This page shows what was measured, who it was measured in, and what that does not settle.
What Fenfluramine does in the body
Fenfluramine forces nerve cells to dump their stored serotonin into the gap between cells and then stops it being cleared away.
At the doses used for weight loss, the flood of serotonin reached receptors on heart valve tissue and made the valves thicken and leak. At the much lower doses used in epilepsy, the same serotonin release calms the runaway electrical activity that produces seizures — and every patient has their valves scanned before, during and after treatment because the mechanism that caused the damage has not gone anywhere.
Why people take it. Used for seizures in two severe childhood epilepsies, and formerly sold for weight loss.
What happened in people
For one childhood epilepsy, convulsive seizures fell about 75%, compared with about 19% after a dummy treatment.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Its earlier weight-loss use damaged heart valves, so current treatment requires regular heart scans.
Where it acts
Serotonergic nerve terminals; the toxicity site is the 5-HT2B receptor on cardiac valve fibroblasts
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 2DS058H2CF · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 119 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.
Change in mean monthly convulsive seizure frequency, fenfluramine 0.7 mg/kg/day versus placebo, over 14 weeks
62.3% greater reduction than placebo (95% CI 47.7 to 72.8), P < 0.0001; 0.2 mg/kg/day 32.4% (6.2 to 52.3), P = 0.0209
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. Decreased appetite and decreased weight occurred at 10% or more and more often on fenfluramine — the anorectic pharmacology persisting at a tenth of the anorectic dose. Fourteen weeks in 119 patients cannot exclude an uncommon valvular effect, which is why the label mandates lifelong echocardiographic monitoring.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral solution, twice daily, dosed by body weight
Interval reported. 95% CI 47
Written into the record, not signed off as a reviewed claim.
54.0% greater reduction in mean monthly convulsive seizure frequency than placebo (95% CI 35.6 to 67.2), P < .001; 54% versus 5% achieved a 50% or greater reduction, P < .001
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. Decreased appetite in 44% versus 11%, fatigue 26% versus 5%, diarrhoea 23% versus 7%, pyrexia 26% versus 9%. Cardiac monitoring showed no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral solution, twice daily, dosed by body weight
Interval reported. 95% CI 35
Written into the record, not signed off as a reviewed claim.
Echocardiographic valve morphology and regurgitation in fen-phen users with no prior cardiac disease
✓ The study showed what it set out to show
Who was studied
Mayo Clinic valvulopathy case series (Connolly et al.)
How many people
24
Study design
Observational case series with histopathology
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Not a hypothesis test; abnormal valve morphology and regurgitation in 24 of 24, with 8 also showing pulmonary hypertension and 5 requiring surgery
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. The series was ascertained from symptomatic patients, so it establishes that the lesion occurs and what it looks like, not how often it occurs. The Jick cohort supplied the rate.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral solution, twice daily, dosed by body weight
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 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
Fenfluramine
What a person takes: Oral solution, twice daily, dosed by body weight.
The measurement behind this step
Oral solution given as an adjunct to existing antiepileptic therapy, dosed in mg/kg per day with a maximum daily amount and a lower cap in patients on stiripentol. Available only through the FINTEPLA REMS, which ties dispensing to documented echocardiographic monitoring.
Getting in
An oral solution, dosed by body weight
A liquid measured against the child's weight, twice a day, on top of their existing epilepsy drugs.
╌╌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
Oral solution dosed in mg/kg per day with a maximum daily cap, given as an adjunct. Trial doses were 0.2 and 0.7 mg/kg/day, roughly an order of magnitude below typical anorectic exposure.
The molecule is not just blocking a pump — it rides the pump into the nerve cell.
╌╌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
Fenfluramine is a SERT substrate: it is transported into the presynaptic terminal rather than merely occupying the transporter. This is the defining pharmacological difference from an SSRI or from sibutramine.
Once inside, it makes the pump run backwards, so stored serotonin pours out into the gap between cells instead of being taken in.
╌╌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
Disrupts vesicular storage and reverses SERT, producing carrier-mediated efflux of 5-HT into the synapse, then inhibits reuptake of what it has released. The N-de-ethylated metabolite norfenfluramine is a potent 5-HT2B agonist.
Two receptor populations, two completely different outcomes
In the brain the extra serotonin damps down seizure activity. On heart valves, a different serotonin receptor tells the tissue to grow, which is what thickened the valves.
╌╌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
Central 5-HT2C and 5-HT1D agonism, with a proposed sigma-1 receptor contribution, is the accepted basis of the anticonvulsant effect. Peripherally, norfenfluramine agonism at 5-HT2B on cardiac valve interstitial cells drives mitogenesis and glycosaminoglycan deposition, producing plaque-like leaflet encasement with intact underlying architecture — the same lesion as carcinoid and ergot valvulopathy.
Seizures fall by three quarters; valves are scanned for life
Convulsive seizures dropped 74.9% against 19.2% on placebo. Every patient has an echocardiogram before, during and after treatment.
──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
Measured endpoints: 62.3% greater reduction in mean monthly convulsive seizure frequency than placebo (95% CI 47.7 to 72.8, p<0.0001); echocardiographic valve function within normal physiological range in all trial patients with no pulmonary arterial hypertension over 14 weeks; a boxed warning and REMS-mandated echocardiography in the marketed product.
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.
Children and adults aged two and over with Dravet or Lennox-Gastaut syndrome, dispensed only through the FINTEPLA REMS. Between 1973 and 1997 it was taken by millions of people for weight loss, most famously in the unapproved fenfluramine-phentermine combination.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness in patients less than 2 years of age have not been established.”
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-30
On older people, the label states: “Clinical studies of FINTEPLA for the treatment of DS or LGS did not include patients 65 years of age and over to determine whether they respond differently from younger patients.”
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · 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 FINTEPLA, during pregnancy.”
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of fenfluramine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-30
On people with reduced liver function, the label states: “Combined molar exposures of fenfluramine and norfenfluramine were increased in subjects with various degrees of hepatic impairment (Child-Pugh Class A, B, and C), necessitating a dosage adjustment in these patients [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] .”
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-30
On people with reduced kidney function, the label states: “In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m 2 , do not exceed the maximum daily dosage of FINTEPLA of 20 mg .”
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-30
Where the result stopped carrying
Withdrawn from the United States market at FDA request on 15 September 1997, alongside dexfenfluramine
The pulmonary hypertension signal was published in August 1996, more than a year before withdrawal
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
Withdrawn
❝ 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 solution, twice daily, dosed by body weight
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S5, S8.
No source is stored against this line.
What is in the pack
Oral solution given as an adjunct to existing antiepileptic therapy, dosed in mg/kg per day with a maximum daily amount and a lower cap in patients on stiripentol. Available only through the FINTEPLA REMS, which ties dispensing to documented echocardiographic monitoring.
✎ 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 and what that means for what is in the pack.
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
Boxed warning for valvular heart disease and pulmonary arterial hypertension: echocardiogram assessments are required before, during and after treatment, and the benefit-risk of starting or continuing must be reconsidered on the basis of those findings. Common adverse effects in the Dravet trial were decreased appetite, diarrhoea, fatigue, lethargy, somnolence and decreased weight. The 1997 withdrawal-era harms — 35.0 valvular disorders per 10,000 at four months or more, and a 23.1-fold odds ratio for pulmonary hypertension beyond three months — are the reason the monitoring exists.
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 solution, twice daily, dosed by body weight
✎ 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
Available only through the FINTEPLA REMS, which ties dispensing to documented echocardiographic monitoring.
✎ 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
5 products list this as an active ingredient in the United States drug directory. 5 of them contain it and nothing else.
FDA National Drug Code directory · 70600-024 · read 2026-08-29
They are sold as powder and solution, taken oral.
FDA National Drug Code directory · 70600-024 · read 2026-08-29
1 published label names it as an active ingredient. 1 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-29
27 marketed supplement labels list this ingredient, classed as botanical with nutrients and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Fintepla is oral at 3 DOSAGE FORMS AND STRENGTHS Oral solution: 2.2 mg/mL fenfluramine as a clear, colorless, cherry flavored liquid., recorded as fda label in effect 2025-10-27 in the United States.
US prescribing information · e88f360e-33ad-4cd6-b2de-5ef885857c5d · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Fenfluramine 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 combining two individually approved anorectics was safe because each component had been approved separately
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 119 patients over 14 weeks with normal echocardiograms establishes that low-dose fenfluramine does not cause valvulopathy — the trial is the right size for efficacy and the wrong size for a rare structural harm
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.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records 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 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 Fenfluramine 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.
Twenty-four women, valve disease in every one, and carcinoid-identical pathology
In plain words
A Mayo Clinic series described 24 women on fen-phen with no prior heart disease. Every one had abnormal, leaking heart valves. Under the microscope the damage was indistinguishable from carcinoid or ergot valve disease.
What was measured
Echocardiographic valvular regurgitation and histopathology in 24 women
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Twenty-four women, mean age 44 (SD 8), evaluated a mean 12.3 (SD 7.1) months after starting fenfluramine-phentermine, all with no history of cardiac disease, presenting with cardiovascular symptoms or a murmur. Echocardiography showed unusual valvular morphology and regurgitation in all 24, involving both right- and left-sided valves. Eight also had newly documented pulmonary hypertension, and five required cardiac surgery. The valves had a glistening white appearance, with plaque-like encasement of leaflets and chordal structures and intact underlying valve architecture — histopathological features the authors describe as identical to carcinoid or ergotamine-induced valve disease. That identity is what pointed at the 5-HT2B receptor and turned a case series into a mechanism. In 1996, United States prescriptions for fenfluramine and phentermine exceeded 18 million.
Written into the record, not signed off as a reviewed claim
Population data: 35 per 10,000 at four months or more, and zero for phentermine alone
In plain words
A study of nearly twenty thousand people found the valve risk rose sharply with duration, and found no cases at all in people who took only phentermine or no appetite suppressant.
What was measured
Five-year cumulative incidence of idiopathic valvular disorders per 10,000
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Population-based follow-up with nested case-control analysis: 6,532 subjects on dexfenfluramine, 2,371 on fenfluramine, 862 on phentermine, and 9,281 obese controls matched for age, sex and weight who had taken no appetite suppressant, all free of diagnosed cardiovascular disease at baseline, mean follow-up about four years. Eleven newly diagnosed idiopathic valvular disorders occurred, five after dexfenfluramine and six after fenfluramine — six aortic, two mitral, three combined. Five-year cumulative incidence per 10,000: 0 in untreated controls (95% CI 0 to 15.4), 0 in phentermine-only users (95% CI 0 to 76.6), 7.1 for fenfluramine or dexfenfluramine under four months (95% CI 3.6 to 17.8, p=0.02), and 35.0 for four months or more (95% CI 16.4 to 76.2, p<0.001).
Written into the record, not signed off as a reviewed claim
Pulmonary hypertension odds ratio 23.1 beyond three months of use
In plain words
A separate European study found that appetite suppressants raised the risk of primary pulmonary hypertension six-fold overall, and twenty-three-fold in people who took them for more than three months.
What was measured
Odds ratio for primary pulmonary hypertension by duration of anorexic drug use
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Case-control study of 95 patients with primary pulmonary hypertension from 35 centres in France, Belgium, the United Kingdom and the Netherlands, against 355 general-practice controls matched for age and sex. Any anorexic drug use gave an odds ratio of 6.3 (95% CI 3.0 to 13.2); use in the preceding year 10.1 (3.4 to 29.9); total use exceeding three months 23.1 (6.9 to 77.7). The drugs involved were mainly fenfluramine derivatives. The paper appeared in August 1996, a year before the valvular findings, and its closing recommendation — active surveillance, "particularly since their use is expected to increase in the near future" — reads very differently in hindsight.
Written into the record, not signed off as a reviewed claim
Withdrawn 1997, re-approved 2020 — same molecule, different disease, different dose
In plain words
The FDA asked for fenfluramine to be pulled in September 1997. Twenty-three years later it approved the same drug for a severe childhood epilepsy, at a fraction of the dose, with heart scans written into the label.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Fenfluramine was approved as an anorectic in 1973 and withdrawn at FDA request on 15 September 1997 alongside dexfenfluramine. Zogenix took the same molecule into Dravet syndrome at 0.2 to 0.7 mg/kg per day — roughly a tenth of typical anorectic exposure — and NDA 212102 was approved as FINTEPLA on 25 June 2020, with a Lennox-Gastaut efficacy supplement approved 25 March 2022. The current label opens with a boxed warning: "FINTEPLA can cause valvular heart disease and pulmonary arterial hypertension. Echocardiogram assessments are required before, during, and after treatment with FINTEPLA." Distribution is restricted through the FINTEPLA REMS. The risk was never declared absent; it was made a condition of use.
Source
FINTEPLA (fenfluramine) US Prescribing Information, boxed warning and REMS; Drugs@FDA NDA 212102, original approval 25 June 2020
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
Dravet syndrome: 74.9% median seizure reduction against 19.2% on placebo
In plain words
In 119 children and young adults with a drug-resistant epilepsy, the higher dose cut convulsive seizures by three quarters. On placebo they fell by a fifth.
What was measured
Change in mean monthly convulsive seizure frequency versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Randomised, double-blind, placebo-controlled trial in children and young adults with Dravet syndrome, run under two identical protocols (NCT02682927 and NCT02826863). After a six-week baseline observation period, 119 patients (mean age 9.0 years, 54% male) were randomised 1:1:1 to placebo (n=40), fenfluramine 0.2 mg/kg/day (n=39) or fenfluramine 0.7 mg/kg/day (n=40), added to existing antiepileptic drugs, for 14 weeks. Median reduction in monthly convulsive seizure frequency was 74.9% on 0.7 mg/kg (median 20.7 to 4.7 seizures per 28 days), 42.3% on 0.2 mg/kg (17.5 to 12.6), and 19.2% on placebo (27.3 to 22.0). The primary endpoint was met: 0.7 mg/kg gave a 62.3% greater reduction in mean monthly convulsive seizure frequency than placebo (95% CI 47.7 to 72.8, p<0.0001); 0.2 mg/kg gave 32.4% (95% CI 6.2 to 52.3, p=0.0209).
Written into the record, not signed off as a reviewed claim
Echocardiography in every trial patient found no valve disease and no pulmonary hypertension
In plain words
Every child in the epilepsy trial had their heart scanned. Valve function stayed within the normal range in all of them, and none developed lung artery hypertension.
What was measured
Echocardiographic valve function and pulmonary arterial pressure during 14 weeks of treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Echocardiographic examinations in the Dravet trial revealed valve function within the normal physiological range in all patients during the trial and no signs of pulmonary arterial hypertension. Commonest adverse events, occurring in at least 10% and more often on fenfluramine, were decreased appetite, diarrhoea, fatigue, lethargy, somnolence and decreased weight — the anorectic pharmacology showing through at a tenth of the anorectic dose. The scope of this result needs stating precisely: 119 patients over 14 weeks is the right size to detect a common problem and the wrong size to exclude an uncommon one, which is exactly why the label mandates echocardiography before, during and after treatment rather than treating the trial as settling the question.
Written into the record, not signed off as a reviewed claim
Replicated on top of stiripentol, the hardest available background
In plain words
A second randomised trial added fenfluramine to patients already taking the standard European treatment for this epilepsy, and it still worked.
What was measured
Convulsive seizure frequency reduction on fenfluramine added to stiripentol-inclusive regimens
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Double-blind, placebo-controlled, parallel-group randomised trial in children aged 2 to 18 with confirmed Dravet syndrome on stable stiripentol-inclusive regimens and at least six convulsive seizures during a six-week baseline. Eighty-seven patients (mean age 9.1 years, 57% male, roughly 25 convulsive seizures per month at baseline) were randomised to fenfluramine 0.4 mg/kg/day, maximum 17 mg/day (n=43), or placebo (n=44), with three weeks of titration and twelve weeks of maintenance. Fenfluramine produced a 54.0% greater reduction in mean monthly convulsive seizure frequency than placebo (95% CI 35.6 to 67.2, p<0.001); 54% versus 5% achieved a reduction of 50% or more (p<0.001); the median longest seizure-free interval was 22 days against 13 (p=0.004). Cardiac monitoring showed no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension. Testing an add-on against an active, already-effective background rather than against bare standard care is a substantially harder design, and this is what raises the Dravet evidence from a single positive trial to a replicated finding.
Written into the record, not signed off as a reviewed claim
Fen-phen was never approved as a combination, and the phentermine half was blameless
In plain words
The famous diet combination was never licensed. Doctors put two separately approved drugs together, and the population data show the valve damage came from the fenfluramine half alone.
What was measured
That combining two individually approved anorectics was safe because each had been approved separately
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Fenfluramine and phentermine were each individually approved; the combination was not, and Connolly et al. note it explicitly while recording that 1996 United States prescriptions for the two drugs exceeded 18 million. The inference that the combination was safe because both components were approved was never tested. The Jick population study then separated the two: five-year cumulative incidence of idiopathic valvular disorders was 0 per 10,000 among phentermine-only users (95% CI 0 to 76.6), identical to untreated controls, against 35.0 per 10,000 for four or more months of fenfluramine or dexfenfluramine. Phentermine is a noradrenaline releasing agent with no meaningful 5-HT2B activity, and it remains licensed today.
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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.
The clearest reversal in modern pharmacology: withdrawn in 1997 after echocardiography found valve disease in fen-phen users, and re-approved in 2020 after cutting median convulsive seizures in Dravet syndrome by 74.9% against 19.2% on placebo, with echocardiography now built into the label.
Recorded evidence blocks (11)
Q2
On the Fenfluramine label: indicated for what?
"FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older. FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older.": indications and usage on Fenfluramine's label. DailyMed label · e88f360e-33ad-4cd6-b2de-5ef885857c5d · 2025-10-27
Q3
24 registered trials of Fenfluramine — at which phases?
"The study was stopped due to low enrollment."; 2 of 24 registered studies
Show the evidence
Trial
NCT03299842
terminated; "The study was stopped due to low enrollment."
NCT05560282
terminated; "Study recruitment was too slow, not enough funds to sustain it."
recorded 2026-09-01 · last checked 2026-09-04
Q6
Fenfluramine's half-life is 20 hours — which schedules were studied?
20 hours, the half-life Fenfluramine's label states: "Elimination The elimination half-life of fenfluramine was 20 hours and the geometric mean (CV%) clearance (CL/F) was 24.8 (29%) L/h, following oral administration of FINTEPLA in healthy subjects." DailyMed label · e88f360e-33ad-4cd6-b2de-5ef885857c5d · 2025-10-27
tmax 3 to 5 hours; bioavailability 68-74 %.
Show the evidence
half lifepharmacokinetics
20 hours; Elimination The elimination half-life of fenfluramine was 20 hours and the geometric mean (CV%) clearance (CL/F) was 24.8 (29%) L/h, following oral administration of FINTEPLA in healthy subjects.
tmaxpharmacokinetics
3 to 5 hours; Absorption Fenfluramine has a time to maximum plasma concentration (T max ) of 3 to 5 hours at steady state.
bioavailabilitypharmacokinetics
68-74 %; The absolute bioavailability of fenfluramine is approximately 68-74%.
metabolismpharmacokinetics
Metabolism Over 75% of fenfluramine is metabolized to norfenfluramine prior to elimination, primarily by CYP1A2, CYP2B6, and CYP2D6.
recorded 2025-10-27 · last checked 2026-09-04
Q7
Which 2 trials of Fenfluramine posted no result?
Posted no result
2 of 2 completed trials
Registrations
NCT00000506 and NCT05026398
Completion dates
oldest 1988-04; newest 2022-06-22
Show the evidence
Trial
NCT00000506
1988-04
NCT05026398
2022-06-22
Q8
At the median, Fenfluramine's trials enrolled 22 people — anything larger?
Median enrolment
22
Largest enrolment
412
Registered trials counted
21
Q9
What do 140 spontaneous reports say about Fenfluramine — 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.
Fenfluramine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 140 reaction mentions were counted: seizure 54; decreased appetite 22; weight decreased 14; somnolence 11. FAERS via Open Targets · CHEMBL2106217 · 2026-06-24
Show the evidence
seizure
54
decreased appetite
22
weight decreased
14
somnolence
11
pulmonary hypertension
10
mitral valve incompetence
7
4 more recorded rows
irritability
6
generalised tonic-clonic seizure
6
aortic valve incompetence
5
abnormal behaviour
5
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Fenfluramine's label not list?
( 2.2 , 2.3 , 7.1 ) Strong CYP1A2 or CYP2D6 inhibitors: a dose adjustment is recommended ( 2.3 , 7.1 ) Strong CYP1A2, CYP2B6, or CYP3A4 inducers: it is recommended to avoid coadministration with FINTEPLA.
drug_interactions
Strong CYP1A2, CYP2B6, or CYP3A Inducers Coadministration of FINTEPLA with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of FINTEPLA [see Clinical Pharmacology (12.3) ] .
drug_interactions
It is recommended to avoid coadministration of strong CYP1A2, CYP2B6 or CYP3A inducers.
drug_interactions
If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed; however, do not exceed the maximum daily dosage of FINTEPLA [see Dosage and Administration (2.2) ].
drug_interactions
If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer [see Warnings and Precautions (5.6) ].
drug_interactions
Strong CYP1A2 or CYP2D6 Inhibitors Coadministration of FINTEPLA with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations [see Clinical Pharmacology (12.3) ] .
2 more recorded rows
Interaction statementdrug_interactions
If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg [see Dosage and Administration (2.3) ].
Interaction statementdrug_interactions
If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors; however, do not exceed the maximum daily dosage of FINTEPLA [see Dosage and Administration (2.2) ].
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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