This page shows what was measured, who it was measured in, and what that does not settle.
What Timolol Anhydrous does in the body
Timolol blocks those signals where they arrive at the pump, so less fluid is made and pressure falls.
Inside the eye, a ring of tissue behind the iris pumps out clear fluid all day. That secretion is switched on partly by the same nerve signals that speed up the heart. The same receptors sit in the heart and airways, and enough of each drop drains down the tear duct into the nose to reach them.
Why people take it. High pressure inside the eye, treated by making the eye produce less fluid
What happened in people
450 serious respiratory and cardiovascular case reports and 32 death reports received by the FDA and the National Registry between 1978 and 1985
✎ 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.
That timolol is innocuous, as its founding paper stated on the basis of 20 patients and one dose
Where it acts
Non-pigmented epithelium of the ciliary body, where aqueous humour is secreted — and, through nasal absorption, the heart and airways
Kind of result
Living longer, or avoiding a major event
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 · 817W3C6175 · read 2026-08-29
Its recorded molecular formula is C13H24N4O3S·C4H4O4, weighing 432.50.
US prescribing information · 72b0d0ec-832a-4c25-b845-2537ab506354 · 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 111 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
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.
Intraocular pressure reduction and duration of action across 0.1%, 0.25%, 0.5% and 1.0%
✓ The study showed what it set out to show
Who was studied
Zimmerman & Kaufman dose-response (1977)
How many people
20
Study design
Single-dose, open, dose-ranging
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Dose response demonstrated; 0.5% gave maximal effect; every concentration acted for at least 24 hours. No inferential statistic reported.
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. Twenty patients, single dose. The paper states no local or systemic side effects were discovered and calls the drug innocuous. The FDA had 32 death reports within seven years of marketing.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Topical ophthalmic solution 0.25% and 0.5%, twice daily; also a gel-forming solution and preservative-free unit-dose vials
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Orzalesi N, Rossetti L, Invernizzi T, Bottoli A, Autelitano A. Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hyperte… · a recorded source, not a stored snapshot
Around-the-clock intraocular pressure reduction, timolol against latanoprost and dorzolamide
Timolol failed to reduce pressure significantly against baseline at 3 AM; latanoprost superior at 3, 6 and 9 AM, noon (P = 0.01), 9 PM and midnight (P = 0.05)
Repeated elsewhere
Partially Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Twenty patients across three treatment periods. Small, and the only study of its kind with masked evaluators and inpatient measurement at eight times of day.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Topical ophthalmic solution 0.25% and 0.5%, twice daily; also a gel-forming solution and preservative-free unit-dose vials
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Orzalesi N, Rossetti L, Invernizzi T, Bottoli A, Autelitano A. Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hyperte… · a recorded source, not a stored snapshot
Intraocular pressure reduction at one year, dorzolamide against timolol and betaxolol
✓ The study showed what it set out to show
Who was studied
International Dorzolamide Study (Strahlman 1995)
How many people
523
Study design
Double-masked, randomised, parallel comparison at 34 international sites
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Approximately 25% peak reduction with timolol against 23% dorzolamide and 21% betaxolol; 20% against 17% and 15% at afternoon trough
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. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Topical ophthalmic solution 0.25% and 0.5%, twice daily; also a gel-forming solution and preservative-free unit-dose vials
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Orzalesi N, Rossetti L, Invernizzi T, Bottoli A, Autelitano A. Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hyperte… · a recorded source, not a stored snapshot
Diurnally corrected intraocular pressure reduction at peak and trough over 3 months
Orzalesi N, Rossetti L, Invernizzi T, Bottoli A, Autelitano A. Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hyperte… · a recorded source, not a stored snapshot
What we know
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Timolol Anhydrous
What a person takes: Topical ophthalmic solution 0.25% and 0.5%, twice daily; also a gel-forming solution and preservative-free unit-dose vials.
The measurement behind this step
A drop onto the ocular surface. A small fraction crosses the cornea to the ciliary body and the rest drains through the nasolacrimal duct, where conjunctival and nasal absorption delivers it to the systemic circulation without hepatic first pass. The gel-forming formulation increases ocular contact time to allow once-daily use, and the preservative-free unit-dose vial exists for patients sensitive to benzalkonium chloride.
Getting in
A drop goes in and most of it goes down the tear duct
The eye can hold only a fraction of a drop. The rest drains through a duct at the inner corner into the nose within minutes. That drainage is not waste, it is the route by which the drug reaches the rest of the body.
──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
Timolol maleate is instilled as a 0.25% or 0.5% aqueous solution. Tear turnover and nasolacrimal drainage clear the majority of the instilled volume within minutes. Published plasma measurement shows rapid systemic absorption after instillation, reduced when punctal occlusion is applied, with the absorption occurring during conjunctival and nasal contact rather than within the duct itself.
The surviving fraction crosses into the front of the eye
What is left soaks through the clear window at the front of the eye and reaches the tissue behind the iris that makes the fluid. Pressure starts falling within half an hour.
╌╌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
Timolol partitions across the corneal epithelium and stroma into the aqueous humour, reaching the ciliary body. The label records onset of pressure reduction within half an hour of a single dose, maximum effect at one to two hours, and significant lowering maintained for as long as 24 hours.
It blocks the signal that tells the eye to make fluid
The fluid pump behind the iris is switched on partly by adrenaline-type signals. Timolol sits on those receptors and blocks them without switching anything on itself.
╌╌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
Timolol is a non-selective antagonist at beta-1 and beta-2 adrenergic receptors on the non-pigmented ciliary epithelium. The label specifies that it lacks intrinsic sympathomimetic activity, direct myocardial depressant activity and membrane-stabilising activity — it is a pure antagonist. Blockade reduces adenylate cyclase activity and cyclic AMP in the secretory epithelium.
With the signal blocked, the pump slows. The drain is untouched, but less is coming in, so the pressure in the chamber settles lower.
╌╌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
Reduced cyclic AMP lowers the rate of active aqueous humour secretion. Outflow facility is essentially unchanged, which is why timolol combines additively with the prostaglandin analogues and the rho kinase inhibitors, which act on outflow. Pooled reduction is 3.70 mmHg (95% credible interval 3.16 to 4.24) at three months.
The same receptors in the heart and lungs are blocked too
The receptors timolol blocks are not unique to the eye. They also control heart rate and keep the airways open. The fraction absorbed through the nose reaches both.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Beta-1 blockade reduces cardiac output and can precipitate failure where sympathetic drive is supporting a weak myocardium. Beta-2 blockade in bronchi and bronchioles increases airway resistance through unopposed parasympathetic activity. Absorption across nasal mucosa enters the systemic circulation without hepatic first-pass extraction, so the effective systemic dose is far larger than the instilled micrograms suggest.
Aqueous production falls naturally overnight, so there is less for the drug to suppress. In a round-the-clock study, timolol was the one drug that failed to lower pressure at 3 AM.
──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
Aqueous humour formation has a strong circadian rhythm, falling substantially during sleep. A drug acting by suppressing secretion therefore has less to act on at night. In the 20-patient crossover study measuring eight times across 24 hours, timolol reduced pressure significantly against baseline at every time point except 3 AM, and dorzolamide — weaker overall — outperformed it at midnight and 3 AM.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with open-angle glaucoma or ocular hypertension, now usually as a second agent rather than the first. It is contraindicated outright in bronchial asthma, in severe chronic obstructive pulmonary disease, in sinus bradycardia and in second- or third-degree atrioventricular block.
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 IOP-lowering effect of Timolol GFS 0.25% and 0.5% have been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-controlled trial.”
US prescribing information · 72b0d0ec-832a-4c25-b845-2537ab506354 · read 2026-08-30
On older people, the label states: “No overall differences in safety or effectiveness have been observed between elderly and younger patients.”
US prescribing information · 72b0d0ec-832a-4c25-b845-2537ab506354 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no adequate and well-controlled studies in pregnant women with timolol maleate to inform a drug-associated risk.”
US prescribing information · 72b0d0ec-832a-4c25-b845-2537ab506354 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Timolol maleate has been detected in human milk following oral and ophthalmic drug administration.”
US prescribing information · 72b0d0ec-832a-4c25-b845-2537ab506354 · read 2026-08-30
Where the result stopped carrying
The registration-era safety claim: two studies totalling 50 patients reported no side effects at all, and the label now carries four absolute contraindications
Nocturnal control: the one time of day the drug does not measurably work is the time nobody was measuring
The premise that ophthalmic administration is local, which plasma measurement disproved and which the label now states plainly in its first Warnings sentence
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Topical ophthalmic solution 0.25% and 0.5%, twice daily; also a gel-forming solution and preservative-free unit-dose vials
✎ 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
A drop onto the ocular surface.
✎ 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: A small fraction crosses the cornea to the ciliary body and the rest drains through the nasolacrimal duct, where conjunctival and nasal absorption delivers it to the systemic circulation without hepatic first pass. The gel-forming formulation increases ocular contact time to allow once-daily use, and the preservative-free unit-dose vial exists for patients sensitive to benzalkonium chloride.
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 bronchial asthma or a history of it, in severe chronic obstructive pulmonary disease, in sinus bradycardia, in second- or third-degree atrioventricular block, in overt cardiac failure and in cardiogenic shock. The label states that severe respiratory and cardiac reactions, including death due to bronchospasm in asthmatic patients and rarely death in association with cardiac failure, have been reported after ophthalmic administration. Beta-blockade may mask the symptoms of hypoglycaemia in diabetes and the signs of thyrotoxicosis. Local effects include burning, stinging, corneal hypoesthesia and dry eye. Unlike the prostaglandin analogues it causes no iris pigmentation and no eyelash change.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Topical ophthalmic solution 0.25% and 0.5%, twice daily; also a gel-forming solution and preservative-free unit-dose vials
✎ 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
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: A small fraction crosses the cornea to the ciliary body and the rest drains through the nasolacrimal duct, where conjunctival and nasal absorption delivers it to the systemic circulation without hepatic first pass. The gel-forming formulation increases ocular contact time to allow once-daily use, and the preservative-free unit-dose vial exists for patients sensitive to benzalkonium chloride.
No source is stored against this line.
What is recorded as being sold
137 products list this as an active ingredient in the United States drug directory. 94 of them contain it and nothing else.
FDA National Drug Code directory · 71921-226 · read 2026-08-29
They are sold as powder, solution, solution, gel forming / drops, solution/ drops and tablet, taken ophthalmic and oral.
FDA National Drug Code directory · 71921-226 · read 2026-08-29
The regulator's established pharmacologic class for it is adrenergic beta-antagonists [moa] and beta-adrenergic blocker [epc].
FDA National Drug Code directory · 71921-226 · read 2026-08-29
78 published labels name it as an active ingredient. 41 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 038cf2ba-ad08-4981-a3cc-bff0e4ba5dfb · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 038cf2ba-ad08-4981-a3cc-bff0e4ba5dfb · read 2026-08-29
Timolol GFS is ophthalmic at 3 DOSAGE FORMS AND STRENGTHS Ophthalmic gel forming solution: slightly opalescent, colorless to nearly colorless solution containing 0.25% or 0.5% of timolol., recorded as fda label in effect 2024-05-28 in the United States.
US prescribing information · 72b0d0ec-832a-4c25-b845-2537ab506354 · read 2026-08-30
Recorded price in US: 0.58434–23.6549 USD per one millilitre, across 57 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: 1.18714–5.85723 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.
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 Timolol Anhydrous studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That timolol is innocuous, as its founding paper stated on the basis of 20 patients and one dose
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 topical eye drop stays in the eye — the absorbed fraction bypasses hepatic first-pass metabolism entirely
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 32 reported deaths give a rate; spontaneous reports have no denominator and establish only that the events occur
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 daytime pressure readings describe 24-hour control for a drug that suppresses secretion, which itself falls at night
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 Timolol Anhydrous are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Sixth of fourteen first-line drops on pressure lowering
In plain words
Pooling 114 trials, timolol lowers pressure by 3.70 millimetres of mercury at three months. That places it behind all four prostaglandin analogues and one other beta-blocker, and ahead of the carbonic anhydrase inhibitors.
What was measured
Mean intraocular pressure reduction at 3 months, pooled across 114 randomised trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the Bayesian network meta-analysis of 114 randomised trials with data from 20,275 participants, mean reduction in intraocular pressure at 3 months for timolol was 3.70 mmHg (95% credible interval 3.16 to 4.24). Ahead of it: bimatoprost 5.61, latanoprost 4.85, travoprost 4.83, levobunolol 4.51, tafluprost 4.37. Behind it: brimonidine 3.59, carteolol 3.44, levobetaxolol 2.56, apraclonidine 2.52, dorzolamide 2.49, brinzolamide 2.42, betaxolol 2.24, unoprostone 1.91. Timolol is the comparator arm in a large share of the included trials, which makes its estimate the most precisely determined in the network and also means the network is anchored on it.
Written into the record, not signed off as a reviewed claim
The 1977 dose-response study that established the drug
In plain words
Two small studies in thirty and twenty patients showed that a single drop halved eye pressure within seven hours and that the effect lasted a full day. That was enough to change glaucoma treatment worldwide.
What was measured
Intraocular pressure reduction after single-dose instillation, by strength
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Zimmerman and Kaufman studied timolol maleate in 30 patients with glaucoma, finding significant pressure lowering at 0.5% and 1.5%, with pressure 50% below pretreatment at seven hours on both strengths. A companion single-dose study in 20 patients with chronic open-angle glaucoma established the dose-response across 0.1%, 0.25%, 0.5% and 1.0%, found 0.5% gave the maximal effect, and found every concentration produced an ocular hypotensive effect lasting at least 24 hours. Both papers report no ocular or systemic side effects detected. The second concludes that timolol "may be an effective, innocuous, once-a-day, topical agent."
Written into the record, not signed off as a reviewed claim
450 serious cardiopulmonary reports and 32 deaths in the first seven years
In plain words
Between 1978 and 1985 the FDA received 450 reports of serious breathing and heart events attributed to timolol eye drops, and 32 reports of death. A third of them happened within a week of starting, and nearly a quarter on the first day.
What was measured
Spontaneous adverse event reports to FDA and the National Registry, 1978 to 1985
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Nelson and colleagues reviewed reports received by the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects between September 1978 and December 1985: 450 case reports of serious respiratory and cardiovascular events and 32 case reports of death attributed to ophthalmic timolol. Of these, 267 patients (55%) had a cardiac arrhythmia or a bronchospasm-related event. Median age was 68. Of 212 patients with a medical history provided, 129 (61%) had respiratory disease, 65 (31%) cardiovascular disease and 5 (2%) no underlying illness. Of 318 with duration data, 106 (33%) had their event within one week of starting and 73 (23%) on the first day. Of 192 with follow-up, 177 (92%) improved after the drug was stopped. These are spontaneous reports without a denominator, so they establish that the events happen and cannot establish how often.
Written into the record, not signed off as a reviewed claim
It stops working at 3 AM
In plain words
A crossover study measured pressure around the clock in hospital. Timolol lowered pressure at every time of day except three in the morning, where it did nothing measurable. Latanoprost and dorzolamide both worked overnight.
What was measured
Intraocular pressure at eight times across 24 hours, three drugs in randomised crossover
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Orzalesi and colleagues admitted 20 patients with primary open-angle glaucoma or ocular hypertension to hospital and measured four 24-hour tonometric curves — at baseline and after each of three randomised one-month treatment periods — with two evaluators masked to assignment. Using Goldmann sitting values, all three drugs significantly reduced pressure against baseline at every measurement time except timolol at 3 AM. Latanoprost was more effective than timolol at 3, 6 and 9 AM, noon, 9 PM and midnight. Dorzolamide, weaker than timolol overall, outperformed it at midnight and 3 AM. The sample is 20 patients in a crossover design, which is small, and the finding has shaped how the class is understood since.
Source
Orzalesi N et al., Invest Ophthalmol Vis Sci 2000;41:2566-2573 (PMID 10937568)
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
"Innocuous" was written before anyone had a denominator
In plain words
The two papers that launched the drug studied fifty patients between them and reported no side effects at all. One of them used the word innocuous. Seven years later the FDA had 32 death reports.
What was measured
That a topical drug is systemically innocuous because two small short studies saw nothing — an inference the postmarketing record contradicted within a decade
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 1977 studies enrolled 30 and 20 patients respectively for single-dose and short-duration observation, and both report that no local or systemic side effects were discovered. The conclusion of the dose-response paper reads that timolol "may be an effective, innocuous, once-a-day, topical agent for the treatment of glaucoma." Neither study was powered to detect an event occurring in a susceptible subgroup, and neither enrolled the asthmatic and cardiac patients in whom the harm concentrates — 61% of the FDA-reported cases with a history had known respiratory disease. The label now carries contraindications in bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia and heart block, and states that death due to bronchospasm in asthmatic patients has been reported after ophthalmic administration.
Written into the record, not signed off as a reviewed claim
A drop in the eye was assumed to stay in the eye
In plain words
The original assumption was that a drop on the eye is a local treatment. It is not. Most of it drains down the tear duct into the nose, where it is absorbed straight into the bloodstream without passing through the liver first.
What was measured
That topical ophthalmic administration confines a drug to the eye — a founding assumption of the field that plasma measurement and 32 death reports overturned
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A review of human plasma concentrations after ophthalmic instillation found that eye drops absorb rapidly into the systemic circulation, with plasma levels lower when punctal occlusion is applied. Occasional early and late plasma peaks in the timolol studies led the author to conclude that systemic absorption is low during nasolacrimal passage itself but occurs during conjunctival and nasal contact. The consequence is the one that matters clinically: absorption across nasal mucosa enters the systemic venous circulation directly and bypasses hepatic first-pass metabolism, so a topical dose measured in micrograms can produce plasma concentrations in the range achieved by oral beta-blockade. The label reflects the shift in a single sentence — "As with many topically applied ophthalmic drugs, this drug is absorbed systemically" — and then reproduces the systemic beta-blocker warnings in full.
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What is not here
7 questions this page could not answer
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How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A non-selective beta-blocker that turns down aqueous secretion at the ciliary epithelium, lowering pressure 3.70 mmHg at three months across 114 pooled trials — sixth of fourteen first-line drops — while drainage down the tear duct delivers enough drug to the nasal mucosa to bypass the liver entirely, producing the 450 serious cardiopulmonary reports and 32 deaths the FDA collected in its first seven years on the market.
Recorded evidence blocks (9)
Q1
On the Timolol Anhydrous label: indicated for what?
"Timolol Maleate Ophthalmic Solution 0.5% is a non-selective beta-adrenergic receptor blocking agent indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Timolol Maleate Ophthalmic Solution 0.5% is a non-selective beta-adrenergic receptor blocking…": indications and usage on Timolol Anhydrous's label. DailyMed label · 3c20b537-88c6-4ec7-a359-e0ba67afe431 · 2026-04-20
Q2
117 registered trials of Timolol Anhydrous — at which phases?
Registered studies posting no result
78 of 117
117 registered studies of Timolol Anhydrous: 40 phase4, 28 phase3, 23 phase2, 11 na, 10 na or unstated, 10 phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
1209 with a PubMed record
Show the evidence
phase4
40
phase3
28
phase2
23
na
11
na or unstated
10
phase1
10
6 more recorded rows
completed
91
terminated
9
withdrawn
8
unknown
5
recruiting
3
active not recruiting
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
14 of Timolol Anhydrous's trials stopped: futility/efficacy, accrual/recruitment, funding/business, other?
futility/efficacy (1), accrual/recruitment (6), funding/business (3) and other (4): Timolol Anhydrous's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Lack of funding."; 14 of 117 registered studies
Show the evidence
Trial
NCT00368602
terminated; "Lack of funding."
NCT00579969
terminated; "Study stopped and data not analyzed"
NCT00862472
withdrawn; "Management decision not to conduct an additional efficacy study."
NCT01250457
withdrawn; "Unknown, PI has left the institution. There was no enrollment."
NCT01426113
terminated; "Study terminated due to corporate decision."
NCT01514721
terminated; "low enrollment"
8 further recorded trials
NCT01514734
terminated; "Low recruitment rate"
NCT01607671
withdrawn; "Unable to recruit participants from recruiting sites."
NCT01696383
withdrawn; "Management decision"
NCT01927406
withdrawn; "Funding source unavailable"
NCT02390284
terminated; "No patients had abnormal PERG and could not be included in the first two arms from the baseline timepoint."
NCT02730871
terminated; "Enrollment Challenges"
NCT03648229
withdrawn; "Funding unavailable"
NCT05479123
terminated; "due to lack of recruitment and follow up compliance"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Timolol Anhydrous used Timolol Maleate Ophthalmic Gel Forming Solution, 0.5% — over how long?
Human studies of Timolol Anhydrous used "Timolol Maleate Ophthalmic Gel Forming Solution, 0.5%". ClinicalTrials.gov · 2026-09-01
Which 53 trials of Timolol Anhydrous posted no result?
Posted no result
53 of 53 completed trials
Registrations
NCT00751049, NCT00751062, NCT00751127, NCT00856622, NCT00006398 and NCT00287521, and 47 more
Completion dates
oldest 1993-12; newest 2023-03-01
Show the evidence
Trial
NCT00751049
1993-12
NCT00751062
1993-12
NCT00751127
1994-02
NCT00856622
1999-06
NCT00006398
2002-09
NCT00287521
2006-02
14 further recorded trials
NCT00333125
2007-02
NCT00273442
2007-04
NCT00159653
2007-06
NCT00277498
2007-06
NCT00314171
2007-08
NCT00519753
2008-12
NCT00672997
2008-12
NCT00753168
2008-12
NCT00760539
2008-12
NCT00680329
2009-07
NCT00887029
2009-11
NCT00879099
2010-01
NCT00676637
2010-02
NCT00966576
2010-08
Q6
At the median, Timolol Anhydrous's trials enrolled 70 people — anything larger?
Median enrolment
70
Largest enrolment
22213
Registered trials counted
117
Q7
What do 1437 spontaneous reports say about Timolol Anhydrous — 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.
Timolol Anhydrous appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1437 reaction mentions were counted: treatment failure 275; eye irritation 230; ocular hyperaemia 176; intraocular pressure increased 164. FAERS via Open Targets · CHEMBL1200870 · 2026-06-24
Show the evidence
treatment failure
275
eye irritation
230
ocular hyperaemia
176
intraocular pressure increased
164
eye pain
138
vision blurred
121
4 more recorded rows
bradycardia
104
hypersensitivity
85
eye pruritus
82
visual acuity reduced
62
recorded 2026-06-24 · last checked 2026-09-04
Q8
Which 10 reactions does Timolol Anhydrous's label not list?
7.5 CYP2D6 Inhibitors Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine) and timolol.
drug_interactions
7.5 CYP2D6 Inhibitors Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine) and timolol.
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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