This page shows what was measured, who it was measured in, and what that does not settle.
What Amlodipine / Valsartan does in the body
Amlodipine keeps calcium out of the muscle cells wrapping those arteries, so the muscle cannot squeeze and the vessels stay open.
Blood pressure is set by how wide the small arteries are. Valsartan blocks the receptor that angiotensin II uses to tighten those same vessels and to make the kidney hold on to salt. Blocking two different points in one loop lowers pressure more than blocking either alone, and it cancels a side effect: when amlodipine alone widens arteries, fluid is pushed out into the ankles, and adding valsartan relaxes the vein side too so less fluid escapes.
Why people take it. High blood pressure that one tablet has not brought down
What happened in people
Placebo-subtracted systolic reduction of 16.2 mmHg at amlodipine 5 mg plus valsartan 320 mg, against 8.6 mmHg for amlodipine alone and 10.1 mmHg for valsartan alone
✎ 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.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
p<0.05 for combination against each component and against placebo at all doses except a few containing amlodipine 2.5 mg; response rate 91.3% at 5/320 mg against 71.9% amlodipine, 73.4% valsartan, 40.9% placebo
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. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Response rates 88.5% at 10/160 mg and 87.5% at 10/320 mg against 86.9% for amlodipine 10 mg alone and 49.3% for placebo
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. At amlodipine 10 mg the combination barely improved on amlodipine alone by response rate — 88.5% against 86.9%. The added value of the second drug is largest at low amlodipine doses and smallest at the maximum, which no promotional summary of the product mentions.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Hazard ratio 1.04, 95% CI 0.94 to 1.15, p=0.49 over a mean 4.2 years
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Blood pressure was 4.0/2.1 mmHg lower on amlodipine at one month and 1.5/1.3 mmHg at one year (p<0.001), so the two arms were never at equal pressure. The comparison the trial was built to make could not be made.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
9.6% against 11.8%; hazard ratio 0.80, 95% CI 0.72 to 0.90, p<0.001; stopped early at a mean 36 months
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. This trial used benazepril, not valsartan. It is the outcome evidence most often invoked for calcium blocker plus renin-angiotensin blocker combinations, and it was generated with a different pair of drugs.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
RNAWiki holds 4 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
Amlodipine / Valsartan
What a person takes: Oral tablet, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg.
The measurement behind this step
A bilayer or blended tablet designed around two actives with opposite solubility behaviour. Amlodipine reaches peak plasma concentration in 6 to 12 hours and has a terminal half-life of 30 to 50 hours, so once-daily coverage is a property of the molecule rather than of the formulation; valsartan is shorter-lived and its effect persists because receptor blockade outlasts plasma exposure.
Getting in
One tablet carrying two unrelated molecules
The tablet holds two drugs that have nothing chemically in common. They are combined because they act on two different points of the same control loop, not because they are related.
╌╌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
Amlodipine besylate is a dihydropyridine with a slow, pH-dependent association kinetic (pKa 8.6) giving a terminal half-life of 30 to 50 hours; valsartan is a biphenyl tetrazole with a half-life of about 6 hours and 94 to 97% albumin binding. The tablet is engineered around their opposite solubility behaviour so that neither release profile disturbs the other.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
The muscle wrapped around small arteries needs calcium flowing in to squeeze. Amlodipine plugs the channel that calcium uses, so the squeeze weakens and the vessel widens.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Amlodipine binds the dihydropyridine site on the alpha-1C subunit of the Cav1.2 L-type channel and inhibits transmembrane calcium influx, with greater effect on vascular smooth muscle than on cardiac muscle. Negative inotropy is detectable in vitro but not seen in intact animals at therapeutic exposure, which is why it does not slow the heart the way verapamil and diltiazem do.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Angiotensin II is the body signal that tightens arteries and tells the kidney to keep salt. Valsartan sits on the receptor that signal binds to, so the message never lands.
╌╌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
Valsartan is a selective, insurmountable antagonist at the angiotensin II type 1 receptor with roughly 20,000-fold selectivity over the AT2 receptor. It blocks vasoconstriction and aldosterone-driven sodium retention on cardiac, vascular smooth muscle, adrenal and renal cells. It does not inhibit angiotensin-converting enzyme, so bradykinin is not accumulated and the ACE-inhibitor cough does not occur.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Blocking two points beats blocking one twice as hard
Widening arteries with one drug makes the body push back by raising the other signal. Blocking both at once removes the counter-move, which is why the pair lowers pressure further than either drug pushed to its maximum.
╌╌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
Dihydropyridine vasodilatation triggers reflex sympathetic activation and renin release, raising circulating angiotensin II. AT1 blockade removes that compensation, producing more than additive pressure reduction: 16.2 mmHg placebo-subtracted systolic at 5/320 mg against 8.6 and 10.1 mmHg for the components alone.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Amlodipine widens the arteries feeding the tiny vessels but not the veins draining them, so fluid is pushed out into the ankles. Relaxing the drainage side lets some of that fluid stay in circulation.
╌╌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
Selective precapillary dilatation raises capillary hydrostatic pressure and drives transudation. AT1 blockade produces postcapillary venodilatation, lowering the gradient. Measured effect: peripheral oedema 5.4% on the combination against 8.7% on amlodipine alone (p=0.014) and 2.1% on valsartan alone.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Everything above is measured in millimetres of mercury. Whether this particular pair prevents more strokes and heart attacks than any other pair has not been tested, and the label says so.
╌╌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
Blood pressure is a validated surrogate at the class level, supported by ALLHAT, ASCOT, VALUE and the ACCOMPLISH comparison of two combination strategies. It is not a hard endpoint for this product: section 1.1 of the label states that there are no controlled trials demonstrating risk reduction with amlodipine and valsartan.
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults whose pressure stayed high on a single agent, and adults starting treatment far enough above goal that one drug was never going to be enough.
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
VALUE failed to separate the two components on its primary endpoint and could not, because blood pressure differed between arms throughout
At amlodipine 10 mg the combination improved the response rate by 1.6 percentage points over amlodipine alone, from 86.9% to 88.5%
Valsartan drug substance was recalled worldwide in 2018 after a manufacturing route change generated N-nitrosodimethylamine that nobody was testing for
The product carries a boxed warning for fetal toxicity that no dose adjustment mitigates
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.
A different form was studied
The studied form is not the form on the shelf.
On this record: This record is linked to 3 related forms. Evidence does not carry across all of them.
There was nothing to correct
Where a level is already normal, topping it up may change nothing.
On this record: The 2018 nitrosamine recalls started here and reshaped impurity testing across the entire generic industry
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 (9)
It was studied for a different goal
The studies measured something else entirely. 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, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg
✎ 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: S3, S6.
No source is stored against this line.
What is in the pack
A bilayer or blended tablet designed around two actives with opposite solubility behaviour.
✎ 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: Amlodipine reaches peak plasma concentration in 6 to 12 hours and has a terminal half-life of 30 to 50 hours, so once-daily coverage is a property of the molecule rather than of the formulation; valsartan is shorter-lived and its effect persists because receptor blockade outlasts plasma exposure.
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 warning for fetal toxicity: discontinue as soon as pregnancy is detected. Commonest adverse reactions are peripheral oedema, dizziness, headache and nasopharyngitis. Hypotension can occur in volume- or salt-depleted patients, and the label directs correcting depletion before starting. Renal function and potassium need monitoring in susceptible patients, particularly with renal artery stenosis, heart failure or existing kidney impairment. Dihydropyridines can rarely worsen angina or precipitate infarction on initiation, chiefly in severe obstructive coronary disease.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy a… · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, taken once daily, at strengths of 5/160, 10/160, 5/320 and 10/320 mg
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Amlodipine reaches peak plasma concentration in 6 to 12 hours and has a terminal half-life of 30 to 50 hours, so once-daily coverage is a property of the molecule rather than of the formulation; valsartan is shorter-lived and its effect persists because receptor blockade outlasts plasma exposure.
No source is stored against this line.
What is recorded as being sold
Exforge is oral at 3 DOSAGE FORMS AND STRENGTHS Exforge (amlodipine and valsartan) tablets are available as follows: 5/160 mg tablets, debossed with NVR/ECE (side 1/side 2) 10/160 mg tablets, debossed with NVR/UIC 5/320 mg tablets, deboss…, recorded as fda label in effect 2026-02-17 in the United States.
US prescribing information · d0caec89-96ec-411d-a933-63eda74a6da7 · read 2026-08-30
Recorded price in US: 0.27577–0.44953 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 32 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.
Evidence on this page does not automatically apply to this one.
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 Amlodipine / Valsartan 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 this fixed-dose pair reduces strokes, infarctions or cardiovascular death — the label states no controlled trial has shown it
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 ACCOMPLISH result transfers to this product, when ACCOMPLISH used benazepril rather than valsartan
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 valsartan prevents heart failure better than amlodipine at matched pressure, which comes from cohorts matched six months after randomisation
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the two components are interchangeable with any other calcium blocker and any other sartan at the same pressure reduction
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 Amlodipine / Valsartan 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.
Two placebo-controlled factorial trials: the pair beat each half at almost every dose
In plain words
Three thousand people were randomised to the combination, to each drug alone, or to a dummy tablet. At the strongest combination the top blood pressure number fell about 16 points further than on the dummy tablet, against about 9 for either drug on its own.
What was measured
Change from baseline in mean sitting diastolic and systolic blood pressure at week 8, against placebo and against each component
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two multinational 8-week, randomised, double-blind, placebo-controlled, parallel-group factorial studies enrolled 1,911 and 1,250 patients with mean sitting diastolic pressure at least 95 and below 110 mmHg. The primary endpoint was change from baseline in mean sitting diastolic pressure at week 8. With the exception of a few combinations containing amlodipine 2.5 mg, every combination lowered both diastolic and systolic pressure significantly more than its own components and than placebo (p<0.05), with a positive dose response. Response rate at amlodipine 5 mg plus valsartan 320 mg was 91.3% against 71.9% for amlodipine 5 mg, 73.4% for valsartan 320 mg and 40.9% for placebo. The FDA label tabulates the same study: placebo-subtracted systolic reduction was 16.2 mmHg at 5/320 mg against 8.6 mmHg for amlodipine 5 mg and 10.1 mmHg for valsartan 320 mg, from a mean baseline of 152.8/99.3 mmHg.
Written into the record, not signed off as a reviewed claim
Adding valsartan cut amlodipine ankle swelling from 8.7% to 5.4%
In plain words
Swollen ankles are the reason most people stop taking amlodipine. In the same trials, swelling was about a third less common on the combination than on amlodipine alone — but still more than twice as common as on valsartan alone.
What was measured
Incidence of peripheral oedema, combination against each monotherapy and against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Pooled from the two factorial studies, peripheral oedema occurred in 5.4% on combination therapy against 8.7% on amlodipine monotherapy (p=0.014), 2.1% on valsartan monotherapy (p<0.001 against the combination) and 3.0% on placebo, a difference from placebo that was not significant. The mechanism is arteriolar dilatation raising capillary hydrostatic pressure without a matching venodilatation; angiotensin receptor blockade relaxes the postcapillary side and reduces the gradient. The finding is a genuine measured advantage of the pairing and it is separate from the blood pressure result.
Written into the record, not signed off as a reviewed claim
The label states in plain words that no trial has shown this product reduces risk
In plain words
The package insert says it outright: lowering blood pressure reduces strokes and heart attacks, that has been shown for other drugs, and there are no controlled trials showing risk reduction with this combination. Everything about outcomes on this page is borrowed.
What was measured
That this fixed-dose pair prevents strokes, infarctions and cardiovascular deaths — supported by class evidence and by the blood pressure result, never tested directly
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 1.1 of the United States prescribing information reads: "There are no controlled trials demonstrating risk reduction with amlodipine and valsartan." The benefit is inferred from two separate arguments. First, class evidence: amlodipine has ALLHAT, ASCOT and VALUE, and the angiotensin receptor blockers have their own outcome programme. Second, the label's own reasoning that "it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits." That is a defensible inference and it is still an inference. The only randomised hard-endpoint evidence for a dihydropyridine paired with a renin-angiotensin blocker comes from ACCOMPLISH, which used benazepril, not valsartan.
Written into the record, not signed off as a reviewed claim
VALUE: the two halves were compared head to head and the trial could not answer itself
In plain words
Fifteen thousand high-risk patients were randomised to a valsartan-based or an amlodipine-based regimen to see which prevented more heart events. Neither won. The trial was undermined by its own design: amlodipine lowered pressure faster, so the two groups were never at the same pressure to compare.
What was measured
Composite of cardiac mortality and morbidity, valsartan-based against amlodipine-based regimen over 4.2 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
VALUE randomised 15,245 patients aged 50 or older with hypertension and high cardiac risk to valsartan-based or amlodipine-based therapy and followed them a mean of 4.2 years. The primary composite of cardiac mortality and morbidity occurred in 810 valsartan patients (10.6%, 25.5 per 1000 patient-years) and 789 amlodipine patients (10.4%, 24.7 per 1000 patient-years); hazard ratio 1.04, 95% CI 0.94 to 1.15, p=0.49. Blood pressure fell more on amlodipine throughout, by 4.0/2.1 mmHg at one month and 1.5/1.3 mmHg at one year (p<0.001 between groups), which the authors state might account for the differences in cause-specific outcomes. The trial answered a different question than the one it asked, and its main usable conclusion is that reaching control early matters more than which of the two drugs does it.
Written into the record, not signed off as a reviewed claim
The VALUE heart failure result came from cohorts matched after randomisation
In plain words
A follow-up analysis of the same trial paired patients with identical blood pressures and reported fewer heart failure admissions on valsartan. Pairing people after the trial has run throws away the randomisation, which is the only thing that made the trial trustworthy.
What was measured
That valsartan prevents heart failure admissions better than amlodipine at equal blood pressure — derived from cohorts matched six months after randomisation, not from the randomised comparison
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Weber and colleagues applied serial median matching at six months, when treatment adjustment was complete, to create 5,006 valsartan-amlodipine patient pairs matched exactly for systolic pressure, age, sex and the presence or absence of previous coronary disease, stroke or diabetes. Subsequent combined cardiac events, myocardial infarction, stroke and mortality were almost identical between the matched cohorts, but hospital admission for heart failure was significantly lower with valsartan. The analysis is transparent about being a post-hoc device to work around the blood pressure imbalance. Matching on a variable measured after randomisation converts a randomised comparison into an observational one, and confounding by whatever drove those six-month pressures cannot be excluded.
Written into the record, not signed off as a reviewed claim
The 2018 nitrosamine recall, and the cohort study that followed it
In plain words
In 2018 valsartan made by one supplier was found to contain a probable human carcinogen produced by the manufacturing route itself, and millions of tablets were recalled worldwide. A Danish study then followed 5,150 valsartan users and found no clear increase in cancer over the following years.
What was measured
That the contaminated tablets caused cancers — the exposure was real and the measured short-term excess risk was not distinguishable from zero, on follow-up too short to settle the question
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
N-nitrosodimethylamine, a probable human carcinogen, was detected in valsartan active pharmaceutical ingredient after a change in synthetic route, triggering recalls across the United States, Europe and Asia and later widening to other sartans and to unrelated drug classes. Pottegard and colleagues then ran an expedited nationwide Danish cohort of 5,150 valsartan users aged 40 or over with no cancer history, followed a median 4.6 years with a one-year lag. With 104 cancers among the unexposed and 198 among the exposed, the adjusted hazard ratio for overall cancer was 1.09 (95% CI 0.85 to 1.41) with no dose-response relation (p=0.70). Colorectal cancer (HR 1.46, 95% CI 0.79 to 2.73) and uterine cancer (HR 1.81, 0.55 to 5.90) were raised with confidence intervals crossing one. The authors state the result does not imply a markedly increased short-term risk and that longer follow-up is needed. The manufacturing failure was real; the population-level cancer signal, so far, is not.
Written into the record, not signed off as a reviewed claim
A boxed warning that is absolute rather than proportional
In plain words
The tablet carries the strongest warning the FDA issues, for harm to a developing fetus. It is not a caution to weigh up: the instruction is to stop the drug as soon as pregnancy is found.
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 product carries a boxed warning for fetal toxicity: drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus, and the label directs discontinuation as soon as pregnancy is detected. Use in the second and third trimesters reduces fetal renal function and increases fetal and neonatal morbidity and death; resulting oligohydramnios is associated with fetal lung hypoplasia and skeletal deformation, and neonatal effects listed include skull hypoplasia, anuria, hypotension, renal failure and death. This is a class warning carried by every angiotensin receptor blocker and every ACE inhibitor, and it is the single most consequential fact about prescribing them to anyone who could become pregnant.
Source
Amlodipine and valsartan United States prescribing information, boxed warning and Warnings and Precautions 5.1 (NDA 021990)
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
Where else this substance is registered
FDA substance identifier (UNII)
80M03YXJ7I
CAS registry number
137862-53-4
PubChem compound
60846
ChEMBL
CHEMBL1069
ChEBI
9927
WHO international nonproprietary name list entry
7016
RxNorm concept
69749
EMA substance identifier
100000088000
DrugBank
DB00177
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A calcium channel blocker and an angiotensin receptor blocker in one tablet, which lowered sitting systolic pressure 16.2 mmHg further than placebo at the highest strength in a 1,911-patient factorial trial and halved the ankle swelling that amlodipine alone causes — and whose own FDA label states that no controlled trial has shown the combination reduces cardiovascular risk.
Recorded evidence blocks (5)
Q2
12 registered trials of Amlodipine / Valsartan — at which phases?
Which 5 trials of Amlodipine / Valsartan posted no result?
Posted no result
5 of 5 completed trials
Registrations
NCT02519010, NCT01776047, NCT02058446, NCT01819220 and NCT03536598
Completion dates
oldest 2011-03; newest 2017-09-04
Show the evidence
Trial
NCT02519010
2011-03
NCT01776047
2012-09
NCT02058446
2014-03
NCT01819220
2014-11
NCT03536598
2017-09-04
Q5
At the median, Amlodipine / Valsartan's trials enrolled 87.5 people — anything larger?
Median enrolment
87.5
Largest enrolment
564
Registered trials counted
12
Q6
What do 16224 spontaneous reports say about Amlodipine / Valsartan — 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.
Amlodipine / Valsartan appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 16224 reaction mentions were counted: hypotension 3757; dizziness 2480; dyspnoea 2468; cough 1390. FAERS via Open Targets · CHEMBL1069 · 2026-06-24
Show the evidence
hypotension
3757
dizziness
2480
dyspnoea
2468
cough
1390
acute kidney injury
1152
cardiac failure
1142
4 more recorded rows
blood pressure increased
1012
blood creatinine increased
1004
hyperkalaemia
957
wrong technique in product usage process
862
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 · 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
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