This page shows what was measured, who it was measured in, and what that does not settle.
What Nitrofurantoin does in the body
Bladder infections caused by susceptible bacteria
Nitrofurantoin is absorbed after swallowing and then concentrated in the urine. Bacterial nitroreductase enzymes convert it into reactive intermediates that damage DNA, ribosomal proteins and other macromolecules. Because several bacterial systems are affected, resistance has remained relatively uncommon despite decades of use.
What happened in people
Roughly 42.7% to 43.6% of a daily amount recovered in urine within 24 hours, with low blood concentrations
✎ 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.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
The limit that matters most
The only large modern randomised trial supporting it was published in 2018, sixty-five years after approval
Where it acts
Bladder urine. Nitrofurantoin reaches antibacterial concentrations in urine but does not spread through tissues as widely as other urinary tract antibiotics.
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 · 927AH8112L · read 2026-08-29
Its recorded molecular formula is C8H6N4O5·H2O, weighing 256.17.
US prescribing information · 04af8b73-7e15-7da8-e063-6294a90af284 · 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 70 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.
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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
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.
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.
Clinical response in the 28 days following completion of therapy in non-pregnant women with uncomplicated lower urinary tract infection
✓ The study showed what it set out to show
Who was studied
Huttner 2018 nitrofurantoin against fosfomycin (NCT01966653)
Clinical resolution 70% (171 of 244) against fosfomycin 58% (139 of 241); difference 12% (95% CI 4 to 21%), P=.004. Microbiologic resolution 74% against 63%; difference 11% (95% CI 1 to 20%), P=.04
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. Open-label rather than double-blind, unavoidable when comparing a five-day course with a single dose. Only 377 of 513 participants (73%) had a confirmed positive baseline culture, so roughly a quarter of the population may not have had culture-confirmed bacterial infection. Thirty percent of the winning arm did not achieve resolution.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsules and suspension, in microcrystalline, macrocrystalline and monohydrate-macrocrystal forms
Interval reported. 95% CI 4 to 21%), P=
Written into the record, not signed off as a reviewed claim.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
Nitrofurantoin United States prescribing information — Contraindications 4, Clinical Pharmacology 12.2 and 12.3, Microbiology 12.4 (openFDA drug label endpoi… · a recorded source, not a stored snapshot
What we know
RNAWiki holds 1 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.
Where a source records it acting
Bladder and urinary tract: Highly soluble in urine; lacks the broader tissue distribution of other therapeutic agents approved for urinary tract infections
US prescribing information · 04af8b73-7e15-7da8-e063-6294a90af284 · read 2026-08-27
Start
Nitrofurantoin
What a person takes: Oral capsules and suspension, in microcrystalline, macrocrystalline and monohydrate-macrocrystal forms.
The measurement behind this step
Absorbed readily and then cleared rapidly into urine, where it reaches antibacterial concentrations that plasma and tissue never do. Bioavailability rises with food or anything delaying gastric emptying. The crystalline form is a genuine clinical variable rather than a manufacturing detail: larger crystals dissolve more slowly, which reduces nausea and changes how often the drug is given. Nitrofurantoin is dialysable, and it may turn urine brown.
Getting in
Absorbed, then dumped straight into the urine
Nitrofurantoin is absorbed from the gut and then cleared by the kidney almost immediately. Blood levels stay low. Urine levels get very high. That is the entire design.
╌╌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 blood concentrations at therapeutic amounts are usually low, that the drug is highly soluble in urine, that it lacks the broader tissue distribution of other agents approved for urinary tract infection, and that roughly 42.7% to 43.6% of a daily amount is recovered in urine in the first 24 hours. Food or anything delaying gastric emptying increases bioavailability.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
Getting in
The crystal size decides how it is tolerated
The same compound is sold in different crystal sizes. The larger crystals dissolve more slowly, which causes less nausea. Nothing about the molecule changes — only how fast it goes into solution.
╌╌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
Microcrystalline, macrocrystalline and monohydrate-macrocrystal products differ in dissolution rate and hence in gastrointestinal tolerability and administration frequency. Particle size is a clinically relevant specification for this drug in a way it is not for most.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
Reaching the cell
Bacteria take it up and activate it themselves
The drug arriving in the bladder is inert. Bacteria absorb it and their own enzymes convert it into something reactive. The bacterium manufactures its own poison.
──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
Bacterial flavoprotein nitroreductases, principally NfsA and NfsB, reduce the nitro group to reactive intermediates. Human cells reduce it far less efficiently, which is the basis of selectivity.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
The change it makes
The fragments attack everything at once
Those reactive fragments do not have a single target. They damage the bacterium’s genetic material, its protein-building machinery and its enzymes simultaneously.
╌╌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 the reactive intermediates damage macromolecules such as DNA and proteins. Ribosomal RNA, cell-wall synthesis and aerobic energy metabolism are all affected. There is no discrete binding site, so there is no discrete resistance mutation.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
What that does for a person
Escaping it costs the bacterium something
To resist, a bacterium has to switch off the enzymes that activate the drug — but those enzymes do other jobs, so the resistant organism is worse at being a bacterium. That is the best explanation for seventy years without widespread resistance.
╌╌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
Resistance requires loss of function at both nfsA and nfsB, a two-step process with an associated fitness cost, in contrast with single-step target mutations that confer trimethoprim and fluoroquinolone resistance. Nitrofurantoin has no useful activity against Pseudomonas and most Proteus and Serratia species — an intrinsic limit rather than acquired resistance.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
What that does for a person
What the reactive chemistry does to the person
The same reactive fragments that kill bacteria can damage lungs, liver, nerves and, in newborns, red blood cells. Lung damage on long courses is the one to know about, and it can appear more than a year after starting.
──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
Acute pulmonary hypersensitivity and chronic interstitial lung disease both occur; in one specialist series of ten patients, mean age 80, all female, mean latency was 17 months and mean pre-treatment eGFR was 76 mL/min/1.73m2. Chronic active hepatitis and peripheral neuropathy are also documented. Haemolytic anaemia in neonates and at term reflects immature erythrocyte glutathione systems and is the basis of two label contraindications.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · a recorded source, not a stored snapshot
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.
Non-pregnant adults, mostly women, with uncomplicated bladder infection, and, in some countries, women with recurrent infection taking it long term.
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: “Nitrofurantoin is contraindicated in pediatric patients younger than 1 month of age because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability). [see Contraindications (4) and Warnings and Precautions (5.4)].”
US prescribing information · 04af8b73-7e15-7da8-e063-6294a90af284 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Nitrofurantoin is contraindicated in pregnant women at term (38 weeks to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent because of the possibility of hemolytic anemia in the infant (see Clinical Considerations).”
US prescribing information · 04af8b73-7e15-7da8-e063-6294a90af284 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Nitrofurantoin is present in human breast milk following oral administration.”
US prescribing information · 04af8b73-7e15-7da8-e063-6294a90af284 · read 2026-08-30
Where the result stopped carrying
Three women in ten in the winning arm did not achieve clinical resolution at 28 days
It cannot treat pyelonephritis, bloodstream infection or anything outside the bladder, because it does not distribute into tissue
It is contraindicated below a creatinine clearance of 60 mL per minute, at term pregnancy and under one month of age, and after any previous cholestatic reaction to it
Long-term prophylactic prescribing, which rose substantially in England over a decade, is the pattern that produced the pulmonary fibrosis series
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 capsules and suspension, in microcrystalline, macrocrystalline and monohydrate-macrocrystal forms
✎ 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
Absorbed readily and then cleared rapidly into urine, where it reaches antibacterial concentrations that plasma and tissue never do. Bioavailability rises with food or anything delaying gastric emptying. The crystalline form is a genuine clinical variable rather than a manufacturing detail: larger crystals dissolve more slowly, which reduces nausea and changes how often the drug is given. Nitrofurantoin is dialysable, and it may turn urine brown.
✎ 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 known hypersensitivity, in previous cholestatic jaundice or hepatic dysfunction associated with the drug, in anuria, oliguria or creatinine clearance under 60 mL per minute, in pregnancy at term from 38 to 42 weeks and during labour, and in infants under one month of age — the last two because immature erythrocyte enzyme systems cannot withstand oxidative stress and haemolytic anaemia results. Acute pulmonary hypersensitivity and chronic interstitial lung disease with fibrosis both occur, the chronic form typically after months of prophylactic use and with a mean latency of 17 months in one specialist series, in patients whose kidney function was normal. Chronic active hepatitis and peripheral neuropathy are also documented. The label records in vitro antagonism with quinolones.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Nitrofurantoin against fosfomycin in uncomplicated lower urinary tract infection (NCT01966653) · 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 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 capsules and suspension, in microcrystalline, macrocrystalline and monohydrate-macrocrystal forms
✎ 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
Bioavailability rises with food or anything delaying gastric emptying. The crystalline form is a genuine clinical variable rather than a manufacturing detail: larger crystals dissolve more slowly, which reduces nausea and changes how often the drug is given. Nitrofurantoin is dialysable, and it may turn urine brown.
✎ 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
171 products list this as an active ingredient in the United States drug directory. 171 of them contain it and nothing else.
FDA National Drug Code directory · 72603-184 · read 2026-08-29
They are sold as capsule, for suspension, powder and suspension, taken oral.
FDA National Drug Code directory · 72603-184 · read 2026-08-29
The regulator's established pharmacologic class for it is nitrofuran antibacterial [epc] and nitrofurans [cs].
FDA National Drug Code directory · 72603-184 · read 2026-08-29
117 published labels name it as an active ingredient. 117 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · c87f65b9-14f7-4962-bff6-58b0d1af75f8 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · c87f65b9-14f7-4962-bff6-58b0d1af75f8 · read 2026-08-29
Nitrofurantoin is oral suspension at Oral Suspension: 25 mg/5 mL, recorded as prescription product; fda label in effect 2024-03-29 in the United States.
US prescribing information · 04af8b73-7e15-7da8-e063-6294a90af284 · read 2026-08-27
Recorded price in US: 1.71824 USD per one millilitre, across 9 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 Nitrofurantoin 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 urinary concentration predicts clinical effect — the label states the pharmacodynamic effects of nitrofurantoin are unknown
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 pharmacokinetics are understood in the people who take it; the label states they are unknown in older adults, children, hepatic impairment and pregnancy
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 normal kidney function protects against pulmonary toxicity — mean pre-treatment eGFR in the fibrosis series was 76 mL/min/1.73m2
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 trial enrolling on symptoms and a dipstick measures the drug against a confirmed bacterial infection in every participant
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 Nitrofurantoin 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.
It beat single-dose fosfomycin, 70% against 58%, in 513 randomised women
In plain words
The two old drugs that came back into first-line use for bladder infection were finally tested against each other. Five days of nitrofurantoin resolved symptoms in seven women in ten. A single dose of fosfomycin resolved them in fewer than six in ten.
What was measured
Clinical resolution through 28 days after completing therapy, and microbiologic resolution
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A multinational, open-label, analyst-blinded randomised trial enrolled 513 non-pregnant women aged 18 and over with lower urinary tract symptoms, a positive urine dipstick, and no known colonisation or previous infection with organisms resistant to the study drugs, at sites in Geneva, Lodz and Petah-Tiqva between October 2013 and April 2017. Clinical resolution through day 28 after completing therapy was 171 of 244 (70%) with 5-day nitrofurantoin against 139 of 241 (58%) with single-dose fosfomycin — difference 12% (95% CI 4 to 21%), P=.004. Microbiologic resolution was 129 of 175 (74%) against 103 of 163 (63%) — difference 11% (95% CI 1 to 20%), P=.04. Adverse events were few and mainly gastrointestinal: nausea in 3% against 2%, diarrhoea in 1% in both arms.
Written into the record, not signed off as a reviewed claim
Three women in ten were not resolved, and a quarter may not have had an infection
In plain words
The winning arm still left nearly a third of women without resolution at four weeks. And only about three-quarters of the participants had a urine culture confirming a bacterial infection in the first place, which is how urinary infection is actually diagnosed and treated in practice.
What was measured
Proportion without clinical resolution, and proportion with a confirmed positive baseline culture
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In the same trial, 70% clinical resolution means 73 of 244 women in the nitrofurantoin arm did not achieve resolution through day 28. Entry required lower urinary tract symptoms plus a positive dipstick for nitrites or leukocyte esterase; only 377 of 513 participants (73%) had a confirmed positive baseline culture. That is representative of real practice rather than a flaw — urinary infection is usually treated on symptoms and a dipstick — but it means roughly a quarter of the randomised population may not have had a culture-confirmed bacterial infection for either drug to resolve. The trial was open-label with analyst blinding rather than double-blind, unavoidable given a five-day course against a single dose.
Written into the record, not signed off as a reviewed claim
Ten women, mean age 80, with lung fibrosis a mean of 17 months after prescription
In plain words
Nitrofurantoin can scar the lungs. In one specialist clinic over eight years, ten patients were diagnosed with it — all women, average age eighty, and on average nearly a year and a half after the prescription that caused it. Stopping the drug helped, but the scarring on the scans did not always reverse.
What was measured
Case count, latency, renal function and CT findings in a single-service interstitial lung disease cohort
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A case series from a single interstitial lung disease service reviewed its database from 2012 to 2020 and identified ten patients with nitrofurantoin-induced interstitial lung disease. Mean age was 80 years and all were female. Mean time from prescription to presentation was 17 months. Mean pre-treatment eGFR was 76 mL/min/1.73m2 — that is, normal kidney function, which is the usual reassurance and did not protect them. Seven of ten had ground-glass opacity and traction bronchiectasis on CT; four received prednisolone. Patients improved symptomatically after stopping the drug with or without steroids, but the authors record that irreversible imaging changes may contribute to long-term morbidity, and conclude that counselling should precede prescription regardless of renal function. The context they give is that national prescribing of nitrofurantoin in England rose significantly over the preceding decade, largely as prophylaxis in women with recurrent infection.
Written into the record, not signed off as a reviewed claim
The label states its pharmacodynamic effects are unknown
In plain words
The current FDA label says, in the section that is supposed to describe what the drug does to the body, that its pharmacodynamic effects are unknown. It also says its pharmacokinetics are unknown in older people, children, people with liver disease and pregnant women. This is a drug taken by millions.
What was measured
That the concentration achieved in urine translates into a predictable clinical effect — the assumption the whole indication rests on, with the label itself stating that the pharmacodynamics are unknown and the pharmacokinetics unstudied in most groups who take it
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 12.2 of the label reads in full that pharmacodynamic effects of nitrofurantoin are unknown. Section 12.3 states that the pharmacokinetics of nitrofurantoin are unknown for geriatric patients, paediatric patients, patients with hepatic impairment or pregnant women, and that differences between male and female patients and between racial or ethnic groups are unknown. What is documented is distribution and excretion: nitrofurantoin is highly soluble in urine, lacks the broader tissue distribution of other agents approved for urinary tract infection, is rapidly excreted in urine to which it may impart a brown colour, and recovered roughly 42.7% to 43.6% of a daily amount in the first 24 hours. The therapeutic rationale is therefore that urinary concentration exceeds what the organism needs, rather than any measured concentration-effect relationship. That is a reasonable inference for a drug that acts only in urine. It is still an inference, and the label says so.
Source
Nitrofurantoin United States prescribing information, Clinical Pharmacology 12.2 and 12.3
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
Displaced twice, restored twice, and still not resistant after seventy years
In plain words
Nitrofurantoin was pushed aside first by trimethoprim-sulfamethoxazole and then by the fluoroquinolones, both newer and easier to take. Both of those then ran into resistance and, in the quinolones’ case, serious safety warnings. Nitrofurantoin came back — and unlike them, it had barely accumulated any resistance in the intervening decades.
What was measured
That newer antibacterials supersede older ones — here two successors were displaced by resistance and safety findings while the 1953 drug held, because a multi-target mechanism is harder to escape than a single-enzyme one
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The reason is mechanistic and is stated in the label: nitrofurantoin is reduced by a wide range of enzymes including bacterial flavoproteins to reactive intermediates that damage macromolecules such as DNA and proteins. There is no single target to alter. Escape requires losing activity at multiple nitroreductases, principally nfsA and nfsB, and those enzymes have metabolic roles, so the resistant organism pays a fitness cost. Trimethoprim inhibits one enzyme and fluoroquinolones inhibit two related ones; single-step target mutations therefore work against both, and community Escherichia coli resistance to them rose accordingly. The 2018 head-to-head trial against fosfomycin is the modern evidence base for a drug whose original approval predates the framework that would now be required to obtain one.
Written into the record, not signed off as a reviewed claim
It is contraindicated in four populations, three of them for the same reason
In plain words
The drug must not be used when the kidneys are not working, because it is cleared by the kidneys and cannot reach the urine — and it accumulates instead. It must not be used at the very end of pregnancy or in newborns, because their red blood cells cannot defend themselves against it.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label contraindicates nitrofurantoin in known hypersensitivity; in a previous history of cholestatic jaundice or hepatic dysfunction associated with the drug; in anuria, oliguria or significant renal impairment defined as creatinine clearance under 60 mL per minute or a clinically significant elevated serum creatinine, because impaired excretion increases toxicity; in pregnancy at term from 38 to 42 weeks, during labour and delivery, or when labour is imminent; and in infants under one month of age. The last two share a mechanism: immature erythrocyte enzyme systems with unstable glutathione cannot withstand the drug’s oxidative intermediates, and haemolytic anaemia results. The renal contraindication is a double bind — the same failure that prevents the drug from reaching the urine where it works also prevents it leaving the body. The label additionally records in vitro antagonism between nitrofurantoin and quinolones, and no activity against Pseudomonas or most Proteus and Serratia species.
Source
Nitrofurantoin United States prescribing information, Contraindications 4 and Microbiology 12.4
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
77 documents were read for this substance.
RNAWiki source record
58 of them state the same bioavailability, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
927AH8112L
CAS registry number
67-20-9
PubChem compound
6604200
RxNorm concept
221129
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No registered study is classified as testing this substance.
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No register row and no identity class settled the question.
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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
34 approved applications cover products containing this substance. The earliest was NDA008693, approved 19530206 to PROCTER AND GAMBLE.
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What is not here
7 questions this page could not answer
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Felt, measured, or meaningful — found nothing in the sources checked.
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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 nitrofuran that bacterial enzymes convert into reactive fragments which damage DNA, ribosomes and proteins simultaneously, concentrated in urine and essentially nowhere else — in the only large modern randomised trial it resolved symptoms in 70% of 244 women against single-dose fosfomycin’s 58% (difference 12%, 95% CI 4 to 21%, P=.004), and in a single interstitial lung disease service ten women, mean age 80, developed pulmonary fibrosis a mean of 17 months after being prescribed it.
Recorded evidence blocks (6)
Q1
On the Nitrofurantoin label: indicated for what?
"Nitrofurantoin oral suspension is indicated in adults and pediatric patients 1 month of age and older for the treatment of urinary tract infections due to susceptible strains of Escherichia coli , Enterococcus species, Staphylococcus aureus , Klebsiella species and Enterobacter species. Limitations of Use…": indications and usage on Nitrofurantoin's label. DailyMed label · dd99ba40-edff-47c3-9ee4-7e5b7774e5b5 · 2026-01-22
Q2
50 registered trials of Nitrofurantoin — at which phases?
terminated; "Not enough patient enrollment and lack of staffing"
NCT02911662
terminated; "Inability to enroll patients at anticipated rate."
NCT03299387
withdrawn; "Study never recruited"
NCT05254808
terminated; "Insufficient participating sites, and insufficient participants from participating sites mainly due to COVID-19 workload. The number of necessary participants could not be reached within the anticipated timelines and the allocated budget."
1 further recorded trialNCT05274672
withdrawn; "Lack of enrollment."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Nitrofurantoin used Nitrofurantoin 100mg twice daily x 5 days — over how long?
Human studies of Nitrofurantoin used "Nitrofurantoin 100mg twice daily x 5 days". ClinicalTrials.gov · 2026-09-01
10 recorded entries; human; also "Nitrofurantoin Monohydrate/Macrocrystals Capsules 100 mg", "Macrobid® Capsules 100 mg", "Nitrofurantoin Macrocrystals 100 mg Capsules"
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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