This page shows what was measured, who it was measured in, and what that does not settle.
What Dextropropoxyphene does in the body
A weak opioid painkiller for mild to moderate pain
Propoxyphene relieves pain by acting on the same receptors as morphine, but weakly — trials put its analgesia in the same range as paracetamol or aspirin. The body converts it into a second compound, norpropoxyphene, which sticks to the sodium channels the heart uses to conduct each beat and lets go of them very slowly. The electrical signal spreads through the heart more slowly, the QRS complex on an electrocardiogram widens, and in overdose the rhythm can collapse.
What happened in people
Use-dependent block of cardiac inward sodium current recovering with a time constant of 20.8 ± 3.9 seconds, against 2 to 3 seconds for lidocaine
✎ 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 substitution objection to withdrawing a poisoning agent was tested empirically here, and largely did not hold
Where it acts
Central nervous system mu opioid receptors; the toxicity site is the cardiac conduction system
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
Its recorded molecular formula is C22H29NO2, weighing 339.5.
PubChem record · 10100 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 113 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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Formulation
A formulation is the exact made-up form a substance comes in.
A picture of it, and where the picture fails
It is like the difference between a whole bean and instant coffee.
Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.
What people get wrong. Two products with the same name are assumed to behave the same. They often do not.
The specific composition and physical form of a product, including salt, excipients and release profile.
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.
Prescriptions and deaths from drug poisoning involving single analgesics — suicides, open verdicts and accidental poisonings — after the January 2005 withdrawal announcement
✓ The study showed what it set out to show
Who was studied
Co-proxamol withdrawal, England and Wales, three-year analysis (Hawton et al. 2009)
Co-proxamol prescriptions fell by 859,000 per quarter (95% CI 653,000 to 1,065,000), about 59%; an estimated 295 fewer suicides and 349 fewer deaths including accidental poisonings, with no statistical evidence of an increase in deaths involving other analgesics or other drugs
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. Prescribing of co-codamol, paracetamol, co-dydramol and codeine rose significantly over the same period, which is the displacement the mortality analysis was designed to detect.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or capsule, alone or fixed-combination with paracetamol or aspirin
Interval reported. 95% CI 653,000 to 1,065,000), about 59%; an estimated 295 fewer suicides and 349 fewer deaths including accidental poisonings, with no statistical evidence of an increase in deaths involving other analgesics or other drugs
Written into the record, not signed off as a reviewed claim.
Quarterly deaths from poisoning involving single analgesics, with suicide, undetermined and accidental verdicts, before and after withdrawal
✓ The study showed what it set out to show
Who was studied
Co-proxamol withdrawal, England and Wales, six-year follow-up (Hawton et al. 2012)
How many people
600
Study design
Population-level interrupted time-series analysis, 1998-2004 versus 2005-2010
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Suicide and undetermined verdicts: -21 deaths per quarter (95% CI -34 to -8), about 500 fewer over six years, -61%; including accidental poisoning: -25 per quarter (95% CI -38 to -12), about 600 deaths, -62%
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The analysis covers deaths involving single drugs alone and could not assess changes in deaths involving prescribed morphine. Oxycodone poisonings rose, on small numbers.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or capsule, alone or fixed-combination with paracetamol or aspirin
Interval reported. 95% CI -34 to -8), about 500 fewer over six years, -61%; including accidental poisoning: -25 per quarter (95% CI -38 to -12), about 600 deaths, -62%
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Dextropropoxyphene
What a person takes: Oral tablet or capsule, alone or fixed-combination with paracetamol or aspirin.
The measurement behind this step
Oral dextropropoxyphene as the hydrochloride or napsylate salt, the two differing in mass per unit of base. Extensive hepatic N-demethylation to norpropoxyphene, which has a much longer half-life than the parent and accumulates with repeated dosing.
Getting in
An oral tablet, usually combined with paracetamol
Taken by mouth, most often as a fixed combination with paracetamol or aspirin rather than alone.
╌╌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
Oral dextropropoxyphene hydrochloride or napsylate, most commonly co-formulated with paracetamol (Darvocet-N, co-proxamol) or aspirin. Extensive first-pass metabolism.
The liver converts a large fraction of it into a second compound that lasts much longer in the body.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Hepatic N-demethylation produces norpropoxyphene, which has a substantially longer elimination half-life than the parent and accumulates on repeated dosing. Propoxyphene also inhibits CYP2D6.
Two targets: mu opioid receptors and cardiac sodium channels
The parent drug weakly activates the receptors that relieve pain. The metabolite binds the sodium channels the heart uses to conduct each beat.
╌╌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
Weak mu opioid receptor agonism gives analgesia comparable to paracetamol or aspirin. Norpropoxyphene binds the cardiac sodium channel at the local-anaesthetic site with slow unbinding kinetics, producing use-dependent block.
Because it lets go of the channel so slowly, each heartbeat adds more block than the interval between beats can undo.
╌╌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
Recovery from block has a time constant of about 21 seconds, an order of magnitude slower than lidocaine. At physiological heart rates the interpulse interval is far shorter than the recovery constant, so steady-state block accumulates during pulse trains and conduction velocity falls.
Modest analgesia; QRS widening, seizures and conduction collapse in overdose
Pain relief about equal to paracetamol. In overdose the electrocardiogram widens, seizures occur, and the rhythm can fail.
╌╌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
Measured: analgesia equated with paracetamol or aspirin alone. Measured: use-dependent sodium current block with 20.8 second recovery constant, producing QRS widening reversible with lidocaine or sodium bicarbonate. Population-level: about 500 fewer suicide deaths over six years after UK withdrawal, without displacement to other analgesics.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 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.
Nobody by prescription in the United States or United Kingdom. Propoxyphene appears in 21 CFR 216.24 as withdrawn for reasons of safety or effectiveness.
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
Introduced in the United States in 1957; the myocyte mechanism was published in 1989; withdrawal came in 2010
Withdrawn in the United Kingdom in stages between 2005 and 2008 over overdose deaths
Approval of 8 new drug applications and 46 abbreviated applications formally withdrawn in the Federal Register in March 2014
Listed in 21 CFR 216.24 as withdrawn for reasons of safety or effectiveness
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 1 related forms. Evidence does not carry across all of them.
The change is too small to feel
A real change can still sit below what a person notices.
On this record: The substitution objection to withdrawing a poisoning agent was tested empirically here, and largely did not hold
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.
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.
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
Withdrawn
❝ 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 or capsule, alone or fixed-combination with paracetamol or aspirin
✎ 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: S1, S8.
No source is stored against this line.
What is in the pack
Oral dextropropoxyphene as the hydrochloride or napsylate salt, the two differing in mass per unit of base. Extensive hepatic N-demethylation to norpropoxyphene, which has a much longer half-life than the parent and accumulates with repeated dosing.
✎ 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
Withdrawn from the United States market in November 2010 and from the United Kingdom between 2005 and 2008. The decisive harm is cardiac: norpropoxyphene produces use-dependent block of the cardiac sodium current with a recovery time constant of about 21 seconds, causing QRS widening, conduction block, and in overdose circulatory collapse, together with seizures. This is not naloxone-reversible; lidocaine and sodium bicarbonate are the described interventions. Standard opioid effects — respiratory depression, sedation, constipation, dependence — apply as well. Propoxyphene inhibits CYP2D6, and accumulation of the metabolite makes the elderly particularly exposed.
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 or capsule, alone or fixed-combination with paracetamol or aspirin
✎ 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
Extensive hepatic N-demethylation to norpropoxyphene, which has a much longer half-life than the parent and accumulates with repeated dosing.
✎ 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.
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, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Dextropropoxyphene studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the fatal toxicity is an opioid class effect — it belongs to a non-opioid metabolite acting on the cardiac sodium channel and is not naloxone-reversible
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 analgesia from a propoxyphene-paracetamol combination demonstrates analgesia from propoxyphene
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.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records 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 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 Dextropropoxyphene 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.
Use-dependent sodium channel block with a 21-second recovery constant
In plain words
In isolated heart cells, propoxyphene blocked the sodium channels that carry each heartbeat and released them roughly ten times more slowly than lidocaine, so the block builds up beat after beat.
What was measured
Recovery time constant of use-dependent inward sodium current block in isolated atrial myocytes
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Whole-cell recordings in rabbit atrial myocytes showed that propoxyphene at 60 micromolar produces use-dependent block of the inward sodium current during pulse-train stimulation, recovering with a time constant of 20.8 plus or minus 3.9 seconds. Lidocaine block recovers with a time constant of 2 to 3 seconds. During exposure to the mixture, recovery followed a double exponential with a half-time of 1.6 plus or minus 0.9 seconds against 14.3 plus or minus 2.9 seconds for propoxyphene alone, and less steady-state block accumulated at interpulse intervals above 0.95 seconds. Both drugs compete for a common receptor and lidocaine dissociates faster, which explains the clinically observed paradox of lidocaine reversing propoxyphene-induced QRS widening.
Written into the record, not signed off as a reviewed claim
Withdrawal in the UK was followed by about 500 fewer suicide deaths in six years
In plain words
After co-proxamol was withdrawn in Britain, poisoning deaths involving it fell by more than sixty per cent, and deaths involving other painkillers did not rise to take their place.
What was measured
Change in quarterly deaths from single-analgesic poisoning after co-proxamol withdrawal, interrupted time series
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Interrupted time-series analysis of prescribing and mortality in England and Wales, comparing 2005 to 2010 with 1998 to 2004, using NHS prescribing data and Office for National Statistics mortality data. Withdrawal of co-proxamol was associated with a reduction of 21 deaths per quarter receiving verdicts of suicide or undetermined cause (95% CI -34 to -8), approximately 500 fewer such deaths over six years, a 61 per cent reduction; including accidental poisoning the figure was 25 fewer per quarter (95% CI -38 to -12), about 600 deaths, a 62 per cent reduction. Prescribing of co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone and morphine all rose, and there was little change in deaths involving those analgesics apart from a small increase in oxycodone poisonings.
Written into the record, not signed off as a reviewed claim
Substitution was the objection, and it was tested rather than assumed
In plain words
The main argument against withdrawing the drug was that people would simply overdose on something else. Six years of data showed they largely did not.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The standard objection to removing a drug used in suicidal poisoning is displacement: the method changes and the death rate does not. The six-year follow-up tested this directly by tracking deaths involving each substituted analgesic over the same period. Prescribing of seven alternative analgesics rose, and deaths involving them showed little observed change apart from an increase in oxycodone poisonings on small numbers. The authors note the limitation that the analysis covers deaths involving single drugs alone and could not assess changes in deaths involving prescribed morphine. This is one of the few places in this file where the counterfactual objection to a withdrawal was measured rather than argued.
Written into the record, not signed off as a reviewed claim
The analgesia was never better than paracetamol or aspirin
In plain words
Reviews of the trial literature put propoxyphene's pain relief at about the level of plain paracetamol or aspirin, which is the reason the risk was never worth carrying.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A critical review of the analgesic literature concludes that propoxyphene's analgesia was equated with that of paracetamol or aspirin taken independently, and that its adverse effects — cardiotoxicity, seizures — outweighed the therapeutic benefit. It was most often prescribed in fixed combination with paracetamol or aspirin, which makes attributing the observed analgesia to the opioid component difficult and was itself part of the problem: a combination product can carry a weak opioid for decades on the strength of the non-opioid component's effect. The toxicity is attributed in part to norpropoxyphene, described as a non-opioid cardiotoxic metabolite.
Written into the record, not signed off as a reviewed claim
The metabolite outlasts the parent, so exposure accumulates
In plain words
The cardiotoxic breakdown product hangs around much longer than the drug itself, so repeated dosing builds it up — particularly in older people.
What was measured
Norpropoxyphene elimination half-life relative to parent, and accumulation on repeated dosing
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Norpropoxyphene has a substantially longer elimination half-life than propoxyphene and accumulates with repeated administration, which is why the review literature specifically advises against use in the elderly on pharmacokinetic and pharmacodynamic grounds. Propoxyphene is also a CYP2D6 inhibitor, generating a list of interacting drugs, and a documented interaction with metoprolol producing profound bradycardia has been reported. The clinical consequence of the metabolite's kinetics is that a plasma propoxyphene concentration, taken alone, understates the cardiac exposure — which is why a laboratory assay for this compound must report parent and metabolite separately.
Written into the record, not signed off as a reviewed claim
Fifty-three years between introduction and withdrawal, and the case was public throughout
In plain words
The drug came to market in 1957 and left in 2010. The evidence about the metabolite's effect on heart cells was published in 1989.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Propoxyphene was introduced in the United States in 1957. The mechanism of its cardiac toxicity was characterised in isolated myocytes in 1989. A critical review calling for it to remain in antiquity appeared in 2006. The United Kingdom withdrew it in stages between 2005 and 2008. The United States withdrawal came in November 2010, and the formal withdrawal of eight new drug applications and forty-six abbreviated applications was published in the Federal Register in March 2014. Propoxyphene now appears in 21 CFR 216.24 as a drug product withdrawn for reasons of safety or effectiveness. The gap between the mechanism being known and the drug being removed is twenty-one years.
Source
Federal Register, 10 March 2014 — Xanodyne Pharmaceuticals et al., withdrawal of approval of 8 NDAs and 46 ANDAs; 21 CFR 216.24
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
It is filed as an opioid harm, and the decisive harm is not opioid
In plain words
Propoxyphene is usually grouped with opioid withdrawals. The property that killed people belongs to a metabolite acting on heart sodium channels, not to opioid receptors.
What was measured
That propoxyphene's fatal toxicity is an opioid class effect shared with codeine and tramadol
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Grouping this withdrawal with the opioid safety actions obscures the mechanism. Respiratory depression from mu agonism is a class effect and is dose-related and reversible with naloxone. Norpropoxyphene's use-dependent sodium channel block is not an opioid effect, is not reversed by naloxone, and produces QRS widening and conduction failure rather than hypoventilation. The clinical management differs accordingly, which is why the case reports on sodium bicarbonate and lidocaine reversal exist. A summary that reads "a weak opioid withdrawn for overdose deaths" is true and omits the part that distinguishes this drug from every other weak opioid.
Written into the record, not signed off as a reviewed claim
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
Suppression classes recorded: S1, S8.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
Withdrawn in European Union; New Zealand; Canada; Iraq; United States, 2009, for "drug misuse" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "cardiotoxicity" (ChEMBL; Open Targets)
Withdrawn in European Union; New Zealand; Canada; Iraq; United States, 2009, for "cardiotoxicity" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "Risk of serious abnormal heart rhythms that have been linked to serious adverse effects including sudden death" (ChEMBL; Open Targets)
Withdrawn in European Union; New Zealand; Canada; Iraq; United States, 2009, for "Adverse drug reactions" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "Deaths. More dangerous than other simple analgesics in overdose, particularly when combined with alcohol" (ChEMBL; Open Targets)
What the approval register records
78 approved applications cover products containing this substance. The earliest was NDA010997, approved 19570816 to XANODYNE PHARM.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A weak opioid marketed for over fifty years whose metabolite norpropoxyphene produces use-dependent block of the cardiac sodium current with a recovery time constant of about 21 seconds, withdrawn on cardiac conduction grounds in 2010 — and whose earlier United Kingdom withdrawal was followed by roughly 500 fewer suicide deaths over six years with no measurable displacement to other analgesics.
Recorded evidence blocks (6)
Q2
2 registered trials of Dextropropoxyphene — at which phases?
Approved in 1957, withdrawn in 2009: what happened to Dextropropoxyphene in Canada; New Zealand; Vietnam and European Union; New Zealand; Canada; Iraq; United States?
14 recorded reasons; Canada; New Zealand; Vietnam, European Union; New Zealand; Canada; Iraq; United States
Show the evidence
Reason
"drug misuse"
"cardiotoxicity"
"cardiotoxicity"
"Risk of serious abnormal heart rhythms that have been linked to serious adverse effects including sudden death"
"Adverse drug reactions"
"Deaths. More dangerous than other simple analgesics in overdose, particularly when combined with alcohol"
8 more recorded rows
Reason
"drug misuse"
Reason
"cardiotoxicity"
Reason
"cardiotoxicity"
Reason
"Risk of serious abnormal heart rhythms that have been linked to serious adverse effects including sudden death"
Reason
"Adverse drug reactions"
Reason
"drug misuse"
Reason
"Deaths. More dangerous than other simple analgesics in overdose, particularly when combined with alcohol"
Reason
"drug misuse"
recorded 2026-06-24 · last checked 2026-09-04
Q4
Which one trial of Dextropropoxyphene posted no result?
Posted no result
1 of 1 completed trials
Registrations
NCT00378937
Completion dates
oldest 2006-02
Show the evidence
TrialNCT00378937
2006-02
Q5
At the median, Dextropropoxyphene's trials enrolled 39 people — anything larger?
Median enrolment
39
Largest enrolment
48
Registered trials counted
2
Q6
What do 52 spontaneous reports say about Dextropropoxyphene — 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.
Dextropropoxyphene appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 52 reaction mentions were counted: drug hypersensitivity 12; respiratory acidosis 6; somnolence 6; deafness neurosensory 5. FAERS via Open Targets · CHEMBL1213351 · 2026-06-24
Show the evidence
drug hypersensitivity
12
respiratory acidosis
6
somnolence
6
deafness neurosensory
5
dyspepsia
5
abortion spontaneous
5
4 more recorded rows
ataxia
4
female genital tract fistula
3
frequent bowel movements
3
macular degeneration
3
recorded 2026-06-24 · last checked 2026-09-04
Q8
Where do the label and the trials disagree about Dextropropoxyphene?
"drug misuse" against "approved": withdrawal status vs register status for Dextropropoxyphene.
OPEN_TARGETS_DRUG_WARNING, Drugs@FDA; 1 recorded pair
Show the evidence
OPEN_TARGETS_DRUG_WARNINGCHEMBL1213351
drug misuse; 2026-06-24
Drugs@FDAANDA083184
approved; 2026-08-28
Where it is registered
Where it’s registered
Withdrawn in European Union; New Zealand; Canada; Iraq; United States, 2009, for "drug misuse" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "cardiotoxicity" (ChEMBL; Open Targets)
Withdrawn in European Union; New Zealand; Canada; Iraq; United States, 2009, for "cardiotoxicity" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "Risk of serious abnormal heart rhythms that have been linked to serious adverse effects including sudden death" (ChEMBL; Open Targets)
Withdrawn in European Union; New Zealand; Canada; Iraq; United States, 2009, for "Adverse drug reactions" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "Deaths. More dangerous than other simple analgesics in overdose, particularly when combined with alcohol" (ChEMBL; Open Targets)
Withdrawn in Canada; New Zealand; Vietnam, 2010, for "drug misuse" (ChEMBL; Open Targets)
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
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 5 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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.