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Tretinoin

  • Prescription medicine
  • Prescription only
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Tretinoin does in the body

The plug in a blocked pore loosens and clears, and new plugs form more slowly.

Tretinoin is vitamin A in the form your cells actually use as a signal. Rubbed onto skin it slips into keratinocytes, finds receptors that sit directly on DNA, and switches on the genes that tell those cells to mature and shed on schedule. In sun-damaged skin the same signal nudges the dermis to lay down collagen again, which is why fine lines soften — and why the skin peels and stings for the first several weeks while the turnover speeds up.

Why people take it. Acne, and fine facial lines from sun damage

What happened in people

Graded photoaging improved on the tretinoin forearm and not the vehicle forearm in all 30 completers of a within-patient randomised study, with matching histology

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 limit that matters most

The photoaging indication is written as palliation of fine wrinkles, adjunctive to sun avoidance, and says in capital letters what it does not do

Where it acts
Epidermis and the follicular infundibulum — the lining of the pore, and the basal keratinocytes beneath it
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · 5688UTC01R · read 2026-08-29

  • Its recorded molecular formula is C20H28O2, weighing 300.44 g/mol.

    US prescribing information · 264138c1-9e5f-45ef-be87-79ca97c989d9 · 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 127 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.

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 peopleRead 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.
GoalLife outcomeWhat a body can doHow a person feelsA test resultA step in the bodyHarmsHow longWho was studied
Healthy ageingWaiting 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.
Which registered measures put each goal on this table
Healthy ageing
mortality rate at 6 weeks

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
Waiting for a reviewer
1 registered study measure of this kind. No reviewed result yet.
Nothing in the sources checked
No registered study lists a performance measure for this goal.
Not recorded
Harms were not a registered measure for this goal.

What happened in peopleRead 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.

Time to new basal cell carcinoma and to new invasive squamous cell carcinoma on the face or ears

The study did not show it

Who was studied
VATTC (NCT00007631)
How many people
1131
Study design
Phase 3, randomised, double-blind, vehicle-controlled
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
P=0.3 for BCC and P=0.4 for SCC. Five-year BCC 53% against 54%, difference 1.0% (95% CI -6.5 to 8.6); invasive SCC 28% against 31%, difference 3.6% (95% CI -3.1 to 10.3)
Repeated elsewhere
Unreplicated

What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.

The limits of this study, and where it came from

Main limit. The intervention was stopped six months early for excess all-cause mortality in the tretinoin group, an endpoint the trial was never designed to measure. The imbalance survived adjustment for age, comorbidity and smoking status and was reported separately in Archives of Dermatology rather than in the main efficacy paper.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Topical cream, gel, lotion and microsphere gel, applied to the skin

Interval reported. 95% CI -6

Written into the record, not signed off as a reviewed claim.

Graded improvement in photoaging at 16 weeks, with histologic confirmation

The study showed what it set out to show

Who was studied
Weiss 1988 University of Michigan photoaging study (PMID 3336176)
How many people
30
Study design
Randomised, double-blind, vehicle-controlled, within-patient design
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Statistically significant improvement on tretinoin-treated forearms and not on vehicle-treated forearms in all 30 completers; 14 of 15 tretinoin-treated faces improved against 0 of the vehicle-treated faces
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. Thirty completers. The within-patient forearm design controls for confounding tightly but the study cannot speak to durability, to coarse wrinkling, or to anything beyond 16 weeks.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Topical cream, gel, lotion and microsphere gel, applied to the skin

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Maintenance of or further improvement in photodamage signs through 48 weeks at 0.05% and 0.01%

The study showed what it set out to show

Who was studied
Olsen 1997 tretinoin emollient cream 48-week extension studies
How many people
298
Study design
Multicentre, double-blind extension of two 24-week studies
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Reported as maintained or continued improvement on investigator and subject assessment, confirmed by skin replica analysis; no comparative p-value against vehicle in the extension phase
Repeated elsewhere
Partially Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. The extension had no vehicle arm. It measures durability within treated groups, not a fresh comparison against no treatment, and only enrolled people who had already tolerated 24 weeks.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Topical cream, gel, lotion and microsphere gel, applied to the skin

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What happened in peopleRead 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.

  1. Living longer, or avoiding a major event Evidence recorded. Death, a heart attack, a stroke, a hospital stay.7 registered measures of this kind. No reviewed result.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life No evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
  5. A number that stands in for health Evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.1 registered measure of this kind.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals Evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in C. elegans (roundworm), Mouse, Dog. A result in animals says what to test next. It does not say what happens in people.
  8. Cells in a dish Evidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
  9. A guess from software No 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 bodyRead 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.

  1. Start

    Tretinoin

    What a person takes: Topical cream, gel, lotion and microsphere gel, applied to the skin.

    The measurement behind this step

    Applied to affected skin rather than swallowed. Percutaneous absorption is minimal, which is the basis for the difference in systemic risk between this drug and oral retinoids. The microsphere formulation holds the drug in a porous polymer to slow its arrival at the skin surface, a tolerability device rather than a potency one. Tretinoin isomerises in light and degrades in the presence of peroxides, which is why it is not co-formulated with benzoyl peroxide.

  2. Getting in

    Applied to the surface, and mostly staying there

    The cream sits on the skin and the drug works its way into the outer layers and down the pore. Very little reaches the bloodstream, which is the single most important fact about this medicine compared with the vitamin A pills it resembles.

    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

    Percutaneous absorption of topical tretinoin is minimal. Partitioning is driven by the molecule being a lipophilic carboxylic acid (formula C20H28O2, 300.40 g/mol) that concentrates in the stratum corneum and follicular infundibulum. The microsphere formulations exist to slow surface delivery further, trading peak concentration for tolerability rather than for potency.

  3. Reaching the cell

    Carried into the nucleus of the cell

    Inside a skin cell, a shuttle protein picks the drug up and carries it to the nucleus, where the cell keeps its DNA. This is a signalling molecule, not a solvent or a scrub.

    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

    Cellular retinoic acid-binding protein 2 (CRABP2) binds all-trans retinoic acid in the cytoplasm and delivers it to the nuclear retinoic acid receptors. CRABP2 is itself retinoic acid-inducible, which produces a short positive-feedback loop on the first exposures and is part of why the response builds over weeks.

  4. What it acts on

    It switches genes on by sitting on the DNA

    The drug clicks into a receptor that is already parked on specific stretches of DNA. Occupied, that receptor stops silencing those genes and starts transcribing them.

    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

    Retinoic acid receptors alpha, beta and gamma heterodimerise with retinoid X receptors and bind retinoic acid response elements as a preformed complex. Unliganded, the complex recruits nuclear corepressors and histone deacetylases. Ligand binding exchanges those for coactivators with histone acetyltransferase activity. Human epidermis expresses predominantly RAR-gamma, and the epidermal effects are attributed to it.

  5. The change it makes

    The pore lining stops sticking together

    The cells lining the pore start maturing and shedding on schedule again instead of clumping. The plug at the top of the pore loosens and clears, and fewer new plugs form behind 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

    Transcriptional reprogramming of follicular keratinocytes normalises the abnormal desquamation that produces the microcomedone, the precursor lesion of both comedonal and inflammatory acne. Keratin expression shifts and corneocyte cohesion falls. This is why a retinoid is a comedolytic rather than an antibacterial, and why it is the component of a regimen that acts on lesion formation rather than on the organism.

  6. What that does for a person

    In sun-damaged skin, the dermis is remodelled

    Deeper down, the same signal shifts the balance between building collagen and breaking it down. Over months the skin thickens slightly and fine creases soften. Deep lines do not change.

    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

    Retinoic acid signalling suppresses ultraviolet-induced AP-1 activation and the matrix metalloproteinase transcription that follows it, while increasing procollagen expression. The clinical endpoints in the registration trials were ordinal grades of fine wrinkling, mottled hyperpigmentation and tactile roughness, not measured collagen content.

  7. What that does for a person

    What the endpoint does not measure

    Every result on this page is somebody looking at skin and grading it, or counting spots. When the drug was finally tested against something that cannot be graded by eye — cancer, and death — it did nothing to the cancer, and the trial was stopped early over the deaths.

    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

    VATTC randomised 1,131 high-risk patients to 0.1% tretinoin or vehicle for up to 5.5 years and found no effect on basal cell carcinoma (P=0.3), invasive squamous cell carcinoma (P=0.4) or actinic keratosis count, and terminated six months early for excess deaths in the tretinoin arm that survived adjustment for age, comorbidity and smoking.

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 takeRead 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.

No registered study measured anything of this kind.

Measured

Things only a test, a scale or a device shows.

  • inflammatory lesion counts at week 12

Meaningful

Things that change how a life goes, not only a number.

  • distributions of event free survival
  • disease free survival
  • survival
  • 3 year disease free survival rate
  • continuous complete remission at 3 years
  • mortality rate at 6 weeks
  • event free 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 (32)
  • response rates
  • response duration
  • long term efficacy
  • response
  • overall response rate
  • response rate as measured by recist criteria
  • time to progression
  • tumor response rate
  • lesion counts at week 12
  • skin aging measured the photonumeric scale
  • severity of erythematotelangiectatic rosacea signs redness
  • severity of erythematotelangiectatic rosacea signs dry skin
  • global photodamage severity
  • solar lentigines count
  • adverse events as a measure of safety
  • adverse events
  • who experienced an adverse event
  • who experienced a serious adverse event
  • who discontinued study treatment due to an adverse event
  • who experienced a dose limiting toxicity

These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.

What it would be like to takeRead from sources, not yet reviewed

How long anything takes

Nine different lengths of time that get confused with each other. None of them is worked out from another.

  1. Before anything is noticed. RNAWiki does not store this separately, and never works it out from another figure on this page.

  2. Before a test result moves. RNAWiki does not store this separately, and never works it out from another figure on this page.

  3. Before performance moves. RNAWiki does not store this separately, and never works it out from another figure on this page.

  4. How long the result was watched. No finished study window is recorded for a study that tested this substance.

  5. How long people took it. How long people actually took it is not stored. The study window is not the same thing.

  6. How long people were followed. Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.

  7. How fast the body clears it. 0.5 to 2 hours hours

    Read from the label, which states: “Elimination The terminal elimination half-life of tretinoin following initial dosing is 0.5 to 2 hours in patients with APL.”

  8. How long effects linger. RNAWiki does not store this separately, and never works it out from another figure on this page.

  9. Beyond the studies. Nothing is recorded about the long term.

    The longest finished study sets the edge of what anyone measured.

A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.

What is missing or unclearRead 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 with comedonal or inflammatory acne, and adults using it for fine lines. It is applied to skin, not swallowed — oral tretinoin is a different medicine with a different risk profile.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What the label states about particular groups

  • On pediatric, the label states: “Safety and effectiveness in pediatric patients less than 1 year of age have not been established.”

    US prescribing information · 264138c1-9e5f-45ef-be87-79ca97c989d9 · read 2026-08-30

  • On older people, the label states: “Across clinical studies of tretinoin capsules, 21% were 60 years and older.”

    US prescribing information · 264138c1-9e5f-45ef-be87-79ca97c989d9 · read 2026-08-30

  • On people who are pregnant, the label states: “Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )], tretinoin capsules can cause embryo-fetal loss and malformations when administered to a pregnant woman.”

    US prescribing information · 264138c1-9e5f-45ef-be87-79ca97c989d9 · read 2026-08-30

  • On people who are breastfeeding, the label states: “There are no data on the presence of tretinoin in human milk, the effects on the breastfeed child or the effects on milk production.”

    US prescribing information · 264138c1-9e5f-45ef-be87-79ca97c989d9 · read 2026-08-30

Where the result stopped carrying

  • VATTC missed both primary endpoints outright, in the largest randomised trial ever run on the drug
  • VATTC was terminated six months early for excess all-cause mortality in the tretinoin arm, and the imbalance survived adjustment
  • The only quality-of-life difference measured in VATTC was worse symptoms in the tretinoin group at 12 months
  • The largest acne network meta-analysis grades its own confidence in the evidence as low, with patient-reported improvement available from only 11 of 40 trials
  • 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 takeRead 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.

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 (9)
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 takeRead 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

Topical cream, gel, lotion and microsphere gel, applied to the skin

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Suppression classes recorded: S1, S3, S4, S6.

No source is stored against this line.

What is in the pack

Applied to affected skin rather than swallowed. Percutaneous absorption is minimal, which is the basis for the difference in systemic risk between this drug and oral retinoids. The microsphere formulation holds the drug in a porous polymer to slow its arrival at the skin surface, a tolerability device rather than a potency one. Tretinoin isomerises in light and degrades in the presence of peroxides, which is why it is not co-formulated with benzoyl peroxide.

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 takeRead 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

Local irritation is the dose-limiting effect: erythema, peeling, dryness, stinging and increased sensitivity to sunlight, wind and cold. The label instructs minimising sun exposure and using protective measures. Systemic exposure is minimal. In the VATTC trial at 0.1% twice daily, the only quality-of-life difference at 12 months was worse symptoms in the tretinoin group, and the trial was stopped early for an unexplained excess of deaths that the authors explicitly declined to call causal. Use in pregnancy is advised against, although a prospective cohort of 106 first-trimester exposures found no increase in adverse outcomes.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Reports sent to a regulator

  • 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.

Tretinoin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 8540 reaction mentions were counted. One report can name several reactions.

The recorded terms (10)
  • depression — 1546 reaction mentions
  • unintended pregnancy — 1526 reaction mentions
  • pregnancy — 1152 reaction mentions
  • abortion induced — 890 reaction mentions
  • suicidal ideation — 847 reaction mentions
  • dry skin — 649 reaction mentions
  • mood altered — 612 reaction mentions
  • blood triglycerides increased — 592 reaction mentions
  • abortion spontaneous — 377 reaction mentions
  • lip dry — 349 reaction mentions
  • 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 unclearRead 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

Topical cream, gel, lotion and microsphere gel, applied to the skin

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

Percutaneous absorption is minimal, which is the basis for the difference in systemic risk between this drug and oral retinoids. The microsphere formulation holds the drug in a porous polymer to slow its arrival at the skin surface, a tolerability device rather than a potency one. Tretinoin isomerises in light and degrades in the presence of peroxides, which is why it is not co-formulated with benzoyl peroxide.

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

  • 111 products list this as an active ingredient in the United States drug directory. 103 of them contain it and nothing else.

    FDA National Drug Code directory · 0574-2225 · read 2026-08-29

  • They are sold as capsule, cream, gel, lotion and powder, taken oral and topical.

    FDA National Drug Code directory · 0574-2225 · read 2026-08-29

  • The regulator's established pharmacologic class for it is retinoid [epc] and retinoids [cs].

    FDA National Drug Code directory · 0574-2225 · read 2026-08-29

  • 67 published labels name it as an active ingredient. 59 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · 654ae869-5bc0-40b3-a423-dcc3270c05d8 · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · 654ae869-5bc0-40b3-a423-dcc3270c05d8 · read 2026-08-29

  • Tretinoin is oral at 3 DOSAGE FORMS AND STRENGTHS Tretinoin Capsules are available as: 10 mg: Pink, oval, soft-gelatin capsules printed with black ‘T 10’ filled with yellow to orange, opaque, viscous suspension., recorded as fda label in effect 2026-01-30 in the United States.

    US prescribing information · 264138c1-9e5f-45ef-be87-79ca97c989d9 · read 2026-08-30

  • Recorded price in US: 0.46837–4.00043 USD per one gram, across 51 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

  • Recorded price in US: 8.53098 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 5 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.

Names and forms linked to this record

  • Stereoisomer of

    Alitretinoin

    Evidence on this page does not automatically apply to this one.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Tretinoin 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 unclearRead 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 tretinoin reverses skin ageing or repairs sun damage — the Renova label denies all four versions of that claim in capital letters

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 an appearance grade assigned by an investigator is a measurement of skin health

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 drug which normalises follicular keratinisation should therefore prevent the cancers arising in the same tissue — plausible, tested, and false

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 topical tretinoin carries oral isotretinoin’s teratogenic risk, inferred from chemical similarity before the prospective data existed

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 unclearRead 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 Tretinoin 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 peopleRead 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.

Photoaging: improvement on the treated forearm and not the other one
In plain words
The trial that started the anti-ageing industry had every patient put tretinoin on one forearm and the plain cream on the other, so each person was their own comparison. All thirty who finished improved on the tretinoin arm and not on the vehicle arm.
What was measured
Graded photoaging score and histology, tretinoin-treated forearm against vehicle-treated forearm in the same patient
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Weiss and colleagues ran a 16-week randomised, double-blind, vehicle-controlled study at the University of Michigan. Every patient applied tretinoin to one forearm and vehicle cream to the other; half additionally received tretinoin to the face and half vehicle. All 30 patients who completed showed statistically significant improvement in photoaging on the tretinoin-treated forearm and not on the vehicle-treated forearm. Fourteen of 15 who received facial tretinoin improved, against none of the vehicle-treated faces. Histologic changes were significant in tretinoin-treated forearm skin only. Side effects were confined to irritation of exposed skin. The within-patient design is the strength of this study and its sample size is the weakness.
Source
Weiss JS et al., JAMA 1988;259:527-532 (PMID 3336176)
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
The effect holds for 48 weeks at two strengths
In plain words
Nearly three hundred people who had already used the cream for six months carried on for another six under blinded conditions. The improvement held or continued, and the side effects got less common rather than more.
What was measured
Investigator and subject assessment of photodamage plus skin replica analysis at 48 weeks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Olsen and colleagues extended two multicentre double-blind studies: subjects who had completed 24 weeks of once-daily tretinoin emollient cream at 0.05% (n=149) or 0.01% (n=149) continued the same strength for a further 24 weeks. Maintenance of improvement or continued reduction in signs of photodamage was recorded by investigators and subjects and confirmed by skin replica analysis. Cutaneous side effects were less common during the extension than during the first 24 weeks. The extension was not vehicle-controlled, so it establishes durability within treated groups rather than a fresh comparison against no treatment.
Source
Olsen EA et al., J Am Acad Dermatol 1997;37:217-226
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
VATTC: no effect on skin cancer in 1,131 randomised patients
In plain words
The largest randomised trial ever run on this drug asked whether it prevents the commonest cancer in the United States. Over five years, about half of both groups developed a basal cell carcinoma. The difference was one percentage point, in a trial designed to find a real one.
What was measured
Time to first new basal cell carcinoma and first new invasive squamous cell carcinoma on the face or ears
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The Veterans Affairs Topical Tretinoin Chemoprevention Trial randomised 1,131 high-risk patients, mean age 71, to 0.1% tretinoin or matching vehicle applied twice daily to the face and ears for 1.5 to 5.5 years. Primary outcomes were time to new basal cell carcinoma and time to new invasive squamous cell carcinoma on the face or ears. Neither was significant (P=0.3 for BCC, P=0.4 for SCC). At five years, 53% of the tretinoin group and 54% of controls had developed a BCC, and 28% against 31% an invasive SCC; the differences were 1.0% (95% CI -6.5 to 8.6) and 3.6% (95% CI -3.1 to 10.3). No differences appeared in any cancer-related endpoint or in actinic keratosis counts. The only quality-of-life difference was worse symptoms in the tretinoin group at 12 months.
Source
Weinstock MA et al., J Invest Dermatol 2012;132:1583-1590 (VATTC, NCT00007631)
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
The same trial was stopped early because more people in the tretinoin group died
In plain words
Death was never meant to be measured in this trial. The monitoring committee stopped the study six months early anyway, because there were too many deaths among people using the cream. The authors adjusted for every difference they could find between the groups, and the gap did not go away.
What was measured
All-cause mortality, a post hoc endpoint in a trial powered for skin cancer incidence
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The VATTC intervention was terminated six months early because of an excessive number of deaths in the tretinoin-treated group. Death was not contemplated as an endpoint in the original design. Post hoc analysis found minor imbalances in age, comorbidity and smoking status, all important predictors of death; after adjusting for them, the difference in mortality between the randomised groups remained statistically significant. The authors state plainly that they observed an association but do not infer a causal one, and that current evidence suggests causation is unlikely — topical tretinoin has minimal systemic absorption, and no mechanism connects it to all-cause death. The finding has not been reproduced in any subsequent randomised trial, and no subsequent trial of this size has been run.
Source
Weinstock MA et al., Arch Dermatol 2009;145:18-24 (PMID 19153339)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
The Renova label denies in capital letters what the category is sold on
In plain words
The approved wrinkle indication is worth reading in the original. The label says the product does not eliminate wrinkles, does not repair sun-damaged skin, does not reverse photoaging and does not restore younger skin. It is approved for the mitigation of fine facial wrinkles, as an adjunct, in people already avoiding the sun.
What was measured
That topical tretinoin reverses skin ageing — a claim the product’s own approved label refuses in capital letters, and one the trials were never designed to test
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The RENOVA 0.02% cream label states the indication as "an adjunctive agent for use in the mitigation (palliation) of fine facial wrinkles in patients who use comprehensive skin care and sunlight avoidance programs", followed by the capitalised sentence "RENOVA (tretinoin cream) 0.02% DOES NOT ELIMINATE WRINKLES, REPAIR SUN-DAMAGED SKIN, REVERSE PHOTOAGING, or RESTORE MORE YOUTHFUL or YOUNGER SKIN." Every trial supporting the indication measured graded fine wrinkling, mottled hyperpigmentation and roughness on ordinal scales. None measured dermal collagen restoration as a clinical outcome, and none measured coarse wrinkling, which the label does not claim.
Source
RENOVA (tretinoin cream) 0.02% United States prescribing information, Indications and Usage, as held on the record
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 pregnancy question moved from case reports to a prospective cohort
In plain words
Because tretinoin is chemically close to a drug that famously causes birth defects, individual case reports in the early 1990s caused alarm. A cohort that followed pregnancies forward, rather than looking back after a bad outcome, found no increase in any measured outcome.
What was measured
That topical tretinoin carries isotretinoin’s teratogenic risk — an inference from chemical similarity and retrospective case reports that a prospective cohort did not support
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Case reports in the Lancet in 1993 linked first-trimester topical tretinoin to congenital disorders and prompted a genuine scare, on the reasonable prior that isotretinoin is an established human teratogen. Loureiro and colleagues then prospectively ascertained 106 pregnant women with first-trimester topical tretinoin exposure through the California Teratogen Information Service between 1983 and 2003 and compared them with 389 prospectively ascertained unexposed women. There were no significant differences in spontaneous abortion (6.6% against 8.5%, P=0.53) or major structural defects (2.2% against 1.2%, P=0.62), and no difference in birth weight, length, head circumference or gestation. In a subset (62 exposed, 191 unexposed) the prevalence of retinoic acid-specific minor malformations did not differ (12.9% against 9.9%, P=0.51). The authors note it remains impossible to exclude individual susceptibility, and the label still advises against use in pregnancy.
Source
Loureiro KD et al., Am J Med Genet A 2005;136:117-121 (PMID 15940677)
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
The largest acne network meta-analysis rates its own confidence in the evidence as low
In plain words
Forty randomised trials in eighteen thousand people were pooled to work out which acne cream works best. The combinations came out ahead of single drugs. The authors then graded their own confidence in the whole exercise as low, because the trials do not report their results consistently enough to compare.
What was measured
That the ranking of topical acne treatments is settled — the network exists, the ranking exists, and the confidence rating attached to it by its own authors is low
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Stuart and colleagues searched CENTRAL, MEDLINE, Embase and the WHO registry to June 2020 and pooled 40 trials with 18,089 participants in a frequentist network meta-analysis. Patient Global Assessment of Improvement was reported in only 11 of the 40 trials. Against vehicle, benzoyl peroxide improved self-reported acne (35% against 26%); benzoyl peroxide with adapalene (54% against 35%) and with clindamycin (49% against 35%) ranked above benzoyl peroxide alone. Withdrawals for adverse events were low throughout, slightly higher for the combinations (2.5% and 2.7%) than for benzoyl peroxide (1.6%) or adapalene alone (1.0%). Overall confidence in the evidence, assessed with CINeMA, was low, and the authors state that inconsistent reporting precluded firmer conclusions.
Source
Stuart B et al., Br J Dermatol 2021;185:512-525 (PMID 33825196)
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

How many documents were read

  • 58 documents were read for this substance.

    RNAWiki source record

  • 5 of them state the same halfLife, and they agree.

    RNAWiki source record

  • 5 of them state the same bioavailability, and they agree.

    RNAWiki source record

  • 5 of them state the same proteinBinding, and they agree.

    RNAWiki source record

Where else this substance is registered

FDA substance identifier (UNII)
5688UTC01R
RxNorm concept
245723

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    Suppression classes recorded: S1, S3, S4, S6.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

What the approval register records

  • 54 approved applications cover products containing this substance. The earliest was NDA016921, approved 19711020 to VALEANT INTL.

    Drugs@FDA application register · NDA016921 · read 2026-08-29

  • Marketing status on the register: discontinued and prescription.

    Drugs@FDA application register · NDA016921 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 19730126.

    FDA National Drug Code directory · 0574-2225 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

3 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 it may clash with — found nothing in the sources checked.
  • Other ways to the same goal — found nothing in the sources checked.
  • What changed on this page — found nothing in the sources checked.

The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

The acid form of vitamin A, which binds retinoic acid receptors in the pore lining and forces the plugged cells to shed — reproducibly effective on acne lesion counts and on graded fine wrinkling, and decisively ineffective at preventing skin cancer in 1,131 randomised veterans, a trial stopped six months early because more people died in the tretinoin group.

Recorded evidence blocks (13)

What did Tretinoin's largest trial (2000 people) and its longest (17 years) measure?


2000 people in Tretinoin's largest registered study, 17 years in its longest registered window, measuring Skin Aging Measured With the Photonumeric Scale. ClinicalTrials.gov · 2026-09-01

37 phase2, 20 phase1, 20 phase3, 10 phase4, 9 na, 5 early phase1, 2 na or unstated; NCT00382200; 2023-01-05. Last human test completed 2026, NCT04919369.

Interpretation These counts include studies where Tretinoin 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
    37
  • phase1
    20
  • phase3
    20
  • phase4
    10
  • na
    9
  • early phase1
    5
2 more recorded rows
  • na or unstated
    2
  • Last recorded human test NCT04919369
    2026-07-03

recorded 2026-09-01 · last checked 2026-09-04

From C. elegans to human: where has Tretinoin shown lifespan?


C. elegans: lifespan, mouse: mechanism-only, dog: lifespan and human: mechanism-only (93): the rungs where Tretinoin has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Interpretation Skin Aging Measured With the Photonumeric Scale. — the recorded outcome words.

Yeast C. elegans lifespanDrosophila Mouse mechanism-onlyRat Dog lifespanNon-human primate Human mechanism-only
Show the evidence
  • C. elegans
    lifespan
  • mouse
    mechanism-only
  • dog
    lifespan
  • human NCT00974480
    mechanism-only; Skin Aging Measured With the Photonumeric Scale.; 93

recorded 2026-09-01 · last checked 2026-09-04

12 of Tretinoin's trials stopped: accrual/recruitment, funding/business, other?


accrual/recruitment (9), funding/business (1) and other (2): Tretinoin's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"Study drug became commercially available."; 12 of 93 registered studies

Show the evidence

Trial

  • NCT00006220
    terminated; "Study drug became commercially available."
  • NCT00240513
    terminated; "Too much difficulty recruiting and retaining patients, PI decided to stop."
  • NCT00528450
    terminated; "Lack of accrual"
  • NCT00669071
    terminated; "Enrollment closed"
  • NCT01067274
    withdrawn; "Study abandoned"
  • NCT01125930
    terminated; "Due to slow recruitment and sponsor request study ended early"
6 further recorded trials
  • NCT01275274
    withdrawn; "no subject enrolled in nearly 2 years"
  • NCT01349556
    withdrawn; "Study withdrawn due to volunteer disinterest in participating."
  • NCT01985477
    terminated; "Terminated Phase I due to slow accrual without progression to Phase II."
  • NCT03878524
    terminated; "Low accrual"
  • NCT04113863
    terminated; "Low enrolment rate"
  • NCT04282668
    terminated; "The study was terminated due to the changing treatment landscape, difficulty in enrolling eligible participants, and little likelihood of providing meaningful clinical benefit for the participants."

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Tretinoin used Fluocinolone acetonide 0.1%/hydroquinone 4%/tretinoin 0.05% Cream in sequence with glycolic acid peels — over how long?


studies of Tretinoin used the recorded amount. ClinicalTrials.gov · 2026-09-01

16 recorded entries; human; also "Fluocinolone acetonide 0.1%/hydroquinone 4%/tretinoin 0.05% Cream in sequence with glycolic acid peels", "Fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%", "Aczone Gel 5%; Tretin-X Gel 0.025%"

Show the evidence

human

  • NCT00472966
    Fluocinolone acetonide 0.1%/hydroquinone 4%/tretinoin 0.05% Cream in sequence with glycolic acid peels
  • NCT00669071
    Fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%
  • NCT00835198
    Aczone Gel 5%; Tretin-X Gel 0.025%
  • NCT00835198
    Tretin-X Gel 0.025%
  • NCT00919191
    Retin-A Micro Gel 0.04% Pump
  • NCT00975312
    Tretinoin 0.05%
10 more recorded rows
  • human NCT01135069
    Tretinoin microsphere 0.1%
  • human NCT01135069
    Brand Retin-A Micro tretinoin microsphere gel 0.1%
  • human NCT01313728
    Aczone Gel 5% plus Retin-A Micro Gel 0.1% Pump
  • human NCT01313728
    Retin-A Micro Gel 0.1% Pump
  • human NCT01406080
    Tretinoin emollient cream 0,05%
  • human NCT01448733
    Benzoyl peroxide 2.5%/clindamycin phosphate 1.2% in the morning with with tretinoin 0.05% gel in the evening
  • human NCT03427554
    Tretinoin cream 0.1%
  • human NCT03433378
    Tretinoin cream, 0.05%
  • human NCT03433378
    RETIN-A® (tretinoin) cream, 0.05%
  • human NCT04724473
    Tretinoin Cream 0.025%

recorded 2026-09-01 · last checked 2026-09-04

Tretinoin's half-life is 0.5 to 2 hours — which schedules were studied?


0.5 to 2 hours, the half-life Tretinoin's label states. openfda-label · 9c4ae9d9-c2a0-4995-a27a-e3f0f0284db9 · 2026-08-30

bioavailability 50% %.

Show the evidence
  • half life
    0.5 to 2 hours hours; Elimination The terminal elimination half-life of tretinoin following initial dosing is 0.5 to 2 hours in patients with APL.
  • bioavailability
    50% %; The absolute bioavailability of tretinoin capsules was approximately 50%.
  • metabolism
    Metabolism Tretinoin induced its own metabolism with plasma concentrations after 1 week of continuous therapy decreased to one-third of their day 1 values.

recorded 2026-08-30 · last checked 2026-09-04

Which of 3 year disease free survival rate, adverse events and adverse events as a measure of safety did Tretinoin's trials measure?


3 year disease free survival rate, adverse events and adverse events as a measure of safety lead 40 outcome terms across Tretinoin's trials. ClinicalTrials.gov · 2026-09-01

survival, response duration, long term efficacy, response, overall response rate and 3 year disease free survival rate follow.

Show the evidence
  • response rates
    1
  • distributions of event free survival
    1
  • disease free survival
    1
  • survival
    1
  • response duration
    1
  • long term efficacy
    1
14 more recorded rows
  • response
    1
  • overall response rate
    1
  • 3 year disease free survival rate
    1
  • response rate as measured by recist criteria
    1
  • time to progression
    1
  • continuous complete remission at 3 years
    1
  • mortality rate at 6 weeks
    1
  • tumor response rate
    1
  • lesion counts at week 12
    1
  • inflammatory lesion counts at week 12
    1
  • event free survival
    1
  • skin aging measured the photonumeric scale
    1
  • severity of erythematotelangiectatic rosacea signs redness
    1
  • severity of erythematotelangiectatic rosacea signs dry skin
    1

recorded 2026-09-01 · last checked 2026-09-04

Which of Tretinoin's 11 ongoing trials reports first?


11 registered trials of Tretinoin are open; earliest completion 2027-01. ClinicalTrials.gov · 2026-09-01

Event free survival; Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients; latest 2029-06-30

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Trial

  • NCT01409161
    "Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia"; n 151; "Event free survival"; 2027-12-18
  • NCT02339740
    "Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia"; n 158; "Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients"; 2029-06-30
  • NCT04241276
    "A Randomised Trial of ATRA in a Novel Drug Combination for Pancreatic Cancer"; n 170; "To assess the efficacy of ATRA when given in combination with gemcitabine and nab-paclitaxel based on progression free survival (PFS)."; 2029-02-28
  • NCT05999812
    "Clinical Trial of All-trans-retinoic Acid, Bevacizumab and Atezolizumab in Colorectal Cancer"; n 22; "Objective Response Rate of of ATRA, bevacizumab and atezolizumab combination"; 2028-10-01
  • NCT06439888
    "Lymphocyte Support to SBRT in Patients With Oligo-metastatic Solid Cancer"; n 58; "Dose-limiting toxicities (DLT)"; 2027-01
  • NCT06528769
    "Study of All-Trans Retinoic Acid (ATRA) and Cemiplimab in Patients With Advanced Leiomyosarcoma"; n 16; "Overall Response Rate (ORR)"; 2027-12-31
5 further recorded trials
  • NCT06706401
    "Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma"; n 460; "Event Free Survival (EFS)"; 2029-01
  • NCT07187505
    "Venetoclax Combined With ATRA and ATO in Hyperleukocytic Acute Promyelocytic Leukemia"; n 28; "Early Mortality (Day 0-30)"; 2027-07-01
  • NCT07586813
    "Romiplostim N01 Plus ATRA for Persistent Isolated Chemotherapy-Induced Thrombocytopenia After Complete Remission of Gastrointestinal Solid Tumors"; n 220; "Overall Platelet Response Rate at Week 12"; 2027-12-31
  • NCT07586826
    "Romiplostim N01 Plus ATRA for Persistent Isolated Chemotherapy-Induced Thrombocytopenia After Complete Remission of Gynecologic, Breast, or Lung Solid Tumors"; n 220; "Overall Platelet Response Rate at Week 12"; 2027-12-31
  • NCT07597395
    "ATRA for Management of Primary ITP"; n 192; "Durable platelet response"; 2028-12-30

recorded 2026-09-01 · last checked 2026-09-04

Which running trial of Tretinoin could settle lifespan?


NCT07187505 measures Early Mortality (Day 0-30), reading out 2027-07-01.

5 open trials; n 28; "Venetoclax Combined With ATRA and ATO in Hyperleukocytic Acute Promyelocytic Leukemia"

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Trial

  • NCT07187505
    "Venetoclax Combined With ATRA and ATO in Hyperleukocytic Acute Promyelocytic Leukemia"; n 28; "Early Mortality (Day 0-30)"; 2027-07-01
  • NCT01409161
    "Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia"; n 151; "Event free survival"; 2027-12-18
  • NCT06706401
    "Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma"; n 460; "Event Free Survival (EFS)"; 2029-01
  • NCT04241276
    "A Randomised Trial of ATRA in a Novel Drug Combination for Pancreatic Cancer"; n 170; "To assess the efficacy of ATRA when given in combination with gemcitabine and nab-paclitaxel based on progression free survival (PFS)."; 2029-02-28
  • NCT02339740
    "Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia"; n 158; "Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients"; 2029-06-30

Which 25 trials of Tretinoin posted no result?


Posted no result
25 of 25 completed trials
Registrations
NCT00017225, NCT00002479, NCT00003601, NCT00005863, NCT00006239 and NCT00472966, and 19 more
Completion dates
oldest 2002-02; newest 2020-11-30
Show the evidence

Trial

  • NCT00017225
    2002-02
  • NCT00002479
    2002-08
  • NCT00003601
    2004-03-02
  • NCT00005863
    2004-12
  • NCT00006239
    2005-03
  • NCT00472966
    2007-04
14 further recorded trials
  • NCT00005823
    2007-12
  • NCT00975312
    2009-02
  • NCT00003598
    2009-11
  • NCT01161550
    2012-08
  • NCT01668615
    2012-08
  • NCT00276601
    2013-06
  • NCT00100906
    2013-07
  • NCT01814852
    2015-02
  • NCT02180425
    2015-07
  • NCT01406080
    2015-11
  • NCT01820624
    2015-11-13
  • NCT02401295
    2016-11
  • NCT02620813
    2017-10-12
  • NCT03427554
    2018-01-26

At the median, Tretinoin's trials enrolled 40 people — anything larger?


Median enrolment
40
Largest enrolment
2000
Registered trials counted
87

What do 8540 spontaneous reports say about Tretinoin — 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.

Tretinoin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 8540 reaction mentions were counted: depression 1546; unintended pregnancy 1526; pregnancy 1152; abortion induced 890. open-targets-adr · CHEMBL38 · 2026-06-24

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  • depression
    1546
  • unintended pregnancy
    1526
  • pregnancy
    1152
  • abortion induced
    890
  • suicidal ideation
    847
  • dry skin
    649
4 more recorded rows
  • mood altered
    612
  • blood triglycerides increased
    592
  • abortion spontaneous
    377
  • lip dry
    349

recorded 2026-06-24 · last checked 2026-09-04

Tretinoin and CYP3A4, BCRP and P-GP: shared by which compounds?


CYP3A4, BCRP and P-GP appear in Tretinoin's recorded interaction sentences, 2 in all. openfda-label+europepmc · 2026-08-30

Interpretation pharmacokinetics

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CYP3A4

  • pharmacokinetics
    Tretinoin is metabolized by cytochrome P450 enzymes, CYP3A4, 2C8, and 2E and undergoes glucuronidation by UGT2B7.
  • pharmacokinetics
    Moderate CYP3A Inhibitors: Increased tretinoin toxicity following concomitant use of tretinoin capsules with certain antimycotics that are moderate CYP3A4 inhibitors has been reported post-marketing.

recorded 2026-08-30 · last checked 2026-09-04

What is recorded about Tretinoin and AMPK?


"Spermidine, in turn, upregulated hepatic ALDH1A2 expression, enhancing retinoic acid synthesis and activating the AMPK-SIRT1 axis, thereby reducing lipid accumulation in hepatocytes." — where Tretinoin and AMPK appear together. Europe PMC · pathway abstract search · 2026-07-17

AMPK, sirtuin, mTOR, autophagy, senolytic, IGF-1; PMID 42259828, 41645896, 41184271, 42492121

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  • AMPK PMID 42259828
    "Spermidine, in turn, upregulated hepatic ALDH1A2 expression, enhancing retinoic acid synthesis and activating the AMPK-SIRT1 axis, thereby reducing lipid accumulation in hepatocytes."
  • sirtuin PMID 42259828
    "Spermidine, in turn, upregulated hepatic ALDH1A2 expression, enhancing retinoic acid synthesis and activating the AMPK-SIRT1 axis, thereby reducing lipid accumulation in hepatocytes."
  • AMPK PMID 42259828
    "Collectively, these findings establish a novel Faecalibacterium-spermidine-ALDH1A2-retinoic acid-AMPK-SIRT1 axis through which inulin alleviates FLHS, highlighting inulin as a dietary intervention targeting the gut-liver axis and offering novel therapeutic avenues for preventing this disorder in laying hens."
  • sirtuin PMID 42259828
    "Collectively, these findings establish a novel Faecalibacterium-spermidine-ALDH1A2-retinoic acid-AMPK-SIRT1 axis through which inulin alleviates FLHS, highlighting inulin as a dietary intervention targeting the gut-liver axis and offering novel therapeutic avenues for preventing this disorder in laying hens."
  • mTOR
    "<title>Abstract</title> <p> <bold>Aim</bold> To determine the mechanism by which fat mass and the obesity-associated protein (FTO)-regulated circNFATC3/miR-23b-3p axis influence RAI14-mediated gastric cancer (GC) progression. <bold>Methods</bold> Retinoic acid-induced protein 14 (RAI14), adenosine 5′-monophosphate-activated protein kinase (AMPK), mTOR (mTOR), sterol regulatory element-binding…"
  • AMPK
    "<title>Abstract</title> <p> <bold>Aim</bold> To determine the mechanism by which fat mass and the obesity-associated protein (FTO)-regulated circNFATC3/miR-23b-3p axis influence RAI14-mediated gastric cancer (GC) progression. <bold>Methods</bold> Retinoic acid-induced protein 14 (RAI14), adenosine 5′-monophosphate-activated protein kinase (AMPK), mTOR (mTOR), sterol regulatory element-binding…"
2 more recorded rows
  • sirtuin PMID 41645896
    "Single-cell sequencing showed abnormal activation of trophoblast <i>Rarres2</i> (retinoic acid receptor responder 2) and macrophage <i>Cmklr1</i> (chemokine-like receptor 1) at the maternal-fetal interface in systemic <i>Sirt1</i> heterozygous knockout mice."
  • mTOR PMID 41184271
    "Once inside, they synchronously activate both autophagy pathways: AR7 antagonizes retinoic acid receptor alpha (RARα) to enhance CMA, while rapamycin inhibits mTOR to promote macroautophagy."

autophagy

  • PMID 41184271
    "Once inside, they synchronously activate both autophagy pathways: AR7 antagonizes retinoic acid receptor alpha (RARα) to enhance CMA, while rapamycin inhibits mTOR to promote macroautophagy."
  • PMID 42492121
    "We identified that pE301R strongly inhibits retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling and suppresses IFN-I production. pE301R impedes RLR signaling by directly degrading RIG-I, and pharmacological inhibition of autophagy rescued pE301R-induced RIG-I degradation. pE301R degrades RIG-I by promoting its interaction with p62."
  • PMID 42061406
    "Multi-omics analyses reveal that all-trans retinoic acid (ATRA) released from ferroptotic tumor cells directly targets CD38 through the transcriptional factor retinoic acid receptor alpha (RARα) and activates transcription factor EB (TFEB) to control MHC-II expression in macrophage by inducing autophagy."
  • senolytic PMID 41471101
    "In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways' modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS's modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling…"
  • IGF-1 PMID 39396656
    "Retinoic acid receptor (RAR) activation in macrophages increases IGF-1 expression and can be achieved with all-trans retinoic acid (ATRA)."
  • mTOR PMID 35532157
    "We employed all-trans retinoic acid (ATRA) as an inducer of profilin expression and showed that profilin induces autophagy through mTOR inhibition, autophagy-activating kinase ULK1 upregulation, and AMPK stabilization as well as its activation."

recorded 2026-07-17 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL38
PubChem CID
444795
CAS number
302-79-4
RxCUI
10753
InChIKey
SHGAZHPCJJPHSC-YCNIQYBTSA-N

Relations

Also called
Tretinoine, Aberel, All-trans retinoic acid, Eudyna, Kerlocal, Oristar rna, Retin a, Retinoic acid, Tretinoina, 13-cis retinoic acid, 9 cis retinoic acid, atra
Trade name
Acticin, Altreno, Atralin, Avita, Renova, Retin-a micro, Tretinoin component of solage, Tretinoin component of tri-luma, Tretinoin component of twyneo, Tretinoin component of veltin, Tretinoin component of ziana, Tretin-x
Development code
NSC-122758
Salt form
retin-a micro gel, tri-luma cream, Tretinoin Cream
Sources (11)

Sources

  • ClinicalTrials.gov clinicaltrials.gov ·
  • ClinicalTrials.gov ClinicalTrials.gov API v2 snapshot 2026-09-01T09:00:05 ·
  • this record's own fields 2,3,5 ·
  • Europe PMC dose-response search ·
  • Europe PMC pathway abstract search ·
  • Europe PMC search ·
5 more sources

ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work

How these records are assembled · Which registers were checked

Index-quality checks
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  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 11 source rows
  • no critical contamination: no quarantine open
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