This page shows what was measured, who it was measured in, and what that does not settle.
What Salmeterol does in the body
Keeping airway muscles relaxed for about twelve hours.
The muscle wrapped around each airway can tighten and squeeze the tube narrow. Salmeterol switches on a receptor on that muscle which raises a chemical messenger inside the cell and makes it let go, holding the airway open for about twelve hours. What makes it last that long is a long fatty tail on the molecule that buries itself in the cell membrane next to the receptor, so the working end keeps swinging back into place instead of washing away. It does nothing at all to the inflammation underneath, which is why using it without a steroid quietens the symptoms while the disease carries on — and that is the exact combination that produced the deaths in SMART.
What happened in people
Used alone for asthma, it caused 13 asthma deaths versus 3 without it. Paired with a steroid, serious events did not rise.
✓ 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
It has not been shown to extend life in chronic lung disease.
Where it acts
Airway smooth muscle of the bronchi and bronchioles — the beta-2 receptor on the muscle cell surface, and the membrane pocket beside it
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 · 2I4BC502BT · read 2026-08-29
Its recorded molecular formula is C25H37NO4•C11H8O3, weighing 603.8.
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 149 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.
Combined respiratory-related deaths or life-threatening experiences, salmeterol added to usual care against placebo added to usual care
Primary endpoint not significant: 50 against 36, relative risk 1.40 (95% CI 0.91 to 2.14). Asthma-related deaths 13 against 3, RR 4.37 (95% CI 1.25 to 15.34).
Repeated elsewhere
Failed to Replicate
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 trial was terminated at interim analysis on the strength of the African-American subgroup, so the planned enrolment of 60,000 was never reached and the primary comparison is underpowered. Background inhaled corticosteroid was not required, which the label now makes mandatory.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Dry-powder inhaler (Diskus, 50 micrograms per blister) and, historically, metered-dose inhalation aerosol
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Hazard ratio 1.28 (95% CI 0.73 to 2.27); noninferiority against an upper bound of 2.675 achieved, P=0.006
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 noninferiority margin in children was 2.675 rather than the 2.0 used in adults, so a wider excess would have been declared acceptable. Every serious asthma-related event in the trial was a hospitalisation.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Dry-powder inhaler (Diskus, 50 micrograms per blister) and, historically, metered-dose inhalation aerosol
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Death from any cause, salmeterol-fluticasone combination against placebo, in chronic obstructive pulmonary disease
✗ The study did not show it
Who was studied
TORCH (NCT00268216)
How many people
6112
Study design
Phase 3/4, randomised, double-blind, placebo-controlled, four-arm, three years
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
Hazard ratio 0.825 (95% CI 0.681 to 1.002), P=0.052 adjusted for interim analyses — the predetermined level of significance was not reached
Repeated elsewhere
Partially Replicated
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. Pneumonia reported as an adverse event in 19.6% on combination and 18.3% on fluticasone against 12.3% on placebo, P<0.001. The mortality result is quoted as a 17.5% risk reduction far more often than as a missed endpoint.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Dry-powder inhaler (Diskus, 50 micrograms per blister) and, historically, metered-dose inhalation aerosol
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Time to first moderate or severe exacerbation, tiotropium against salmeterol
✓ The study showed what it set out to show
Who was studied
POET-COPD (NCT00563381)
How many people
7376
Study design
Phase 4, randomised, double-blind, double-dummy, active comparator, one year
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Hazard ratio 0.83 favouring tiotropium (95% CI 0.77 to 0.90), P<0.001; 187 days against 145 days to first exacerbation
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. This trial met its endpoint against salmeterol, not for it. It is the largest head-to-head evidence that a long-acting antimuscarinic prevents more exacerbations than this drug in chronic obstructive pulmonary disease.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Dry-powder inhaler (Diskus, 50 micrograms per blister) and, historically, metered-dose inhalation aerosol
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Where a source records it acting
Lungs and airways: Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially mast cells
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-28
Start
Salmeterol
What a person takes: Dry-powder inhaler (Diskus, 50 micrograms per blister) and, historically, metered-dose inhalation aerosol.
The measurement behind this step
Inhaled twice daily. Salmeterol is a partial agonist with an onset of roughly fifteen to twenty minutes, so it cannot function as a reliever, and the label states it is not indicated for relief of acute bronchospasm and must not be initiated in acutely deteriorating asthma. In asthma it is used almost exclusively inside a fixed-dose combination with an inhaled corticosteroid, because two separate inhalers can be reduced to one by a patient who feels better.
Getting in
Breathed in as a dry powder
The inhaler releases a measured puff of powder. Only a fraction of it reaches the small airways; the rest lands in the mouth and throat and is swallowed.
──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
Salmeterol xinafoate, 50 micrograms of the base per blister in the Diskus, micronised and blended with lactose carrier. Plasma concentrations after inhalation are very low and often undetectable, so systemic exposure is a poor guide to lung effect; the drug is measured by what it does to FEV1, not by what appears in blood.
Half the molecule is a long greasy chain that does nothing to the receptor. It slides into the fatty layer of the muscle cell and stays there, holding the rest of the molecule permanently within reach.
╌╌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 phenylbutoxyhexyl side chain partitions into the lipid bilayer and occupies a hydrophobic exosite adjacent to the orthosteric pocket of ADRB2. This anchoring is the accepted structural explanation for a duration of action near twelve hours from a molecule whose head group binds no more tightly than a short-acting agonist.
The active head switches the receptor on, again and again
The working end of the molecule swings into the receptor, activates it, drifts out, and swings back in — because the tail will not let it leave.
╌╌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 saligenin head engages the orthosteric site of the beta-2 adrenoceptor. Replacing the catechol of adrenaline with a saligenin ring removes the substrate for catechol-O-methyltransferase, which is why the molecule is not degraded the way endogenous catecholamines are. Salmeterol is a partial agonist: its maximal response is below that of isoprenaline on the same preparation.
The switched-on receptor makes the cell produce a signalling chemical. The more of it there is, the more the muscle lets go.
╌╌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 receptor couples to Gs, which activates adenylyl cyclase and converts ATP to cyclic AMP. The label attributes the pharmacologic effect at least in part to that step. Cyclic AMP activates protein kinase A, which lowers intracellular calcium and reduces myosin light-chain kinase activity.
The muscle relaxes and the tube widens. It takes fifteen to twenty minutes to start, which is why this inhaler is useless in an attack, and it lasts about twelve hours, which is why it is taken twice a day.
──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
Bronchodilation with a duration near twelve hours, in contrast to four to six for albuterol. The label additionally records that salmeterol is a potent and long-lasting inhibitor of mast cell mediator release — histamine, leukotrienes and prostaglandin D2 — from human lung in vitro, and that single inhaled doses attenuate allergen-induced bronchial hyper-responsiveness in humans.
Nothing in the chain above reaches the swollen, mucus-filled lining that causes asthma attacks. A person on salmeterol alone breathes more easily while the disease continues, and that is what the boxed warning is about.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
The mast-cell stabilising effect measured in vitro does not translate into control of eosinophilic airway inflammation in vivo, and salmeterol produces no change in the transcriptional programme that inhaled corticosteroids act on. In SMART, run without required background steroid, asthma-related deaths were 13 against 3. In AUSTRI, run with fluticasone in the same inhaler, the hazard ratio for serious asthma events was 1.03 (95% CI 0.64 to 1.66).
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.
In asthma, only people already on an inhaled corticosteroid whose asthma is not controlled by it, and in practice almost always inside a single combination inhaler so the steroid cannot be skipped. In chronic obstructive pulmonary disease, where there is no equivalent death signal, it is used as maintenance treatment on its own or with other bronchodilators.
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: “The safety and efficacy of SEREVENT DISKUS have been evaluated in over 2,500 subjects aged 4 to 11 years with asthma, 346 of whom were administered SEREVENT DISKUS for 1 year.”
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-30
On older people, the label states: “Of the total number of adult and adolescent subjects with asthma who received SEREVENT DISKUS in chronic dosing clinical trials, 209 were aged 65 years and older.”
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary The available data from published epidemiological studies and case reports with use of SEREVENT DISKUS in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) .”
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of salmeterol in human milk, the effects on the breastfed child, or the effects on milk production.”
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-30
On people with reduced liver function, the label states: “Formal pharmacokinetic studies using SEREVENT DISKUS have not been conducted in patients with hepatic impairment.”
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-30
Where the result stopped carrying
SMART was stopped early and never reached its planned enrolment, leaving the primary endpoint underpowered and the mortality finding a secondary one
TORCH failed its primary mortality endpoint by three thousandths of a p-value and found pneumonia in 19.6% against 12.3% on placebo
POET-COPD showed a long-acting antimuscarinic prevents exacerbations better than salmeterol in 7,376 people
The genetic explanation offered for the African-American excess in SMART was not confirmed when tested directly in LARGE
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
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: S6.
No source is stored against this line.
What is in the pack
Inhaled twice daily.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Salmeterol is a partial agonist with an onset of roughly fifteen to twenty minutes, so it cannot function as a reliever, and the label states it is not indicated for relief of acute bronchospasm and must not be initiated in acutely deteriorating asthma. In asthma it is used almost exclusively inside a fixed-dose combination with an inhaled corticosteroid, because two separate inhalers can be reduced to one by a patient who feels better.
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 asthma-related death when used as monotherapy without an inhaled corticosteroid; monotherapy in asthma is contraindicated. Not for acute symptoms. Do not combine with another long-acting beta-agonist. Paradoxical bronchospasm requires discontinuation. Caution in cardiovascular and central nervous system disorders, convulsive disorders, thyrotoxicosis, diabetes and ketoacidosis, and alertness to hypokalaemia and hyperglycaemia. Most common adverse reactions at 5% or more in asthma were headache, influenza, nasal or sinus congestion, pharyngitis, rhinitis and tracheitis or bronchitis; in chronic obstructive pulmonary disease, cough, headache, musculoskeletal pain, throat irritation and viral respiratory infection.
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.
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Salmeterol is a partial agonist with an onset of roughly fifteen to twenty minutes, so it cannot function as a reliever, and the label states it is not indicated for relief of acute bronchospasm and must not be initiated in acutely deteriorating asthma. In asthma it is used almost exclusively inside a fixed-dose combination with an inhaled corticosteroid, because two separate inhalers can be reduced to one by a patient who feels better.
No source is stored against this line.
What is recorded as being sold
74 products list this as an active ingredient in the United States drug directory. 16 of them contain it and nothing else.
FDA National Drug Code directory · 0527-6011 · read 2026-08-29
They are sold as aerosol, metered, powder and powder, metered, taken oral and respiratory (inhalation).
FDA National Drug Code directory · 0527-6011 · read 2026-08-29
The regulator's established pharmacologic class for it is adrenergic beta2-agonists [moa] and beta2-adrenergic agonist [epc].
FDA National Drug Code directory · 0527-6011 · read 2026-08-29
34 published labels name 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 · 80b36523-4ae4-463e-b1fd-b929fb802b76 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 80b36523-4ae4-463e-b1fd-b929fb802b76 · read 2026-08-29
SEREVENT DISKUS is inhalation powder at Inhaler containing salmeterol (50 mcg) as a powder formulation for oral inhalation, recorded as prescription product; fda label in effect 2022-10-10 in the United States.
US prescribing information · 12d9728e-6b5c-4aee-bfb0-745e542ed2e4 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Salmeterol 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 salmeterol with a steroid has been shown to prolong survival in chronic obstructive pulmonary disease — TORCH is the trial that asked, and it missed at p=0.052
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 ADRB2 Arg16 variant explains the SMART deaths, an idea a genotype-stratified randomised trial tested and did not support on its primary endpoint
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 December 2017 withdrawal of the class boxed warning applies to salmeterol used on its own, when the current label still carries it and calls asthma monotherapy contraindicated
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 relaxing airway muscle addresses asthma — the drug does nothing to the airway inflammation, and the whole safety history follows from that
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 Salmeterol 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.
SMART: 13 asthma deaths against 3 on placebo in 26,355 people
In plain words
A safety trial added salmeterol or a dummy inhaler to whatever asthma treatment people were already on, and did not require them to be on a steroid. It was stopped early. Thirteen people died of asthma on salmeterol; three did on placebo.
What was measured
Asthma-related deaths on salmeterol added to usual care against placebo added to usual care
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Salmeterol Multicenter Asthma Research Trial was a 28-week randomised, double-blind, placebo-controlled study of salmeterol 42 micrograms twice daily by metered-dose inhaler added to usual asthma care, terminated at an interim analysis of 26,355 subjects. The primary outcome, respiratory-related deaths or life-threatening experiences, was not significantly different: 50 against 36, relative risk 1.40 (95% CI 0.91 to 2.14). Significant differences appeared in respiratory-related deaths (24 against 11, RR 2.16, 95% CI 1.06 to 4.41), asthma-related deaths (13 against 3, RR 4.37, 95% CI 1.25 to 15.34) and combined asthma-related deaths or life-threatening experiences (37 against 22, RR 1.71, 95% CI 1.01 to 2.89). Background inhaled corticosteroid use was not required by the protocol.
Written into the record, not signed off as a reviewed claim
AUSTRI: with a steroid in the same inhaler, no excess and 21% fewer exacerbations
In plain words
The FDA made the manufacturer run the trial the first one should have been. Eleven and a half thousand people took salmeterol and fluticasone in one inhaler or fluticasone alone. Serious asthma events were the same in both groups, and the combination group had a fifth fewer severe attacks.
What was measured
First serious asthma-related event and first severe exacerbation, fluticasone-salmeterol against fluticasone alone
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
AUSTRI randomised 11,679 patients aged 12 and over with persistent asthma and a severe exacerbation in the preceding year to fluticasone plus salmeterol or fluticasone alone for 26 weeks. Sixty-seven patients had 74 serious asthma-related events: 36 events in 34 patients on the combination against 38 events in 33 patients on fluticasone alone, hazard ratio 1.03 (95% CI 0.64 to 1.66), meeting the prespecified noninferiority margin of an upper bound below 2.0 (P=0.003). There were no asthma-related deaths; two intubations occurred, both in the fluticasone-only group. Severe exacerbations occurred in 480 of 5,834 (8%) on the combination against 597 of 5,845 (10%) on fluticasone alone, hazard ratio 0.79 (95% CI 0.70 to 0.89), P<0.001.
Written into the record, not signed off as a reviewed claim
VESTRI: the same question asked again in 6,208 children aged 4 to 11
In plain words
Children were the group where the original alarm was about hospital admissions rather than deaths, so the trial was repeated in them. Twenty-seven children on the combination and twenty-one on the steroid alone were admitted. All the serious events were admissions; none was a death.
What was measured
First serious asthma-related event in children aged 4 to 11
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
VESTRI randomised 6,208 children aged 4 to 11 requiring daily asthma medication with an exacerbation in the previous year to fluticasone plus salmeterol or fluticasone alone for 26 weeks. Twenty-seven patients on the combination and 21 on fluticasone alone had a serious asthma-related event, every one of them a hospitalisation, hazard ratio 1.28 (95% CI 0.73 to 2.27). Noninferiority was declared against a prespecified upper bound of 2.675 (P=0.006). Severe exacerbations occurred in 265 (8.5%) against 309 (10.0%), hazard ratio 0.86 (95% CI 0.73 to 1.01).
Written into the record, not signed off as a reviewed claim
TORCH: the survival trial missed at p=0.052 and found more pneumonia
In plain words
Six thousand people with chronic obstructive pulmonary disease were followed for three years to see whether salmeterol with a steroid helps them live longer. Fewer died on the combination, but not by enough to clear the threshold the trial had set. Meanwhile one in five on the steroid-containing arms got pneumonia, against one in eight on placebo.
What was measured
Death from any cause at three years, combination against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
TORCH randomised 6,112 patients in the efficacy population to salmeterol 50 micrograms plus fluticasone propionate 500 micrograms twice daily, salmeterol alone, fluticasone alone or placebo for three years. All-cause mortality was 12.6% on combination, 13.5% on salmeterol, 16.0% on fluticasone and 15.2% on placebo. The hazard ratio for combination against placebo was 0.825 (95% CI 0.681 to 1.002, P=0.052 adjusted for interim analyses), missing the predetermined level of significance. Neither monotherapy differed significantly from placebo. The combination cut annual exacerbations from 1.13 to 0.85 and improved health status and spirometry (P<0.001). Pneumonia reported as an adverse event was 19.6% on combination and 18.3% on fluticasone against 12.3% on placebo, P<0.001.
Written into the record, not signed off as a reviewed claim
POET-COPD: beaten head to head by an anticholinergic in 7,376 patients
In plain words
The largest direct comparison of salmeterol against tiotropium in chronic obstructive pulmonary disease ran for a year. Tiotropium delayed the next flare-up by six weeks and cut the risk by seventeen per cent. Salmeterol lost.
What was measured
Time to first moderate or severe exacerbation, tiotropium against salmeterol
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
POET-COPD randomised 7,376 patients with moderate to very severe chronic obstructive pulmonary disease and an exacerbation in the preceding year to tiotropium 18 micrograms once daily or salmeterol 50 micrograms twice daily for one year, double-blind and double-dummy. Tiotropium increased time to first exacerbation from 145 to 187 days, hazard ratio 0.83 (95% CI 0.77 to 0.90, P<0.001), increased time to first severe exacerbation (HR 0.72, 95% CI 0.61 to 0.85, P<0.001), and reduced annual moderate or severe exacerbations from 0.72 to 0.64 (rate ratio 0.89, 95% CI 0.83 to 0.96, P=0.002). There were 64 deaths (1.7%) on tiotropium and 78 (2.1%) on salmeterol.
Written into the record, not signed off as a reviewed claim
The class warning was lifted in 2017 — but not from salmeterol on its own
In plain words
The boxed warning came off the combination inhalers in December 2017 after four trials in 36,010 people found no excess risk when the beta-agonist is given with a steroid. It stayed on salmeterol by itself, and using salmeterol alone in asthma is now not merely warned against but forbidden.
What was measured
That the 2017 withdrawal cleared long-acting beta-agonists generally — it cleared them in fixed-dose combination with a steroid, and left salmeterol monotherapy in asthma contraindicated
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SMART led to a boxed warning applied to every long-acting beta-agonist. In 2010 the FDA required the four manufacturers to run harmonised safety trials; the combined analysis of AUSTRI, VESTRI and the two sibling trials covered 36,010 adolescents and adults and found three asthma-related intubations and two asthma-related deaths in total, with serious asthma-related events in 108 of 18,006 (0.60%) on inhaled glucocorticoid alone against 119 of 18,004 (0.66%) on combination therapy, relative risk 1.09 (95% CI 0.83 to 1.43, P=0.55), and exacerbations in 2,100 (11.7%) against 1,768 (9.8%), relative risk 0.83 (95% CI 0.78 to 0.89, P<0.001). The boxed warning was removed from fixed-dose combination products in December 2017. The current SEREVENT DISKUS label still carries WARNING: ASTHMA-RELATED DEATH and states that use as monotherapy for asthma without a concomitant inhaled corticosteroid is contraindicated. A reader who has heard that the class warning was withdrawn will find this page contradicting them, and the label is why.
Written into the record, not signed off as a reviewed claim
The genetic explanation for the SMART deaths did not survive its own trial
In plain words
Most of the excess deaths in SMART were in African-American participants, and a popular explanation was a common variant in the receptor the drug acts on. A trial built specifically to test that gave the two genotypes the same lung-function response to salmeterol, to within a tenth of a litre per minute.
What was measured
That the excess deaths among African-American participants in SMART are explained by the ADRB2 Arg16 variant — a hypothesis that a genotype-stratified randomised trial tested directly and did not support on its primary endpoint
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In SMART the imbalance concentrated in African-American subjects: respiratory-related deaths or life-threatening experiences 20 against 5, relative risk 4.10 (95% CI 1.54 to 10.90), and combined asthma-related deaths or life-threatening experiences 19 against 4, RR 4.92 (95% CI 1.68 to 14.45). The paper itself says whether the risk reflects a physiologic treatment effect, genetic factors or patient behaviours remains unknown. LARGE then enrolled adults matched in pairs by FEV1 and ethnic origin and stratified by ADRB2 codon 16 genotype — 42 Arg/Arg and 45 Gly/Gly — and crossed them over between salmeterol and placebo on open-label beclometasone. Morning peak expiratory flow rose 21.4 L/min (95% CI 11.8 to 31.1) in Arg/Arg and 21.5 L/min (11.0 to 32.1) in Gly/Gly, a between-genotype difference of -0.1 L/min (95% CI -14.4 to 14.2, p=0.99). A genotype-specific difference did appear in methacholine responsiveness, 1.32 doubling doses (0.43 to 2.21, p=0.0038), which is a secondary outcome and a different question.
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A beta-2 receptor agonist whose long greasy tail anchors it in the membrane beside the receptor so airway muscle stays relaxed for about twelve hours — given alone in asthma it produced 13 asthma deaths against 3 on placebo in 26,355 people, and given with an inhaled steroid to 11,679 people it produced no excess of serious asthma events and 21% fewer severe exacerbations, which is why it is contraindicated by itself and routine inside a combination inhaler.
Recorded evidence blocks (10)
Q2
On the Salmeterol label: indicated for what?
"Fluticasone Propionate Nasal Spray, USP 50 mcg per spray is indicated for the management of the nasal symptoms of perennial nonallergic rhinitis in adult and pediatric patients aged 4 years and older. Fluticasone Propionate Nasal Spray, USP 50 mcg per spray is a corticosteroid indicated for the management of the nasal…": indications and usage on Salmeterol's label. DailyMed label · 549ff4f2-fa68-3dd8-e054-00144ff8d46c · 2024-07-15
Q3
113 registered trials of Salmeterol — at which phases?
"The study was terminated due to difficulties with finding sites and subjects willing to participate."; 6 of 113 registered studies
Show the evidence
Trial
NCT00346749
terminated; "The study was terminated due to difficulties with finding sites and subjects willing to participate."
NCT00411372
withdrawn; "No subjects enrolled. Study was canceled before active"
NCT00546234
withdrawn; "No subjects enrolled and no ongoing funding."
NCT00706446
terminated; "Funding was terminated"
NCT03662711
terminated; "Contract terminated between AIFA and the Sponsor (University of Ferrara)"
NCT06282861
terminated; "Delays in the opening and activation of participating sites, and a low recruitment rate, with only 48 participants enrolled over the course of one year"
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Salmeterol used Salmeterol 50mcg — over how long?
studies of Salmeterol used the recorded amount. ClinicalTrials.gov · 2026-09-01
13 recorded entries; human; also "Salmeterol 50mcg", "salmeterol 50mcg", "Fluticasone Propionate/Salmeterol 500/50mcg combination"
Salmeterol's half-life is 7.8 hours — which schedules were studied?
7.8 hours, the half-life Salmeterol's label states: "Elimination Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours." DailyMed label · 549ff4f2-fa68-3dd8-e054-00144ff8d46c · 2024-07-15
bioavailability 2 %.
Show the evidence
half lifepharmacokinetics
7.8 hours; Elimination Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours.
bioavailabilitypharmacokinetics
2 %; Absorption Indirect calculations indicate that fluticasone propionate delivered by the intranasal route has an absolute bioavailability averaging less than 2%.
metabolismpharmacokinetics
Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver.
recorded 2024-07-15 · last checked 2026-09-04
Q7
Which 41 trials of Salmeterol posted no result?
Posted no result
41 of 41 completed trials
Registrations
NCT00685841, NCT00274534, NCT00064402, NCT00064415, NCT00950794 and NCT00354874, and 35 more
Completion dates
oldest 2003-06; newest 2021-08-09
Show the evidence
Trial
NCT00685841
2003-06
NCT00274534
2003-07
NCT00064402
2004-03
NCT00064415
2004-12
NCT00950794
2005-02
NCT00354874
2005-06
14 further recorded trials
NCT00269126
2005-08
NCT01488773
2006-06
NCT00364273
2006-07-06
NCT00525564
2006-10
NCT00144911
2006-12
NCT00102882
2007-01
NCT00358488
2007-01
NCT00347139
2007-01-10
NCT00358358
2007-02
NCT00736801
2007-04
NCT00315744
2007-04-12
NCT00422604
2007-05
NCT00115492
2007-06
NCT00605891
2007-06
Q8
At the median, Salmeterol's trials enrolled 134 people — anything larger?
Median enrolment
134
Largest enrolment
8716
Registered trials counted
112
Q9
What do 4528 spontaneous reports say about Salmeterol — 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.
Salmeterol appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4528 reaction mentions were counted: asthma 1223; dyspnoea 760; wheezing 435; cough 397. FAERS via Open Targets · CHEMBL1082607 · 2026-06-24
Show the evidence
asthma
1223
dyspnoea
760
wheezing
435
cough
397
pneumonia
371
therapeutic product effect incomplete
337
4 more recorded rows
drug hypersensitivity
286
obstructive airways disorder
259
blood count abnormal
241
malaise
219
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Salmeterol's label not list?
Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended.
drug_interactions
( 7.1 ) 7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone propionate is a substrate of CYP3A4.
drug_interactions
The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, nefazodone, voriconazole) with Fluticasone Propionate Nasal Spray is not recommended because increased systemic corticosteroid adverse effects may occur.
drug_interactions
Ritonavir A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology (12.3) ].
pharmacokinetics
Metabolism: The only circulating metabolite detected in man is the 17β-carboxylic acid derivative of fluticasone propionate, which is formed through the CYP3A4 pathway.
pharmacokinetics
Drug Interactions Inhibitors of Cytochrome P450 3A4: Ritonavir: Fluticasone propionate is a substrate of CYP3A4.
2 more recorded rows
Interaction statementpharmacokinetics
Coadministration of fluticasone propionate and the strong CYP3A4 inhibitor, ritonavir, is not recommended based upon a multiple-dose, crossover drug interaction trial in 18 healthy subjects.
Interaction statementclinical_pharmacology
Metabolism: The only circulating metabolite detected in man is the 17β-carboxylic acid derivative of fluticasone propionate, which is formed through the CYP3A4 pathway.
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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