This page shows what was measured, who it was measured in, and what that does not settle.
What Clavulanic acid does in the body
Bacterial infections of the ear, sinuses, chest, skin or urinary tract.
Amoxicillin kills bacteria by jamming the tool they use to stitch their cell wall together. Bacteria fight back with an enzyme that snips amoxicillin open before it arrives. Clavulanate is a lookalike that the enzyme grabs instead and cannot let go of, so it is used up. With the enzyme occupied, the amoxicillin gets through and the wall fails.
What happened in people
In young children with ear infection, treatment failure fell from about 45 in 100 to 19 in 100.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
The added ingredient may not help when the infecting bacterium lacks the enzyme it blocks.
Where it acts
The bacterial periplasm — the space between a bacterium’s outer membrane and its cell wall, where both molecules do their work
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 23521W1S24 · read 2026-08-29
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.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 90 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.
Time to treatment failure from first dose to the day 8 visit
✓ The study showed what it set out to show
Who was studied
Tähtinen 2011 (NCT00299455)
How many people
319
Study design
Randomised, double-blind, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Treatment failure 18.6% against 44.9%; hazard ratio 0.38 (95% CI 0.25 to 0.59), P<0.001
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Diarrhoea 47.8% against 26.6% on placebo (P<0.001) and eczema 8.7% against 3.2% (P=0.04). The trial did not follow children long enough to measure recurrence or resistance selection.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablets, chewable tablets and reconstituted oral suspension, in fixed amoxicillin-to-clavulanate ratios
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Symptomatic response and rate of clinical failure over 10 to 12 days in children aged 6 to 23 months
✓ The study showed what it set out to show
Who was studied
Hoberman 2011 (NCT00377260)
How many people
291
Study design
Randomised, double-blind, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Clinical failure 16% against 51% at day 10 to 12 (P<0.001); initial symptom resolution P=0.14, not significant; sustained resolution P=0.04
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The headline symptomatic comparison was not statistically significant and is easily lost behind the otoscopic result. Nasopharyngeal colonisation with non-susceptible Streptococcus pneumoniae did not change significantly in either group, but the trial was not powered to detect resistance selection.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablets, chewable tablets and reconstituted oral suspension, in fixed amoxicillin-to-clavulanate ratios
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 2 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
Clavulanic acid
What a person takes: Oral tablets, chewable tablets and reconstituted oral suspension, in fixed amoxicillin-to-clavulanate ratios.
The measurement behind this step
A ratio product rather than two co-packaged drugs: different products hold different amoxicillin-to-clavulanate ratios, and they are not interchangeable unit for unit, because substituting on total amoxicillin content changes the clavulanate delivered. Clavulanate potassium is hygroscopic, which is why suspensions are reconstituted at the pharmacy rather than sold ready-made.
Getting in
Two different molecules in one tablet
One of them kills bacteria. The other kills almost nothing — its whole job is to protect the first one. They are made in a fixed ratio, and the ratio is part of the product.
╌╌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
Amoxicillin is an aminopenicillin; clavulanate potassium is a clavam produced by Streptomyces clavuligerus fermentation. Clavulanate’s own antibacterial activity is negligible. Both are acid-stable enough for oral administration, and both are largely renally cleared.
A bacterium has an outer skin, then a gap, then the wall it is constantly rebuilding. Both molecules have to get into that gap. In Gram-negative bacteria they squeeze through protein pores.
╌╌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
Entry into the Gram-negative periplasm is through outer-membrane porins, chiefly OmpF and OmpC in Escherichia coli. Loss of porins produces beta-lactam resistance that is indistinguishable from enzymatic resistance on a susceptibility plate, which is why the laboratory workflow on this page tests them separately.
The bacterial enzyme grabs the decoy and is destroyed by it
Resistant bacteria flood that gap with scissors that cut penicillins open. The decoy looks enough like a penicillin that the scissors close on it — and then cannot open again. Each enzyme molecule is spent permanently.
╌╌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
Clavulanate is a mechanism-based, irreversible inactivator of class A serine beta-lactamases including TEM-1, SHV-1 and ROB-1. The active-site serine opens its beta-lactam ring; the resulting acyl-enzyme undergoes further rearrangement to a stable cross-linked adduct rather than hydrolysing off. It does not inhibit class B metallo-beta-lactamases, class C AmpC enzymes or most class D carbapenemases, which is the precise boundary of what the combination can do.
With the scissors used up, the amoxicillin reaches its target: the tool a bacterium uses to stitch its wall into a mesh. Amoxicillin latches onto it permanently and the stitching stops.
╌╌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
Amoxicillin acylates the active-site serine of penicillin-binding proteins, the DD-transpeptidases that cross-link peptidoglycan. The beta-lactam ring is a structural mimic of the D-alanyl-D-alanine terminus the enzyme normally acts on, so the enzyme attacks it and is left covalently modified.
The wall fails while the bacterium is still trying to grow
Bacteria constantly break their own wall open to expand it. With the repair jammed, the breaking carries on unopposed and the cell bursts under its own internal pressure.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Beta-lactams are bactericidal only against actively dividing cells: autolysins continue to cleave peptidoglycan while cross-linking is blocked, and osmotic lysis follows. A non-dividing or dormant organism is not killed, which is one reason abscesses and biofilms respond poorly to any beta-lactam.
The same broad reach that makes the combination useful hits the bacteria in the gut. Roughly one child in two got diarrhoea in the Finnish trial, against one in four on placebo.
╌╌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
Diarrhoea occurred in 47.8% on amoxicillin-clavulanate against 26.6% on placebo (P<0.001) and eczema in 8.7% against 3.2% (P=0.04) in the Tähtinen trial. Separately, hepatic injury is idiosyncratic rather than dose-related, is predominantly cholestatic, has a mean latency of 31 days, and is associated with specific HLA class I and class II haplotypes rather than with cumulative exposure.
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 and children with ear, sinus, chest, skin, dental or urinary infections judged likely to involve a beta-lactamase-producing organism.
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.
Where the result stopped carrying
The American trial’s headline symptomatic endpoint missed significance at P=0.14 while its otoscopic endpoint was overwhelming
Antibiotics do not clear middle-ear fluid at six to eight weeks or at three months, and do not reduce later recurrences
Earlier trials using loose diagnostic criteria found small effects and were read as showing the drug did not work
Post-marketing hepatotoxicity, never seen at trial scale, made this the single commonest cause of drug-induced liver injury in the United States registry
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 tablets, chewable tablets and reconstituted oral suspension, in fixed amoxicillin-to-clavulanate ratios
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
A ratio product rather than two co-packaged drugs: different products hold different amoxicillin-to-clavulanate ratios, and they are not interchangeable unit for unit, because substituting on total amoxicillin content changes the clavulanate delivered.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Clavulanate potassium is hygroscopic, which is why suspensions are reconstituted at the pharmacy rather than sold ready-made.
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
Diarrhoea is the dominant adverse event and was roughly twice as common as on placebo in the paediatric trials. Hepatic dysfunction — usually cholestatic, mean onset 31 days, often after the course has finished — is the serious one: it is the most frequent single cause of idiosyncratic drug-induced liver injury in the United States DILIN registry, occurs disproportionately in older men, and led to liver transplantation in three of 117 registry cases. A previous cholestatic reaction to the combination is a contraindication. Clostridioides difficile-associated diarrhoea has been reported with essentially all antibacterials including this one.
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 tablets, chewable tablets and reconstituted oral suspension, in fixed amoxicillin-to-clavulanate ratios
✎ 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
Clavulanate potassium is hygroscopic, which is why suspensions are reconstituted at the pharmacy rather than sold ready-made.
✎ 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
164 published labels name it as an active ingredient. None of them describes this substance alone, so no label text on this page can be attributed to it rather than to a combination.
US prescribing information · ab1dbe70-696f-4ff9-a0c7-7406bff590ae · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · ab1dbe70-696f-4ff9-a0c7-7406bff590ae · read 2026-08-29
107355 marketed supplement labels list this ingredient, classed as mineral 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.
Amoxicillin and Clavulanate Potassium is oral at 3 DOSAGE FORMS AND STRENGTHS Tablets 500 mg/125 mg Tablets: White, oblong-shaped, biconvex, film-coated, unscored tablets, debossed 93 on one side and 2274 on the other side., recorded as fda label in effect 2024-10-01 in the United States.
US prescribing information · 482511ed-4531-45ec-a4eb-c600aeb03325 · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Clavulanic acid 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 clavulanate component contributes benefit in an infection where no beta-lactamase-producing organism is present — neither placebo-controlled trial separated the two components
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 treating an ear infection prevents serious complications: severe complications were rare in every trial and did not differ between groups
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 an antibiotic makes a child feel better tonight — the 24-hour pain comparison is flat, with high-certainty evidence
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 liver injury from this drug is a dose or duration effect; it is idiosyncratic, HLA-associated, and usually begins after the course has ended
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 Clavulanic acid 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.
Treatment failure fell from 44.9% to 18.6% against placebo in 319 children
In plain words
Finnish children aged six months to three years with ear infection diagnosed by strict criteria got either the drug or an identical-looking placebo. Roughly one in five on the drug failed treatment. Roughly two in five on placebo did.
What was measured
Time to treatment failure through day 8, against matching placebo, double-blind
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the double-blind trial by Tähtinen and colleagues, 161 children received amoxicillin-clavulanate and 158 placebo for 7 days. Treatment failure by day 8 occurred in 18.6% against 44.9% (P<0.001). Progression to failure was reduced by 62% (hazard ratio 0.38, 95% CI 0.25 to 0.59) and the need for rescue treatment by 81% (6.8% against 33.5%; hazard ratio 0.19, 95% CI 0.10 to 0.36). The separation was already present at the first scheduled visit on day 3. Analgesic or antipyretic agents were given to 84.2% and 85.9% of the two groups respectively, so the antibiotic effect sits on top of pain relief rather than in place of it.
Written into the record, not signed off as a reviewed claim
The American trial found the same thing on signs and much less on symptoms
In plain words
A near-simultaneous American trial found the drug cleared the physical signs of infection far better than placebo. On how quickly children stopped feeling unwell, the headline comparison was not statistically significant.
What was measured
Otoscopic clinical failure and symptomatic response against matching placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hoberman and colleagues randomised 291 children aged 6 to 23 months to amoxicillin-clavulanate or placebo for 10 days. Clinical failure — persistent otoscopic signs of acute infection — was 4% against 23% at or before day 4 to 5 and 16% against 51% at or before day 10 to 12, both P<0.001. But initial resolution of symptoms was 35%, 61% and 80% at days 2, 4 and 7 on drug against 28%, 54% and 74% on placebo, P=0.14 for the overall comparison, which is not significant. Sustained resolution reached P=0.04 and mean symptom scores over the first 7 days P=0.02. Diarrhoea and diaper-area dermatitis were more common on the drug, and one child in the placebo group developed mastoiditis.
Written into the record, not signed off as a reviewed claim
Pooled across 13 trials, antibiotics do not reduce ear pain at 24 hours
In plain words
The single thing a parent most wants — the child to hurt less tonight — is the thing the pooled evidence says antibiotics do not deliver. The benefit arrives on day two or three, and roughly one child in fourteen gets vomiting, diarrhoea or a rash instead.
What was measured
Pooled risk ratios for pain, adverse events, tympanometry and recurrence across 13 placebo-controlled trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The 2023 Cochrane review pooled 13 placebo-controlled trials in 3,401 children. Antibiotics did not reduce pain at 24 hours (RR 0.89, 95% CI 0.78 to 1.01; 5 trials, 1,394 children; high-certainty evidence) or at 4 to 7 days (RR 0.76, 95% CI 0.50 to 1.14). They reduced pain at 2 to 3 days (RR 0.71, 95% CI 0.58 to 0.88; number needed to treat 20) and increased adverse events (RR 1.38, 95% CI 1.16 to 1.63; number needed to harm 14). They did not reduce abnormal tympanometry at 6 to 8 weeks (RR 0.89, 95% CI 0.70 to 1.13) or at three months (RR 0.94, 95% CI 0.66 to 1.34), or late recurrence (RR 0.94, 95% CI 0.79 to 1.11). Serious complications were rare and did not differ.
Written into the record, not signed off as a reviewed claim
It is the commonest single cause of drug-induced liver injury in the United States
In plain words
One in nine cases in the American drug-induced liver injury registry is caused by this one antibiotic. The injury usually starts about a month after the course, often after the tablets have finished, which is why the link is missed.
What was measured
Share of adjudicated cases in a prospective drug-induced liver injury registry
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In the DILIN prospective registry, 117 of 1,038 adjudicated cases (11%) were caused by amoxicillin-clavulanate, representing 24% of the 479 cases attributed to antimicrobial agents — the most frequent single cause. Affected patients were older than the cohort as a whole (mean 60 against 48 years) and predominantly male (62% against 39% male in the overall cohort, P<0.001), an inversion of the usual sex distribution for drug-induced liver injury. Mean time to symptom onset was 31 days. Median values at onset were total bilirubin 7 mg/dL, ALT 478 U/L and ALP 325 U/L, and nearly all biopsies showed prominent cholestatic features. Resolution took a mean 55 days from the peak. Three women required liver transplantation; none died of the injury.
Written into the record, not signed off as a reviewed claim
The label restricts it to beta-lactamase producers; prescribing does not
In plain words
The indication is written for infections caused by bacteria that make the enzyme clavulanate blocks. In practice the drug is chosen before anyone knows which bacterium is there. Whether adding clavulanate helps when the organism does not make the enzyme has not been measured in most of the situations where it is used.
What was measured
That the clavulanate component contributes to the observed benefit in an unselected community infection — plausible in proportion to how much beta-lactamase-producing organism is present, and not measured by either placebo-controlled trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The United States label for the oral suspension names lower respiratory tract infection, acute bacterial otitis media and sinusitis "caused by beta-lactamase-producing isolates of Haemophilus influenzae and Moraxella catarrhalis". Clavulanate has essentially no intrinsic antibacterial activity and no effect on an organism that produces no class A beta-lactamase, so against beta-lactamase-negative Streptococcus pneumoniae — still the commonest bacterial cause of otitis media and sinusitis — the combination is pharmacologically amoxicillin plus an inert companion that raises the diarrhoea rate. The two placebo-controlled trials on this page tested the combination against placebo, not against amoxicillin alone, so they cannot separate the two components. No adequately powered head-to-head trial of amoxicillin against amoxicillin-clavulanate in unselected community otitis media has been identified for this dossier.
Source
Amoxicillin and clavulanate potassium for oral suspension, United States prescribing information, Indications and Usage; Tähtinen PA et al., N Engl J Med 2011;364:116-126
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
The field changed its mind twice about whether to treat ear infection at all
In plain words
For years the answer was always treat. Then trials suggested most children got better anyway and watchful waiting became an option. Then two strict trials in 2011 showed a real effect on the infection itself, and the guidance tightened again for the youngest children. All three positions were reasonable on the evidence available at the time.
What was measured
That the earlier negative trials showed the drug did not work — they showed that a diagnosis made on loose criteria dilutes any effect, which is a statement about the entry criteria rather than about the molecule
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Earlier placebo-controlled trials used loose diagnostic criteria and found small effects, which supported observation as an option. The two 2011 trials both used stringent otoscopic entry criteria — the change that mattered — and both found large reductions in treatment failure and in persistent otoscopic signs. The 2023 Cochrane update, pooling all 13 trials, then confirmed both halves of the picture at once: a real effect on signs and on pain from day two, no effect on pain at 24 hours, no effect on middle-ear effusion beyond six weeks, no effect on recurrence, and a number needed to harm of 14. The disagreement was never mainly about the drug. It was about who was enrolled and what was counted.
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What is not here
8 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
How this medicine reached us — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A penicillin paired with a decoy that soaks up the bacterial enzyme which would otherwise destroy it — in the two 2011 placebo-controlled trials it cut treatment failure in young children with ear infection from 44.9% to 18.6% and persistent otoscopic signs from 51% to 16%, while causing diarrhoea in 47.8% against 26.6% on placebo, and it is the single commonest cause of drug-induced liver injury in the United States registry.
Recorded evidence blocks (6)
Q1
72 registered trials of Clavulanic acid — at which phases?
Registered studies posting no result
49 of 72
72 registered studies of Clavulanic acid: 22 phase4, 13 na, 12 phase1, 12 phase2, 6 phase3, 5 early phase1, 3 na or unstated. CLINICALTRIALS_SNAPSHOT · 2026-09-01
9 with a PubMed record
Show the evidence
phase4
22
na
13
phase1
12
phase2
12
phase3
6
early phase1
5
8 more recorded rows
na or unstated
3
completed
49
unknown
10
terminated
5
recruiting
4
active not recruiting
2
not yet recruiting
1
withdrawn
1
recorded 2026-09-01 · last checked 2026-09-04
Q2
6 of Clavulanic acid's trials stopped: accrual/recruitment, other?
"The primary objective of the study was met."; 6 of 72 registered studies
Show the evidence
Trial
NCT01511107
terminated; "The primary objective of the study was met."
NCT02099240
terminated; "Not enough patient enrollment and lack of staffing"
NCT02570347
terminated; "Slower than anticipated recruitment and emergent COVID-19 situation"
NCT03795194
terminated; "Due to low enrollment."
NCT05079620
terminated; "Under-enrollment"
NCT07625267
withdrawn; "Study was never approved by the institutional review board."
recorded 2026-09-01 · last checked 2026-09-04
Q3
Human studies of Clavulanic acid used RX-10100 5mg — over how long?
Human studies of Clavulanic acid used "RX-10100 5mg". ClinicalTrials.gov · 2026-09-01
8 recorded entries; human; also "RX-10100 10mg", "RX-10100 15mg", "Augmentin ES-600™ 600 mg/42.9 mg/5 mL Suspension"
Show the evidence
human
NCT00693056
RX-10100 5mg
NCT00693056
RX-10100 10mg
NCT00693056
RX-10100 15mg
NCT00840099
Augmentin ES-600™ 600 mg/42.9 mg/5 mL Suspension
NCT02393586
Amoxicillin/clavulanic acid 500mg/125mg
NCT04980170
Amoxicillin with Clavulanic Acid 635mg
2 more recorded rows
humanNCT05804123
Augmentin 500Mg Tablet
humanNCT06154720
Augmentin 625 mg
recorded 2026-09-01 · last checked 2026-09-04
Q4
Which 28 trials of Clavulanic acid posted no result?
Posted no result
28 of 28 completed trials
Registrations
NCT01559753, NCT00185939, NCT00520949, NCT01406275, NCT00693056 and NCT00839176, and 22 more
Completion dates
oldest 2002-11; newest 2024-08-01
Show the evidence
Trial
NCT01559753
2002-11
NCT00185939
2005-11
NCT00520949
2008-06
NCT01406275
2008-12
NCT00693056
2009-05
NCT00839176
2009-10
14 further recorded trials
NCT01267942
2009-10
NCT01205984
2010-04
NCT01273376
2011-10
NCT01015417
2012-11
NCT00818610
2013-04
NCT02143323
2014-09
NCT01697059
2015-05
NCT02393586
2015-10
NCT02089568
2016-08
NCT02018094
2017-01-02
NCT03616301
2018-08-13
NCT01967758
2018-08-15
NCT02258763
2018-10
NCT03702894
2018-10-08
Q5
At the median, Clavulanic acid's trials enrolled 89 people — anything larger?
Median enrolment
89
Largest enrolment
3720
Registered trials counted
72
Q6
What do 2843 spontaneous reports say about Clavulanic acid — 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.
Clavulanic acid appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2843 reaction mentions were counted: drug hypersensitivity 1171; cholestasis 281; pruritus 237; hepatocellular injury 234. FAERS via Open Targets · CHEMBL1003 · 2026-06-24
Show the evidence
drug hypersensitivity
1171
cholestasis
281
pruritus
237
hepatocellular injury
234
rash maculo-papular
201
acute kidney injury
183
4 more recorded rows
drug reaction with eosinophilia and systemic symptoms
162
jaundice
159
hepatitis cholestatic
110
drug-induced liver injury
105
recorded 2026-06-24 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 5 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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