the patient should be closely monitored for clinical response and tolerability.
pharmacokinetics
The pharmacokinetics of perampanel are similar when used as monotherapy or as adjunctive therapy for the treatment of partial-onset seizures (in the absence of concomitant moderate or strong CYP3A4 inducers).
2 more recorded rows
Interaction statementpharmacokinetics
Oxidative metabolism is primarily mediated by CYP3A4/5 and to a lesser extent by CYP1A2 and CYP2B6, based on results of in vitro studies using recombinant human CYPs and human liver microsomes.
Interaction statementpharmacokinetics
Drug Interaction Studies In Vitro Assessment of Drug Interactions Drug Metabolizing Enzymes In human liver microsomes, perampanel at a concentration of 30 µmol/L, about 10 fold the steady state C max at a 12 mg dose, had a weak inhibitory effect on CYP2C8, CYP3A4, UGT1A9, and UGT2B7.
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
✗ 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
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.