This page shows what was measured, who it was measured in, and what that does not settle.
What Entecavir Anhydrous does in the body
Long-standing hepatitis B infection of the liver
Hepatitis B copies itself in an unusual way for a DNA virus: it first makes an RNA transcript, then copies that back into DNA using an enzyme it carries inside its own shell. Entecavir is a counterfeit version of one of the four DNA building blocks, and the cell converts it into an active form that the viral enzyme picks up instead of the real thing. It jams all three of the jobs that enzyme does, so no new viral DNA is finished. What it does not touch is the master ring of viral DNA already parked in the cell nucleus, which is why the virus returns when the tablets stop.
What happened in people
Histologic improvement at 48 weeks in 72% against 62% (HBeAg-positive) and 70% against 61% (HBeAg-negative), double-blind against lamivudine
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
The entecavir-versus-tenofovir cancer question remains open, argued entirely on observational data since a randomised comparison for that endpoint has not been run
Where it acts
Hepatocyte cytoplasm, inside the assembling viral core particle — and pointedly not the nucleus, where the covalently closed circular DNA reservoir sits untouched
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 5968Y6H45M · read 2026-08-29
Its recorded molecular formula is C12H15N5O3•H2O, weighing 295.3.
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · 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 138 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.
Histologic improvement at week 48 — decrease of at least two points in the Knodell necroinflammatory score without worsening of fibrosis
✓ The study showed what it set out to show
Who was studied
BEHoLD AI463022 (NCT00035633)
How many people
715
Study design
Phase 3, randomised, double-blind, active-controlled against lamivudine
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
72% (226/314) against 62% (195/314) on lamivudine, P=0.009
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. HBeAg seroconversion, the endpoint closest to a durable off-treatment response, was 21% against 18% and did not separate (P=0.33). The trial measured a biopsy score at one year, not clinical events.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral solution, taken on an empty stomach
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
HBV DNA below 300 copies/mL at week 48 in patients with a Child-Turcotte-Pugh score of 7 or higher
✓ The study showed what it set out to show
Who was studied
AI463048 (NCT00065507)
How many people
195
Study design
Phase 3, randomised, open-label, against adefovir dipivoxil, decompensated liver disease
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
57% against 20% undetectable HBV DNA; stable or improved Child-Turcotte-Pugh score 61% against 67%; HBsAg loss 5% against 0
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 virological endpoint separated by nearly threefold while the clinical score did not separate. The trial was open-label and was not powered for the Child-Turcotte-Pugh comparison.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral solution, taken on an empty stomach
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
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
Entecavir Anhydrous
What a person takes: Oral tablet and oral solution, taken on an empty stomach.
The measurement behind this step
Once daily, at least two hours before or after a meal, because food substantially reduces absorption. The oral solution exists for children from age 2 and for adults who cannot swallow tablets. Treatment is indefinite in most patients: there is no defined stopping point in the way there is for interferon.
Getting in
One small tablet daily, on an empty stomach
The dose is half a milligram — hundreds of times smaller than most antivirals — and food substantially reduces how much is absorbed.
──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
Oral tablet or solution, 0.5 mg once daily in nucleoside-naive patients and 1 mg in lamivudine-refractory or decompensated patients. The very small daily dose is why one year of active ingredient was costed at about US$4 and why supply tonnage is roughly 600 times lower than for tenofovir disoproxil fumarate.
Phosphorylated inside the liver cell and held there
The tablet itself does nothing. The cell attaches three phosphate groups to it, and that active form persists for most of a day.
╌╌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
Efficiently phosphorylated to entecavir triphosphate, which has an intracellular half-life of 15 hours. Because entecavir is a carbocyclic nucleoside with no ring oxygen, it resists the phosphorylases that degrade ordinary nucleoside analogues.
Hepatitis B uses a single enzyme to start the copy, to write DNA from RNA, and to finish the second strand. Entecavir blocks all three.
──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
Entecavir triphosphate competes with deoxyguanosine triphosphate and functionally inhibits base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA. It is only a weak inhibitor of human polymerases alpha, beta, delta and mitochondrial gamma, with Ki values of 18 to more than 160 micromolar.
Escape needs three mutations at once, which is why it almost never happens
The virus cannot become resistant with one change. It needs the lamivudine escape mutations first, and then a second, separate change on top. Very few viruses manage all of it.
──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
Resistance requires rtM204I/V with or without rtL180M, plus a change at rtT184, rtS202 or rtM250. Lamivudine-resistant backbones alone cost 8- to 30-fold; adding the second-site change costs more than 70-fold. Cumulative resistance in nucleoside-naive patients was 1.2% at 240 weeks.
Virus disappears from the blood, and the liver inflammation settles
Nine in ten HBeAg-negative patients had undetectable virus at a year, and seven in ten had measurably less inflammation on biopsy.
╌╌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
Undetectable HBV DNA by PCR in 67% (HBeAg-positive) and 90% (HBeAg-negative) at week 48, against 36% and 72% on lamivudine. Histologic improvement in 72% and 70% against 62% and 61%.
Entecavir stops the virus making new copies. It does not remove the original ring of viral DNA sitting in the cell nucleus, so treatment is indefinite and stopping can cause a severe flare.
╌╌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
Covalently closed circular DNA persists in the hepatocyte nucleus and is not a substrate for reverse transcriptase inhibition. HBsAg loss — functional cure — occurred in 5% at week 48 even in the decompensated study. Severe acute exacerbations of hepatitis B after discontinuation are a boxed warning.
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 aged 2 and over with active chronic hepatitis B, usually indefinitely. Anyone co-infected with untreated HIV should not take it alone, and anyone stopping it needs months of monitoring.
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: “BARACLUDE was evaluated in two clinical trials of pediatric subjects 2 years of age and older with HBeAg-positive chronic HBV infection and compensated liver disease.”
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · read 2026-08-30
On older people, the label states: “Clinical studies of BARACLUDE did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.”
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · read 2026-08-30
On people who are pregnant, the label states: “Entecavir use during pregnancy has been evaluated in a limited number of individuals reported to the APR and the number of exposures to entecavir is insufficient to make a risk assessment compared to a reference population.”
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary It is not known whether BARACLUDE is present in human breast milk, affects human milk production, or has effects on the breastfed infant.”
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · read 2026-08-30
On people with reduced kidney function, the label states: “Dosage adjustment of BARACLUDE is recommended for patients with creatinine clearance less than 50 mL/min, including patients on hemodialysis or CAPD [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ].”
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · read 2026-08-30
Where the result stopped carrying
In lamivudine-refractory patients only 40% reached undetectable HBV DNA and 12% developed resistance within 96 weeks
HBeAg seroconversion, the endpoint that would allow treatment to stop, did not separate from lamivudine (21% against 18%, P=0.33)
Positive for carcinogenic findings in both mice and rats, with mouse lung adenomas at three times human exposure
Severe acute exacerbations of hepatitis B on discontinuation, because the nuclear cccDNA reservoir is never cleared
Selects HIV resistance substitution M184V if given to a co-infected patient whose HIV is untreated
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 and oral solution, taken on an empty stomach
✎ 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
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6.
No source is stored against this line.
What is in the pack
Once daily, at least two hours before or after a meal, because food substantially reduces absorption. The oral solution exists for children from age 2 and for adults who cannot swallow tablets. Treatment is indefinite in most patients: there is no defined stopping point in the way there is for interferon.
✎ 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
Boxed warnings for severe acute exacerbations of hepatitis B after discontinuation, for the risk of selecting HIV resistance in untreated HIV co-infection, and for lactic acidosis and severe hepatomegaly with steatosis as a nucleoside analogue class effect. Day-to-day tolerability in the pivotal trials was similar to lamivudine. Rodent carcinogenicity studies were positive in both species; the label states it is not known how predictive those findings are for humans. Renal dose adjustment is required.
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 and oral solution, taken on an empty stomach
✎ 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
The oral solution exists for children from age 2 and for adults who cannot swallow tablets. Treatment is indefinite in most patients: there is no defined stopping point in the way there is for interferon.
✎ 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
47 products list this as an active ingredient in the United States drug directory. 47 of them contain it and nothing else.
FDA National Drug Code directory · 63285-887 · read 2026-08-29
They are sold as granule, powder, solution, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 63285-887 · read 2026-08-29
The regulator's established pharmacologic class for it is hepatitis b virus nucleoside analog reverse transcriptase inhibitor [epc], nucleoside analog [ext] and nucleoside reverse transcriptase inhibitors [moa].
FDA National Drug Code directory · 63285-887 · read 2026-08-29
17 published labels name it as an active ingredient. 17 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 0e3b2a0a-9076-4907-bbaf-eb6a65bb9481 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 0e3b2a0a-9076-4907-bbaf-eb6a65bb9481 · read 2026-08-29
BARACLUDE is oral at 3 DOSAGE FORMS AND STRENGTHS • BARACLUDE 0.5 mg film-coated tablets are white to off-white, triangular-shaped, and debossed with “BMS” on one side and “1611” on the other side. • BARACLUDE 1 mg film-coated tablets are p…, recorded as fda label in effect 2019-11-06 in the United States.
US prescribing information · 046e61c9-9298-4b2e-b76e-b26b81fecd20 · read 2026-08-30
Recorded price in US: 0.21342–0.36576 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 20 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.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Entecavir Anhydrous 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 entecavir prevents hepatocellular carcinoma — the placebo-controlled outcome evidence in hepatitis B tested lamivudine, not entecavir
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 threefold virological advantage produces a proportional clinical one; in decompensated patients at 48 weeks it produced none
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 observational cancer difference between entecavir and tenofovir is causal — all 20 studies in the pooled analysis are cohort studies subject to channelling
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 rodent carcinogenicity findings and the human hepatocellular carcinoma cohort signal are the same phenomenon; no mechanistic link has been shown
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 high resistance barrier in a naive patient transfers to a lamivudine-experienced one — the same drug, the same dose, a tenfold difference in failure
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 Entecavir Anhydrous 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.
Beat lamivudine on liver biopsy in 715 double-blind patients
In plain words
In the main trial, 715 people who had never taken a hepatitis B antiviral were randomly assigned entecavir or lamivudine for at least a year, with neither they nor their doctors knowing which. More of the entecavir group had measurably less inflammation on biopsy, and nearly twice as many had undetectable virus.
What was measured
Histologic improvement at week 48 on the Knodell necroinflammatory score, double-blind against lamivudine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study AI463022 randomised 715 nucleoside-naive HBeAg-positive patients to entecavir 0.5 mg or lamivudine 100 mg once daily for a minimum of 52 weeks, double-blind. Histologic improvement at week 48, defined as a decrease of at least two points in the Knodell necroinflammatory score without worsening of fibrosis, occurred in 226 of 314 (72%) on entecavir against 195 of 314 (62%) on lamivudine, P=0.009. Undetectable HBV DNA by PCR was 67% against 36% (P<0.001) and ALT normalisation 68% against 60% (P=0.02). Mean HBV DNA reduction was 6.9 against 5.4 log10 copies/mL, P<0.001. HBeAg seroconversion, the endpoint closest to a durable off-treatment response, was 21% against 18% and did not separate (P=0.33).
Written into the record, not signed off as a reviewed claim
Replicated in the HBeAg-negative population, 648 patients
In plain words
The companion trial in a different form of the disease found the same pattern: better biopsies, and nine in ten with undetectable virus against seven in ten on the older drug.
What was measured
Histologic improvement at week 48 in HBeAg-negative disease
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study AI463027 randomised 648 nucleoside-naive HBeAg-negative patients to entecavir 0.5 mg or lamivudine 100 mg for a minimum of 52 weeks, double-blind. Histologic improvement occurred in 208 of 296 evaluable patients (70%) against 174 of 287 (61%), P=0.01. Undetectable HBV DNA was 90% against 72% (P<0.001) and ALT normalisation 78% against 71% (P=0.045). No resistance to entecavir was detected in either trial at 48 weeks.
Written into the record, not signed off as a reviewed claim
A cumulative 1.2% resistance at five years — the best barrier in the disease
In plain words
Across five years of continuous treatment in people who had never taken a hepatitis B antiviral before, just over one in a hundred developed resistance. Lamivudine, the drug it replaced, reaches roughly half in the same period.
What was measured
Cumulative probability of entecavir resistance substitutions at 48 to 240 weeks in nucleoside-naive patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Genotypic evaluation of 562 nucleoside-naive subjects treated for up to 96 weeks found emerging resistance substitutions in fewer than 1%. In the long-term rollover cohort the cumulative probability of developing rtT184, rtS202 or rtM250 substitutions in the presence of rtL180M and rtM204V was 0.2%, 0.5%, 1.2%, 1.2% and 1.2% at weeks 48, 96, 144, 192 and 240. For comparison, in the lamivudine outcome trial in advanced fibrosis, genotypic YMDD resistance emerged in 49% of lamivudine-treated patients. The structural reason is that entecavir resistance requires the lamivudine-resistance substitutions plus a second-site change, so three or more mutations must accumulate before the virus escapes.
Source
BARACLUDE United States prescribing information, Clinical Pharmacology, resistance in clinical studies (NDA 021797); lamivudine comparison from Liaw YF et al., N Engl J Med 2004;351:1521-1531
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
In lamivudine-refractory patients the barrier collapses and most are never suppressed
In plain words
The same drug that almost never fails in a fresh patient fails often in someone whose virus already escaped lamivudine. Twelve per cent developed resistance within two years, and only four in ten ever got their virus down to undetectable.
What was measured
12% resistance by week 96 and 40% virologic suppression in lamivudine-refractory patients, against 1.2% and near-universal suppression in naive patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Genotypic evaluation of 190 lamivudine-refractory subjects treated for up to 96 weeks found resistance substitutions at rtT184, rtS202 or rtM250 in 22 subjects (12%), of whom 16 had virologic rebound and 4 were never suppressed below 300 copies/mL. Among those who rebounded with emergent resistance, the median fold-change in entecavir EC50 was 19-fold at baseline and 106-fold at rebound — meaning these viruses were already partly resistant before entecavir was started. Of subjects continuing beyond 48 weeks, only 40% (31 of 77) reached HBV DNA below 300 copies/mL. In cell culture, lamivudine-resistant strains alone cost 8- to 30-fold, and adding rtT184, rtS202 or rtM250 costs more than 70-fold.
Source
BARACLUDE United States prescribing information, Clinical Pharmacology, lamivudine-refractory subjects (NDA 021797)
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
In failing livers the virology separated and the clinical score did not
In plain words
In patients whose livers were already decompensating, entecavir cleared the virus in 57% against 20% on the comparator. The score that describes how well the liver is actually working improved in 61% against 67% — slightly fewer.
What was measured
That the size of the virological advantage translates proportionally into clinical benefit — over 48 weeks in decompensated patients it visibly did not
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study AI463048 randomised 195 adults with HBeAg-positive or -negative chronic hepatitis B and hepatic decompensation, defined as a Child-Turcotte-Pugh score of 7 or higher, to entecavir 1 mg or adefovir dipivoxil 10 mg, open-label; 191 were treated and analysed by intention to treat. At week 48, HBV DNA was undetectable in 57% on entecavir against 20% on adefovir, and ALT normalised in 63% against 46%. Stable or improved CTP score — defined as a decrease or no change from baseline — occurred in 61% against 67%. HBsAg loss was 5% against 0. The trial was not powered for the CTP comparison and the difference is not presented as significant in either direction; the point is not that adefovir was better but that a nearly threefold difference in viral suppression produced no corresponding difference in the measure of liver function at one year.
Source
BARACLUDE United States prescribing information, Clinical Studies, subjects with decompensated liver disease, Study AI463048 (NCT00065507)
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 randomised evidence that treatment prevents cancer belongs to a different drug
In plain words
One placebo-controlled trial has shown that suppressing hepatitis B reduces liver failure and liver cancer. It tested lamivudine, not entecavir. Entecavir has never been randomised against placebo for those outcomes, and it never will be.
What was measured
That entecavir reduces hepatocellular carcinoma and hepatic decompensation — demonstrated by randomisation for lamivudine, extrapolated to entecavir from surrogate superiority
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Liaw and colleagues randomised 651 patients with histologically confirmed cirrhosis or advanced fibrosis 2:1 to lamivudine or placebo for up to five years. The trial was stopped early at a median 32.4 months: disease progression endpoints were reached by 7.8% on lamivudine against 17.7% on placebo (hazard ratio 0.45, P=0.001), and hepatocellular carcinoma occurred in 3.9% against 7.4% (hazard ratio 0.49, P=0.047). That is the randomised foundation for treating hepatitis B at all. Entecavir was approved on histologic, virologic and biochemical endpoints against an active comparator; once lamivudine had shown benefit, a placebo arm in this disease became unethical. The inference that a drug which suppresses virus better than lamivudine must also prevent cancer better is reasonable, widely made, and untested by randomisation.
Written into the record, not signed off as a reviewed claim
The liver cancer argument against entecavir, from a paper that was retracted and replaced
In plain words
A large Korean study reported that people on entecavir developed liver cancer more often than people on tenofovir. That paper was retracted and republished after an error, and its conclusion survived. Later reviews mostly agree with it — and every single study involved is observational.
What was measured
Adjusted hazard ratio 0.61 (95% CI 0.54 to 0.70) favouring tenofovir in the Korean cohort; pooled odds ratio 1.66 (95% CI 1.35 to 2.05) across 20 cohort studies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Choi and colleagues analysed 24,156 treatment-naive patients from the Korean National Health Insurance Service who started entecavir (n=11,464) or tenofovir disoproxil fumarate (n=12,692) between 2012 and 2014, with a 2,701-patient hospital cohort as validation. Annual hepatocellular carcinoma incidence was 1.06 per 100 person-years on entecavir against 0.64 on tenofovir; adjusted hazard ratio for tenofovir 0.61 (95% CI 0.54 to 0.70) for HCC and 0.77 (95% CI 0.65 to 0.92) for death or transplant, with the effect holding in a 10,923-pair propensity-matched analysis. The article was formally retracted and replaced in June 2019 and the replacement retained the finding. A 2023 meta-analysis of 20 cohort studies covering 62,860 entecavir-treated and 27,544 tenofovir-treated patients reported a pooled odds ratio of 1.66 (95% CI 1.35 to 2.05) for hepatocellular carcinoma on entecavir relative to tenofovir. None of the 20 was randomised, and channelling by prescriber, era and comorbidity is not removed by propensity matching. International guidelines continue to list both as first-line.
Written into the record, not signed off as a reviewed claim
Positive for carcinogenic findings in both mouse and rat
In plain words
In the standard two-year animal cancer studies, entecavir produced tumours in both species tested. Lung tumours appeared in mice at only three times the human exposure. Nobody knows how much of this applies to people.
What was measured
Lung adenomas increased in mice at 3 times human exposure; positive carcinogenic findings in both rodent species
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Long-term oral carcinogenicity studies at exposures up to 42 times (mice) and 35 times (rats) those at the highest recommended human dose were positive in both species. Lung adenomas were increased in male and female mice at exposures 3 and 40 times human, and lung carcinomas at 40 times; tumour development was preceded by pneumocyte proliferation not seen in rats, dogs or monkeys, which supports a species-specific mechanism. Hepatocellular carcinomas were increased in male mice at 42 times human exposure, vascular tumours in female mice at 40 times, hepatocellular adenomas in female rats at 24 times, and brain gliomas in rats. The label states plainly that it is not known how predictive the rodent findings are for humans. The temptation to connect this to the observational human hepatocellular carcinoma signal should be resisted: the rodent liver tumours occurred at 42 times human exposure in animals without hepatitis B, and no mechanistic link between the two observations has been established.
Source
BARACLUDE United States prescribing information, Nonclinical Toxicology 13.1, carcinogenesis (NDA 021797)
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
Three boxed warnings, and the first one is about stopping
In plain words
Coming off entecavir can trigger a severe flare of hepatitis. It can also compromise future HIV treatment if given to someone whose HIV is untreated. And it belongs to a class associated with a rare, sometimes fatal metabolic complication.
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 boxed warning covers three things. Severe acute exacerbations of hepatitis B have been reported after discontinuation of anti-hepatitis B therapy including entecavir, and hepatic function must be monitored clinically and biochemically for at least several months afterwards. Entecavir has weak anti-HIV activity and can select the M184V substitution, so it is not recommended in HIV/HBV co-infected patients who are not also receiving antiretroviral therapy — HIV variants carrying M184V show loss of susceptibility to entecavir in vitro. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogues as a class. The discontinuation flare is a direct consequence of the mechanism: entecavir never removes the nuclear cccDNA, so stopping releases an intact template into an immune system that has been primed.
Source
BARACLUDE United States prescribing information, boxed warning and Warnings and Precautions 5.1 to 5.3 (NDA 021797)
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
16 documents were read for this substance.
RNAWiki source record
16 of them state the same halfLife, and they agree.
RNAWiki source record
12 of them state the same bioavailability, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
5968Y6H45M
CAS registry number
209216-23-9
PubChem compound
135526609
ChEMBL
CHEMBL713
ChEBI
59902
RxNorm concept
306266
EMA substance identifier
100000089463
DrugBank
DB00442
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Suppression classes recorded: S6.
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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
20 approved applications cover products containing this substance. The earliest was NDA021798, approved 20050329 to BRISTOL MYERS SQUIBB.
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7 questions this page could not answer
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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 deoxyguanosine analogue that blocks all three activities of the hepatitis B reverse transcriptase and has the highest resistance barrier of any drug in this disease — a cumulative 1.2% resistance at five years in previously untreated patients — which beat lamivudine on liver histology in two 700-patient double-blind trials, but which in patients whose livers were already failing suppressed virus three times better than adefovir (57% against 20% undetectable) while their Child-Turcotte-Pugh scores improved slightly less often (61% against 67%).
Recorded evidence blocks (10)
Q2
On the Entecavir Anhydrous label: indicated for what?
"Entecavir is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients 2 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease Entecavir is a…": indications and usage on Entecavir Anhydrous's label. DailyMed label · 73dea2a4-a596-477f-b66d-5a80dd019837 · 2026-07-07
Q3
191 registered trials of Entecavir Anhydrous — at which phases?
Registered studies posting no result
149 of 191
191 registered studies of Entecavir Anhydrous: 65 phase4, 53 phase2, 27 phase3, 21 phase1, 17 na, 15 na or unstated, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Business Objectives Have Changed"; 22 of 191 registered studies
Show the evidence
Trial
NCT00605384
terminated; "Business Objectives Have Changed"
NCT00986778
withdrawn; "Business Objectives Changed"
NCT01179594
withdrawn; "This study was canceled for operational reasons."
NCT01217632
terminated; "Study terminated due to an unexpected prominent effect of entecavir alone in this patient population."
NCT01627223
terminated; "Slow progress in recruiting study patients"
NCT01694264
terminated; "Delayed recruitment, unable to meet calculated sample size"
14 further recorded trials
NCT02065336
terminated; "Company decision to discontinue trial"
NCT02452528
terminated; "Company decision to discontinue trial"
NCT02577029
terminated; "Company decision to discontinue trial"
NCT02604199
terminated; "Company decision to discontinue trial"
NCT02604212
terminated; "Company decision to discontinue trial"
NCT02738008
terminated; "Company decision to discontinue trial"
NCT02797522
terminated; "Company decision to discontinue trial"
NCT03032536
terminated; "Sponsor decision."
NCT03164889
terminated; "no enough participant can be enrolled"
NCT03887702
terminated; "inability to accrue"
NCT04398134
terminated; "Study stopped due to a safety signal of drug-induced liver injury in subjects receiving 2158"
NCT04536532
terminated; "Company decision to discontinue trial"
NCT04781647
terminated; "Study ABI-H0731-203 was terminated early by the study Sponsor for strategic reasons to prioritize research and development efforts on finite and curative HBV therapies."
NCT04820686
terminated; "Sponsor decision"
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Entecavir Anhydrous used Baraclude 0.5mg — over how long?
studies of Entecavir Anhydrous used the recorded amount. ClinicalTrials.gov · 2026-09-01
14 recorded entries; human; also "Baraclude 0.5mg", "Baraclude 1.0mg", "entecavir 0.5 mg"
Show the evidence
human
NCT00625339
Baraclude 0.5mg
NCT00625560
Baraclude 1.0mg
NCT01026610
entecavir 0.5 mg
NCT01242787
Entecavir 0.5 mg
NCT01694264
Baraclude (Bristol-Myers Squibb) 0.5mg
NCT01711567
entecavir(baraclude) 0.5 mg qd
8 more recorded rows
humanNCT01894269
Lamivudine 100mg once daily; or Entecavir 0.5mg once daily.
humanNCT01894269
Entecavir 0.5mg tablets (Bristol-Myers Squibb)
humanNCT02850848
(Baraclude 0.5mg Tablets
humanNCT03308890
0.5mg Baraclude(entecavir)
humanNCT03469583
Entecavir 1 MG
humanNCT03680183
Entecavir 1Mg Oral Tablet
humanNCT03847246
Baraclude® tablets,1.0 mg
humanNCT03847246
Entecavir tablets,1.0 mg
recorded 2026-09-01 · last checked 2026-09-04
Q6
Entecavir Anhydrous's half-life is 128–149 hours — which schedules were studied?
128–149 hours, the half-life Entecavir Anhydrous's label states: "After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128–149 hours." DailyMed label · 73dea2a4-a596-477f-b66d-5a80dd019837 · 2026-07-07
tmax 1.5 hours; bioavailability 100 %.
Show the evidence
half lifepharmacokinetics
128–149 hours; After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128–149 hours.
tmaxpharmacokinetics
1.5 hours; Absorption Following oral administration in healthy subjects, entecavir peak plasma concentrations occurred between 0.5 and 1.5 hours.
bioavailabilitypharmacokinetics
100 %; In healthy subjects, the bioavailability of the tablet was 100% relative to the oral solution.
metabolismpharmacokinetics
Metabolism and Elimination Following administration of 14 C-entecavir in humans and rats, no oxidative or acetylated metabolites were observed.
recorded 2026-07-07 · last checked 2026-09-04
Q7
Which running trial of Entecavir Anhydrous could settle lifespan?
NCT03920618 measures Survival rate in the follow-up, reading out 2024-12-31.
2 open trials; n 150; "Three Types of Nucleotide/Nucleoside Analogues Treatment in HBV Related ACLF"
Show the evidence
Trial
NCT03920618
"Three Types of Nucleotide/Nucleoside Analogues Treatment in HBV Related ACLF"; n 150; "Survival rate in the follow-up"; 2024-12-31
NCT07493109
"Chidamide for Maintenance Treatment of HBV-infected Diffuse DLBCL in Patients Initially Treated With R-CHOP"; n 200; "Progression-free survival (PFS)"; 2030-09-30
Q8
Which 61 trials of Entecavir Anhydrous posted no result?
Posted no result
61 of 61 completed trials
Registrations
NCT00035633, NCT00036608, NCT01020565, NCT01037166, NCT01022801 and NCT00035789, and 55 more
Completion dates
oldest 2005-02; newest 2023-12-30
Show the evidence
Trial
NCT00035633
2005-02
NCT00036608
2005-02
NCT01020565
2005-02
NCT01037166
2005-02
NCT01022801
2005-03
NCT00035789
2005-05
14 further recorded trials
NCT00051038
2005-10
NCT01037062
2006-12
NCT00975091
2007-08
NCT00614471
2009-10
NCT01018381
2009-11
NCT01013272
2010-07
NCT00625339
2010-11
NCT00625560
2010-11
NCT00637663
2010-11
NCT00824707
2010-12
NCT01254994
2010-12
NCT01323452
2011-03
NCT01023230
2011-05
NCT01026610
2011-05
Q9
At the median, Entecavir Anhydrous's trials enrolled 99 people — anything larger?
Median enrolment
99
Largest enrolment
12522
Registered trials counted
186
Q10
What do 809 spontaneous reports say about Entecavir Anhydrous — 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.
Entecavir Anhydrous appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 809 reaction mentions were counted: drug resistance 219; viral mutation identified 99; pathogen resistance 82; renal impairment 76. FAERS via Open Targets · CHEMBL5314362 · 2026-06-24
Show the evidence
drug resistance
219
viral mutation identified
99
pathogen resistance
82
renal impairment
76
hepatitis b
70
hepatitis b dna increased
56
4 more recorded rows
viral load increased
55
alanine aminotransferase increased
53
blood creatinine increased
50
hepatocellular carcinoma
49
recorded 2026-06-24 · last checked 2026-09-04
Q11
Which 10 reactions does Entecavir Anhydrous'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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This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.