This page shows what was measured, who it was measured in, and what that does not settle.
What Darifenacin does in the body
The bladder wall contracts when acetylcholine lands on muscarinic receptors, and darifenacin blocks them so the involuntary squeeze during filling is weakened.
There are five varieties of that receptor. The bladder uses mostly one of them, called M3; the brain relies heavily on a different one, M1. Darifenacin binds M3 fifty-nine times more tightly than M2 or M4, which is a large margin — but only nine times more tightly than M1, which is the one the cognitive argument is actually about. That is why the evidence for brain-sparing rests on measured cognitive testing rather than on the binding numbers.
Why people take it. An overactive bladder — sudden urgency, going too often, and leaking — treated with the most M3-selective drug in the class
What happened in people
Delayed recall at three weeks did not differ from placebo (mean difference -0.06, p=0.908) while oxybutynin ER differed by -1.30 (p=0.011) in 150 healthy subjects over 60
✎ 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.
Darifenacin versus placebo mean difference -0.06, p=0.908. Oxybutynin ER versus placebo -1.30, p=0.011; versus darifenacin -1.24, p=0.022
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No between-treatment difference in self-rated memory: the impaired group did not know they were impaired. The trial ran three weeks in healthy volunteers and cannot address cumulative exposure over years.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet, once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Cognitive function, quantitative EEG, salivation, visual nearpoint and heart rate variability on day 7 of each period
✓ The study showed what it set out to show
Who was studied
Darifenacin versus dicyclomine pharmacodynamics (Kay and Wesnes 2005)
How many people
27
Study design
Double-blind four-way crossover, 7-day treatment periods
Compared against
Not recorded for this study
Kind of result
What a body can do day to day
What was found
Darifenacin 7.5 and 15 mg: no cognitive effect versus placebo and no clinically relevant EEG change. Dicyclomine impaired 5 of 12 cognitive variables — simple reaction time p=0.009, numeric working memory speed p=0.012, spatial working memory speed p=0.048, picture recognition speed p=0.04 and sensitivity p=0.03
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Both agents decreased salivary flow rate against placebo, so peripheral antimuscarinic activity was demonstrated for darifenacin in the same study that found no central effect. Twenty-seven healthy men aged 19 to 44 is not the population the cognitive concern is about.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet, once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
No results are posted on the registry record. `endpoint met: false` records the absence of a public result, not a missed endpoint.
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. Warning time is the endpoint closest to the complaint patients actually bring, and it is rarely used. A completed 445-patient placebo-controlled trial of it has no public result.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet, once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Long-term safety and tolerability, by adverse events, laboratory values, vital signs and physical condition
✓ The study showed what it set out to show
Who was studied
Long-term safety and tolerability study (NCT00170755)
How many people
718
Study design
Phase 3 open-label long-term safety
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
A safety endpoint with no efficacy hypothesis test and no placebo arm; it describes tolerability over extended exposure and not effect size
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The longest exposure dataset for this drug measures spontaneously reported adverse events. The Kay trial showed that an anticholinergic cognitive effect can be invisible to the person experiencing it, which is exactly what a spontaneous-reporting safety study cannot capture.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet, once daily
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What 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
Darifenacin
What a person takes: Oral extended-release tablet, once daily.
The measurement behind this step
Swallowed whole and not chewed, crushed or divided, because the release rate is engineered into the tablet. Dose is capped in the presence of strong CYP3A4 inhibitors and in moderate hepatic impairment, and the drug is not recommended in severe hepatic impairment. Metabolism runs through both CYP2D6 and CYP3A4.
Getting in
A once-daily extended-release tablet
One tablet daily, swallowed whole. The extended-release design keeps the level steady rather than spiking, which is what the tolerability of the whole class depends on.
╌╌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
Oral extended-release tablet, once daily. Metabolised by CYP2D6 and CYP3A4, so strong inhibitors of either raise exposure and the label caps the dose accordingly. Dispensed as the hydrobromide. A dedicated QT study at doses up to 75 mg found no QT or QTc prolongation.
The target sits on the outer face of the bladder muscle cell. The drug arrives from the bloodstream and occupies it; nothing has to be carried inside.
──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
Muscarinic receptors are plasma-membrane G-protein-coupled receptors with an outward-facing orthosteric pocket, so no transporter step exists. Darifenacin is a lipophilic tertiary amine, which is the physical property that governs how much of it reaches tissues behind the blood-brain barrier — a separate question from which subtype it binds once there.
It prefers M3 by 59-fold over two subtypes and 9-fold over the one that matters
The drug picks out the receptor variety the bladder uses. It picks it out very strongly over two varieties that have little to do with memory, and only moderately over the one that does.
╌╌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
Competitive muscarinic antagonism with the label-stated ratios: 59-fold M3 over M2 and M4, 12-fold over M5, 9-fold over M1. M1 is the subtype most implicated in cognitive function. The ordering of those four numbers is the drug's entire pharmacological story, and the smallest of them is the one the marketing argument depends on.
The calcium signal driving the contraction is blunted
A contraction needs a burst of calcium inside the muscle cell. With M3 blocked, the burst is smaller and the involuntary squeeze during filling weakens.
╌╌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
Loss of M3-Gq/11 coupling reduces phospholipase C activity, inositol trisphosphate falls, sarcoplasmic reticulum calcium release drops and myosin light-chain phosphorylation declines. The identical cascade is interrupted in gut smooth muscle, which is why constipation is more prominent for this drug than for the rest of the class: M3 is the subtype the intestine uses too, so selectivity offers no escape from it.
A fifth to three fifths of an episode a day, and no measurable memory effect
Weekly leaks fall by one and a half to four more than on placebo, depending on dose and trial — a fraction of an episode a day. Memory testing over three weeks found no difference from placebo, where oxybutynin in the same study did worse.
╌╌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
Weekly urge incontinence episodes fell 1.5 to 2.8 more than placebo at 7.5 mg and 2.1 to 4.3 at 15 mg — 0.21 to 0.61 episodes a day. Dry mouth 20.2% and 35.3% against 8.2%; constipation 14.8% and 21.3% against 6.2%. Delayed recall at three weeks did not differ from placebo (p=0.908) while oxybutynin ER differed by -1.30 (p=0.011).
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 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 overactive bladder, and specifically older adults in whom anticholinergic cognitive burden is the deciding concern. That is the population the drug was positioned for and the population in which the supporting evidence is thinnest.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of darifenacin extended-release tablets in pediatric patients have not been established.”
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
On older people, the label states: “In the fixed-dose, placebo-controlled, clinical studies, 30% of patients treated with darifenacin extended-release tablets were over 65 years of age.”
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no available data on darifenacin use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.”
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of darifenacin in human milk, the effects on the breastfed infant, or the effects of darifenacin on milk production.”
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
On people with reduced liver function, the label states: “Subjects with severe hepatic impairment (Child-Pugh C) have not been studied, therefore darifenacin extended-release tablet is not recommended for use in these patients [see Dosage and Administration ( 2 ) and Warnings and Precautions ( 5.6 )] .”
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
On people with reduced kidney function, the label states: “A study of subjects with varying degrees of renal impairment (creatinine clearance between 10 and 136 mL/min) demonstrated no clear relationship between renal function and darifenacin clearance.”
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
Where the result stopped carrying
The public reporting of the 445-patient warning-time trial, which has no results section on the registry record
The premise that receptor selectivity relocates side effects out of existence — constipation is more prominent here than elsewhere in the class, because the gut uses M3 too
Any attempt to test the cognitive claim on a dementia endpoint: the observational datasets treat bladder antimuscarinics as one class and have never separated this drug out
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
Oral extended-release tablet, once daily
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
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
Swallowed whole and not chewed, crushed or divided, because the release rate is engineered into the tablet. Dose is capped in the presence of strong CYP3A4 inhibitors and in moderate hepatic impairment, and the drug is not recommended in severe hepatic impairment. Metabolism runs through both CYP2D6 and CYP3A4.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Dry mouth and constipation dominate and are clearly dose-dependent, with constipation more prominent than for most of the class because M3 governs gut smooth muscle as well as bladder. Contraindicated in patients with or at risk for urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. A dedicated QT study at up to five times the maximum dose found no prolongation. The cognitive question that the drug was positioned to answer has been tested for three weeks in healthy volunteers and never over the exposure windows the epidemiology concerns.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral extended-release tablet, once daily
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Dose is capped in the presence of strong CYP3A4 inhibitors and in moderate hepatic impairment, and the drug is not recommended in severe hepatic impairment. Metabolism runs through both CYP2D6 and CYP3A4.
✎ 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
24 products list this as an active ingredient in the United States drug directory. 24 of them contain it and nothing else.
FDA National Drug Code directory · 72162-2570 · read 2026-08-29
They are sold as powder, tablet, extended release and tablet, film coated, extended release, taken oral.
FDA National Drug Code directory · 72162-2570 · read 2026-08-29
The regulator's established pharmacologic class for it is cholinergic muscarinic antagonist [epc] and cholinergic muscarinic antagonists [moa].
FDA National Drug Code directory · 72162-2570 · read 2026-08-29
10 published labels name it as an active ingredient. 10 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-29
Darifenacin is oral at 3 DOSAGE FORMS AND STRENGTHS Extended-release tablets 7.5 mg and 15 mg ( 3 ) Darifenacin extended-release tablets 7.5 mg are white to off white colored circular biconvex film coated tablet debossed with “C” on one side…, recorded as fda label in effect 2025-10-27 in the United States.
US prescribing information · 6e8470d1-c3e6-4644-b70a-aa47ddf79676 · read 2026-08-30
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 Darifenacin 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 M3 selectivity delivers cognitive safety — the margin over M1 is nine-fold, the smallest of the four ratios the label quotes
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 three-week trial in healthy volunteers answers a question about cumulative exposure over years
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 weekly episode counts describe a larger benefit than the class average — converted to a daily rate they sit in the same band as every other drug in this file
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 long-term open-label safety study can characterise cognitive risk — it relies on spontaneous reporting of an effect the pivotal cognitive trial showed to be unnoticeable
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 Darifenacin 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.
No memory effect at three weeks, where oxybutynin aged the brain ten years
In plain words
A hundred and fifty healthy people over 60 took darifenacin, oxybutynin or placebo for three weeks and had their memory tested. Darifenacin was indistinguishable from placebo. Oxybutynin produced impairment the authors compared to ten years of brain ageing.
What was measured
Delayed recall accuracy on the Name-Face Association Test at week 3, darifenacin and oxybutynin ER versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Kay and colleagues randomised 150 healthy subjects aged 60 and over to darifenacin, oxybutynin ER or placebo in a multicentre, double-blind, double-dummy, parallel-group, three-week study, with doses escalated according to US labels. The primary endpoint was accuracy on the Name-Face Association Test for delayed recall at week 3. Darifenacin did not differ from placebo (mean difference -0.06, p=0.908). Oxybutynin ER scored significantly worse than both placebo (mean difference -1.30, p=0.011) and darifenacin (-1.24, p=0.022), with the authors describing the magnitude as comparable to brain ageing of ten years. Additional delayed-recall tests agreed. This is a real, well-designed, positive-control-bearing result, and it establishes exactly what it measured: three weeks, healthy volunteers, one memory instrument.
Written into the record, not signed off as a reviewed claim
Nobody could tell they had been impaired
In plain words
The same trial asked participants how their memory felt. The group with measurable impairment reported no more problems than anyone else.
What was measured
Self-rated memory scores by treatment arm, against objectively measured delayed-recall performance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Kay and colleagues report that no between-treatment differences were detected in self-rated memory, and state the conclusion explicitly: subjects were unaware of memory deterioration. That is a finding about the oxybutynin arm, not the darifenacin arm, and it is included on this page because it changes how every other cognitive claim in this drug class should be read. An adverse effect large enough to show up on a validated instrument and invisible to the person having it cannot be monitored by asking the patient, and will not appear in a spontaneous adverse-event table. Every antimuscarinic trial that relies on volunteered adverse-event reporting to characterise cognitive safety is measuring the wrong thing.
Written into the record, not signed off as a reviewed claim
The selectivity margin over the memory receptor is nine-fold
In plain words
Darifenacin's case is that preferring the bladder receptor spares the brain. Its own label says it prefers the bladder receptor fifty-nine times over two irrelevant ones — and only nine times over the one the brain uses for memory.
What was measured
Reported affinity ratios of M3 over M1, M2, M4 and M5 as stated on the US label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The US label states darifenacin has 9-fold and 12-fold greater affinity for M3 than for M1 and M5 respectively, and 59-fold greater affinity for M3 than for M2 or M4. M1 is the subtype most closely tied to cognitive function; M2 and M4 are the subtypes over which the drug's selectivity is greatest and whose blockade has least to do with memory. Presenting darifenacin as "M3-selective" without stating which ratios apply to which subtype describes the drug at its strongest and omits its weakest number. Nine-fold is a genuine preference — it is not nothing — but it is the margin on which the cognitive argument rests, and it is the smallest of the four.
Source
US prescribing information for darifenacin extended-release tablets, Mechanism of Action section (openFDA drug label endpoint)
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
Three weeks in healthy volunteers is not a dementia study
In plain words
The cognitive evidence for this drug is a three-week trial in healthy people. The concern it is meant to answer is about years of use in people who are already frail.
What was measured
That short-term pharmacodynamic equivalence to placebo predicts long-term dementia risk — the exposure windows differ by three orders of magnitude and no study bridges them
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Kay trial ran for three weeks in healthy subjects aged 60 and over. A companion crossover study in 27 healthy men aged 19 to 44 found darifenacin at 7.5 and 15 mg produced no cognitive effect, no clinically relevant EEG change and no effect on visual nearpoint or heart rate, while dicyclomine as an M1-selective comparator impaired five of twelve cognitive variables and slowed the EEG. Both are clean, informative pharmacodynamic studies. Neither addresses the epidemiological question, which concerns cumulative exposure measured in years: Coupland and colleagues reported an adjusted odds ratio of 1.65 (95% CI 1.56 to 1.75) for bladder antimuscarinics as a class across exposure windows of 1 to 11 years, and Gray and colleagues a hazard ratio of 1.54 (1.21 to 1.96) above 1,095 standardised daily doses over ten years. Those datasets treat the class as one thing and have never been powered to separate darifenacin out of it.
Written into the record, not signed off as a reviewed claim
The dry mouth and constipation are ordinary for the class, and dose-dependent
In plain words
Sparing the brain does not spare the mouth or the gut. One in five patients at the lower dose and one in three at the higher dose report dry mouth, and one in five at the higher dose reports constipation.
What was measured
Incidence of dry mouth and constipation at 7.5 mg and 15 mg against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The US label reports dry mouth in 20.2% at 7.5 mg and 35.3% at 15 mg against 8.2% on placebo, and constipation in 14.8% and 21.3% against 6.2%. Those rates sit at the higher end of the class: solifenacin reports 10.9% and 27.6% dry mouth against 4.2%, and trospium extended-release reported 8.7% against 3% in its pivotal trial. Constipation in particular is more prominent here than elsewhere in the group, which is consistent with the label's own selectivity data — M3 is the subtype that drives gut smooth muscle as well as bladder smooth muscle, so an M3-preferring drug has no route to sparing the intestine. Selectivity relocates the side-effect burden; it does not remove it.
Source
US prescribing information for darifenacin extended-release tablets, Adverse Reactions section (openFDA drug label endpoint)
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
A clean QT study at five times the maximum dose
In plain words
At doses up to 75 mg — five times the highest licensed dose — darifenacin did not lengthen the heart's electrical interval. The antibiotic used as a control in the same study did.
What was measured
QT and QTc interval change at doses up to 75 mg against a moxifloxacin positive control, in 179 healthy adults
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A controlled electrophysiology trial in 179 healthy adults receiving doses up to 75 mg found that darifenacin did not result in QT or QTc interval prolongation, while moxifloxacin as active control produced an increase of approximately 7 msec. Five times the maximum recommended dose with a demonstrably sensitive assay is about as strong as a negative QT finding gets. It is recorded rather than omitted because within this file the same study design produced 11.84 msec for tolterodine at twice its therapeutic dose with confidence intervals overlapping the positive control, and nothing at all for silodosin at three times its dose. A negative result is only interpretable next to the assay that produced it.
Source
US prescribing information for darifenacin extended-release tablets, Clinical Pharmacology section (openFDA drug label endpoint)
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
A 445-patient trial of "warning time" with no result on the registry
In plain words
Novartis ran a 445-patient placebo-controlled trial of how much warning a patient gets before an urgent need to void. No result is posted on the public registry record.
What was measured
Presence or absence of a posted results section for a completed 445-patient randomised trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
NCT00171145 was a 12-week randomised trial of darifenacin 15 mg against placebo in 445 patients, with change from baseline in warning time at week 12 as the primary outcome. Warning time — the interval between first sensation of urgency and involuntary voiding — is arguably the endpoint that maps most directly onto what patients complain about, and it is far less common than the episode counts every other trial in this indication uses. The registry record carries no results section. A completed 445-patient placebo-controlled trial of a novel patient-centred endpoint, with no public result, is a gap in the evidence base for this drug rather than a criticism of it — but it is a gap, and it is the kind that only shows up when the registry is read alongside the label.
Source
ClinicalTrials.gov record, NCT00171145
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 weekly numbers convert to a fraction of an episode a day
In plain words
The label reports the benefit in episodes per week, which sounds larger than it is. At the lower dose it works out at about one fifth to two fifths of an accident a day.
What was measured
Mean weekly reduction in urge incontinence episodes against placebo at 7.5 mg and 15 mg, converted to a daily rate
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Across three pivotal trials the label reports mean weekly reductions in urge incontinence episodes against placebo of 1.5 to 2.8 at 7.5 mg and 2.1 to 4.3 at 15 mg. Divided by seven, those are 0.21 to 0.40 episodes a day at 7.5 mg and 0.30 to 0.61 at 15 mg. Reporting in weekly units is entirely legitimate and matches the diary period, and it also makes the same effect look between three and seven times larger than the daily figures every other drug in this file is reported in. Placed on the common scale, darifenacin sits in the same band as everything else in the class: solifenacin 0.45 against placebo in SYNERGY, mirabegron 0.34 to 0.59 across three trials, tolterodine 0.12 to 0.15 in the Pfizer studies.
Source
US prescribing information for darifenacin extended-release tablets, Clinical Studies section (openFDA drug label endpoint)
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
How many documents were read
10 documents were read for this substance.
RNAWiki source record
10 of them state the same halfLife, and they agree.
RNAWiki source record
2 of them state the same bioavailability, and they agree.
RNAWiki source record
10 of them state the same volumeOfDistribution, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
CR02EYQ8GV
RxNorm concept
485421
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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No register row and no identity class settled the question.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read 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
10 approved applications cover products containing this substance. The earliest was NDA021513, approved 20041222 to ABBVIE.
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What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
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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.
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The record as stored
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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 most M3-selective antimuscarinic licensed, marketed on the premise that M3 preference spares cognition: its label reports weekly urge incontinence episodes falling 1.5 to 2.8 more than placebo at 7.5 mg and 2.1 to 4.3 at 15 mg, and a three-week randomised trial in 150 healthy volunteers over 60 found no memory effect against placebo (p=0.908) while oxybutynin ER in the same trial produced impairment equivalent to ten years of brain ageing — but the label's own selectivity figure over M1, the receptor that governs memory, is only nine-fold.
Recorded evidence blocks (10)
Q1
On the Darifenacin label: indicated for what?
"Darifenacin extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Darifenacin extended-release tablets are a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence,…": indications and usage on Darifenacin's label. DailyMed label · e84f1ae3-b9a2-4a15-a299-c75373891cc1 · 2026-02-10
Q2
24 registered trials of Darifenacin — at which phases?
13 to 19 hours; The elimination half-life of darifenacin following chronic dosing is approximately 13 to 19 hours.
tmaxpharmacokinetics
3.3 hours; Effect of Food Following single dose administration of darifenacin extended-release tablets with food, the AUC of darifenacin was not affected, while the C max was increased by 22% and T max was shortened by 3.3 hours.
bioavailabilitypharmacokinetics
15 %; The mean oral bioavailability of darifenacin extended-release tablets in EMs at steady-state is estimated to be 15% and 19% for 7.5 mg and 15 mg tablets, respectively.
metabolismpharmacokinetics
Regarding EM and PM [see Clincal Pharmacology, Pharmacokinetics, Variability in Metabolism (12.3)].
recorded 2026-02-10 · last checked 2026-09-04
Q6
Which 17 trials of Darifenacin posted no result?
Posted no result
17 of 17 completed trials
Registrations
NCT00171145, NCT00170755, NCT00170768, NCT00127270, NCT00171184 and NCT00366002, and 11 more
Completion dates
oldest 2004-12; newest 2023-12-20
Show the evidence
Trial
NCT00171145
2004-12
NCT00170755
2005-01
NCT00170768
2005-05
NCT00127270
2006-02
NCT00171184
2006-06
NCT00366002
2007-09
11 further recorded trials
NCT00413426
2007-09
NCT00413790
2007-09
NCT00703703
2008-10
NCT00921245
2009-02
NCT00800462
2012-12
NCT02143570
2016-04
NCT02386072
2017-08-04
NCT03602508
2019-09-13
NCT03572231
2020-03-30
NCT07206706
2022-12-28
NCT06616675
2023-12-20
Q7
At the median, Darifenacin's trials enrolled 98.5 people — anything larger?
Median enrolment
98.5
Largest enrolment
5589
Registered trials counted
24
Q8
What do 187 spontaneous reports say about Darifenacin — 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.
Darifenacin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 187 reaction mentions were counted: dry mouth 41; constipation 32; urinary retention 24; drug hypersensitivity 18. FAERS via Open Targets · CHEMBL1200935 · 2026-06-24
Show the evidence
dry mouth
41
constipation
32
urinary retention
24
drug hypersensitivity
18
vision blurred
14
urinary incontinence
14
4 more recorded rows
confusional state
13
pollakiuria
13
dry eye
9
hallucination
9
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Darifenacin's label not list?
Caution should be taken when darifenacin extended-release tablets is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine and tricyclic antidepressants ( 7.2 ) The concomitant use of darifenacin extended-release tablets with other anticholinergic agents may increase the frequency and/or…
drug_interactions
Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects of gastrointestinal motility ( 7.3 ) 7.1 CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors.
drug_interactions
The daily dose of darifenacin extended-release tablets should not exceed 7.5 mg when co-administered with potent CYP3A4 inhibitors (for example, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone).
drug_interactions
No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (for example, erythromycin, fluconazole, diltiazem and verapamil) [see Dosage and Administration (2) and Clinical Pharmacology (12.3)] .
drug_interactions
7.2 CYP2D6 Inhibitors No dosing adjustments are recommended in the presence of CYP2D6 inhibitors (for example, paroxetine, fluoxetine, quinidine and duloxetine) [see Clinical Pharmacology (12.3)] .
drug_interactions
7.3 CYP2D6 Substrates Caution should be taken when darifenacin extended-release tablets are used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window (for example, flecainide, thioridazine and tricyclic antidepressants) [see Clinical Pharmacology (12.3)] .
2 more recorded rows
Interaction statementdrug_interactions
7.4 CYP3A4 Substrates Darifenacin (30 mg daily) did not have a significant impact on midazolam (7.5 mg) pharmacokinetics [ see Clinical Pharmacology (12.3)] .
Interaction statementpharmacokinetics
Figure 1 Mean (SD) Steady-State Darifenacin Plasma Concentration-Time Profiles for Darifenacin 7.5 mg and 15 mg in Healthy Volunteers Including Both CYP2D6 EMs and PMs* *Includes 95 EMs and 6 PMs for 7.5 mg;
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
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
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