This page shows what was measured, who it was measured in, and what that does not settle.
What Hydromorphone does in the body
Pain severe enough to need an opioid, especially where the dose must fit into a small injection
Hydromorphone is morphine with two small chemical changes that make it bind the opioid receptor much more tightly and cross into the brain more readily. Everything it does — quieting the pain signal in the spinal cord, strengthening the brain’s own pain suppression, slowing the breathing centre — is what morphine does, at roughly a fifth to a seventh of the milligrams. That is its whole purpose: it lets a large opioid dose fit into a small injection. It is not a stronger painkiller in the sense of relieving pain that morphine cannot; it is the same painkiller in a smaller package.
What happened in people
No clear difference in pain intensity against oxycodone (381 participants), morphine (433) or fentanyl, all at very low certainty in the 2021 Cochrane review
✎ 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.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · a recorded source, not a stored snapshot
The limit that matters most
That greater potency per milligram means greater efficacy — the head-to-head trials show no clear difference against three other opioids
Where it acts
Mu-opioid receptors of the spinal dorsal horn and brainstem — the same sites as morphine, reached at a fraction of the milligram dose
Kind of result
Symptoms and quality of life
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 · Q812464R06 · read 2026-08-29
Its recorded molecular formula is C17H19NO3•HCl.
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · 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 143 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.
Mean change in patient diary numerical rating scale pain intensity from baseline to the final visit of a 12-week double-blind phase, once-daily OROS hydromorphone ER against placebo in opioid-tolerant patients with chronic moderate to severe low back pain
✓ The study showed what it set out to show
Who was studied
NCT00549042 (Hale et al., Curr Med Res Opin 2010;26:1505-1518)
p<0.001 on the primary endpoint; median diary NRS change 0.2 units on hydromorphone ER against 1.6 units on placebo; at least 30% pain reduction in 60.6% against 42.9% (p<0.01)
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. Of 459 patients entering the titration and conversion phase, 268 were randomised and 110 completed the double-blind phase. Sixty patients (13%) discontinued during the enrichment phase for adverse events, and more active (9, 6.7%) than placebo (4, 3.0%) patients discontinued for adverse events during the randomised phase. The authors state that the enrichment phase and the restriction to opioid-tolerant patients may limit generalisability. The product licensed on this programme is now discontinued.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablets and solution; solution for intravenous, intramuscular and subcutaneous injection, including a high-potency concentrate for opioid-tolerant patients; suppositories. Schedule II controlled substance in the United States.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Peak plasma hydromorphone concentration after a 12 mg extended-release capsule taken with 240 mL of 40% alcohol against the same capsule with water
✗ The study did not show it
Who was studied
Palladone in vivo alcohol interaction study (FDA alert, July 2005)
How many people
48
Study design
Open-label, four-arm, crossover pharmacokinetic study in healthy adult subjects
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Approximately six-fold higher mean peak plasma concentration with 8 ounces of 80-proof alcohol than with water; one subject sixteen-fold; approximately doubled peak concentrations with 4% alcohol
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. The FDA alert describes an open-label four-arm crossover design including 24 healthy adults tested fasted and 24 tested under standardised fed conditions. The effect sizes and the regulatory conclusion are taken from that alert; no peer-reviewed publication of the study was located. The finding ended the product: Purdue suspended sales and marketing at FDA request in July 2005 and NDA 021044 is listed as discontinued.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablets and solution; solution for intravenous, intramuscular and subcutaneous injection, including a high-potency concentrate for opioid-tolerant patients; suppositories. Schedule II controlled substance in the United States.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Hydromorphone
What a person takes: Oral tablets and solution; solution for intravenous, intramuscular and subcutaneous injection, including a high-potency concentrate for opioid-tolerant patients; suppositories. Schedule II controlled substance in the United States..
The measurement behind this step
Oral bioavailability is limited by first-pass metabolism, so oral and parenteral doses differ several-fold. The clinical reason to choose hydromorphone is usually volume: a subcutaneous infusion has a physical limit on how much fluid can be delivered, and hydromorphone puts more opioid effect into each millilitre than morphine does. The high-potency concentrate exists for that reason and carries the corresponding hazard of being confused with the ordinary strength.
Getting in
The same drug, in fewer milligrams
Hydromorphone exists so that a large opioid dose can fit into a small injection. That is a packaging advantage, and it is the honest description of what it offers.
──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
Morphine with the 6-hydroxyl oxidised to a ketone and the 7,8-double bond saturated: higher mu-receptor affinity and greater lipophilicity than the parent. Supplied as ordinary injection and as a high-potency concentrate for opioid-tolerant patients.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · a recorded source, not a stored snapshot
Reaching the cell
Into the brain faster than morphine
Being more fat-soluble, it crosses into the brain more readily, which is why an injection acts quickly.
╌╌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
Greater lipophilicity than morphine gives faster blood-brain barrier transit. Oral bioavailability is limited by first-pass metabolism, so oral and parenteral doses differ several-fold — one of the conversions the equianalgesic tables disagree about.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · a recorded source, not a stored snapshot
The change it makes
Cleared to an inactive glucuronide
The liver attaches a sugar to it and the kidneys remove the result. Unlike morphine, that by-product is not itself a painkiller — which is why it is often chosen when kidneys are failing.
╌╌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
Principal clearance by glucuronidation to hydromorphone-3-glucuronide, which has no analgesic activity and no counterpart to morphine-6-glucuronide. H3G nonetheless accumulates in renal impairment and has been associated with neuroexcitatory phenomena.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · a recorded source, not a stored snapshot
What that does for a person
Where the slow-release version failed
A once-daily capsule taken with a glass of spirits released its whole day’s dose at once. Peak levels rose about six-fold on average and sixteen-fold in one volunteer, and the product was pulled.
──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
Palladone 12 mg with 240 mL of 40% alcohol: approximately six-fold higher mean peak plasma hydromorphone against water, one subject at sixteen-fold, and roughly doubled peak concentrations at 4% alcohol. FDA concluded the elevated levels may be lethal; Purdue suspended sales in July 2005.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · a recorded source, not a stored snapshot
What that does for a person
What the trials could and could not measure
Against morphine, oxycodone and fentanyl there is no clear difference in pain relief, on evidence graded very low certainty. The once-daily product’s pivotal trial removed its non-responders before it started.
──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
Cochrane 2021: 8 studies, 1,283 participants, all at high risk of bias, no clear difference against any comparator, insufficient evidence to support or refute. NCT00549042: 459 entered the enrichment phase, 268 randomised, 110 completed the double-blind phase; median diary NRS change 0.2 on drug against 1.6 on placebo.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · 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.
People with severe acute pain in hospital, people with cancer pain, and people in palliative care where subcutaneous infusion volume is the limiting factor.
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: “The safety and effectiveness of hydromorphone hydrochloride extended-release tablets in patients 17 years of age and younger have not been established.”
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
On older people, the label states: “Elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone.”
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )].”
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
On people who are breastfeeding, the label states: “8.3 Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential.”
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
On people with reduced liver function, the label states: “In a study that used a single 4 mg oral dose of immediate-release hydromorphone tablets, four-fold increases in plasma levels of hydromorphone (C max and AUC 0-∞ ) were observed in patients with moderate hepatic impairment (Child-Pugh Group B).”
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
On people with reduced kidney function, the label states: “Administration of a single 4 mg dose of immediate-release hydromorphone tablets resulted in two-fold and four-fold increases in plasma levels of hydromorphone (C max and AUC 0-48h ) in moderate (CLcr = 40 to 60 mL/min) and severe (CLcr < 30 mL/min) impairment, respectively.”
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
Where the result stopped carrying
Palladone, suspended at FDA request in July 2005 after the alcohol interaction study and now listed as discontinued
Exalgo, licensed on the enriched-enrolment programme and now also listed as discontinued
The Cochrane evidence base: eight studies, every one judged at high risk of bias, no possible meta-analysis of the primary outcome, no placebo comparison and no paediatric data
The consistency of published equianalgesic tables, which their surveyors call dangerous to the public
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
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablets and solution; solution for intravenous, intramuscular and subcutaneous injection, including a high-potency concentrate for opioid-tolerant patients; suppositories. Schedule II controlled substance in the United States.
✎ 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, S2, S5, S6.
No source is stored against this line.
What is in the pack
Oral bioavailability is limited by first-pass metabolism, so oral and parenteral doses differ several-fold.
✎ 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: The clinical reason to choose hydromorphone is usually volume: a subcutaneous infusion has a physical limit on how much fluid can be delivered, and hydromorphone puts more opioid effect into each millilitre than morphine does. The high-potency concentrate exists for that reason and carries the corresponding hazard of being confused with the ordinary strength.
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
Class boxed warnings for addiction, abuse and misuse; life-threatening respiratory depression; and profound sedation, respiratory depression, coma and death with concomitant benzodiazepines, other CNS depressants or alcohol; plus neonatal opioid withdrawal syndrome after prolonged use in pregnancy. The Palladone withdrawal established that alcohol can defeat a modified-release hydromorphone matrix outright. Hydromorphone-3-glucuronide accumulates in renal impairment and has been associated with neuroexcitatory effects, so the renal advantage over morphine is relative rather than absolute.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Hale et al. trial registration — ClinicalTrials.gov NCT00549042 (NCT00549042) · 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 tablets and solution; solution for intravenous, intramuscular and subcutaneous injection, including a high-potency concentrate for opioid-tolerant patients; suppositories. Schedule II controlled substance in the United States.
✎ 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: The clinical reason to choose hydromorphone is usually volume: a subcutaneous infusion has a physical limit on how much fluid can be delivered, and hydromorphone puts more opioid effect into each millilitre than morphine does. The high-potency concentrate exists for that reason and carries the corresponding hazard of being confused with the ordinary strength.
No source is stored against this line.
What is recorded as being sold
93 products list this as an active ingredient in the United States drug directory. 93 of them contain it and nothing else.
FDA National Drug Code directory · 0409-3365 · read 2026-08-29
They are sold as injection, injection, solution, powder, solution, suppository and tablet, taken intramuscular, intravenous, oral and rectal.
FDA National Drug Code directory · 0409-3365 · read 2026-08-29
The regulator's established pharmacologic class for it is full opioid agonists [moa] and opioid agonist [epc].
FDA National Drug Code directory · 0409-3365 · read 2026-08-29
30 published labels name it as an active ingredient. 30 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · c729424e-e483-4bf8-b86c-ce56636dcffa · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · c729424e-e483-4bf8-b86c-ce56636dcffa · read 2026-08-29
hydromorphone hydrochloride is oral at 3 DOSAGE FORMS AND STRENGTHS Extended-release tablets: available in 8 mg, 12 mg, 16 mg or 32 mg dosage strengths. 8 mg tablets: round, biconvex, dark beige tablets imprinted with “P293” over “8” on one side. 12 mg table…, recorded as fda label in effect 2025-12-22 in the United States.
US prescribing information · 780a2616-0392-4715-bc50-71799bea1957 · read 2026-08-30
Recorded price in US: 0.16713–0.56832 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 16 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
Recorded price in US: 0.23639–2.74032 USD per one millilitre, across 10 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 Hydromorphone 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 greater potency per milligram means greater efficacy — the head-to-head trials show no clear difference against three other opioids
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That an enriched-enrolment randomised-withdrawal result estimates the benefit for a patient starting the drug
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 published equianalgesic ratios convert reliably between opioids, when the surveyed tables disagree with one another
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That an absent active metabolite makes hydromorphone a better analgesic in renal impairment rather than a more predictable one
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 Hydromorphone 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.
A glass of spirits raised the peak concentration sixteen-fold, and the product went
In plain words
Palladone was a once-daily hydromorphone capsule. When healthy volunteers took one with eight ounces of 80-proof alcohol, the peak drug level in blood rose about six times on average, and sixteen times in one person. Even a third of a beer roughly doubled it. Purdue suspended sales in July 2005 at the FDA’s request.
What was measured
Peak plasma hydromorphone concentration after a 12 mg extended-release capsule taken with 240 mL of 40% alcohol against water
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The FDA alert of July 2005 records that Purdue Pharma agreed to the agency’s request to voluntarily suspend sales and marketing of Palladone in the United States. An in vivo alcohol interaction study in healthy subjects found that co-ingestion of a 12 mg Palladone capsule — the lowest marketed strength — with 240 mL (8 ounces) of a 40% (80 proof) alcoholic beverage produced an average peak hydromorphone plasma concentration approximately six times higher than with water, with one subject showing a sixteen-fold increase, and that even 4% alcohol, roughly two-thirds of a serving of beer, approximately doubled peak concentrations. The agency concluded that co-ingestion of Palladone and alcohol results in dangerous increases in peak plasma hydromorphone and that these elevated levels may be lethal, noting that the risk is higher still for the 16, 24 and 32 mg strengths. Drugs@FDA now lists NDA 021044 as discontinued. The finding changed the field: in vitro and in vivo alcohol dose-dumping testing became a standard expectation for modified-release opioid formulations.
Source
FDA alert, July 2005: Palladone (hydromorphone hydrochloride) extended-release capsules — information for healthcare professionals; FDA Drugs@FDA record for NDA 021044, all products discontinued
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
retracted
Review state
Written into the record, not signed off as a reviewed claim
The pivotal trial only randomised the people it had already worked in
In plain words
Four hundred and fifty-nine people entered the once-daily hydromorphone study. Only those who tolerated it and responded were randomised — 268 of them — and 110 finished the blinded phase. The measured result is what happens when you take the drug away from people it already suited.
What was measured
That an enriched-enrolment randomised-withdrawal result estimates what the drug does for a patient starting it — when everyone who could not tolerate or did not respond to the drug was removed before randomisation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hale and colleagues ran a multicentre, double-blind, placebo-controlled study using a randomised withdrawal design in opioid-tolerant patients with chronic moderate to severe low back pain (NCT00549042). Patients were first converted and titrated onto once-daily OROS hydromorphone ER in an open enrichment phase; only those who succeeded were randomised to continue it or switch to placebo. On the primary endpoint, mean change in diary numerical rating scale pain from baseline to the final visit of the 12-week double-blind phase, hydromorphone ER significantly beat placebo (p<0.001), with median diary NRS change of 0.2 units on hydromorphone against 1.6 units on placebo — that is, pain worsened much less on the drug rather than improving on it. A higher proportion on hydromorphone reached at least a 30% reduction from screening to endpoint, 60.6% against 42.9% (p<0.01). Sixty patients (13%) discontinued during the enrichment phase for adverse events. The authors state their own limitation: "Other trial design elements such as the use of an enrichment phase and the inclusion of only opioid tolerant patients may limit the generalizability of these results." A secondary analysis of the same study records the attrition explicitly: 459 patients entered the titration and conversion phase, 268 were successfully randomised, and 110 completed the double-blind phase. Exalgo, the product licensed on this programme, is now listed as discontinued in Drugs@FDA.
Written into the record, not signed off as a reviewed claim
Against every comparator, no clear difference and very low certainty
In plain words
The Cochrane review pooled eight trials in cancer pain comparing hydromorphone with oxycodone, morphine or fentanyl. It found no clear difference on pain or on side effects, judged every study at high risk of bias, and concluded there is not enough evidence to support or refute the drug against the alternatives.
What was measured
Participant-reported pain intensity and specific adverse events, hydromorphone against oxycodone, morphine and fentanyl in cancer pain
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Li and colleagues included eight studies with 1,283 participants, data analysable for 1,181, comparing hydromorphone with oxycodone (four studies), morphine (three) or fentanyl (one), in adults with cancer pain of mean age 53 to 59. Every study was judged at high risk of bias overall, and no meta-analysis of the primary pain-intensity outcome was possible because of skewed data and differing comparators. No study compared hydromorphone with placebo, and no study included children. Against oxycodone there was no clear difference in pain intensity (3 RCTs, 381 participants) or in nausea (RR 1.13, 95% CI 0.74 to 1.73), vomiting (RR 1.18, 0.72 to 1.94), dizziness (RR 0.91, 0.58 to 1.44) or constipation (RR 0.92, 0.72 to 1.19). Against morphine there was no clear difference in pain intensity (2 RCTs, 433 participants) or in the proportion achieving at least 50% pain relief (RR 0.99, 0.84 to 1.18, 1 RCT, 233 participants), though morphine may reduce constipation at 24 days (RR 1.56, 1.12 to 2.17, 1 RCT, 200 participants). Against fentanyl there was no clear difference in pain intensity at 60 minutes. Every one of these findings was graded very low certainty. No study reported quality of life. The reviewers concluded there is insufficient evidence to support or refute the use of hydromorphone for cancer pain in comparison with other analgesics.
Written into the record, not signed off as a reviewed claim
The conversion tables disagree with each other
In plain words
Switching a patient from morphine to hydromorphone means dividing by a ratio out of a published table. A survey of those tables found the ratios inconsistent between sources, and its authors called the current information confusing for physicians and dangerous to the public.
What was measured
That a published equianalgesic ratio converts one opioid into another with useful accuracy in a tolerant patient at steady state — a claim the surveyed tables do not agree on among themselves
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Shaheen, Walsh, Lasheen, Davis and Lagman surveyed commercially available educational materials — package inserts, teaching materials provided by pharmaceutical companies, and the Physicians’ Desk Reference — for equianalgesic tables of commonly used opioids. They found inconsistent and variable equianalgesic ratios recommended for both opioid rotation and route conversion. They identify the reasons: inter- and intra-individual differences in opioid pharmacology, and the heterogeneity of study design used to derive the ratios in the first place. Their conclusion is that equianalgesic tables should serve only as a general guideline, that systematic research on equianalgesic dose calculation is needed to avoid adverse public health consequences of incorrect dosing, and that current information in equianalgesic tables is confusing for physicians and dangerous to the public. This matters more for hydromorphone than for most opioids, because it is the molecule most often reached for precisely when a conversion is being made.
Written into the record, not signed off as a reviewed claim
Two of the three extended-release products are gone
In plain words
Palladone was withdrawn in 2005 over alcohol. Exalgo, licensed a decade later on an enriched-enrolment trial, is also now discontinued. What remains of hydromorphone is the plain injection and the plain tablet.
What was measured
Marketing status of each hydromorphone extended-release application in Drugs@FDA
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Drugs@FDA lists NDA 021044 (PALLADONE) as discontinued following the July 2005 voluntary suspension, and NDA 021217 (EXALGO) as discontinued. The Dilaudid injection under NDA 019034 and the Dilaudid tablets under NDA 019891 and 019892 remain prescription products. The pattern is worth naming: the commercial activity in hydromorphone over three decades has been in modified-release delivery systems rather than in the molecule, and both of the major ones failed — one on a safety finding the development programme did not anticipate, one commercially after a licence built on a trial that removed its non-responders before randomising.
Source
FDA Drugs@FDA records for NDA 021044 (PALLADONE, discontinued), NDA 021217 (EXALGO, discontinued) and NDA 019034 (DILAUDID, prescription)
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
No morphine-6-glucuronide, which is a genuine and narrow advantage
In plain words
Morphine leaves behind an active by-product that builds up when kidneys fail. Hydromorphone does not produce an equivalent. That is a real difference, and it is a difference about kidneys rather than about pain.
What was measured
Presence of a renally excreted active glucuronide metabolite: morphine yes, hydromorphone no
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hydromorphone is cleared principally by glucuronidation to hydromorphone-3-glucuronide, which has no analgesic activity, and it has no counterpart to morphine-6-glucuronide — the renally excreted active metabolite whose accumulation produces delayed sedation in renal impairment. This is the pharmacological basis for the common clinical preference for hydromorphone over morphine in kidney disease. It should be stated for what it is: a pharmacokinetic argument about metabolite handling, not evidence that hydromorphone relieves pain better. The Cochrane review found no clear difference in pain intensity against morphine in two randomised trials totalling 433 participants, at very low certainty, and hydromorphone-3-glucuronide itself accumulates in renal failure and has been associated with neuroexcitatory effects.
Written into the record, not signed off as a reviewed claim
How many documents were read
31 documents were read for this substance.
RNAWiki source record
17 of them state the same bioavailability, and they agree.
RNAWiki source record
4 of them state the same tMax, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
Q812464R06
CAS registry number
466-99-9
PubChem compound
5284570
ChEMBL
CHEMBL398707
ChEBI
5790
WHO international nonproprietary name list entry
1770
RxNorm concept
3423
EMA substance identifier
100000090462
European Chemicals Agency number
207-383-5
DrugBank
DB00327
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, S2, S5, S6.
✓ 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 United States, 2012, for "Superpotent (Single Ingredient) Drug: Some of the prefilled cartridge units have been found to be overfilled and contain more than the 1 mL labeled fill volume." (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2012, for "Superpotent (Single Ingredient) Drug: The prefilled cartridge unit has been found to be overfilled and contain more than the 1 mL labeled fill volume." (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2018, for "Non-Sterility: Confirmed customer complaints of glass product container vials that may be empty or cracked." (openFDA drug enforcement Class I recall)
What the approval register records
30 approved applications cover products containing this substance. The earliest was NDA019034, approved 19840111 to FRESENIUS KABI USA.
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 full mu-opioid agonist whose Cochrane review of eight trials and 1,283 participants found no clear difference from morphine, oxycodone or fentanyl on any reported outcome at very low certainty, whose extended-release capsule Palladone was withdrawn in July 2005 after 8 ounces of 80-proof alcohol raised peak hydromorphone concentration about six-fold on average and sixteen-fold in one subject, and whose surviving once-daily product was licensed on a randomised-withdrawal trial in which 459 patients entered the enrichment phase and 110 completed the blinded one.
Recorded evidence blocks (10)
Q2
On the Hydromorphone label: indicated for what?
"Hydromorphone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist…": indications and usage on Hydromorphone's label. DailyMed label · 59d88866-e1ba-9d97-e063-6394a90a7b27 · 2026-08-25
Q3
143 registered trials of Hydromorphone — at which phases?
Registered studies posting no result
80 of 143
143 registered studies of Hydromorphone: 52 phase4, 26 phase2, 26 phase3, 21 na, 12 phase1, 8 na or unstated, 4 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
2.3 hours; The terminal elimination half-life of hydromorphone after an intravenous dose is about 2.3 hours.
tmaxpharmacokinetics
0.8 hour; (hrs) 8 mg Tablet 5.5 (33%) 0.74 (34%) 23.7 (28%) 2.6 (18%) Food Effects In a study conducted with a single 8 mg dose of hydromorphone (2 mg hydromorphone immediate-release tablets), food lowered C max by 25%, prolonged T max by 0.8 hour, and increased AUC by 35%.
bioavailabilitypharmacokinetics
24 %; In vivo bioavailability following single-dose administration of the 8 mg tablet is approximately 24% (coefficient of variation 21%).
metabolismpharmacokinetics
Hydromorphone is rapidly absorbed from the gastrointestinal tract after oral administration and undergoes extensive first-pass metabolism.
recorded 2026-08-25 · last checked 2026-09-04
Q7
Which 37 trials of Hydromorphone posted no result?
Posted no result
37 of 37 completed trials
Registrations
NCT00158236, NCT00853554, NCT00003115, NCT00195910, NCT00218309 and NCT00710086, and 31 more
Completion dates
oldest 1998-03; newest 2024-07-01
Show the evidence
Trial
NCT00158236
1998-03
NCT00853554
2002-12
NCT00003115
2004-02
NCT00195910
2005-01
NCT00218309
2005-07
NCT00710086
2009-09
14 further recorded trials
NCT00295945
2009-12
NCT01273454
2009-12
NCT01172782
2010-07
NCT01487564
2012-01
NCT00982891
2012-06
NCT01824524
2012-08
NCT01621100
2012-09
NCT01442818
2012-10
NCT03411109
2013-12-31
NCT03757559
2014-03-08
NCT02461056
2014-07
NCT02035709
2015-04
NCT01946555
2015-12
NCT02295124
2016-01
Q8
At the median, Hydromorphone's trials enrolled 90 people — anything larger?
Median enrolment
90
Largest enrolment
27034
Registered trials counted
143
Q9
What do 3464 spontaneous reports say about Hydromorphone — 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.
Hydromorphone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 3464 reaction mentions were counted: drug hypersensitivity 997; pain 502; nausea 464; vomiting 322. FAERS via Open Targets · CHEMBL1237055 · 2026-06-24
Show the evidence
drug hypersensitivity
997
pain
502
nausea
464
vomiting
322
constipation
236
somnolence
226
4 more recorded rows
back pain
193
drug withdrawal syndrome
193
drug dependence
182
rheumatoid arthritis
149
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Hydromorphone's label not list?
In vitro data suggest that hydromorphone in clinically relevant concentrations has minimal potential to inhibit the activity of human hepatic CYP450 enzymes including CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A11.
Withdrawn in United States, 2012, for "Superpotent (Single Ingredient) Drug: Some of the prefilled cartridge units have been found to be overfilled and contain more than the 1 mL labeled fill volume." (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2012, for "Superpotent (Single Ingredient) Drug: The prefilled cartridge unit has been found to be overfilled and contain more than the 1 mL labeled fill volume." (openFDA drug enforcement Class I recall)
Withdrawn in United States, 2018, for "Non-Sterility: Confirmed customer complaints of glass product container vials that may be empty or cracked." (openFDA drug enforcement Class I recall)
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work · openFDA enforcement — US Government work
✗ 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: 8 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.