This page shows what was measured, who it was measured in, and what that does not settle.
What Isosorbide dinitrate does in the body
The only fix anyone has found is to stop taking it for part of every day.
Isosorbide dinitrate is a nitrate ester. Once in the body it releases nitric oxide, the signalling molecule blood vessels use to relax themselves, and the veins relax more than the arteries do. With the veins holding more blood, less returns to the heart, so the heart does less work per beat and needs less oxygen — and the chest pain that comes from an oxygen shortfall eases. The problem is that blood vessels adapt: keep nitric oxide arriving continuously and within a day the vessels stop responding.
Why people take it. Preventing angina — chest pain from narrowed heart arteries
What happened in people
Oral bioavailability ranging from 10% to 90% with a mean of about 25%, and a serum half-life of about one hour
✎ 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.
Its licensed single-agent indication remains angina prevention only, explicitly not the aborting of an attack
Where it acts
Vascular smooth muscle, predominantly on the venous side — the veins dilate more than the arteries, which is why the drug works by reducing what returns to the heart rather than by opening the blockage
Kind of result
A number that stands in for health
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 · IA7306519N · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 131 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Weighted composite score of death from any cause, first hospitalisation for heart failure and change in quality of life, in black patients with NYHA class III or IV heart failure and dilated ventricles
Composite −0.1 ± 1.9 against −0.5 ± 2.0, p=0.01; all-cause mortality 6.2% against 10.2%, p=0.02 (hazard ratio 0.57, p=0.01); first heart failure hospitalisation 16.4% against 22.4%, p=0.001
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 trial was terminated early for the mortality difference, which tends to overstate effect size. It enrolled only black patients, so it cannot establish that the benefit is confined to that group — it can only show the drug worked in the group studied. The label notes there is little experience in NYHA class IV.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sublingual tablet and extended-release capsule; also available as a fixed-dose oral combination with hydralazine
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Isosorbide dinitrate tablets United States prescribing information — Indications and Usage, Contraindications, Warnings, Clinical Pharmacology and Dosage and… · a recorded source, not a stored snapshot
Mortality in men with impaired cardiac function and reduced exercise tolerance on digoxin and a diuretic, randomised to placebo, prazosin, or hydralazine 300 mg plus isosorbide dinitrate 160 mg daily
✓ The study showed what it set out to show
Who was studied
V-HeFT I — Veterans Administration Cooperative Study (N Engl J Med 1986;314:1547-1552)
Mortality at two years, a protocol-specified endpoint, 25.6% against 34.3% — a 34% risk reduction, p<0.028; at three years 36.2% against 46.9%. Mortality over the entire follow-up was lower on the combination but of borderline statistical significance
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The BiDil label describes this trial as showing no overall significant difference in mortality between the two groups, with the favourable trend attributable on retrospective analysis to an effect in 128 black participants and no difference among 324 white participants. Both descriptions are accurate about different analyses of the same trial, and the difference between them is the whole origin of the race-specific indication. Prazosin performed like placebo.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sublingual tablet and extended-release capsule; also available as a fixed-dose oral combination with hydralazine
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Isosorbide dinitrate tablets United States prescribing information — Indications and Usage, Contraindications, Warnings, Clinical Pharmacology and Dosage and… · a recorded source, not a stored snapshot
Mortality with enalapril 20 mg daily against hydralazine 300 mg plus isosorbide dinitrate 160 mg daily, in men on digoxin and diuretics
Two-year mortality 18% on enalapril against 25% on hydralazine-isosorbide dinitrate, p=0.016, a 28% reduction favouring enalapril; overall mortality tended lower on enalapril at p=0.08
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The nitrate-hydralazine arm was not without merit: peak exercise oxygen consumption increased only in that arm (p<0.05) and ejection fraction rose more in the first 13 weeks. The enalapril advantage came from fewer sudden deaths and was more prominent in less symptomatic patients. The BiDil label reports that retrospective analysis located the enalapril advantage in the 574 white participants, with essentially no difference among the 215 black participants — again a post-hoc subgroup, and again the basis for the eventual indication.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, sublingual tablet and extended-release capsule; also available as a fixed-dose oral combination with hydralazine
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Isosorbide dinitrate tablets United States prescribing information — Indications and Usage, Contraindications, Warnings, Clinical Pharmacology and Dosage and… · a recorded source, not a stored snapshot
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 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
Isosorbide dinitrate
What a person takes: Oral tablet, sublingual tablet and extended-release capsule; also available as a fixed-dose oral combination with hydralazine.
The measurement behind this step
Oral absorption is nearly complete but heavily first-pass extracted, so bioavailability ranges from 10% to 90% with a mean of about 25% and rises progressively during chronic therapy. Serum concentrations peak about an hour after ingestion and the serum half-life is about an hour, with clearance exceeding hepatic blood flow, implying considerable extrahepatic metabolism. Every regimen must include a daily dose-free interval — at least 14 hours for immediate-release tablets — because continuous plasma levels produce refractory tolerance. The label states that no dosing regimen should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
Getting in
A sugar alcohol with two nitrate groups on it
Isosorbide is a small ring molecule derived from sorbitol. Attaching two nitrate groups turns it into a drug that releases nitric oxide inside the body.
╌╌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
A dinitrate ester of isosorbide, the bicyclic dianhydro-sorbitol. Both available hydroxyls are nitrated, so no trinitrate is possible. The 2- and 5-mononitrate metabolites are themselves active, and isosorbide 5-mononitrate is separately marketed.
Absorption from the gut is nearly complete, but the liver removes most of the dose before it reaches the circulation — and how much varies enormously between people.
╌╌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
Bioavailability ranges from 10% to 90% with a mean of about 25% because of extensive hepatic first-pass metabolism; most studies show progressive increases during chronic therapy. Serum levels peak about an hour after ingestion, half-life is about an hour, and clearance of 2 to 4 L/min exceeds hepatic blood flow, implying substantial extrahepatic metabolism.
It relaxes vascular smooth muscle, veins most of all
What survives reaches blood vessel walls and relaxes them. The veins relax more than the arteries.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label describes the principal pharmacological action as relaxation of vascular smooth muscle with consequent dilatation of peripheral arteries and veins, especially the latter, along with dilatation of the coronary arteries.
With blood pooling in the veins, less returns to the heart with each beat, filling pressures fall and the muscle needs less oxygen. That is what stops the pain.
╌╌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
Venodilatation promotes peripheral pooling and decreases venous return, reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure — preload. Arteriolar relaxation reduces systemic vascular resistance and mean arterial pressure — afterload. The label states the relative importance of preload reduction, afterload reduction and coronary dilatation remains undefined.
Keep the drug in the blood continuously and the effect disappears. More drug does not restore it. Only time without any 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
The label states that in the large majority of well-controlled exercise trials, continuously delivered nitrates were no more effective than placebo after 24 hours or less; that dose escalation far beyond acute doses has consistently failed; and that efficacy is restored only after nitrates have been absent for several hours. A dose-free interval of at least 14 hours is required for immediate-release tablets.
Paired with hydralazine in one tablet and given to black patients with advanced heart failure, it cut deaths from about ten per cent to about six.
──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
A-HeFT: all-cause mortality 6.2% against 10.2%, p=0.02, hazard ratio 0.57 (p=0.01); first heart failure hospitalisation 16.4% against 22.4%, p=0.001, in 1,050 patients on standard therapy including neurohormonal blockers. The trial was terminated early for the mortality difference.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with stable angina, as prevention rather than rescue. In the fixed combination with hydralazine, adults with heart failure — an indication written for self-identified black patients, and one of the most contested labelling decisions in modern regulatory history.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness in pediatric patients have not been established.”
US prescribing information · 33d14f59-3ae8-4414-b826-06274cf0f3d9 · read 2026-08-30
On older people, the label states: “Clinical studies of isosorbide dinitrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 33d14f59-3ae8-4414-b826-06274cf0f3d9 · read 2026-08-30
On people who are pregnant, the label states: “At oral doses 35 and 150 times the maximum recommendedhuman daily dose, isosorbide dinitrate has been shown to cause a dose-related increase in embryotoxicity (increase in mummified pups) in rabbits.”
US prescribing information · 33d14f59-3ae8-4414-b826-06274cf0f3d9 · read 2026-08-30
On people who are breastfeeding, the label states: “It is not known whether isosorbide dinitrate is excreted in human milk.”
US prescribing information · 33d14f59-3ae8-4414-b826-06274cf0f3d9 · read 2026-08-30
Where the result stopped carrying
Continuous nitrate dosing, which the label reports as no better than placebo within 24 hours
Dose escalation as a remedy for tolerance, which the label describes as having consistently failed
Hydralazine plus isosorbide dinitrate against enalapril in V-HeFT II, where the combination was inferior on two-year mortality
Overall mortality in V-HeFT I, which the BiDil label describes as showing no significant difference between groups
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 tablet, sublingual tablet and extended-release capsule; also available as a fixed-dose oral combination with hydralazine
✎ 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
Oral absorption is nearly complete but heavily first-pass extracted, so bioavailability ranges from 10% to 90% with a mean of about 25% and rises progressively during chronic therapy. Serum concentrations peak about an hour after ingestion and the serum half-life is about an hour, with clearance exceeding hepatic blood flow, implying considerable extrahepatic metabolism. Every regimen must include a daily dose-free interval — at least 14 hours for immediate-release tablets — because continuous plasma levels produce refractory tolerance. The label states that no dosing regimen should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
✎ 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
Contraindicated in allergy to isosorbide dinitrate, with phosphodiesterase-5 inhibitors including sildenafil, tadalafil and vardenafil — concomitant use can cause severe hypotension, syncope or myocardial ischaemia — and with the soluble guanylate cyclase stimulator riociguat. The label notes that the time course and dose dependence of the sildenafil interaction have not been studied, and suggests treating amplified hypotension as a nitrate overdose with elevation of the extremities and central volume expansion. Benefits in acute myocardial infarction or congestive heart failure have not been established for the immediate-release oral form, which is not recommended in those settings because its effects are difficult to terminate rapidly; if used, careful clinical or haemodynamic monitoring is required to avoid hypotension and tachycardia.
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 tablet, sublingual tablet and extended-release capsule; also available as a fixed-dose oral combination with hydralazine
✎ 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
Serum concentrations peak about an hour after ingestion and the serum half-life is about an hour, with clearance exceeding hepatic blood flow, implying considerable extrahepatic metabolism. Every regimen must include a daily dose-free interval — at least 14 hours for immediate-release tablets — because continuous plasma levels produce refractory tolerance. The label states that no dosing regimen should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
✎ 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
64 products list this as an active ingredient in the United States drug directory. 58 of them contain it and nothing else.
FDA National Drug Code directory · 72319-012 · read 2026-08-29
They are sold as powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 72319-012 · read 2026-08-29
The regulator's established pharmacologic class for it is nitrate vasodilator [epc], nitrates [cs] and vasodilation [pe].
FDA National Drug Code directory · 72319-012 · read 2026-08-29
27 published labels name it as an active ingredient. 21 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 2a6fe05a-fcd4-42d1-bf5d-1d39ac273363 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 2a6fe05a-fcd4-42d1-bf5d-1d39ac273363 · read 2026-08-29
10 marketed supplement labels list this ingredient, classed as non-nutrient/non-botanical and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
ISOSORBIDE DINITRATE is oral at HOW SUPPLIED Isosorbide dinitrate Tablets are available as follows: 10 mg, Light green to green mottled round tablets, debossed with, "Λ" on one side and score line on the other side. 22 NDC 82804-117-90, bottles of 90…, recorded as fda label in effect 2024-07-01 in the United States.
US prescribing information · 33d14f59-3ae8-4414-b826-06274cf0f3d9 · read 2026-08-30
Recorded price in US: 0.15958–3.21377 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 55 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Isosorbide dinitrate 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 the benefit of the combination is specific to self-identified black patients — an inference from retrospective subgroups of 128 and 215 people, never tested head to head
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 single-agent isosorbide dinitrate carries the heart failure survival benefit, when its own label says that benefit has not 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 anti-anginal mechanism is understood, when the label states the relative importance of preload, afterload and coronary dilatation remains undefined
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 higher nitrate dose overcomes loss of effect — the label says dose escalation has consistently failed
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 Isosorbide dinitrate 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.
The label says continuous use makes it stop working
In plain words
Take a nitrate around the clock and within a day it does no more than a placebo. The prescribing information states this directly, and adds that taking more does not help.
What was measured
Anti-anginal efficacy on exercise testing after 24 hours or less of continuous nitrate delivery, across several well-controlled trials summarised in the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The Clinical Pharmacology section reads: "Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continuously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the anti-anginal efficacy of continuously-delivered nitrates. In the large majority of these trials, active agents were no more effective than placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their anti-anginal efficacy been restored." The dosage section follows through: every regimen must provide a daily dose-free interval, at least 14 hours long for immediate-release tablets, the effects of the second and later doses have been smaller and shorter-lasting than the first, and no regimen should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day. This is a drug whose licensed performance ceiling is half a day, stated by the regulator.
Source
Isosorbide dinitrate tablets United States prescribing information, Clinical Pharmacology and Dosage and Administration
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
A-HeFT: a 43% reduction in death, and the trial stopped early
In plain words
A fixed-dose combination of this drug with hydralazine was tested in a thousand black patients with advanced heart failure. Deaths fell from 10.2% to 6.2% and the trial was halted early.
What was measured
All-cause mortality and a weighted composite in 1,050 black patients with advanced heart failure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A-HeFT randomised 1,050 black patients with NYHA class III or IV heart failure and dilated ventricles to a fixed dose of isosorbide dinitrate plus hydralazine or placebo, on top of standard therapy including neurohormonal blockade. The primary endpoint was a weighted composite of death from any cause, first heart failure hospitalisation and change in quality of life. The study was terminated early because mortality was significantly higher on placebo: 10.2% against 6.2%, p=0.02, a 43% relative reduction in death from any cause (hazard ratio 0.57, p=0.01). First hospitalisation for heart failure fell 33% in relative terms, 16.4% against 22.4%, p=0.001, and quality of life improved (p=0.02). The composite score was −0.1 ± 1.9 against −0.5 ± 2.0, p=0.01. This is a real, substantial, placebo-controlled mortality result on top of modern background therapy, and it is the strongest evidence either molecule holds.
Written into the record, not signed off as a reviewed claim
A race-specific indication built on retrospective subgroups
In plain words
The combination is licensed specifically for self-identified black patients. That restriction came not from A-HeFT but from re-examining two older trials after the fact, and finding an effect in one racial subgroup and not the other.
What was measured
That the benefit of isosorbide dinitrate with hydralazine is confined to self-identified black patients — an inference from retrospective subgroups of 128 and 215 people, never tested by a randomised comparison across groups
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The BiDil label narrates its own origin with unusual clarity. Of V-HeFT I it states there was no overall significant difference in mortality between the treatment groups, but a trend favouring hydralazine and isosorbide dinitrate which "on retrospective analysis, was attributable to an effect in blacks (n=128)", with survival in white patients (n=324) similar on placebo and combination. Of V-HeFT II it states the combination was inferior to enalapril overall, but that retrospective analysis showed the difference was observed in the white population (n=574) with essentially no difference in the black population (n=215). The label then states: "Based on these retrospective analyses suggesting an effect on survival in black patients, but showing little evidence of an effect in the white population, a third study was conducted among black patients." That third study was A-HeFT, which enrolled only black patients and therefore could not test whether the effect is race-specific — it could only confirm that the drug works in the group it enrolled. The indication reads: for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients. Two things are true at once. The trial result is solid. The racial restriction rests on post-hoc subgroups from trials in 128 and 215 black participants, and no trial has ever compared the combination against placebo in a non-black population on modern background therapy.
Written into the record, not signed off as a reviewed claim
The generic label says the heart failure benefit has not been established
In plain words
The same molecule, sold on its own, carries a warning that its benefit in heart failure and after a heart attack has not been established. Sold in a fixed combination it carries a survival claim.
What was measured
That the survival benefit demonstrated for the fixed combination transfers automatically to isosorbide dinitrate used alone, when the single-agent label states the heart failure benefit has not been established
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The generic isosorbide dinitrate tablet label states: "The benefits of immediate-release oral isosorbide dinitrate in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use isosorbide dinitrate in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia. Because the effects of oral isosorbide dinitrate are so difficult to terminate rapidly, this formulation is not recommended in these settings." The BiDil label, for the same nitrate at a fixed dose with hydralazine, is indicated to improve survival in heart failure. Both statements are correct, and the distinction between them is not pharmacological but evidentiary: the combination was tested and the single agent at these doses and schedules was not. A reader should draw the specific conclusion rather than the general one — this nitrate is not interchangeable with the combination product, and prescribing the two generics separately reproduces the tested doses only if the doses and schedule match, which is a question for a prescriber rather than an assumption.
Source
Isosorbide dinitrate tablets United States prescribing information, Warnings; BiDil United States prescribing information, section 1.1 (NDA 020727)
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
Bioavailability varies ninefold between people
In plain words
How much of a swallowed tablet reaches the bloodstream ranges from a tenth to nearly all of it depending on the person, and it drifts upward the longer someone takes it.
What was measured
Oral bioavailability range and mean, serum half-life and total clearance, from the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that oral absorption is nearly complete but bioavailability is highly variable, from 10% to 90%, with extensive hepatic first-pass metabolism, and that average bioavailability is about 25%. It adds that most studies have observed progressive increases in bioavailability during chronic therapy — so the same tablet delivers more drug after weeks than on the first day, in a drug that also becomes less effective with continuous exposure. Serum half-life is about an hour, and because clearance of 2 to 4 L/min exceeds hepatic blood flow, the label concludes considerable extrahepatic metabolism must also occur. This is the pharmacological reason isosorbide 5-mononitrate exists as a separate product: it is the active metabolite, and giving it directly removes the first-pass step that makes the parent so unpredictable.
Source
Isosorbide dinitrate tablets United States prescribing information, Clinical Pharmacology, Pharmacokinetics
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 label declines to say which of its three actions does the work
In plain words
Nitrates dilate veins, dilate arteries and dilate the coronary vessels. After sixty years on the market the prescribing information still says the relative importance of the three is undefined.
What was measured
That the anti-anginal effect of nitrates is understood well enough to attribute to one mechanism, when the label states the relative importance of the three candidate mechanisms remains undefined
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The Clinical Pharmacology section describes three separate effects: dilatation of veins promoting peripheral pooling and reducing preload; arteriolar relaxation reducing systemic vascular resistance and afterload; and dilatation of the coronary arteries. It then states plainly that the relative importance of preload reduction, afterload reduction and coronary dilatation remains undefined. That matters more than it looks. A mechanism that is not resolved cannot be optimised, and it is why the tolerance problem has never been engineered around — nobody can say with confidence which of the three effects is being lost. The label also does not name nitric oxide, soluble guanylate cyclase or any molecular target anywhere in this section; the nitric-oxide account of nitrate action is well established in the laboratory literature and is not what the regulatory document asserts.
Source
Isosorbide dinitrate tablets United States prescribing information, Clinical Pharmacology
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
21 documents were read for this substance.
RNAWiki source record
21 of them state the same halfLife, and they agree.
RNAWiki source record
21 of them state the same bioavailability, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
IA7306519N
RxNorm concept
381056
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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
44 approved applications cover products containing this substance. The earliest was NDA012093, approved 19591109 to BAUSCH.
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What is not here
7 questions this page could not answer
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A nitrate whose FDA label states that in the large majority of controlled exercise trials continuously delivered nitrates were no more effective than placebo after 24 hours or less, that attempts to overcome this by dose escalation "have consistently failed", and that no regimen should be expected to provide more than about twelve hours of anti-anginal efficacy a day — and which, combined with hydralazine, produced a 43% reduction in death in A-HeFT (6.2% against 10.2%, p=0.02) in an indication written for one self-identified racial group on the strength of retrospective subgroup analyses.
Recorded evidence blocks (9)
Q1
On the Isosorbide dinitrate label: indicated for what?
"Isosorbide dinitrate tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.": indications and usage on Isosorbide dinitrate's label. DailyMed label · 6df6a2fa-c56c-4eb6-a485-c16585420eb0 · 2026-07-31
Q2
24 registered trials of Isosorbide dinitrate — at which phases?
Human studies of Isosorbide dinitrate used Isosorbide Dinitrate 10Mg Tablet — over how long?
Human studies of Isosorbide dinitrate used "Isosorbide Dinitrate 10Mg Tablet". ClinicalTrials.gov · 2026-09-01
2 recorded entries; human; also "Isosorbide Dinitrate 5 MG"
Show the evidence
human
NCT03011775
Isosorbide Dinitrate 10Mg Tablet
NCT04425993
Isosorbide Dinitrate 5 MG
recorded 2026-09-01 · last checked 2026-09-04
Q5
Isosorbide dinitrate's half-life is 5 hours — which schedules were studied?
5 hours, the half-life Isosorbide dinitrate's label states: "With an overall half-life of about 5 hours, the 5-mononitrate is cleared from the serum by denitration to isosorbide, glucuronidation to the 5-mononitrate glucuronide, and denitration/hydration to sorbitol." DailyMed label · 6df6a2fa-c56c-4eb6-a485-c16585420eb0 · 2026-07-31
bioavailability 10 %.
Show the evidence
half lifepharmacokinetics
5 hours; With an overall half-life of about 5 hours, the 5-mononitrate is cleared from the serum by denitration to isosorbide, glucuronidation to the 5-mononitrate glucuronide, and denitration/hydration to sorbitol.
bioavailabilitypharmacokinetics
10 %; Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver.
metabolismpharmacokinetics
Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver.
recorded 2026-07-31 · last checked 2026-09-04
Q6
Which 8 trials of Isosorbide dinitrate posted no result?
Posted no result
8 of 8 completed trials
Registrations
NCT00000478, NCT00810381, NCT01769079, NCT02488642, NCT01513070 and NCT01478022, and 2 more
Completion dates
oldest 1997-06; newest 2024-03-26
Show the evidence
Trial
NCT00000478
1997-06
NCT00810381
1999-06
NCT01769079
2013-12
NCT02488642
2014-05
NCT01513070
2014-06
NCT01478022
2016-03
2 further recorded trials
NCT02135315
2020-12-31
NCT06400784
2024-03-26
Q7
At the median, Isosorbide dinitrate's trials enrolled 95 people — anything larger?
Median enrolment
95
Largest enrolment
2700
Registered trials counted
23
Q8
What do 513 spontaneous reports say about Isosorbide dinitrate — 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.
Isosorbide dinitrate appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 513 reaction mentions were counted: hypotension 92; dizziness 67; dyspnoea 54; syncope 53. FAERS via Open Targets · CHEMBL6622 · 2026-06-24
Show the evidence
hypotension
92
dizziness
67
dyspnoea
54
syncope
53
headache
49
drug hypersensitivity
45
4 more recorded rows
asthenia
41
pruritus
39
chest pain
37
loss of consciousness
36
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Isosorbide dinitrate's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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