This page shows what was measured, who it was measured in, and what that does not settle.
What Theophylline Anhydrous does in the body
An old oral tablet that opens the airways, with a narrow margin between a helpful dose and a dangerous one
Theophylline is a chemical cousin of caffeine, swallowed as a tablet. It blocks an enzyme inside airway muscle cells so a relaxing signal accumulates, and it blocks a second receptor that would otherwise make the airway twitchy — which is also where most of its side effects come from. At very low concentrations it does something else again, reactivating an enzyme that steroids need in order to switch inflammatory genes off. The gap between a dose that helps and a dose that causes vomiting, racing heart and seizures is narrow, and a great many ordinary medicines shift a person across it.
What happened in people
Serum cortisol falling from 18.4 to 15.9 micrograms per decilitre on doubled budesonide and unchanged on the theophylline combination
✎ 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.
114 registered substances share the start of this name, which is why a search for it can return more than one thing.
FDA substance registry · C229N9DX94 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 143 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.
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.
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.
Number of participant-reported moderate or severe COPD exacerbations treated with antibiotics, oral corticosteroids or both, over one year
✗ The study did not show it
Who was studied
TWICS (ISRCTN27066620)
How many people
1578
Study design
Phase 4, pragmatic, randomised, double-blind, placebo-controlled, one year
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Mean 2.24 (95% CI 2.10 to 2.38) against 2.23 (2.09 to 2.37) exacerbations per year; unadjusted mean difference 0.01 (95% CI -0.19 to 0.21); adjusted incidence rate ratio 0.99 (95% CI 0.91 to 1.08)
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. Nausea 10.9% against 7.9%, headache 9.0% against 7.9%, gastrointestinal serious adverse events 2.7% against 1.3%. A null efficacy result with a non-null harm profile is a net negative rather than a neutral one.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablets and capsules, and an intravenous solution in dextrose for hospital use
Interval reported. 95% CI 2
Written into the record, not signed off as a reviewed claim.
TWICS — theophylline with inhaled corticosteroids, registration record (https://www.isrctn.com/ISRCTN27066620) · a recorded source, not a stored snapshot
Lung function, peak expiratory flow, symptoms and albuterol use, low-dose budesonide plus theophylline against doubled budesonide
✓ The study showed what it set out to show
Who was studied
Evans 1997 — theophylline against doubled inhaled budesonide
How many people
62
Study design
Randomised, double-blind, placebo-controlled, active comparator, three months
Compared against
A dummy treatment
Kind of result
What a body can do day to day
What was found
Greater improvement in FVC (P=0.03) and FEV1 (P=0.03) on the combination; serum cortisol fell from 18.4±2.4 to 15.9±2.1 micrograms per decilitre on doubled budesonide (P=0.02) and was unchanged on the combination
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. Sixty-two patients over three months, with lung function rather than exacerbations as the endpoint. The effect was achieved at a median serum theophylline concentration of 8.7 micrograms per millilitre, below the stated therapeutic range of 10 to 20 — an observation that seeded two decades of low-dose theophylline research.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablets and capsules, and an intravenous solution in dextrose for hospital use
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
TWICS — theophylline with inhaled corticosteroids, registration record (https://www.isrctn.com/ISRCTN27066620) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Where a source records it acting
Lungs and airways: Two distinct actions in the airways of patients with reversible obstruction: smooth muscle relaxation (bronchodilation) and suppression of the response of the airways to stimuli
US prescribing information · 04f1d1da-ce61-45b3-acf4-903cc81d16da · read 2026-08-27
Muscle: Increases the force of contraction of diaphragmatic muscles, apparently through enhancement of calcium uptake through an adenosine-mediated channel
US prescribing information · 04f1d1da-ce61-45b3-acf4-903cc81d16da · read 2026-08-27
Start
Theophylline Anhydrous
What a person takes: Oral extended-release tablets and capsules, and an intravenous solution in dextrose for hospital use.
The measurement behind this step
Taken once or twice daily. There is no inhaler and no technique to get wrong, which is the drug’s single practical advantage and the reason it survives in settings where devices are unaffordable or unavailable. The cost of that simplicity is that dosing is by serum concentration rather than by a fixed strength, and the correct dose changes when the patient’s circumstances do.
Getting in
Swallowed as an extended-release tablet
It is taken by mouth once or twice a day. No inhaler, no technique, no coordination — which is exactly why it is still used where inhalers are hard to get.
╌╌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
Theophylline anhydrous in an extended-release matrix, most often 200 to 400 mg once or twice daily. Absorption is complete; the constraint is not getting the drug in but keeping the serum concentration inside a narrow window.
The liver decides the blood level, and many things change its mind
How much drug ends up in the blood depends on an enzyme in the liver, and that enzyme is sped up by cigarette smoke and slowed down by fever, heart failure, liver disease, age and a long list of other medicines.
╌╌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
Clearance is predominantly hepatic via CYP1A2 with a contribution from CYP3A4, and it is the reason the label devotes tables to interactions. Tobacco smoke induces CYP1A2, so smoking cessation raises the serum concentration of an unchanged dose. Cimetidine, erythromycin and tacrine inhibit clearance; carbamazepine and rifampin induce it.
It blocks the enzyme that destroys the muscle’s relaxing signal
Airway muscle holds a messenger that tells it to relax, and an enzyme constantly breaks it down. Theophylline blocks that enzyme, so the messenger builds up and the airway opens.
╌╌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 attributes bronchodilation to inhibition of phosphodiesterase III and, to a lesser extent, phosphodiesterase IV, based on animal studies. PDE III is also expressed in cardiac and vascular smooth muscle, which is where hypotension and tachycardia come from — the same inhibition, in the wrong tissue.
It also blocks adenosine, which is where the jitteriness comes from
A second, separate action blocks adenosine receptors. That contributes to keeping the airway open and it is also why the drug feels like strong coffee, and why an overdose causes seizures.
╌╌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
Adenosine receptor antagonism is a mechanism theophylline shares with caffeine, its close structural relative. The label attributes alterations in cerebral blood flow to it. It also records that theophylline increases the force of contraction of diaphragmatic muscles through enhanced calcium uptake via an adenosine-mediated channel — a genuinely distinctive effect no inhaled drug has.
At very low concentrations it does something different again
Well below the level needed to open an airway, theophylline reactivates an enzyme that steroids depend on to switch inflammatory genes off. This is the mechanism the 2018 trial was built around.
╌╌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
Ito and colleagues showed that low-dose theophylline enhances histone deacetylase activity in epithelial cells and macrophages, making it available for corticosteroid recruitment, at therapeutic concentrations and dissociated from both phosphodiesterase inhibition and adenosine antagonism. TWICS dosed to 1 to 5 mg/L specifically to exploit this.
The airway opens, and the flare-up rate does not move
Symptoms and reversible obstruction improve, which is what the label claims. Adding it to a steroid inhaler to prevent flare-ups was tested in 1,578 people and the rates came out at 2.24 against 2.23 per year.
╌╌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 indication is limited to symptoms and reversible airflow obstruction in chronic asthma and other chronic lung diseases. TWICS gave an adjusted incidence rate ratio of 0.99 (95% CI 0.91 to 1.08) for exacerbations, with more nausea (10.9% against 7.9%) and more gastrointestinal serious adverse events (2.7% against 1.3%) on theophylline.
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 whose asthma or chronic obstructive pulmonary disease is not controlled by inhaled treatment, and — far more commonly — people for whom inhaled treatment is unaffordable or unavailable.
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: “Theophylline is safe and effective for the approved indications in pediatric patients.”
US prescribing information · c6ca5cc9-4e5e-40cf-a36e-227aa4cb55c6 · read 2026-08-30
On older people, the label states: “Elderly patients are at a significantly greater risk of experiencing serious toxicity from theophylline than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging.”
US prescribing information · c6ca5cc9-4e5e-40cf-a36e-227aa4cb55c6 · read 2026-08-30
On people who are pregnant, the label states: “Teratogenic Effects: In studies in which pregnant mice, rats and rabbits were dosed during the period of organogenesis, theophylline produced teratogenic effects.”
US prescribing information · c6ca5cc9-4e5e-40cf-a36e-227aa4cb55c6 · read 2026-08-30
On people who are breastfeeding, the label states: “Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants.”
US prescribing information · c6ca5cc9-4e5e-40cf-a36e-227aa4cb55c6 · read 2026-08-30
Where the result stopped carrying
TWICS found no reduction in exacerbations and more nausea and gastrointestinal serious adverse events
The histone deacetylase hypothesis produced a clinical prediction that a purpose-built trial did not confirm
The therapeutic index is narrow enough that fever, heart failure, quitting smoking or a course of erythromycin can push a stable patient into toxicity
The label’s own mechanism section identifies the mechanisms behind the side effects and not the one behind the prophylactic benefit
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
Oral extended-release tablets and capsules, and an intravenous solution in dextrose for hospital use
✎ 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
Taken once or twice daily. There is no inhaler and no technique to get wrong, which is the drug’s single practical advantage and the reason it survives in settings where devices are unaffordable or unavailable. The cost of that simplicity is that dosing is by serum concentration rather than by a fixed strength, and the correct dose changes when the patient’s circumstances do.
✎ 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
A narrow therapeutic index drug. Extreme caution in active peptic ulcer disease, seizure disorders and cardiac arrhythmias other than bradyarrhythmias. Numerous conditions reduce clearance and require dose reduction — neonates and children under 1, adults over 60, acute pulmonary oedema, congestive heart failure, cor pulmonale, sustained fever of 102°F, hypothyroidism, cirrhosis and acute hepatitis, sepsis with multi-organ failure, shock, and cessation of smoking. Interactions are extensive: adding cimetidine, erythromycin or tacrine, or stopping carbamazepine or rifampin, raises concentrations, and the label warns that severe and potentially fatal toxicity can follow if the dose is not reduced. Nausea or repetitive vomiting requires doses to be withheld and a serum concentration measured, even when another cause is suspected.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral extended-release tablets and capsules, and an intravenous solution in dextrose for hospital use
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
There is no inhaler and no technique to get wrong, which is the drug’s single practical advantage and the reason it survives in settings where devices are unaffordable or unavailable. The cost of that simplicity is that dosing is by serum concentration rather than by a fixed strength, and the correct dose changes when the patient’s circumstances do.
✎ 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
58 products list this as an active ingredient in the United States drug directory. 58 of them contain it and nothing else.
FDA National Drug Code directory · 82638-105 · read 2026-08-29
They are sold as capsule, extended release, powder, solution and tablet, extended release, taken oral.
FDA National Drug Code directory · 82638-105 · read 2026-08-29
The regulator's established pharmacologic class for it is methylxanthine [epc] and xanthines [cs].
FDA National Drug Code directory · 82638-105 · read 2026-08-29
29 published labels name it as an active ingredient. 29 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 62fb84a9-4e75-4f4b-8f15-1fd1bb7ae4dd · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 62fb84a9-4e75-4f4b-8f15-1fd1bb7ae4dd · read 2026-08-29
Theophylline (Anhydrous) is extended-release tablets at 400 mg and 600 mg, recorded as prescription product; fda label in effect 2025-12-04 in the United States.
US prescribing information · 04f1d1da-ce61-45b3-acf4-903cc81d16da · read 2026-08-27
Recorded price in US: 0.11183 USD per one millilitre, across 2 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
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 Theophylline Anhydrous 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 low-dose theophylline reduces exacerbations by restoring corticosteroid sensitivity — the prediction was dosed precisely and tested in 1,578 people, and returned 0.99
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 anti-inflammatory mechanism is understood, when the label states it is probably something other than the two mechanisms it can name
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 62-patient three-month lung-function trial establishes a steroid-sparing strategy
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 worldwide use reflects demonstrated benefit rather than an acquisition price of about a dollar a tablet and no device requirement
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 Theophylline Anhydrous 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.
TWICS: 1,578 patients, and the exacerbation rate went from 2.23 to 2.24
In plain words
The trial built to test theophylline’s most attractive modern claim gave a low dose or a placebo to more than fifteen hundred people with chronic obstructive pulmonary disease already on a steroid inhaler. Over a year they had 3,430 flare-ups between them, and the two groups were indistinguishable.
What was measured
Participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids or both, over one year
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
TWICS was a pragmatic, double-blind, placebo-controlled randomised trial in 121 UK primary and secondary care sites, enrolling 1,578 participants with FEV1/FVC below 0.7, at least two exacerbations in the previous year and current inhaled corticosteroid use. Participants received low-dose theophylline 200 mg once or twice daily, dosed by ideal body weight and smoking status to give plasma concentrations of 1 to 5 mg/L (n=791), or placebo (n=787). Primary outcome data were available for 1,536 of 1,567 analysed participants (98%). There were 3,430 exacerbations in total: 1,727 on theophylline (mean 2.24 per year, 95% CI 2.10 to 2.38) against 1,703 on placebo (mean 2.23, 95% CI 2.09 to 2.37); unadjusted mean difference 0.01 (95% CI -0.19 to 0.21), adjusted incidence rate ratio 0.99 (95% CI 0.91 to 1.08). Nausea was reported by 10.9% against 7.9% and headache by 9.0% against 7.9%; gastrointestinal serious adverse events were 2.7% against 1.3%. The authors conclude that the findings do not support this use.
Written into the record, not signed off as a reviewed claim
A beautiful mechanism from 2002 that a trial in 2018 did not confirm
In plain words
In 2002 a paper explained why a tiny dose of theophylline should make steroids work better: it reactivates an enzyme steroids need, and it does so at concentrations far below the ones that cause side effects. It was elegant, widely cited and dosed precisely in the trial that followed. The trial found nothing.
What was measured
That low-dose theophylline restores corticosteroid sensitivity to a degree that reduces exacerbations — a mechanism-derived prediction tested at the predicted concentration in 1,578 patients, with an incidence rate ratio of 0.99
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Ito and colleagues showed in vitro and in vivo that low-dose theophylline enhances histone deacetylase activity in epithelial cells and macrophages, that the increased activity is then available for corticosteroid recruitment, and that this occurs at therapeutic concentrations and is dissociated from phosphodiesterase inhibition — the bronchodilator mechanism — and from adenosine receptor blockade, which causes side effects. The prediction was a cooperative interaction between corticosteroids and theophylline. TWICS was designed around it: 200 mg once or twice daily titrated by ideal body weight and smoking status specifically to hit 1 to 5 mg/L, in 1,578 patients all taking an inhaled corticosteroid. The adjusted incidence rate ratio for exacerbations was 0.99 (95% CI 0.91 to 1.08). The mechanism is not thereby disproved; the clinical prediction drawn from it was tested and did not hold.
Written into the record, not signed off as a reviewed claim
It matched a doubled steroid dose in 62 patients, without touching cortisol
In plain words
A small trial in moderate asthma compared adding theophylline to a low steroid dose against simply doubling the steroid. The combination did slightly better on two lung-function measures, and unlike the doubled steroid it did not suppress the body’s own cortisol. The theophylline levels achieved were below the range the drug is supposed to need.
What was measured
FVC, FEV1, beta-agonist use, peak-flow variability and serum cortisol at three months, low-dose budesonide plus theophylline against doubled budesonide
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A double-blind, placebo-controlled trial randomised 62 patients with persistent asthma symptoms despite inhaled glucocorticoid to budesonide 400 micrograms twice daily plus theophylline 250 or 375 mg twice daily by body weight, or budesonide 800 micrograms twice daily, for three months. Both improved lung function and both sustained it. Compared with high-dose budesonide, low-dose budesonide plus theophylline produced greater improvements in forced vital capacity (P=0.03) and FEV1 (P=0.03). Reductions in beta-agonist use and in peak-flow variability were significant and similar in both arms. Serum cortisol fell in the high-dose budesonide group, from 18.4±2.4 to 15.9±2.1 micrograms per decilitre (P=0.02), and was unchanged in the theophylline group. The median serum theophylline concentration was 8.7 micrograms per millilitre, against a stated therapeutic range of 10 to 20.
Written into the record, not signed off as a reviewed claim
An antibiotic course can make a correct prescription lethal
In plain words
Theophylline has a narrow gap between a helpful blood level and a dangerous one, and dozens of ordinary medicines and conditions move a person across it. The label lists the causes: some antibiotics, a fever lasting a day, heart failure, liver disease, being over sixty, and quitting smoking.
What was measured
Documented causes of reduced theophylline clearance and their consequence for serum concentration
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label states that there are several readily identifiable causes of reduced theophylline clearance and that if the total daily dose is not appropriately reduced in their presence, severe and potentially fatal theophylline toxicity can occur. Named risk factors include neonates, children under 1, adults over 60, acute pulmonary oedema, congestive heart failure, cor pulmonale, fever of 102°F for 24 hours or more, hypothyroidism, cirrhosis and acute hepatitis, reduced renal function in infants under 3 months, sepsis with multi-organ failure, shock, and cessation of smoking. Drug interactions are handled in whole tables; the label singles out adding cimetidine, erythromycin or tacrine, or stopping carbamazepine or rifampin. Theophylline is to be used with extreme caution in active peptic ulcer disease, seizure disorders and cardiac arrhythmias. The label instructs withholding doses and measuring a serum concentration whenever nausea or repetitive vomiting occurs, even if another cause is suspected.
Source
Theophylline anhydrous extended-release United States prescribing information — Warnings, Concurrent Illness and Conditions That Reduce Theophylline Clearance; Precautions, Drug Interactions
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 label admits it does not know how the useful half works
In plain words
The prescribing information says the mechanisms are not known with certainty. It attributes the airway-opening effect to blocking one enzyme, and then says the anti-inflammatory effect is probably something else entirely that it cannot name — while attributing the side effects to the two mechanisms it can.
What was measured
That the anti-inflammatory action of theophylline is understood — the label says it is not, and names only the mechanisms responsible for the adverse effects
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Mechanism of Action section states that theophylline has two distinct actions in the airways — smooth muscle relaxation and suppression of airway responsiveness — that the mechanisms are not known with certainty, that animal studies suggest bronchodilation is mediated by inhibition of phosphodiesterase III and to a lesser extent IV, and that the non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms that do not involve PDE III inhibition or adenosine receptor antagonism. It then assigns hypotension, tachycardia, headache and emesis to PDE III inhibition and altered cerebral blood flow to adenosine antagonism. In other words the two mechanisms that are identified are the ones that produce harm, and the mechanism behind the prophylactic benefit is explicitly unnamed. That is a rare and honest statement to find in a mechanism-of-action section, and it is the context in which the histone deacetylase hypothesis was proposed as the missing piece.
Source
Theophylline anhydrous extended-release United States prescribing information, Clinical Pharmacology — Mechanism of Action
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
Its continued use worldwide is an argument about price, not about evidence
In plain words
Theophylline remains one of the most widely used respiratory drugs on earth, and the reason is that it costs about a dollar a tablet and needs no inhaler. That is a real and serious argument. It is not the same argument as the drug being effective.
What was measured
That theophylline’s continued global use reflects demonstrated benefit — it substantially reflects an acquisition price of about a dollar per tablet and the absence of a device requirement
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The CMS acquisition survey lists theophylline at a median US$1.05 per tablet across 30 generic presentations, against US$6.74 to US$11.73 per unit for the branded long-acting inhalers in this file. Against that: TWICS found an incidence rate ratio of 0.99 for exacerbations in 1,578 patients, and the label’s indication is limited to symptoms and reversible airflow obstruction rather than exacerbation prevention. The hidden cost is monitoring — serum concentrations, dose adjustment for a long list of conditions and drugs, and re-checking after any change — which is precisely the infrastructure least available in the settings where the price advantage matters most. Inferring effectiveness from persistence of use inverts the causation: the drug persists because it is affordable, and its affordability says nothing about what it does.
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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.
A methylxanthine that relaxes airway muscle by inhibiting phosphodiesterase III and IV, blocks adenosine receptors, and at low concentrations restores histone deacetylase activity to make steroids work better — a mechanism published in 2002 and tested in 1,578 patients in 2018, where adding it to an inhaled steroid changed the exacerbation rate from 2.23 to 2.24 per year, incidence rate ratio 0.99 (95% CI 0.91 to 1.08).
Recorded evidence blocks (7)
Q1
On the Theophylline Anhydrous label: indicated for what?
": Theophylline extended-release tablets are indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.": indications and usage on Theophylline Anhydrous's label. DailyMed label · 5e64036a-ee3e-42e7-9e59-881f88a4e298 · 2026-07-29
Q2
82 registered trials of Theophylline Anhydrous — at which phases?
Registered studies posting no result
62 of 82
82 registered studies of Theophylline Anhydrous: 21 phase2, 17 phase4, 15 phase1, 15 phase3, 13 na, 5 na or unstated, 3 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
469 with a PubMed record
Show the evidence
phase2
21
phase4
17
phase1
15
phase3
15
na
13
na or unstated
5
8 more recorded rows
early phase1
3
completed
56
unknown
12
recruiting
5
terminated
3
withdrawn
3
active not recruiting
2
not yet recruiting
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
6 of Theophylline Anhydrous's trials stopped: accrual/recruitment, funding/business, other?
accrual/recruitment (2), funding/business (1) and other (3): Theophylline Anhydrous's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Due to nationwide shortage of Aminophylline. Enrolled subjects did not complete study."; 6 of 82 registered studies
Show the evidence
Trial
NCT01250496
terminated; "Due to nationwide shortage of Aminophylline. Enrolled subjects did not complete study."
NCT01655524
withdrawn; "Due to nationwide shortage of Aminophylline. No subjects enrolled."
NCT01799161
withdrawn; "Insufficient funding"
NCT02080078
terminated; "REB decision"
NCT02270827
terminated; "Study was set up by an MSc student who left her post."
NCT05666219
withdrawn; "we could not find patients fulfilling all of our inclusion criteria"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Theophylline Anhydrous used Theophylline 200 mg — over how long?
Human studies of Theophylline Anhydrous used "Theophylline 200 mg". ClinicalTrials.gov · 2026-09-01
12 recorded entries; human; IV; also "Theophylline 300 mg", "Aminophylline (250mg IV +/- a second dose of 250mg IV)", "Theophylline 300mg"
Show the evidence
human
NCT00252863
Theophylline 200 mg
NCT00252863
Theophylline 300 mg
NCT00312273
IV; Aminophylline (250mg IV +/- a second dose of 250mg IV)
NCT00779259
Theophylline 300mg
NCT00983905
Elixophyllin® Elixir (Theophylline Anhydrous) 80/15 ml concentrate
NCT01696214
Theophylline 400 mg
6 more recorded rows
humanNCT01794078
Aminophylline 400 mg
humanNCT02184247
anhydrous theophylline, 350 mg
humanNCT02184247
anhydrous theophylline, 300 mg
humanNCT02261727
Theophylline (100 mg twice a day)
humanNCT07528118
Inj Aminophylline 100mg with Inj Acetaminophen 1000mg in 100ml Normal Saline
humanNCT07528118
Inj Aminophylline 100mg , with 0.1mg/kg Dexamethasone in 100ml Normal Saline
recorded 2026-09-01 · last checked 2026-09-04
Q5
Theophylline Anhydrous's half-life is 3 to 15 days — which schedules were studied?
3 to 15 days, the half-life Theophylline Anhydrous's label states: "Values listed were generally determined at serum theophylline concentrations <20 mcg/mL; clearance may decrease and half-life may increase at higher serum concentrations due to non-linear pharmacokinetics. †† Reported range or estimated range (mean ±2 SD) where actual range not reported. † NR = not reported or not…" DailyMed label · 5e64036a-ee3e-42e7-9e59-881f88a4e298 · 2026-07-29
tmax 8.31 hours.
Show the evidence
half lifepharmacokinetics
3 to 15 days; Values listed were generally determined at serum theophylline concentrations <20 mcg/mL; clearance may decrease and half-life may increase at higher serum concentrations due to non-linear pharmacokinetics. †† Reported range or estimated range (mean ±2 SD) where actual range not reported. † NR = not reported or not reported in a comparable format. ** Median Population Characteristics Total body…
tmaxpharmacokinetics
8.31 hours; Mean peak theophylline serum levels (C max ) was 6.69 mcg/mL and mean time of peak serum concentration (T max ) was 8.31 hours.
metabolismpharmacokinetics
Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver.
recorded 2026-07-29 · last checked 2026-09-04
Q6
Which 33 trials of Theophylline Anhydrous posted no result?
Posted no result
33 of 33 completed trials
Registrations
NCT00000578, NCT00312273, NCT00756418, NCT00492518, NCT00252863 and NCT00252785, and 27 more
Completion dates
oldest 2000-10; newest 2024-07-08
Show the evidence
Trial
NCT00000578
2000-10
NCT00312273
2004-07
NCT00756418
2004-08-28
NCT00492518
2004-10
NCT00252863
2006-05
NCT00252785
2006-11
14 further recorded trials
NCT01066728
2007-03
NCT00119496
2007-06
NCT00671151
2007-12
NCT00003684
2008-12-15
NCT00299858
2010-05
NCT01240824
2011-02
NCT01017939
2012-04
NCT01132781
2012-06
NCT01594489
2012-09
NCT02001935
2014-07
NCT01684683
2014-09
NCT01769898
2014-11
NCT01794078
2014-12
NCT01599871
2016-09
Q7
At the median, Theophylline Anhydrous's trials enrolled 50 people — anything larger?
Median enrolment
50
Largest enrolment
1670
Registered trials counted
79
Where it is registeredIdentifiers, relations and other names
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · 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
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