This page shows what was measured, who it was measured in, and what that does not settle.
What Adrenaline does in the body
On the heart it increases output.
In anaphylaxis two things go wrong at once: blood vessels leak until blood pressure fails, and the airway swells shut. Adrenaline is one of the few molecules that fixes both, because it is not selective — it hits every adrenaline receptor there is. On blood vessels it tightens them, so pressure comes back and the swelling in the throat retreats. On the airway muscle it relaxes the squeeze. And it partly shuts down the mast cells that are still firing. Injected into the thigh muscle it starts working within minutes, and that is the whole treatment.
Why people take it. A severe allergic reaction — the adrenaline pen
What happened in people
Comparable plasma epinephrine concentrations and blood pressure and heart rate responses for nasal spray against injection in 175 healthy adults
✎ 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.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
That epinephrine reduces mortality in anaphylaxis — accepted universally, supported by mechanism and case series, and never tested against any control
Where it acts
Every adrenergic receptor in the body at once: alpha-1 on blood vessels, beta-1 on the heart, beta-2 on airway smooth muscle and mast cells
Kind of result
A number that stands in for health
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 128 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.
Formulation
A formulation is the exact made-up form a substance comes in.
A picture of it, and where the picture fails
It is like the difference between a whole bean and instant coffee.
Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.
What people get wrong. Two products with the same name are assumed to behave the same. They often do not.
The specific composition and physical form of a product, including salt, excipients and release profile.
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.
Benefits and harms of adrenaline against no intervention, placebo or another adrenergic agonist in anaphylaxis
✗ The study did not show it
Who was studied
Cochrane adrenaline for anaphylaxis with and without shock (CD006312.pub2)
How many people
0
Study design
Systematic review — no eligible studies found
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No studies satisfied the inclusion criteria after searching CENTRAL, MEDLINE, EMBASE, CINAHL, BIOSIS, ISI Web of Knowledge, LILACS and three trial registries, and contacting manufacturers and international experts
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The authors concluded that such trials are unlikely to be performed and might be unethical, because prompt treatment is deemed critically important for survival and anaphylaxis occurs without warning, usually outside medical settings, with variable severity.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Peak plasma epinephrine significantly higher after intramuscular thigh injection than after intramuscular or subcutaneous upper-arm injection, p<0.01
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. Healthy volunteers, no anaphylaxis, and a pharmacokinetic surrogate endpoint. Every auto-injector label in the world restricts injection to the thigh on the strength of this design, and no outcome study has tested whether the higher peak translates into survival.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Circumstances, timing and treatment of fatal anaphylactic reactions in the United Kingdom since 1992
✓ The study showed what it set out to show
Who was studied
United Kingdom fatal anaphylaxis register (Clin Exp Allergy 2000;30:1144-1150)
How many people
164
Study design
National case register from certified causes of death
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Median time to respiratory or cardiac arrest 30 minutes for foods, 15 for venom, 5 for iatrogenic reactions; adrenaline used in 62% of fatal reactions but before arrest in only 14%; 28% resuscitated and died 3 hours to 30 days later
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Adrenaline overdose caused at least three deaths in the series, and self-treatment kits had proved unhelpful for a variety of reasons. The register also notes that deaths certified as anaphylaxis underestimate the true incidence, so the denominator is uncertain.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Epinephrine blood concentrations after nasal spray against approved epinephrine injection products, with blood pressure and heart rate responses
✓ The study showed what it set out to show
Who was studied
neffy pharmacokinetic and pharmacodynamic bridging programme (NDA 214697)
How many people
175
Study design
Four pharmacokinetic and pharmacodynamic studies in healthy adults
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Comparable epinephrine blood concentrations to approved injection products, and similar increases in blood pressure and heart rate; a paediatric study above 30 kg showed concentrations similar to adults
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. None of the 175 participants had anaphylaxis. Absorption depends on a nasal mucosa that anaphylaxis itself inflames, and the label warns that nasal polyps or a history of nasal surgery may affect absorption and that such patients should consider an injectable product.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Adrenaline
What a person takes: Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray.
The measurement behind this step
Each EpiPen delivers 0.3 mg of epinephrine in 0.3 mL from a device containing 2 mL, with approximately 1.7 mL remaining and discarded after activation. The solution contains sodium chloride, 0.5 mg of sodium metabisulfite as antioxidant, and hydrochloric acid to a pH of 2.2 to 5.0. It may be injected through clothing. The solution should be inspected through the clear window and replaced if pink, brown, cloudy or particulate.
Getting in
Into the muscle of the outer thigh
Through clothing if necessary, into the outer thigh — the one site with pharmacokinetic evidence behind it.
──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
A fixed 0.3 mg dose in 0.3 mL delivered intramuscularly or subcutaneously into the anterolateral thigh. Peak plasma concentrations were significantly higher after intramuscular thigh injection than after intramuscular or subcutaneous injection into the upper arm (p<0.01) in a six-way crossover in young men. The device must not be used intravenously, in the buttock, or in digits, hands or feet.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Adrenaline is not selective, and in anaphylaxis that is the point. Selectivity is what you want in a lung drug and the last thing you want here.
╌╌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’s entire mechanism of action section: epinephrine acts on both alpha- and beta-adrenergic receptors. Non-selectivity across alpha-1, alpha-2, beta-1 and beta-2 is the property no other single agent in the allergy cabinet has, and it maps onto the three simultaneous failures of anaphylaxis.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Blood pressure comes back up, and the swelling in the throat and tongue starts to retreat.
╌╌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
Alpha-1 agonism on vascular smooth muscle produces vasoconstriction, raising systemic vascular resistance and reversing the distributive shock and mucosal oedema of anaphylaxis. This is the component antihistamines and corticosteroids do not supply at all.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Beta-2 opens the airway and quietens the mast cells
The same receptor a rescue inhaler works on relaxes the airway, and it also reduces further release from the cells causing the reaction.
╌╌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
Beta-2 agonism relaxes bronchial smooth muscle by the adenylate cyclase and cyclic AMP route familiar from albuterol, and raised cyclic AMP in mast cells and basophils inhibits further mediator release. Beta-1 agonism increases cardiac rate and contractility.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
Given early it reverses the collapse. Given after the heart or breathing has stopped, it usually does not.
╌╌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
In a national fatal anaphylaxis register the median time to respiratory or cardiac arrest was 30 minutes for food, 15 for venom and 5 for iatrogenic reactions, and adrenaline was given before arrest in only 14% of fatal cases. Twenty-eight per cent of fatal cases were resuscitated and died later, mostly of hypoxic brain damage.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · a recorded source, not a stored snapshot
No randomised controlled trial of adrenaline in anaphylaxis exists. A Cochrane search found none and concluded one would probably be unethical.
──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
Cochrane 2008: we found no studies that satisfied the inclusion criteria. The recommendation rests on mechanism, on plasma-concentration studies in healthy volunteers, and on what fatal-case registers show about what happens when it is given late or not at all. The 2024 nasal spray was licensed on the same kind of bridging evidence: four studies in 175 healthy adults without anaphylaxis.
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · 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 6 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 at risk of severe allergic reactions, carrying an auto-injector; and anyone in an emergency department, ambulance or clinic where anaphylaxis occurs.
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 epinephrine in pediatric patients with septic shock have not been established.”
US prescribing information · 1e8ebac1-5b32-47f9-a930-86a98a24dccc · read 2026-08-30
On older people, the label states: “Clinical studies of epinephrine for the treatment of hypotension associated with septic shock did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 1e8ebac1-5b32-47f9-a930-86a98a24dccc · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, does not identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.”
US prescribing information · 1e8ebac1-5b32-47f9-a930-86a98a24dccc · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of epinephrine in human milk or the effects of epinephrine on the breastfed infant or on milk production.”
US prescribing information · 1e8ebac1-5b32-47f9-a930-86a98a24dccc · read 2026-08-30
Where the result stopped carrying
A Cochrane search of seven databases, three registries, manufacturers and international experts found no eligible randomised trial at all
Self-treatment kits had proved unhelpful for a variety of reasons in the fatal-reactions register, with success depending on medication choice, ease of use and training
Adrenaline was given before cardiorespiratory arrest in only one in seven fatal reactions
The device throws away about 85% of the drug it holds, at the highest per-unit acquisition cost in this file
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.
A different form was studied
The studied form is not the form on the shelf.
On this record: This record is linked to 1 related forms. Evidence does not carry across all of them.
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 (10)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray
✎ 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
7 mL remaining and discarded after activation. 0. It may be injected through clothing. The solution should be inspected through the clear window and replaced if pink, brown, cloudy or particulate.
✎ 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
No contraindications. The device is emergency supportive therapy only and not a substitute for immediate medical care, and more than two sequential doses should be given only under direct medical supervision. Do not inject intravenously — large or intravenous doses may cause cerebral haemorrhage from a sharp rise in blood pressure. Do not inject into the buttock, which may fail to treat the anaphylaxis and has been associated with clostridial gas gangrene that alcohol cleansing does not prevent. Do not inject into digits, hands or feet, where vasoconstriction may cause loss of blood flow. Rare serious skin and soft tissue infections have been reported. Use with caution in heart disease: it may aggravate angina or produce ventricular arrhythmias. The sulfite content should not deter use. In young children the leg should be held firmly to prevent injection injury.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
EPIPEN and EPIPEN Jr (epinephrine injection, USP) auto-injectors United States prescribing information — Indications 1, Dosage and Administration 2.1 and 2.2… · 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
Single-dose intramuscular auto-injector delivering 0.3 mg (or 0.15 mg for the junior device) into the anterolateral thigh; also 1 mg/mL solution in vials and ampoules, and since 2024 a nasal spray
✎ 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
7 mL remaining and discarded after activation. 0. It may be injected through clothing. The solution should be inspected through the clear window and replaced if pink, brown, cloudy or particulate.
✎ 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
411 products list this as an active ingredient in the United States drug directory. 154 of them contain it and nothing else.
FDA National Drug Code directory · 0409-9045 · read 2026-08-29
They are sold as aerosol, aerosol, foam, cream, gel, injection and injection, solution, taken cutaneous, dental, epidural and infiltration.
FDA National Drug Code directory · 0409-9045 · read 2026-08-29
The regulator's established pharmacologic class for it is adrenergic alpha-agonists [moa], adrenergic beta-agonists [moa] and catecholamine [epc].
FDA National Drug Code directory · 0409-9045 · read 2026-08-29
318 published labels name it as an active ingredient. 96 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 4f11bb06-c71b-4d96-9baa-2a17ad473a05 · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 4f11bb06-c71b-4d96-9baa-2a17ad473a05 · read 2026-08-29
40 marketed supplement labels list this ingredient, classed as amino acid/protein, botanical 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.
Epinephrine is intramuscular at 3 DOSAGE FORMS AND STRENGTHS Injection solution: 1 mL single-dose clear glass ampule containing 1 mg/mL epinephrine as a sterile, non-pyrogenic, clear, colorless to slightly yellow solution., recorded as fda label in effect 2026-05-05 in the United States.
US prescribing information · 1e8ebac1-5b32-47f9-a930-86a98a24dccc · read 2026-08-30
Recorded price in US: 1.22626 USD per one millilitre, for the one priced product, 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: 112.98701–141.85384 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 12 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.
Evidence on this page does not automatically apply to this one.
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 Adrenaline 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 epinephrine reduces mortality in anaphylaxis — accepted universally, supported by mechanism and case series, and never tested against any control
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 higher peak plasma concentration in a healthy volunteer predicts survival in a patient in shock
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 plasma-concentration bridging in people without anaphylaxis predicts clinical effect through a nasal mucosa the condition is swelling
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 absence of a contraindication means the drug is safe, when the same label describes cerebral haemorrhage, gas gangrene and digital ischaemia and a fatal-case register attributes at least three deaths to overdose
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 Adrenaline 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.
There is no randomised trial, and there is not going to be one
In plain words
A Cochrane review searched every major medical database, the trial registries and the manufacturers, looking for a randomised trial of adrenaline in anaphylaxis. It found none. Its authors concluded such a trial would probably be unethical.
What was measured
That epinephrine reduces death in anaphylaxis — universally accepted, mechanistically compelling, supported by fatal-case series, and never tested against a control
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Cochrane review of adrenaline for the treatment of anaphylaxis with and without shock searched CENTRAL, MEDLINE, EMBASE, CINAHL, BIOSIS, ISI Web of Knowledge and LILACS, plus three trial registries, and contacted pharmaceutical companies and international experts for unpublished material. Its inclusion criteria were randomised and quasi-randomised controlled trials comparing adrenaline with no intervention, placebo or another adrenergic agonist. Its main results section reads, in full: we found no studies that satisfied the inclusion criteria. The authors concluded they were unable to make any new recommendations, that trials of high methodological quality are needed to define the true extent of benefit, that such trials are unlikely to be performed and might be unethical because prompt treatment is deemed critically important for survival, and that they would be difficult to conduct because anaphylaxis occurs without warning, usually in non-medical settings, and varies in severity between and within individuals. The fatal-reactions register reached the same conclusion independently: the unpredictability of anaphylaxis and the need for immediate, often improvised treatment make controlled trials impracticable. This is the strongest case in this file for a drug being correctly used on mechanism, pharmacokinetics and observational evidence alone — and it is worth stating explicitly rather than leaving as an assumption.
Written into the record, not signed off as a reviewed claim
The thigh beat the arm, in eleven healthy volunteers
In plain words
The instruction to inject into the outer thigh rather than the upper arm rests on a crossover study in young men that measured blood adrenaline levels after each route and site.
What was measured
Peak plasma epinephrine concentration by route and injection site in a six-way crossover
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A prospective, randomised, blinded, placebo-controlled six-way crossover study of intramuscular versus subcutaneous epinephrine in young men found peak plasma epinephrine concentrations significantly higher (p<0.01) after intramuscular injection into the thigh than after either intramuscular or subcutaneous injection into the upper arm, and the authors recommended intramuscular thigh injection as the preferred route and site for initial treatment of anaphylaxis. That recommendation is now in every guideline and in the labelling of every auto-injector — the EpiPen label states the device should only be injected into the anterolateral aspect of the thigh. The evidence underneath it is a pharmacokinetic study in healthy volunteers with no anaphylaxis, using peak plasma concentration as the endpoint. That is the appropriate design given the impossibility of the alternative, and it is also a surrogate: nobody has shown that a higher peak plasma concentration in a healthy young man translates into survival in an anaphylactic one.
Written into the record, not signed off as a reviewed claim
In fatal anaphylaxis it was given before arrest in one case in seven
In plain words
A national register of deaths from anaphylaxis found adrenaline was used in 62% of fatal reactions but given before the heart or breathing stopped in only 14%. The median time from reaction to arrest was thirty minutes for food, fifteen for stings and five for reactions to a drug.
What was measured
Proportion of fatal anaphylactic reactions in which adrenaline was given, and given before cardiorespiratory arrest, and median time from reaction to arrest by trigger
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A register of all fatal anaphylactic reactions in the United Kingdom traceable from certified cause of death since 1992 recorded approximately 20 deaths a year, about half iatrogenic and a quarter each from food and insect venom. All fatal food reactions caused difficulty breathing, which in 86% led to respiratory arrest; shock predominated in iatrogenic and venom reactions. The median time to respiratory or cardiac arrest was 30 minutes for foods, 15 minutes for venom and 5 minutes for iatrogenic reactions. Twenty-eight per cent of fatal cases were resuscitated but died between 3 hours and 30 days later, mostly from hypoxic brain damage. Adrenaline was used in treatment of 62% of fatal reactions but before arrest in only 14%. The author’s conclusions include three findings that get quoted less often than the timing data: that a few reactions will be fatal whatever treatment is given, so avoidance remains the optimal management; that adrenaline overdose caused at least three deaths and must be avoided; and that self-treatment kits had proved unhelpful for a variety of reasons, with success depending on appropriate medication, ease of use and good training. The last of those is a device finding, not a drug finding, and it is the one the market spent the following two decades not solving.
Written into the record, not signed off as a reviewed claim
A whole new route approved on blood levels in people who were not having a reaction
In plain words
The first non-injected adrenaline product was approved in August 2024 on the basis of four studies in 175 healthy adults, measuring how much adrenaline got into their blood. Nobody in those studies was having an allergic reaction.
What was measured
That comparable plasma epinephrine concentrations and comparable blood pressure and heart rate responses in healthy volunteers predict comparable clinical effect in anaphylaxis
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
FDA approved neffy, epinephrine nasal spray, on 9 August 2024 for emergency treatment of Type I allergic reactions including anaphylaxis in adults and children weighing at least 30 kg. The agency’s announcement states the approval is based on four studies in 175 healthy adults, without anaphylaxis, that measured epinephrine concentrations in the blood after neffy or approved injection products, and showed comparable blood concentrations and similar increases in blood pressure and heart rate — described as two critical effects of epinephrine in the treatment of anaphylaxis. A study in children over 30 kg showed concentrations similar to adults. The product carries a warning that nasal conditions such as polyps or a history of nasal surgery may affect absorption, and that such patients should consider an injectable product. This is bridging on pharmacokinetics and pharmacodynamics rather than efficacy, and given the Cochrane finding that no randomised efficacy trial exists or is likely to be ethical, it is the only path available. It should still be read for what it is: a new route of administration for the most time-critical drug in allergy, licensed without a single dose ever having been given to a person in anaphylaxis in a controlled study, and dependent on absorption across a nasal mucosa that the condition being treated causes to swell.
Source
US Food and Drug Administration news release, 9 August 2024 — FDA Approves First Nasal Spray for Treatment of Anaphylaxis (neffy, NDA 214697)
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 device holds 2 mL, delivers 0.3, and discards the rest
In plain words
Each EpiPen contains two millilitres of adrenaline solution. It injects three tenths of a millilitre. The label says the remaining 1.7 mL is not available for future use and should be thrown away — at about a hundred and forty United States dollars a unit at what pharmacies pay.
What was measured
Solution volume held, volume delivered and volume discarded per device, against per-unit acquisition cost
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Section 2.2 of the EpiPen label states, under Discarding After Use, that the device contains 2 mL of epinephrine solution, that approximately 1.7 mL remains in the auto-injector after activation, that it is not available for future use, and that it should be discarded. Section 11 states each 0.3 mL delivered dose contains 0.3 mg of epinephrine. The CMS National Average Drug Acquisition Cost survey effective 19 August 2026 puts epinephrine at US$141.85 per unit as the median across 24 listed generic products — the most expensive per-unit acquisition cost in this file by two orders of magnitude, for a molecule that has never held a patent and costs a trivial amount to synthesise. The value is entirely in the device, which was approved in 1987 under a Type 5 classification for a new formulation or manufacturer rather than as a new molecular entity. In 2017 Mylan resolved False Claims Act allegations for US$465 million, relating to the classification of EpiPen and EpiPen Jr as generic rather than brand for Medicaid Drug Rebate Program purposes, with no admission or finding of wrongdoing, and entered a Corporate Integrity Agreement with the HHS Office of Inspector General.
Source
EPIPEN United States prescribing information, sections 2.2 and 11 (NDA 019430); CMS NADAC survey effective 19 August 2026; HHS Office of Inspector General corporate integrity agreement record for Mylan Inc. and Mylan Specialty L.P.
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
No contraindications, an 87-character mechanism section, and real ways to be hurt
In plain words
The contraindications section of the EpiPen label says: None. The mechanism section is one sentence. The warnings section lists brain haemorrhage, gas gangrene and dead fingers.
What was measured
Contents of the contraindications, mechanism of action and warnings sections of the current label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 4 of the EpiPen label reads: None. Section 12.1, Mechanism of Action, reads in its entirety: epinephrine acts on both alpha- and beta-adrenergic receptors. Section 5 nonetheless records that large doses or accidental intravenous injection may cause cerebral haemorrhage from a sharp rise in blood pressure; that injection into the buttock may not treat anaphylaxis effectively and has been associated with clostridial gas gangrene, which alcohol cleansing does not prevent because it does not kill bacterial spores; that injection into digits, hands or feet may cause loss of blood flow because epinephrine is a strong vasoconstrictor; that rare serious skin and soft tissue infections have been reported; that it should be administered with caution in heart disease because it may aggravate angina or produce ventricular arrhythmias; and that more than two sequential doses should be given only under direct medical supervision. The absence of a contraindication is not a statement that the drug is harmless. It is a statement that in the indication, nothing outweighs it — and the fatal-reactions register recorded at least three deaths caused by adrenaline overdose, which is the reason the two-dose limit exists.
Source
EPIPEN United States prescribing information, sections 4, 5.1 to 5.5 and 12.1 (NDA 019430); Pumphrey RS, Clin Exp Allergy 2000;30:1144-1150
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
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
94 approved applications cover products containing this substance. The earliest was NDA021381, approved 19481119 to DENTSPLY PHARM.
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 only drug that reverses both the airway obstruction and the circulatory collapse of anaphylaxis, for which a Cochrane review searching every major database found no randomised trial that met its inclusion criteria and concluded none is likely to be ethical — sold in a device that holds 2 mL and delivers 0.3, at US$141.85 a unit at pharmacy acquisition cost for a molecule that has never been patented.
Recorded evidence blocks (7)
Q1
On the Adrenaline label: indicated for what?
"Epinephrine injection is indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which includes bees, wasps, hornets, yellow jackets and fire ants), and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs,…": indications and usage on Adrenaline's label. DailyMed label · 28642ad9-b839-ce3a-e063-6394a90ab866 · 2026-01-12
Q2
221 registered trials of Adrenaline — at which phases?
Registered studies posting no result
161 of 221
221 registered studies of Adrenaline: 73 phase4, 70 na, 33 phase2, 29 phase3, 23 phase1, 7 early phase1, 2 na or unstated. CLINICALTRIALS_SNAPSHOT · 2026-09-01
safety (1), futility/efficacy (2), accrual/recruitment (7), sponsor decision unspecified (1) and other (10): Adrenaline's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Difficult accrual"; 21 of 221 registered studies
Show the evidence
Trial
NCT00401882
terminated; "Difficult accrual"
NCT00548886
terminated; "Lack of enrollment"
NCT00678145
terminated; "Protocol was terminated due to enrollment + feasibility issues. Aim 2 not conducted. Aims 1 + 3 were conducted in part. During Aim 3 the IRB requested that the study be transitioned under a new protocol (2018-9208) in order to simplify…"
NCT01025648
terminated; "Optimization of protocol"
NCT01737892
terminated; "unable to validate analytical method"
NCT01759407
terminated; "Interim analysis showed no significant difference between study arms."
14 further recorded trials
NCT02164929
terminated; "Poor recruitment"
NCT02365727
withdrawn; "Protocol not feasible as written"
NCT02428062
suspended; "Pending Pilot study results evaluation"
NCT02570503
terminated; "Study's primary aims are no longer clinically impactful, as intrathecal morphine has fallen out of favor and replaced with different agents so that outpatient/23 hr surgery is more predictably achievable."
NCT02571283
withdrawn; "PI decided to focus on more current topics of interest."
NCT02586961
terminated; "Removal of Adrénaline lots for safety reasons."
NCT02895035
terminated; "Data analysis was never performed by sub-investigator"
NCT02959112
terminated; "Because previous studies had found no difference, and one recent study even reported a higher incidence of PEP in treatment arm"
NCT03335293
withdrawn; "Due to FDA constraints on the off label use of the medications we will not be able to conduct this evaluation."
NCT03383588
terminated; "study was published during initial recruitment that showed no difference"
NCT03408340
terminated; "The study activities were suspended due to COVID-19, and the interim analysis did not yield positive results once resumed."
NCT03513445
withdrawn; "No participants enrolled"
NCT04148261
withdrawn; "Principal Investigator left lab before study start"
NCT05972681
terminated; "Difficulty with enrollment"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Adrenaline used epinephrine (1 mg/1 mL) — over how long?
Human studies of Adrenaline used "epinephrine (1 mg/1 mL)". ClinicalTrials.gov · 2026-09-01
ClinicalTrials.gov — US Government work · 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: 5 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.