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Hydrochlorothiazide

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

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

What Hydrochlorothiazide does in the body

High blood pressure, and fluid retention

Deep in the kidney tubule there is a single doorway that pulls sodium and chloride back out of the fluid destined to become urine. Hydrochlorothiazide plugs that doorway, so more salt and water leave the body. Blood pressure falls over days from fluid loss, and over weeks the arteries themselves relax, which is where most of the long-term effect comes from.

What happened in people

A primary composite of 10.0% on hydrochlorothiazide against 10.4% on chlorthalidone in 13,523 randomised patients, hazard ratio 1.04

Source-linked record

Where this came from

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

The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.

The limit that matters most

That chlorthalidone prevents more cardiovascular events than hydrochlorothiazide — the direct randomised comparison found a hazard ratio of 1.04

Where it acts
Luminal membrane of the distal convoluted tubule
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · 0J48LPH2TH · read 2026-08-29

  • Its recorded molecular formula is C7H8ClN3O4S2, weighing 297.74.

    US prescribing information · 41aaea48-6c1b-42c8-a96f-5923d49dc934 · read 2026-08-30

Where each sentence above came from

No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.

Shown as the opening line on this page.

A limit recorded against this substance. Not signed off as a reviewed claim.

The four opening statements run to 91 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Stand-in result

A stand-in result is a number measured because the real result takes too long.

A picture of it, and where the picture fails

It is like judging a journey by the speedometer rather than by arriving.

Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.

What people get wrong. A stand-in result is often reported as the result itself.

A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.

Randomisation

Randomisation means chance decides who gets which treatment.

A picture of it, and where the picture fails

It is like a coin toss deciding the groups.

Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.

What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.

Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

Pathway

A pathway is a chain of steps inside a cell, each one setting off the next.

A picture of it, and where the picture fails

A pathway is like a row of dominoes.

Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.

What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.

An ordered series of molecular interactions producing a defined cellular change.

What happened in peopleRead from sources, not yet reviewed

What was measured, goal by goal

One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.

Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.

There is no single score. A strong test result and a weak life result are different facts.

Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
GoalLife outcomeWhat a body can doHow a person feelsA test resultA step in the bodyHarmsHow longWho was studied
Blood sugarNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Only a number moved4 registered test measure.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
FocusNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
CholesterolNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Nothing in the sources checkedNo registered study lists a symptom measure for this goal.Only a number moved1 registered test measure.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Blood sugar
insulin resistance week16; glycated hemoglobin a1c; plasma insulin; plasma glucose
Focus
cognitive assessment trail making test part b; cognitive assessment forward digit span test
Cholesterol
myocardial triglyceride levels

Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.

What each mark on this table means
Nothing in the sources checked
No registered study lists a life outcome for this goal.
Only a number moved
4 registered test measure.
Not recorded
Harms were not a registered measure for this goal.
Waiting for a reviewer
Who was studied is listed further down the page.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Composite of non-fatal myocardial infarction, stroke, heart failure hospitalisation, urgent revascularisation for unstable angina and non-cancer death

The study did not show it

Who was studied
Diuretic Comparison Project (NCT02185417)
How many people
13523
Study design
Pragmatic randomised open-label trial, median 2.4 years
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
HR 1.04 (95% CI 0.94-1.16), P = 0.45 — no difference in either direction
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. Hypokalaemia was more frequent on chlorthalidone (6.0% against 4.4%, p<0.001). Participants were already established on hydrochlorothiazide, which is a survivor population for that drug.

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

Form and route. Oral tablet and capsule, and a very large number of fixed-dose combination products

Interval reported. 95% CI 0

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

Combined fatal coronary heart disease or non-fatal myocardial infarction across three first-line strategies

The study showed what it set out to show

Who was studied
ALLHAT thiazide arm (NCT00000542)
How many people
33357
Study design
Randomised double-blind active-controlled trial, mean 4.9 years
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No difference on the primary endpoint; the diuretic arm was superior on heart failure against amlodipine (RR 1.38) and on stroke, heart failure and combined cardiovascular disease against lisinopril
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. The trial used chlorthalidone, not hydrochlorothiazide. Applying its result to hydrochlorothiazide was an assumption until the Diuretic Comparison Project tested it.

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

Form and route. Oral tablet and capsule, and a very large number of fixed-dose combination products

Interval reported. Not recorded in this summary

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

Odds of basal cell and squamous cell carcinoma by cumulative hydrochlorothiazide exposure

The study showed what it set out to show

Who was studied
Danish nationwide case-control study of non-melanoma skin cancer
How many people
0
Study design
Population-based case-control study using national registries, 2004-2012
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
OR 3.98 (95% CI 3.68-4.31) for squamous cell carcinoma at ≥50,000 mg cumulative use, rising to 7.38 (6.32-8.60) at ≥200,000 mg
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. Sample size is entered as 0 because this is a registry case-control study with matched controls rather than a randomised trial with an enrolled cohort. Sun exposure, the dominant risk factor, was not recorded.

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

Form and route. Oral tablet and capsule, and a very large number of fixed-dose combination products

Interval reported. 95% CI 3

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

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

What happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event Evidence recorded. Death, a heart attack, a stroke, a hospital stay.2 registered measures of this kind. 1 written-up study measured this and did not show a benefit.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life No evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
  5. A number that stands in for health Evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.26 registered measures of this kind.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals Evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Rat. A result in animals says what to test next. It does not say what happens in people.
  8. Cells in a dish Evidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

Where a source records it acting

  • Kidneys: Affects the distal renal tubular mechanism of electrolyte reabsorption; increases excretion of sodium and chloride, as recorded

    US prescribing information · 00b266d9-ac4a-e931-e063-6294a90a6a0b · read 2026-08-27

  1. Start

    Hydrochlorothiazide

    What a person takes: Oral tablet and capsule, and a very large number of fixed-dose combination products.

    The measurement behind this step

    Once daily in the morning, because diuresis lasting into the evening disturbs sleep. Duration of action is 6 to 12 hours, considerably shorter than chlorthalidone, which was the basis of the argument that it must be less effective — an argument the head-to-head trial did not support.

  2. Getting in

    Absorbed moderately and cleared unchanged by the kidney

    Around two thirds of a dose is absorbed and the body does not chemically alter it. It leaves in the urine as the same molecule that went in.

    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 bioavailability is roughly 65 to 75%, with onset of diuresis within two hours and duration of 6 to 12 hours. There is essentially no metabolism; elimination is renal as unchanged drug. This is the pharmacokinetic difference from chlorthalidone, whose much longer half-life was the main mechanistic argument for its supposed superiority.

  3. Reaching the cell

    It is actively pumped from blood into the tubule to reach its target

    Its target faces the urine, so the drug has to be secreted into the tubule to get at it. That pump is shared with other drugs, which is why some painkillers blunt the effect.

    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

    Hydrochlorothiazide is an organic anion secreted into the proximal tubular lumen by OAT1 and OAT3 and then carried downstream to the distal convoluted tubule. Non-steroidal anti-inflammatories compete for the same transporters and blunt the diuresis; declining glomerular filtration reduces delivery, which is why thiazides lose effectiveness in advanced chronic kidney disease.

  4. What it acts on

    It plugs the sodium-chloride doorway of the distal tubule

    A single transporter pulls sodium and chloride back together at this point in the tubule. The drug blocks it, and about one twentieth of the filtered sodium is left behind.

    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

    Binding to NCC, encoded by SLC12A3, from the luminal face inhibits electroneutral sodium-chloride cotransport in the distal convoluted tubule, which normally reabsorbs about 5% of filtered sodium. Loss-of-function mutations in the same gene cause Gitelman syndrome, whose electrolyte picture — hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria — is a near-exact phenocopy of chronic thiazide use.

  5. The change it makes

    Salt leaves, potassium follows, calcium stays

    The extra sodium arriving downstream is exchanged for potassium, which is why potassium falls. At the same time the block makes the cell pull more calcium in, so less calcium ends up in the urine.

    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

    Increased sodium delivery to the cortical collecting duct raises the electrochemical gradient for potassium secretion through ROMK, producing hypokalaemia and metabolic alkalosis. Intracellular sodium depletion in the distal convoluted tubule cell enhances basolateral sodium-calcium exchange and apical TRPV5-mediated calcium entry, lowering urinary calcium — the basis for stone prevention. Volume contraction raises proximal urate reabsorption and serum uric acid.

  6. What that does for a person

    Pressure falls, and the long-term effect is vascular rather than volume

    In the first weeks blood pressure falls because there is less fluid. After that, plasma volume returns almost to normal and the pressure stays down because the arteries themselves have relaxed.

    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

    Initial blood pressure reduction reflects reduced plasma volume and cardiac output. Over weeks, plasma volume partially normalises while peripheral vascular resistance falls, and the sustained effect is attributed to that vascular change rather than to continuing natriuresis. In the Diuretic Comparison Project, mean baseline systolic pressure was 139 mm Hg in both arms and the primary event rates were 10.0% and 10.4%.

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

Felt, measured, or meaningful

Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.

Felt

Things a person could notice without a test.

No registered study measured anything of this kind.

Measured

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

  • blood pressure
  • insulin resistance week16
  • supine diastolic blood pressure at trough
  • trough seated diastolic blood pressure
  • decrease in supine systolic blood pressure
  • blood pressure response
  • diastolic blood pressure after 8 weeks
  • sitting systolic blood pressure to week 12
  • trough sitting diastolic blood pressure
  • achieving blood pressure goals

and 16 more.

Meaningful

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

  • any adverse events serious adverse events and death
  • adverse events serious adverse events and deaths

A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.

Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.

Measured, but not felt. A number moves. The person notices nothing. Both can be true.

Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.

Matters, but takes years. The result that counts may take longer than anyone would keep watching.

Names that fit none of the three (12)
  • change in sitting bp
  • overall percentage of adverse events
  • reactive hyperemic index by period
  • cognitive assessment trail making test part b
  • cognitive assessment forward digit span test
  • bioequivalence
  • area under the curve of losartan
  • area under the curve of hctz
  • incidence of adverse events
  • renal function
  • c terminal propeptide of procollagen type i
  • at least 1 adverse event

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

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

How long anything takes

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

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

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

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

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

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

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

  7. How fast the body clears it. 5.6 to 14.8 hours hours

    Read from the label, which states: “When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours.”

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

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

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

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

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • One of the most-dispensed drugs in the world for hypertension, alone and inside a very large number of fixed-dose combination products. On the WHO Model List of Essential Medicines.

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: “INZIRQO is approved for use in pediatric patients for the following: Treatment of hypertension to lower blood pressure Treatment of edema associated with congestive heart failure, hepatic cirrhosis, and renal disease, including the nephrotic syndrome”

    US prescribing information · 41aaea48-6c1b-42c8-a96f-5923d49dc934 · read 2026-08-30

  • On people who are pregnant, the label states: “Risk Summary Untreated hypertension during pregnancy can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations).”

    US prescribing information · 41aaea48-6c1b-42c8-a96f-5923d49dc934 · read 2026-08-30

  • On people who are breastfeeding, the label states: “Risk Summary Available data from published literature indicate hydrochlorothiazide is present in human milk (see Data) .”

    US prescribing information · 41aaea48-6c1b-42c8-a96f-5923d49dc934 · read 2026-08-30

  • On people with reduced liver function, the label states: “Monitor for mental status changes when using INZIRQO in patients with hepatic impairment because fluid shifts may precipitate hepatic coma.”

    US prescribing information · 41aaea48-6c1b-42c8-a96f-5923d49dc934 · read 2026-08-30

Where the result stopped carrying

  • Two decades of guideline preference for chlorthalidone rested on indirect comparison and did not survive a direct one
  • The Diuretic Comparison Project could not show a difference in any component of its primary endpoint
  • The lip cancer association reported earlier, and later extended to non-melanoma skin cancer, was not detected in the randomised trials because none ran long enough
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

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

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

It was studied in different people

The people in the studies were not much like the reader.

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

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

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

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Prescription only

Quoted from a source

Where this came from

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

Read from the recorded approval status.

No source is stored against this line.

Form and route

Oral tablet and capsule, and a very large number of fixed-dose combination products

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

Once daily in the morning, because diuresis lasting into the evening disturbs sleep.

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: Duration of action is 6 to 12 hours, considerably shorter than chlorthalidone, which was the basis of the argument that it must be less effective — an argument the head-to-head trial did not support.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

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

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Hypokalaemia, hyponatraemia, hypomagnesaemia and metabolic alkalosis follow directly from the mechanism; the electrolyte picture is a phenocopy of Gitelman syndrome. Hyperuricaemia and gout, and impaired glucose tolerance with new-onset diabetes, are class effects. The drug is photosensitising and carries labelled information on non-melanoma skin cancer following Danish registry findings. Efficacy falls as glomerular filtration declines, and non-steroidal anti-inflammatories blunt it by competing for tubular secretion.

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

Where this came from

Reports sent to a regulator

  • These are reports people sent to a regulator. They do not show the medicine caused the reaction.
  • Nobody counted how many people took the medicine and reported nothing.
  • The same event can be reported more than once, and many reports are incomplete.
  • News coverage, lawsuits and new warnings change how often people report.
  • A count is not a rate and not a risk.

Hydrochlorothiazide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 11194 reaction mentions were counted. One report can name several reactions.

The recorded terms (10)
  • hyponatraemia — 1911 reaction mentions
  • sprue-like enteropathy — 1565 reaction mentions
  • acute kidney injury — 1449 reaction mentions
  • hypotension — 1245 reaction mentions
  • dizziness — 1161 reaction mentions
  • hypokalaemia — 963 reaction mentions
  • gastrooesophageal reflux disease — 957 reaction mentions
  • syncope — 710 reaction mentions
  • dehydration — 618 reaction mentions
  • haemorrhoids — 615 reaction mentions
  • open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

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

What is missing or unclearRead from sources, not yet reviewed

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Oral tablet and capsule, and a very large number of fixed-dose combination products

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: Duration of action is 6 to 12 hours, considerably shorter than chlorthalidone, which was the basis of the argument that it must be less effective — an argument the head-to-head trial did not support.

No source is stored against this line.

What is recorded as being sold

  • 952 products list this as an active ingredient in the United States drug directory. 186 of them contain it and nothing else.

    FDA National Drug Code directory · 71335-9730 · read 2026-08-29

  • They are sold as capsule, capsule, gelatin coated, powder, powder, for suspension, solution/ drops and tablet, taken oral.

    FDA National Drug Code directory · 71335-9730 · read 2026-08-29

  • The regulator's established pharmacologic class for it is increased diuresis [pe], thiazide diuretic [epc] and thiazides [cs].

    FDA National Drug Code directory · 71335-9730 · read 2026-08-29

  • 550 published labels name it as an active ingredient. 143 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · 1898f438-4571-4aab-ae06-9bf1aabf0486 · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · 1898f438-4571-4aab-ae06-9bf1aabf0486 · read 2026-08-29

  • Recorded price in US: 0.01165–0.0373 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 72 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 takeRead from sources, not yet reviewed

What you could measure

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

RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.

Questions worth asking

  • Which of the trials of Hydrochlorothiazide studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That chlorthalidone prevents more cardiovascular events than hydrochlorothiazide — the direct randomised comparison found a hazard ratio of 1.04

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 ALLHAT result applies unchanged to hydrochlorothiazide because both are thiazide-type — an assumption that happened to survive testing, which is not the same as having been established

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 skin cancer odds ratios translate into a quantified absolute risk for any individual — the study has no sun exposure data and no randomisation

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 longer plasma half-life implies better outcomes — the mechanistic argument for chlorthalidone that the trial did not bear out

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Hydrochlorothiazide are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

The Diuretic Comparison Project: chlorthalidone was not better after all
In plain words
For twenty years the standard teaching was that chlorthalidone is the superior thiazide. Thirteen thousand veterans were randomised to keep taking hydrochlorothiazide or switch, and the event rates came out the same.
What was measured
Composite of non-fatal infarction, stroke, heart failure hospitalisation, urgent revascularisation and non-cancer death over a median 2.4 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Diuretic Comparison Project randomised 13,523 Department of Veterans Affairs patients aged 65 or older already receiving hydrochlorothiazide at 25 or 50 mg daily, to continue it or switch to chlorthalidone 12.5 or 25 mg daily. Mean age was 72; 12,781 (94.5%) had been on 25 mg hydrochlorothiazide; mean baseline systolic pressure was 139 mm Hg in each group. At a median 2.4 years the primary composite of non-fatal myocardial infarction, stroke, heart failure requiring hospitalisation, urgent coronary revascularisation for unstable angina and non-cancer death occurred in 702 (10.4%) on chlorthalidone against 675 (10.0%) on hydrochlorothiazide: hazard ratio 1.04 (95% CI 0.94 to 1.16), p=0.45. There were no between-group differences in any component. Hypokalaemia was more frequent on chlorthalidone, 6.0% against 4.4%, p<0.001.
Source
Ishani A et al., Diuretic Comparison Project, N Engl J Med 2022;387:2401-2410 (NCT02185417)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The chlorthalidone superiority claim was always an indirect comparison
In plain words
The argument rested on chlorthalidone having been the drug in the big successful trials and on it lasting longer in the body. Neither of those is a comparison, and when a comparison was finally run the difference disappeared.
What was measured
That the choice of thiazide-type diuretic in the landmark trials explains their results — a between-trial comparison that a within-trial randomisation contradicted
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The case for chlorthalidone rested on three things: its longer plasma half-life and duration of action; greater ambulatory blood pressure reduction at nominally equivalent doses in small crossover studies; and the fact that ALLHAT, SHEP and MRFIT used chlorthalidone while several trials with weaker results used hydrochlorothiazide. The last of these is a comparison between trials, not within one, and confounds the drug with the population, the era, the dose and the co-therapy. The Diuretic Comparison Project removed all of those by randomising within a single population at doses actually used in practice, and found a hazard ratio of 1.04 with no component differing. What survived was the metabolic difference in the expected direction: more hypokalaemia on chlorthalidone.
Source
Ishani A et al., N Engl J Med 2022;387:2401-2410; ALLHAT Officers and Coordinators, JAMA 2002;288:2981-2997
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
ALLHAT: the thiazide arm was the one that won
In plain words
In the largest hypertension trial ever run, the thiazide-type diuretic matched a calcium channel blocker and an ACE inhibitor on heart attacks and death, and beat both on other endpoints, at a fraction of the cost.
What was measured
Six-year rates of coronary events, heart failure, stroke and combined cardiovascular disease across three first-line strategies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ALLHAT randomised 33,357 hypertensive participants aged 55 or older with at least one other coronary risk factor to chlorthalidone 12.5-25 mg (n=15,255), amlodipine 2.5-10 mg (n=9,048) or lisinopril 10-40 mg (n=9,054), mean follow-up 4.9 years. The primary endpoint of fatal coronary disease plus non-fatal infarction did not differ, with six-year rates of 11.5%, 11.3% and 11.4% respectively, and all-cause mortality did not differ either. Against chlorthalidone, amlodipine had a higher six-year heart failure rate (10.2% against 7.7%; RR 1.38, 95% CI 1.25 to 1.52) and lisinopril had higher rates of combined cardiovascular disease (33.3% against 30.9%; RR 1.10), stroke (6.3% against 5.6%; RR 1.15) and heart failure (8.7% against 7.7%; RR 1.19). The stated conclusion was that thiazide-type diuretics should be preferred for first-step therapy. Read alongside the Diuretic Comparison Project, the class conclusion holds and does not single out one member of it.
Source
ALLHAT Officers and Coordinators, JAMA 2002;288:2981-2997 (NCT00000542)
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 dose-response association with squamous cell skin cancer, from registry data
In plain words
Danish national registry data found that people with high cumulative hydrochlorothiazide exposure had roughly four times the odds of squamous cell skin cancer, rising to more than seven times at the highest exposure. Other diuretics showed nothing.
What was measured
Odds ratios for basal cell and squamous cell carcinoma by cumulative hydrochlorothiazide exposure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Pedersen and colleagues identified non-melanoma skin cancer cases in the Danish Cancer Registry from 2004 to 2012 and matched 20 controls per case by age and sex, assessing cumulative hydrochlorothiazide use from the Danish Prescription Registry over 1995 to 2012. High cumulative use of 50,000 mg or more carried odds ratios of 1.29 (95% CI 1.23 to 1.35) for basal cell carcinoma and 3.98 (3.68 to 4.31) for squamous cell carcinoma. Clear dose-response relationships were present for both, and at the highest cumulative category of 200,000 mg or more the odds ratios were 1.54 (1.38 to 1.71) and 7.38 (6.32 to 8.60). Use of other diuretics and antihypertensives was not associated with non-melanoma skin cancer. The authors note the absence of sun exposure data as a limitation.
Source
Pedersen SA et al., J Am Acad Dermatol 2018;78:673-681
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The skin cancer finding is a strong association, and it is not a randomised result
In plain words
The dose-response pattern and the absence of any similar signal with other blood pressure drugs make chance and simple confounding unlikely. There is still no trial, and sun exposure was not measured.
What was measured
That hydrochlorothiazide causes squamous cell carcinoma at a quantified rate — the association is strong and dose-dependent, and no trial has measured it or the absolute risk
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Three features strengthen the case that this is causal: a monotonic dose-response across cumulative exposure categories, biological plausibility from the drug's known photosensitising property and its earlier association with lip cancer, and specificity — no association was seen for other diuretics or antihypertensives, which argues against confounding by indication or by the general characteristics of treated hypertensive patients. Three features limit it: the design is case-control on registry data, sun exposure was not recorded and is the dominant risk factor for both cancers, and no randomised trial has been or realistically could be run at the required duration. Both regulators added labelling. The honest statement is a well-characterised association with a dose-response and no randomised confirmation, and the absolute risk depends on a person's baseline skin cancer risk, which the study cannot supply.
Source
Pedersen SA et al., J Am Acad Dermatol 2018;78:673-681
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 metabolic effects are the class trade, and one of them cuts the other way
In plain words
Thiazides lower potassium, raise uric acid and raise blood sugar. They also reduce calcium in the urine, which is why they are used to prevent kidney stones and are associated with better bone density.
What was measured
Randomised rates of hypokalaemia, and the mechanistic basis of the class metabolic profile
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Blocking NCC increases sodium delivery to the collecting duct, raising the electrochemical driving force for potassium secretion: in the Diuretic Comparison Project hypokalaemia occurred in 4.4% on hydrochlorothiazide against 6.0% on chlorthalidone, p<0.001. Volume contraction increases proximal urate reabsorption, raising serum uric acid and precipitating gout. Impaired insulin secretion, partly potassium-dependent, underlies the new-onset diabetes signal seen across thiazide trials. The same transporter block that causes all of these also increases distal calcium reabsorption and reduces urinary calcium excretion, which is the basis for using thiazides in recurrent calcium stone disease and for the observed association with higher bone mineral density. One mechanism, four consequences, three unwanted and one useful.
Source
Ishani A et al., N Engl J Med 2022;387:2401-2410; ALLHAT Officers and Coordinators, JAMA 2002;288:2981-2997
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

  • 144 documents were read for this substance.

    RNAWiki source record

  • 35 of them state the same tMax, and they agree.

    RNAWiki source record

Where else this substance is registered

CAS registry number
58-93-5
PubChem compound
3639
RxNorm concept
5487

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

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

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Not passed

    Safety mode resolved

    No register row and no identity class settled the question.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

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

What the approval register records

  • 465 approved applications cover products containing this substance. The earliest was NDA011793, approved 19590212 to NOVARTIS.

    Drugs@FDA application register · NDA011793 · read 2026-08-29

  • Marketing status on the register: discontinued, none (tentative approval) and prescription.

    Drugs@FDA application register · NDA011793 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 19730112.

    FDA National Drug Code directory · 71335-9730 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

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

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

What is not here

3 questions this page could not answer

These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.

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

The record as stored

The full record, for auditing

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

The older medicine-wide conclusion held in this record

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

The most-prescribed thiazide-type diuretic on earth, long argued to be inferior to chlorthalidone on indirect evidence, and shown in a 13,523-patient randomised comparison to produce an identical event rate (10.0% against 10.4%, hazard ratio 1.04) with less hypokalaemia — alongside a Danish registry dose-response association with squamous cell skin cancer that reaches an odds ratio of 7.38 at the highest cumulative exposure.

Recorded evidence blocks (13)

What did Hydrochlorothiazide's largest trial (2953748 people) and its longest (16 years) measure?


2953748 people in Hydrochlorothiazide's largest registered study, 16 years in its longest registered window, measuring All-cause mortality at 60 days after inclusion. ClinicalTrials.gov · 2026-09-01

58 phase4, 35 phase3, 21 na, 19 phase1, 17 phase2, 11 na or unstated, 5 early phase1; NCT00223717; 2017-01. Last human test completed 2025, NCT04423627.

Interpretation These counts include studies where Hydrochlorothiazide was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase4
    58
  • phase3
    35
  • na
    21
  • phase1
    19
  • phase2
    17
  • na or unstated
    11
2 more recorded rows
  • early phase1
    5
  • Last recorded human test NCT04423627
    2025-07-31

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

From rat to human: where has Hydrochlorothiazide shown lifespan?


rat: mechanism-only and human: lifespan (163): the rungs where Hydrochlorothiazide has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

All-cause mortality at 60 days after inclusion — the recorded outcome words.

Yeast C. elegans Drosophila Mouse Rat mechanism-onlyDog Non-human primate Human lifespan
Show the evidence
  • rat
    mechanism-only
  • human NCT02765009
    lifespan; All-cause mortality at 60 days after inclusion; 163

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

14 of Hydrochlorothiazide's trials stopped: safety, futility/efficacy, accrual/recruitment, funding/business, other?


safety (1), futility/efficacy (1), accrual/recruitment (2), funding/business (3) and other (7): Hydrochlorothiazide's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"terminated"; 14 of 163 registered studies

Show the evidence

Trial

  • NCT00638482
    terminated; "terminated"
  • NCT00994253
    withdrawn; "Due to safety concerns re: the concomitant use of aliskiren with an ACEi or ARB."
  • NCT01259297
    terminated; "Terminated early in agreement with Health Authorities for feasibility reasons"
  • NCT01302899
    terminated; "In consequence of termination of ALTITUDE. A number of studies were continued in consultation with the Altitude Data Monitoring Committee."
  • NCT01480791
    withdrawn; "Because of results of Altitude trial, this trial was cancelled."
  • NCT01748123
    withdrawn; "Slow enrollment"
8 further recorded trials
  • NCT01804777
    terminated; "Currently closed for data analysis."
  • NCT01822860
    withdrawn; "Study subjects were not able to be recruited"
  • NCT01983462
    terminated; "Funding expired"
  • NCT03109795
    terminated; "Funding ended"
  • NCT03179163
    terminated; "COVID shut down human subjects research and then the grant funding expired"
  • NCT03298802
    terminated; "Futility of the study"
  • NCT03423355
    withdrawn; "change in sponsor"
  • NCT03640221
    withdrawn; "Study withdrawn prior to IRB approval and enrollment"

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

Human studies of Hydrochlorothiazide used Hydrochlorothiazide Tablets 50 mg — over how long?


Human studies of Hydrochlorothiazide used "Hydrochlorothiazide Tablets 50 mg". ClinicalTrials.gov · 2026-09-01

13 recorded entries; human; tablet; also "Hydrochlorothiazide Tablets (50 mg", "hydrochlorothiazide 50 mg tablet", "Hydrochlorothiazide 12.5mg"

Show the evidence

human

  • NCT00649324
    Hydrochlorothiazide Tablets 50 mg
  • NCT00649324
    Hydrochlorothiazide Tablets (50 mg
  • NCT00776646
    tablet; hydrochlorothiazide 50 mg tablet
  • NCT01050062
    Hydrochlorothiazide 12.5mg
  • NCT01506505
    Hydrochlorothiazide 12,5 mg
  • NCT01822860
    Hydrochlorothiazide 25 mg
7 more recorded rows
  • human NCT03057431
    12.5 mg hydrochlorothiazide
  • human NCT03057431
    25.0 mg hydrochlorothiazide
  • human NCT03057431
    50.0 mg hydrochlorothiazide
  • human NCT03298802
    Hydrochlorothiazide 50mg Tablet
  • human NCT03658850
    Hydrochlorothiazide 50Mg
  • human NCT03928145
    Hydrochlorothiazide 50 mg
  • human NCT04934228
    Hydrochlorothiazide 12.5Mg Tab

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

Hydrochlorothiazide's half-life is 5.6 to 14.8 hours — which schedules were studied?


5.6 to 14.8 hours, the half-life Hydrochlorothiazide's label states. openfda-label · 8e0683e2-5473-4246-97ae-b71c21c39ac7 · 2026-08-27

Show the evidence
  • half life
    5.6 to 14.8 hours hours; When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours.
  • metabolism
    Pharmacokinetics and Metabolism Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney.

recorded 2026-08-27 · last checked 2026-09-04

Could one person measure Hydrochlorothiazide's effect on blood pressure?


Blood pressure: measured in Hydrochlorothiazide's trials.

Interpretation blood pressure is the recorded endpoint.

Show the evidence

biomarkers

  • blood pressure; 2026-09-01
  • insulin resistance week16; 2026-09-01
  • supine diastolic blood pressure at trough; 2026-09-01
  • trough seated diastolic blood pressure; 2026-09-01
  • decrease in supine systolic blood pressure; 2026-09-01
  • blood pressure response; 2026-09-01
14 more recorded rows
  • biomarkers
    diastolic blood pressure after 8 weeks; 2026-09-01
  • biomarkers
    sitting systolic blood pressure to week 12; 2026-09-01
  • biomarkers
    change in sitting bp; 2026-09-01
  • biomarkers
    overall percentage of adverse events; 2026-09-01
  • biomarkers
    reactive hyperemic index by period; 2026-09-01
  • biomarkers
    cognitive assessment trail making test part b; 2026-09-01
  • biomarkers
    cognitive assessment forward digit span test; 2026-09-01
  • biomarkers
    trough sitting diastolic blood pressure; 2026-09-01
  • biomarkers
    bioequivalence; 2026-09-01
  • biomarkers
    achieving blood pressure goals; 2026-09-01
  • biomarkers
    any adverse events serious adverse events and death; 2026-09-01
  • biomarkers
    myocardial triglyceride levels; 2026-09-01
  • biomarkers
    sitting systolic blood pressure from baseline to week 4; 2026-09-01
  • biomarkers
    sitting systolic blood pressure; 2026-09-01
  • half life
    2026-09-04; halfLife; hours; 5.6 to 14.8 hours; 2026-08-27
  • human trials at or under30
    37
  • smallest human trial
    0; NCT00745953; PHASE4; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN

Which of achieving blood pressure goals, adverse events serious adverse events and deaths and any adverse events serious adverse events and death did Hydrochlorothiazide's trials measure?


achieving blood pressure goals, adverse events serious adverse events and deaths and any adverse events serious adverse events and death lead 40 outcome terms across Hydrochlorothiazide's trials. ClinicalTrials.gov · 2026-09-01

trough seated diastolic blood pressure, decrease in supine systolic blood pressure, blood pressure response, diastolic blood pressure after 8 weeks, sitting systolic blood pressure to week 12 and change in sitting bp follow.

Show the evidence
  • blood pressure
    1
  • insulin resistance week16
    1
  • supine diastolic blood pressure at trough
    1
  • trough seated diastolic blood pressure
    1
  • decrease in supine systolic blood pressure
    1
  • blood pressure response
    1
14 more recorded rows
  • diastolic blood pressure after 8 weeks
    1
  • sitting systolic blood pressure to week 12
    1
  • change in sitting bp
    1
  • overall percentage of adverse events
    1
  • reactive hyperemic index by period
    1
  • cognitive assessment trail making test part b
    1
  • cognitive assessment forward digit span test
    1
  • trough sitting diastolic blood pressure
    1
  • bioequivalence
    1
  • achieving blood pressure goals
    1
  • any adverse events serious adverse events and death
    1
  • myocardial triglyceride levels
    1
  • sitting systolic blood pressure from baseline to week 4
    1
  • sitting systolic blood pressure
    1

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

Which of Hydrochlorothiazide's 9 ongoing trials reports first?


9 registered trials of Hydrochlorothiazide are open; earliest completion 2026-10. ClinicalTrials.gov · 2026-09-01

Hydrochlorothiazide concentration in blood serum (area under curve (AUC)); M/P ratio; latest 2039-12-01

Show the evidence

Trial

  • NCT03476551
    "Bariatric Surgery and Pharmacokinetics of Hydrochlorothiazide"; n 12; "Hydrochlorothiazide concentration in blood serum (area under curve (AUC))"; 2026-10
  • NCT03511118
    "Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants"; n 1600; "M/P ratio"; 2028-07-31
  • NCT04278404
    "Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)"; n 5000; "Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling"; 2026-12
  • NCT04676399
    "Improving Pain Management Via Spinal Cord Stimulation and Blood Pressure Reduction"; n 36; "Change in Blood Pressure Measurement From Visit 1 to Visit 2"; 2027-12
  • NCT04934228
    "Mitigating the Pro-inflammatory Phenotype of Obesity"; n 60; "Blood Work: Efficacy of 4-week supply of Clonidine Compared VS 4-week supply of control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment"; 2027-08-01
  • NCT05373264
    "HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life"; n 300; "Changes in kidney function decline"; 2031-07
3 further recorded trials
  • NCT06111885
    "Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention"; n 99; "Primary outcome component 1 - calcium oxalate supersaturation in urine"; 2027-06-30
  • NCT07020104
    "The Role of Skin Sodium Accumulation in Chronic Kidney Disease"; n 60; "Skin sodium content at baseline (A)"; 2039-12-01
  • NCT07593612
    "TACTIC-HF: Sequential Diuretic Strategies in Ambulatory Worsening Heart Failure"; n 60; "Total Urinary Sodium Excretion at 6 Hours"; 2027-01-15

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

Which 62 trials of Hydrochlorothiazide posted no result?


Posted no result
62 of 62 completed trials
Registrations
NCT00306696, NCT03276598, NCT00642096, NCT00185068, NCT00153049 and NCT00649324, and 56 more
Completion dates
oldest 2004-01; newest 2023-01-16
Show the evidence

Trial

  • NCT00306696
    2004-01
  • NCT03276598
    2004-04-01
  • NCT00642096
    2004-07
  • NCT00185068
    2004-10
  • NCT00153049
    2005-06
  • NCT00649324
    2005-10
14 further recorded trials
  • NCT03921736
    2005-11-17
  • NCT00185185
    2006-02
  • NCT00214825
    2006-03
  • NCT00282178
    2006-04
  • NCT00247910
    2006-06
  • NCT00776646
    2006-08
  • NCT00311740
    2006-09
  • NCT00374855
    2006-11
  • NCT00327145
    2007-01
  • NCT00110422
    2007-02
  • NCT00821574
    2007-03
  • NCT00171132
    2007-08
  • NCT00220233
    2007-08
  • NCT00383929
    2007-10

At the median, Hydrochlorothiazide's trials enrolled 103 people — anything larger?


Median enrolment
103
Largest enrolment
2953748
Registered trials counted
163

What do 11194 spontaneous reports say about Hydrochlorothiazide — 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.

Hydrochlorothiazide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 11194 reaction mentions were counted: hyponatraemia 1911; sprue-like enteropathy 1565; acute kidney injury 1449; hypotension 1245. open-targets-adr · CHEMBL435 · 2026-06-24

Show the evidence
  • hyponatraemia
    1911
  • sprue-like enteropathy
    1565
  • acute kidney injury
    1449
  • hypotension
    1245
  • dizziness
    1161
  • hypokalaemia
    963
4 more recorded rows
  • gastrooesophageal reflux disease
    957
  • syncope
    710
  • dehydration
    618
  • haemorrhoids
    615

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

Was Hydrochlorothiazide studied with fasting?


fasting is named in Hydrochlorothiazide's label sentences: "The objective of this research was to evaluate and compare the pharmacokinetic profiles and safety of lisinopril/hydrochlorothiazide (10 mg/12.5 mg) tablets in the test and reference formulations administered to participants in both fasting and postprandial states and to evaluate the bioequivalence…" openfda-label+europepmc · 2023-09-18

1 recorded statement; fasting

Show the evidence
  • fasting
    The objective of this research was to evaluate and compare the pharmacokinetic profiles and safety of lisinopril/hydrochlorothiazide (10 mg/12.5 mg) tablets in the test and reference formulations administered to participants in both fasting and postprandial states and to evaluate the bioequivalence of the 2 products in healthy Chinese volunteers.

recorded 2023-09-18 · last checked 2026-09-04

What is recorded about Hydrochlorothiazide and NAD+?


"We developed methods for prolonged (12 h), sterile, normothermic perfusion of rat kidneys and screened compounds for renal preservation including: mitochondrial transition pore inhibitor (decylubiquinone); caspase inhibitor (Z-VAD); peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists (gemfibrozil, WY-14643);…" — where Hydrochlorothiazide and NAD+ appear together. Europe PMC · pathway abstract search · 2007-03-01

NAD+, IGF-1; PMID 17291221

Show the evidence
  • NAD+ PMID 17291221
    "We developed methods for prolonged (12 h), sterile, normothermic perfusion of rat kidneys and screened compounds for renal preservation including: mitochondrial transition pore inhibitor (decylubiquinone); caspase inhibitor (Z-VAD); peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists (gemfibrozil, WY-14643); antioxidants (trolox, luteolin, quercetin); growth factors (HGF, PDGF,…"
  • IGF-1 PMID 17291221
    "We developed methods for prolonged (12 h), sterile, normothermic perfusion of rat kidneys and screened compounds for renal preservation including: mitochondrial transition pore inhibitor (decylubiquinone); caspase inhibitor (Z-VAD); peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists (gemfibrozil, WY-14643); antioxidants (trolox, luteolin, quercetin); growth factors (HGF, PDGF,…"

recorded 2007-03-01 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL435
PubChem CID
3639
CAS number
58-93-5
RxCUI
5487
InChIKey
JZUFKLXOESDKRF-UHFFFAOYSA-N
Trade name
Apo-hydro, Esidrex, Esidrix, Hydrochlorothiazide component of accuretic, Hydrochlorothiazide component of aldactazide, Hydrochlorothiazide component of aldoril, Hydrochlorothiazide component of amturnide, Hydrochlorothiazide component of apresazide, Hydrochlorothiazide component of apresoline-esidrix, Hydrochlorothiazide component of avalide, Hydrochlorothiazide component of benicar hct, Hydrochlorothiazide component of cam-ap-es
Also called
Apresazide, Carozide, Chlorosulthiadil, Copalia-hct, Dafiro-hct, Dihydrochlorurite, Exforge-hct, Hidroclorotiazida, Hidrotiazida, Hydrochlorothiaizide
Salt form
Hydrochlorothiazide component of hydralazine hydrochloride--reserpine
Sources (11)

Sources

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

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

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 11 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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