This page shows what was measured, who it was measured in, and what that does not settle.
What Roflumilast does in the body
Roflumilast blocks that enzyme, so the messenger builds up and the cells calm down.
Inflammatory cells hold a chemical messenger called cyclic AMP that acts as a brake on them, and an enzyme inside those cells constantly destroys it. It is a tablet, not an inhaler, so the effect reaches inflammatory cells everywhere in the body — which is why it works, and also why it causes diarrhoea, nausea, weight loss and mood changes that an inhaled drug would not.
Why people take it. A daily tablet that damps down inflammation in severe smokers’ lung disease, and — as a cream — a treatment for psoriasis and eczema
What happened in people
A 17% reduction in moderate or severe exacerbations, 1.14 against 1.37 per patient per year, in 3,091 patients across two 52-week trials
✎ 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.
The only oral anti-inflammatory approved for chronic obstructive pulmonary disease and the only non-inhaled drug in this group
Where it acts
Inflammatory cells of the airway wall — neutrophils, macrophages, T cells — and, for the cream, keratinocytes and immune cells in the skin
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 0P6C6ZOP5U · read 2026-08-29
Its recorded molecular formula is C17H14Cl2F2N2O3, weighing 403.22.
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 126 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
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.
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.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Blood sugar
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved4 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Body weight
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved2 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Focus
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
…Waiting for a reviewer1 registered performance measure of this kind.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Healthy ageing
…Waiting for a reviewer1 registered study measure of this kind. No reviewed result yet.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Cholesterol
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
main outcome was change in body weight; body weight
Focus
who develop cognitive decline
Healthy ageing
all cause mortality
Cholesterol
blood lipid levels
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
4 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
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.
Co-primary: change in prebronchodilator FEV1 and rate of moderate or severe exacerbations
✓ The study showed what it set out to show
Who was studied
M2-124 and M2-125 (NCT00297102 and NCT00297115)
How many people
3091
Study design
Phase 3, two identically designed randomised, double-blind, placebo-controlled trials, 52 weeks
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Pooled FEV1 +48 mL (p<0.0001); exacerbations 1.14 against 1.37 per patient per year, 17% reduction (95% CI 8 to 25), p<0.0003
Repeated elsewhere
Failed to Replicate
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. Adverse events 67% against 62%, discontinuation for adverse events 14% against 12%, and a pooled weight difference of -2.17 kg against placebo in a disease where weight loss is itself a poor prognostic sign.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, 250 and 500 micrograms once daily; separately, topical cream at 0.3%, 0.15% and 0.05%
Interval reported. 95% CI 8 to 25), p<0
Written into the record, not signed off as a reviewed claim.
Rate of moderate or severe COPD exacerbations per patient per year on inhaled corticosteroid plus long-acting beta-agonist, with or without a long-acting muscarinic antagonist
Rate ratio 0.92 (95% CI 0.81 to 1.04), P=0.163 — an 8.5% reduction, not significant
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 reported positive finding is a post hoc subgroup of participants with more than three prior exacerbations or at least one hospitalisation. Adverse-event-related discontinuation was 11.7% against 5.4%.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, 250 and 500 micrograms once daily; separately, topical cream at 0.3%, 0.15% and 0.05%
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Investigator Global Assessment success at week 8 in chronic plaque psoriasis, roflumilast cream 0.3% against vehicle
✓ The study showed what it set out to show
Who was studied
DERMIS-1 and DERMIS-2 (NCT04211363 and NCT04211389)
How many people
881
Study design
Phase 3, two randomised, double-blind, vehicle-controlled trials, 8 weeks
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Trial 1: 42.4% against 6.1% (difference 39.6%, 95% CI 32.3 to 46.9). Trial 2: 37.5% against 6.9% (difference 28.9%, 95% CI 20.8 to 36.9). P<0.001 for both.
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. Eight weeks of follow-up, and a vehicle rather than an active comparator. The authors state that further research is needed to assess efficacy against other active treatments and longer-term efficacy and safety.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, 250 and 500 micrograms once daily; separately, topical cream at 0.3%, 0.15% and 0.05%
Interval reported. 95% CI 32
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.3 registered measures of this kind. No reviewed result.
■What a body can do day to dayEvidence recorded. Walking, dressing, breathing, recovering.1 registered measure of this kind.
■Measured performanceEvidence recorded. How much was lifted, how far was run, how fast.1 registered measure of this kind.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.1 registered measure of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.10 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Roflumilast
What a person takes: Oral tablet, 250 and 500 micrograms once daily; separately, topical cream at 0.3%, 0.15% and 0.05%.
The measurement behind this step
The tablet is taken once daily with or without food. The 250 microgram strength exists only as a four-week starting dose to improve tolerability and is stated in the label not to be the therapeutic dose. The cream is a different product for a different disease, and is included on this page because it is the same molecule and the contrast in tolerability between the two routes is the clearest evidence of where the tablet’s side effects come from.
Getting in
Swallowed, not inhaled
It is a tablet taken once a day. That is the whole difference between this drug and everything else on this list, and it explains both what it does and what it costs the person taking it.
╌╌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
Roflumilast 500 micrograms once daily, with a 250 microgram starting strength for the first four weeks only, which the label states explicitly is not the therapeutic dose. Contraindicated in moderate to severe hepatic impairment, and not recommended with strong cytochrome P450 inducers such as rifampicin, phenobarbital, carbamazepine and phenytoin.
The liver converts part of it into a second active drug
The body turns some of the tablet into a related molecule that is also active. Both forms do the same job, which is why the effect lasts through the day from a single dose.
╌╌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
Roflumilast is oxidised to roflumilast N-oxide by CYP3A4 and CYP1A2. The label treats parent and N-oxide together as selective inhibitors of phosphodiesterase 4, and the N-oxide contributes the majority of total PDE4 inhibitory activity in humans.
It blocks the enzyme that destroys the cell’s brake signal
Inflammatory cells hold a messenger that damps them down, and an enzyme inside them constantly chews it up. Roflumilast stops that enzyme.
╌╌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
Selective inhibition of phosphodiesterase 4, described in the label as the major cyclic AMP-metabolising enzyme in lung tissue. Selectivity for PDE4 over PDE3 is the property that separates this drug from the non-selective xanthines and from their cardiac toxicity.
With the enzyme blocked, the brake signal builds up. Neutrophils and other inflammatory cells become less active.
╌╌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 states that inhibition leads to accumulation of intracellular cyclic AMP, and that the specific mechanism by which the drug exerts its therapeutic action in COPD is not well defined but is thought to relate to the effects of increased intracellular cyclic AMP in lung cells. This is unusually explicit uncertainty for a mechanism-of-action section.
Over a year, flare-ups fall from about 1.4 per person to about 1.1. Lung function rises by 48 millilitres, which the label is careful to say is not bronchodilation.
──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
Pooled across the two pivotal 52-week trials: moderate or severe exacerbations 1.14 against 1.37 per patient per year, a 17% reduction (95% CI 8 to 25, p<0.0003), and prebronchodilator FEV1 +48 mL (p<0.0001). In the two later trials on inhaled combination background the same endpoint gave rate ratios of 0.868 (p=0.0529) and 0.92 (p=0.163).
Phosphodiesterase 4 is not confined to the lung. Blocking it in the gut causes diarrhoea and nausea, blocking it elsewhere causes weight loss, and blocking it in the brain is why the label warns about mood and suicidal thinking.
╌╌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
Pooled weight change against placebo was -2.17 kg. Psychiatric adverse reactions occurred in 5.9% against 3.3% across 8 controlled trials, most commonly insomnia, anxiety and depression. Discontinuation for adverse events ran 11.7% against 5.4% in RE2SPOND. The topical formulation exists precisely because keeping the same pharmacology out of the circulation removes this step.
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 it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
quality of life questionnaire
Measured
Things only a test, a scale or a device shows.
cd8+ inflammatory cells in bronchial biopsy tissue
amount of serum alanine transaminase at baseline
serum alt at month 4
main outcome was change in body weight
urinary albumin creatinine
body weight
blood glucose
plasma insulin level
fasting blood glucose
hba1c
Meaningful
Things that change how a life goes, not only a number.
who develop cognitive decline
all cause mortality
tumor burden and tumor free survival
survival
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (25)
pulmonary function
lung function
lung function parameters
pre bronchodilator forced expiratory volume in first second
rate of moderate or severe copd exacerbations per per year
sputum neutrophil counts at day 14 post exacerbation
vital signs
total number of adverse events
adverse events and adverse drug reactions
hopkins verbal learning test
asthma control test
24 hour sputum volume
1 adverse event
1 serious adverse event
pasi75
estimated glomerular filtration rate
homa ir index
blood lipid levels
primary outcome measure
homa b index
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
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.
A specific and small group: severe chronic obstructive pulmonary disease, with chronic bronchitis, and a history of exacerbations. It is not for breathlessness, not for emphysema without bronchitis, and not for an attack happening now.
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 effectiveness of roflumilast in pediatric patients have not been established.”
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
On older people, the label states: “Of the 4438 COPD subjects exposed to roflumilast for up to 12 months in 8 controlled clinical trials, 2022 were >65 years of age and 471 were >75 years of age.”
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no randomized clinical studies of roflumilast in pregnant women.”
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of roflumilast in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
On people with reduced liver function, the label states: “Roflumilast 250 mcg once daily for 14 days was studied in subjects with mild-to-moderate hepatic impairment classified as Child-Pugh A and B (8 subjects in each group).”
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
On people with reduced kidney function, the label states: “In twelve subjects with severe renal impairment administered a single dose of 500 mcg roflumilast, the AUCs of roflumilast and roflumilast N-oxide were decreased by 21% and 7%, respectively and C max were reduced by 16% and 12%, respectively.”
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
Where the result stopped carrying
REACT missed its primary Poisson analysis at p=0.0529 and is generally cited from its sensitivity analysis instead
RE2SPOND failed outright in 2,354 patients, rate ratio 0.92 (95% CI 0.81 to 1.04, P=0.163)
Weight loss of 2.17 kg on average, in a disease where weight loss is an independent marker of poor outcome
Psychiatric adverse reactions including suicidality at nearly twice the placebo rate, and discontinuation for adverse events up to 11.7% against 5.4%
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 for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
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 (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet, 250 and 500 micrograms once daily; separately, topical cream at 0.3%, 0.15% and 0.05%
✎ 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
The tablet is taken once daily with or without food. The 250 microgram strength exists only as a four-week starting dose to improve tolerability and is stated in the label not to be the therapeutic dose.
✎ 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: The cream is a different product for a different disease, and is included on this page because it is the same molecule and the contrast in tolerability between the two routes is the clearest evidence of where the tablet’s side effects come from.
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
Contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C). Not a bronchodilator and not for acute bronchospasm. Warnings for psychiatric events including suicidality — insomnia, anxiety, depression, suicidal thoughts or other mood changes, reported in 5.9% against 3.3% on placebo across 8 controlled trials — and for weight decrease, with instructions to monitor weight regularly and consider discontinuation. Strong cytochrome P450 inducers such as rifampicin, phenobarbital, carbamazepine and phenytoin are not recommended. The most common adverse reactions at 2% or more were diarrhoea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness and decreased appetite.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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.
Roflumilast appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 969 reaction mentions were counted. One report can name several reactions.
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, 250 and 500 micrograms once daily; separately, topical cream at 0.3%, 0.15% and 0.05%
✎ 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
The 250 microgram strength exists only as a four-week starting dose to improve tolerability and is stated in the label not to be the therapeutic dose.
✎ 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. The rest of the recorded wording: The cream is a different product for a different disease, and is included on this page because it is the same molecule and the contrast in tolerability between the two routes is the clearest evidence of where the tablet’s side effects come from.
No source is stored against this line.
What is recorded as being sold
52 products list this as an active ingredient in the United States drug directory. 52 of them contain it and nothing else.
FDA National Drug Code directory · 80610-430 · read 2026-08-29
They are sold as aerosol, foam, cream, powder and tablet, taken oral and topical.
FDA National Drug Code directory · 80610-430 · read 2026-08-29
The regulator's established pharmacologic class for it is phosphodiesterase 4 inhibitor [epc] and phosphodiesterase 4 inhibitors [moa].
FDA National Drug Code directory · 80610-430 · read 2026-08-29
19 published labels name it as an active ingredient. 19 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-29
ROFLUMILAST is oral at 3 DOSAGE FORMS AND STRENGTHS Roflumilast 250 mcg tablets are white to off-white, round tablets, flat faced beveled edge, debossed with “T” and “250” on one side and plain on the other side., recorded as fda label in effect 2025-05-27 in the United States.
US prescribing information · 7cb11d48-6bb9-437b-bc7f-382050a2d3e6 · read 2026-08-30
Recorded price in US: 0.31601–1.99687 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 34 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Roflumilast 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 roflumilast added to inhaled combination therapy reduces exacerbations — the two trials designed to test that both missed their primary analyses
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 labelled phenotype identifies who benefits, when the confirmation for it comes from a post hoc subgroup in a failed trial
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 48 mL FEV1 improvement represents bronchodilation, which the Limitations of Use section rules out in one sentence
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 tablet and the cream can be discussed as one drug — same molecule, different route, and effect sizes an order of magnitude apart
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 Roflumilast 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.
M2-124 and M2-125: a 17% cut in exacerbations, and 48 mL of lung function
In plain words
Two identical year-long trials in just over three thousand people with severe smokers’ lung disease and chronic bronchitis. Exacerbations fell from 1.37 to 1.14 per person per year. Lung function rose by 48 millilitres, which is about half of what a person would normally notice.
What was measured
Change in prebronchodilator FEV1 and rate of moderate or severe exacerbations over 52 weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two placebo-controlled, double-blind, 52-week trials of identical design in patients over 40 with severe airflow limitation, bronchitic symptoms and a history of exacerbations randomised 1,537 to roflumilast 500 micrograms once daily and 1,554 to placebo. Both co-primary endpoints were achieved. Pooled, prebronchodilator FEV1 increased by 48 mL against placebo (p<0.0001) and moderate or severe exacerbations fell from 1.37 to 1.14 per patient per year, a 17% reduction (95% CI 8 to 25, p<0.0003). Adverse events were more common on roflumilast, 1,040 of 1,537 (67%) against 963 of 1,554 (62%), and discontinuation for adverse events was 219 (14%) against 177 (12%). The pooled difference in weight change was -2.17 kg.
Written into the record, not signed off as a reviewed claim
REACT missed its primary analysis at p=0.0529 and is quoted from its sensitivity one
In plain words
The trial that asked whether roflumilast helps people already on inhaled combination treatment reported a 13.2% reduction in flare-ups — and a p-value of 0.0529, just the wrong side of the line. The figure usually quoted from this trial comes from a different, prespecified statistical method that gave 0.0424.
What was measured
Rate of moderate to severe COPD exacerbations per patient per year, primary Poisson analysis
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
REACT enrolled 1,945 patients aged 40 or over with at least 20 pack-years, severe airflow limitation, chronic bronchitis and at least two exacerbations in the previous year, all on a fixed inhaled corticosteroid and long-acting beta-agonist combination with tiotropium permitted, and randomised 973 to roflumilast 500 micrograms and 972 to placebo for one year. The primary outcome, rate of moderate to severe exacerbations per patient per year by Poisson regression, was 13.2% lower on roflumilast (0.805 against 0.927; rate ratio 0.868, 95% CI 0.753 to 1.002, p=0.0529). A predefined sensitivity analysis by negative binomial regression gave 14.2% lower (0.823 against 0.959; rate ratio 0.858, 95% CI 0.740 to 0.995, p=0.0424). Adverse events were reported by 67% on roflumilast against 59% on placebo, and withdrawal for adverse events by 104 of 968 (11%) against 52 of 967 (5%).
Written into the record, not signed off as a reviewed claim
RE2SPOND failed outright in 2,354 patients, and reported a post hoc subgroup instead
In plain words
The larger follow-up trial gave roflumilast or placebo to more than two thousand three hundred people already on inhaled combination treatment. Flare-ups fell by 8.5% and the difference was not statistically significant. The positive result from this trial is a subgroup found after the fact.
What was measured
Rate of moderate or severe COPD exacerbations per patient per year in the overall randomised population
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
RE2SPOND randomised 2,354 participants aged 40 or over with severe or very severe COPD, chronic bronchitis and two or more exacerbations or hospitalisations in the previous year, all on inhaled corticosteroid plus long-acting beta-agonist with or without a long-acting muscarinic antagonist for three months or more, equally to roflumilast 500 micrograms (n=1,178) or placebo (n=1,176) for 52 weeks. The rate of moderate or severe exacerbations per patient per year was 8.5% lower on roflumilast, and the between-group difference was not statistically significant: rate ratio 0.92 (95% CI 0.81 to 1.04, P=0.163). The authors state that roflumilast failed to significantly reduce exacerbations in the overall population, and report a post hoc analysis showing a significant reduction in participants with more than three exacerbations or one or more hospitalisations in the prior year. Adverse-event-related discontinuation was 11.7% against 5.4%; deaths were 2.5% against 2.1%.
Written into the record, not signed off as a reviewed claim
Weight loss of 2.17 kg and psychiatric reactions in 5.9% against 3.3%
In plain words
This is the price of a tablet rather than an inhaler. People lost more than two kilograms on average, in a disease where losing weight is already a bad sign, and psychiatric side effects including suicidal thinking were roughly twice as common as on placebo.
What was measured
Weight change against placebo and rate of psychiatric adverse reactions across 8 controlled trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In the pooled M2-124 and M2-125 analysis the difference in weight change against placebo was -2.17 kg, and the label instructs regular weight monitoring with consideration of discontinuation for unexplained or clinically significant loss. Across 8 controlled clinical trials, psychiatric adverse reactions were reported by 5.9% (263) of patients on roflumilast 500 micrograms daily against 3.3% (137) on placebo, most commonly insomnia, anxiety and depression, and the label carries a Warnings and Precautions entry for psychiatric events including suicidality. The most common adverse reactions at 2% or more were diarrhoea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness and decreased appetite. Discontinuation for adverse events ran 14% against 12% in the pivotal pair and 11.7% against 5.4% in RE2SPOND. The drug is contraindicated in moderate to severe hepatic impairment.
Source
DALIRESP United States prescribing information, Contraindications 4, Warnings and Precautions 5.2 and 5.3, Adverse Reactions 6.1; Calverley PMA et al., Lancet 2009;374:685-694
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 same molecule on skin produced effects the tablet never approached
In plain words
A decade after the lung indication, roflumilast was reformulated as a cream. In two psoriasis trials, four in ten treated patients reached clear or almost-clear skin against roughly one in fifteen on the cream base alone — and the weight loss and mood effects of the tablet did not appear.
What was measured
That roflumilast is a marginal drug — true of the swallowed tablet in COPD, and not true of the same molecule applied to skin, where the comparison against vehicle is one of the largest in topical dermatology
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DERMIS-1 and DERMIS-2 randomised 881 patients aged 2 or over with plaque psoriasis covering 2% to 20% of body surface area, 2:1, to roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. Investigator Global Assessment success at week 8 was 42.4% against 6.1% in trial 1 (difference 39.6%, 95% CI 32.3 to 46.9) and 37.5% against 6.9% in trial 2 (difference 28.9%, 95% CI 20.8 to 36.9), P<0.001 for both. Intertriginous IGA success was 71.2% against 13.8% and 68.1% against 18.5%; PASI-75 was 41.6% against 7.6% and 39.0% against 5.3%. Treatment-emergent adverse events were 25.2% against 23.5% and 25.9% against 18.4%; serious adverse events were 0.7% against 0.7% and 0% against 0.7%. Keeping a PDE4 inhibitor out of the bloodstream removes the tolerability problem that constrains the oral drug, and the effect sizes are of a different order from the 17% exacerbation reduction in the lung trials.
Written into the record, not signed off as a reviewed claim
The 48 mL lung-function gain is not bronchodilation, and the label says so
In plain words
Roflumilast improves a breathing test by 48 millilitres. That is real, and it is roughly half the change a person would be expected to notice, and it does not happen by opening the airway. The label states outright that this is not a bronchodilator.
What was measured
That the FEV1 improvement makes roflumilast a bronchodilator — a reading the label explicitly forecloses in its Limitations of Use
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The DALIRESP Limitations of Use state that the drug is not a bronchodilator and is not indicated for the relief of acute bronchospasm. The 48 mL prebronchodilator FEV1 improvement in the pooled pivotal trials is therefore an indirect consequence of reduced airway inflammation rather than smooth-muscle relaxation. For comparison, tiotropium produced 87 to 103 mL in UPLIFT and umeclidinium 127 mL at 12 weeks, both by relaxing muscle. Reading a 48 mL figure as though it were a bronchodilator response overstates what the drug does and understates what makes it unusual, which is that it is the only oral anti-inflammatory approved for this disease.
Written into the record, not signed off as a reviewed claim
The indication is narrower than the population that failed to benefit
In plain words
The label restricts the drug to severe disease with chronic bronchitis and a history of flare-ups. The two large trials in exactly that kind of population — people still flaring despite inhaled treatment — are the ones that missed. The narrowing came from the trials that worked, not from the ones that did not.
What was measured
That the labelled phenotype identifies the patients in whom roflumilast works — a claim the two trials run in that phenotype on modern background therapy did not confirm on their primary endpoints
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The indication reads: to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. M2-124 and M2-125, which met their endpoints, enrolled that phenotype on variable background therapy. REACT and RE2SPOND enrolled the same phenotype but required an inhaled corticosteroid and long-acting beta-agonist combination as background, and both missed their primary analyses — REACT at p=0.0529, RE2SPOND at p=0.163. RE2SPOND’s positive result is a post hoc subgroup of the most frequent exacerbators. A phenotype restriction derived from responder analyses is a hypothesis about who benefits, and the trials designed to test it in the modern treatment context did not confirm it on their primary endpoints.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 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.
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 phosphodiesterase-4 inhibitor taken as a tablet, which raises cyclic AMP inside airway inflammatory cells; across two 52-week trials in 3,091 people it cut moderate or severe exacerbations by 17% and raised FEV1 by 48 mL, and then missed its primary endpoint in both of the larger trials that followed — REACT at p=0.0529 and RE2SPOND at p=0.163 — while causing 2.17 kg of weight loss and psychiatric adverse reactions in 5.9% against 3.3% on placebo.
Recorded evidence blocks (12)
Q1
What did Roflumilast's largest trial (135856 people) and its longest (13 years) measure?
135856 people in Roflumilast's largest registered study, 13 years in its longest registered window, measuring Time to All-cause Mortality or Re-hospitalization During the 180 Days Post-randomization. ClinicalTrials.gov · 2026-09-01
41 phase2, 35 phase3, 15 phase1, 14 phase4, 5 na or unstated, 3 early phase1, 1 na; NCT06643221; 2031-05-31; no ageing endpoint recorded. Last human test completed 2026, NCT04069312.
Interpretation These counts include studies where Roflumilast was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
41
phase3
35
phase1
15
phase4
14
na or unstated
5
early phase1
3
2 more recorded rows
na
1
Last recorded human testNCT04069312
2026-03-01
recorded 2026-09-01 · last checked 2026-09-04
Q2
From mouse to human: where has Roflumilast shown lifespan?
8 recorded entries; human; tablet, topical; also "Roflumilast Foam 0.3%", "Roflumilast foam 0.3%", "roflumilast cream 0.3%"
Show the evidence
human
NCT03532490
Roflumilast 500 Mcg Oral Tablet
NCT04091646
Roflumilast Foam 0.3%
NCT04128007
Roflumilast foam 0.3%
NCT05763082
roflumilast cream 0.3%
NCT06440473
Vehicle (Roflumilast 0.3% vehicle cream)
NCT06648772
Roflumilast Cream 0.3%
2 more recorded rows
humanNCT07233291
tablet; Roflumilast 500 mcg tablet (formulation identifier)
humanNCT07263230
topical; Roflumilast 0.3% topical foam
recorded 2026-09-01 · last checked 2026-09-04
Q5
Could one person measure Roflumilast's effect on pulmonary function?
Pulmonary function: measured in Roflumilast's trials.
Interpretation pulmonary function is the recorded endpoint.
Show the evidence
biomarkers
pulmonary function; 2026-09-01
lung function; 2026-09-01
lung function parameters; 2026-09-01
pre bronchodilator forced expiratory volume in first second; 2026-09-01
rate of moderate or severe copd exacerbations per per year; 2026-09-01
sputum neutrophil counts at day 14 post exacerbation; 2026-09-01
14 more recorded rows
biomarkers
cd8+ inflammatory cells in bronchial biopsy tissue; 2026-09-01
biomarkers
amount of serum alanine transaminase at baseline; 2026-09-01
biomarkers
serum alt at month 4; 2026-09-01
biomarkers
vital signs; 2026-09-01
biomarkers
total number of adverse events; 2026-09-01
biomarkers
adverse events and adverse drug reactions; 2026-09-01
biomarkers
hopkins verbal learning test; 2026-09-01
biomarkers
main outcome was change in body weight; 2026-09-01
biomarkers
who develop cognitive decline; 2026-09-01
biomarkers
all cause mortality; 2026-09-01
biomarkers
asthma control test; 2026-09-01
biomarkers
quality of life questionnaire; 2026-09-01
biomarkers
24 hour sputum volume; 2026-09-01
biomarkers
1 adverse event; 2026-09-01
human trials at or under30
30
Not recorded for this substance
a recorded half-life
smallest human trial
0; NCT00746382; PHASE2; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN
Q6
Which of 1 adverse event, 1 serious adverse event and 24 hour sputum volume did Roflumilast's trials measure?
1 adverse event, 1 serious adverse event and 24 hour sputum volume lead 40 outcome terms across Roflumilast's trials. ClinicalTrials.gov · 2026-09-01
pre bronchodilator forced expiratory volume in first second, rate of moderate or severe copd exacerbations per per year, sputum neutrophil counts at day 14 post exacerbation, cd8+ inflammatory cells in bronchial biopsy tissue, amount of serum alanine transaminase at baseline and serum alt at month 4 follow.
Show the evidence
pulmonary function
1
lung function
1
lung function parameters
1
pre bronchodilator forced expiratory volume in first second
1
rate of moderate or severe copd exacerbations per per year
1
sputum neutrophil counts at day 14 post exacerbation
1
14 more recorded rows
cd8+ inflammatory cells in bronchial biopsy tissue
1
amount of serum alanine transaminase at baseline
1
serum alt at month 4
1
vital signs
1
total number of adverse events
1
adverse events and adverse drug reactions
1
hopkins verbal learning test
1
main outcome was change in body weight
1
who develop cognitive decline
1
all cause mortality
1
asthma control test
1
quality of life questionnaire
1
24 hour sputum volume
1
1 adverse event
1
recorded 2026-09-01 · last checked 2026-09-04
Q7
Which of Roflumilast's 14 ongoing trials reports first?
Change in EEG Relative Gamma Power; Motor evoked potential amplitude; latest 2031-05-31
Show the evidence
Trial
NCT05418049
"Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge"; n 45; "Change in EEG Relative Gamma Power"; 2026-03-05
NCT06457191
"Roflumilast and TMS Motor Plasticity"; n 20; "Motor evoked potential amplitude"; 2026-06
NCT06643221
"Exercise as an Immune Adjuvant for Allogeneic Cell Therapies"; n 200; "Immune Cell Enumeration and Phenotyping"; 2031-05-31
NCT06860958
"Roflumilast as an Adjunct to Antidepressants in Major Depressive Disorder Patients"; n 60; "The principal measure of the outcome will be the 17-item Ham-D"; 2027-08-20
NCT06977711
"Loncastuximab and Roflumilast Added to R-CHOP (Lo-(Rituximab and Roflumilast) RR-CHOP) for Naïve High-Risk Diffuse Large B-cell Lymphoma (DLBCL)"; n 10; "Estimation of number of adverse events"; 2027-04-01
NCT07233291
"A Pilot Study to Assess How Safe and Effective Oral Roflumilast is for Treating Moderate to Severe Psoriasis in Adults"; n 36; "Mean change in Psoriasis Area and Severity Index (PASI) score"; 2026-02-28
8 further recorded trials
NCT07263230
"The Safety and Efficacy of Roflumilast Foam in HS"; n 20; "Mean Change from Baseline in Abscess and Inflammatory Nodule (AN) Count at Week 16."; 2029-05
NCT07297602
"Evaluation of Efficacy and Safety of Oral Roflumilast for Treatment of Moderate to Severe Atopic Dermatitis in Patients Aged 12 Years and Older: A Pilot Study"; n 36; "The primary outcome of the study is the change in the SCORAD Index from baseline to the end of treatment"; 2026-05-20
NCT07314242
"A Study to Investigate the Biomarkers of Hemay005 in Adult Participants With Moderate to Severe COPD"; n 120; "Sputum biomarkers"; 2027-12-31
NCT07352566
"Utilization of a Microdevice for Psoriasis and Atopic Dermatitis"; n 10; "Number of participants with adverse events"; 2030-06-01
NCT07543640
"EFFICACY OF ROFLUMILAST IN THE TREATMENT OF FLEXURAL AND/OR GENITAL PSORIASIS: A RANDOMIZED CONTROLLED TRIAL."; n 56; "Clinical Success at flexural (I-IGA 0/1) and/or genital (sPGA-G 0/1) psoriasis"; 2026-08
NCT07566351
"Effect of Roflumilast and Desloratadine as Add-On Therapy in Patients With Rheumatoid Arthritis"; n 90; "Change in Disease Activity Score (DAS28)"; 2027-07
NCT07632846
"Effect of Roflumilast as Add-On Therapy in Rheumatoid Arthritis"; n 50; "Change in Disease Activity Score (DAS28)"; 2026-12
NCT07795086
"Comparative Effectiveness of Roflumilast and Azithromycin in Reducing Exacerbations in Severe Chronic Obstructive Pulmonary Disease ( COPD ) Patients With Chronic Bronchitis Phenotype"; n 70; "Number of moderate/severe chronic obstructive pulmonary disease (COPD) exacerbations over 6 months"; 2027-02
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which 32 trials of Roflumilast posted no result?
Posted no result
32 of 32 completed trials
Registrations
NCT00940329, NCT00076076, NCT01365533, NCT00163475, NCT00163527 and NCT00076089, and 26 more
Completion dates
oldest 2004-12; newest 2024-01-16
Show the evidence
Trial
NCT00940329
2004-12
NCT00076076
2005-06
NCT01365533
2005-07
NCT00163475
2005-08
NCT00163527
2005-11
NCT00076089
2005-12
14 further recorded trials
NCT00242294
2007-03
NCT00242307
2007-06-01
NCT00242320
2007-08
NCT00246935
2007-10
NCT00246922
2007-10-01
NCT01140542
2008-03
NCT01354782
2011-09
NCT01285167
2012-02
NCT01285180
2012-08
NCT01480661
2013-04
NCT01433666
2013-09
NCT01730404
2013-10
NCT02187250
2014-06
NCT04122547
2015-12
Q9
At the median, Roflumilast's trials enrolled 60 people — anything larger?
Median enrolment
60
Largest enrolment
135856
Registered trials counted
108
Q10
What do 969 spontaneous reports say about Roflumilast — 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.
Roflumilast appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 969 reaction mentions were counted: diarrhoea 159; dyspnoea 133; weight decreased 130; chronic obstructive pulmonary disease 113. open-targets-adr · CHEMBL193240 · 2026-06-24
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diarrhoea
159
dyspnoea
133
weight decreased
130
chronic obstructive pulmonary disease
113
nausea
105
decreased appetite
89
4 more recorded rows
suicidal ideation
72
insomnia
64
pneumonia
59
cough
45
recorded 2026-06-24 · last checked 2026-09-04
Q11
Roflumilast and CYP3A4, CYP1A2 and CYP2B6: shared by which compounds?
CYP3A4, CYP1A2 and CYP2B6 appear in Roflumilast's recorded interaction sentences, 8 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
Show the evidence
CYP1A2
pharmacokinetics
In vitro studies and clinical drug-drug interaction studies suggest that the biotransformation of roflumilast to its N-oxide metabolite is mediated by CYP1A2 and 3A4.
pharmacokinetics
In addition, in vitro studies demonstrated no induction of the CYP 1A2, 2A6, 2C9, 2C19, or 3A4/5 and only a weak induction of CYP2B6 by roflumilast.
pharmacokinetics
Based on further in vitro results in human liver microsomes, therapeutic plasma concentrations of roflumilast and roflumilast N-oxide do not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.
CYP2B6pharmacokinetics
In addition, in vitro studies demonstrated no induction of the CYP 1A2, 2A6, 2C9, 2C19, or 3A4/5 and only a weak induction of CYP2B6 by roflumilast.
CYP3A4
pharmacokinetics
Ketoconazole: In an open-label crossover study in 16 healthy volunteers, the coadministration of a strong CYP3A4 inhibitor ketoconazole (200 mg twice daily for 13 days) with a single oral dose of 500 mcg roflumilast resulted in 23% and 99% increase in C max and AUC for roflumilast, respectively, and a 38% reduction and 3% increase in C max and AUC for roflumilast N-oxide, respectively.
pharmacokinetics
Fluvoxamine: In an open-label crossover study in 16 healthy volunteers, the coadministration of dual CYP 3A4/1A2 inhibitor fluvoxamine (50 mg daily for 14 days) with a single oral dose of 500 mcg roflumilast showed a 12% and 156% increase in roflumilast C max and AUC along with a 210% decrease and 52% increase in roflumilast N-oxide C max and AUC, respectively.
pharmacokinetics
Enoxacin: In an open-label crossover study in 16 healthy volunteers, the coadministration of dual CYP 3A4/1A2 inhibitor enoxacin (400 mg twice daily for 12 days) with a single oral dose of 500 mcg roflumilast resulted in an increased C max and AUC of roflumilast by 20% and 56%, respectively.
pharmacokinetics
Cimetidine: In an open-label crossover study in 16 healthy volunteers, the coadministration of a dual CYP 3A4/1A2 inhibitor cimetidine (400 mg twice daily for 7 days) with a single dose of 500 mcg oral roflumilast resulted in a 46% and 85% increase in roflumilast C max and AUC; and a 4% decrease in C max and 27% increase in AUC for roflumilast N-oxide, respectively.
recorded 2026-08-30 · last checked 2026-09-04
Q12
What is recorded about Roflumilast and autophagy?
"This study explores the effects of phosphodiesterase inhibitors (PDEIs) roflumilast (RF), rolipram (ROL), and tadalafil (TAD) on SESN2 expression and autophagy in Aβ25-35-treated hippocampal neuron (HT-22) cell cultures." — where Roflumilast and autophagy appear together. Europe PMC · pathway abstract search · 2025-07-21
"This study explores the effects of phosphodiesterase inhibitors (PDEIs) roflumilast (RF), rolipram (ROL), and tadalafil (TAD) on SESN2 expression and autophagy in Aβ25-35-treated hippocampal neuron (HT-22) cell cultures."
AMPKPMID 40516667
"Overall, activation of AMPK/Nrf2/HO-1 signaling by roflumilast attenuated neuronal ferroptosis and improved motor function after SCI in rats."
mTORPMID 37257579
"Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression."
AMPKPMID 37257579
"Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression."
autophagyPMID 37257579
"Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression."
mTORPMID 37257579
"The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities."
4 more recorded rows
AMPKPMID 37257579
"The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities."
autophagyPMID 37257579
"The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities."
sirtuinPMID 37541971
"Moreover, roflumilast increased cAMP level and activated the PI3K/AKT axis via stimulation of CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling cascades."
IGF-1PMID 37541971
"Moreover, roflumilast increased cAMP level and activated the PI3K/AKT axis via stimulation of CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling cascades."
recorded 2025-07-21 · last checked 2026-09-04
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