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Methadone

  • Prescription medicine
  • Prescription only
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Methadone does in the body

Opioid dependence, as maintenance or detoxification treatment; and severe long-term pain

Methadone is a synthetic opioid that does not look like morphine but binds the same receptor. What makes it different is how long it lasts: taken once a day it holds a steady level, so there is no cycle of rush and withdrawal, and enough receptor is occupied that another opioid on top produces much less effect. The problem is the same property. Methadone leaves the body at a rate that varies enormously between people — its own label reports a half-life anywhere from eight to fifty-nine hours — so it accumulates over days, and the label warns that its peak effect on breathing comes later and lasts longer than its peak painkilling effect. It also blocks a potassium channel in the heart, which can lengthen the electrical cycle and trigger a dangerous rhythm.

What happened in people

Methadone involved in 31.4% of opioid pain reliever deaths in 13 states while accounting for 4.5% to 18.5% of opioids distributed by state

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 limit that matters most

That methadone maintenance has a demonstrated randomised mortality benefit — the point estimate favours it, the confidence interval does not exclude harm, and the case rests on cohort data

Where it acts
Mu-opioid receptors of the brain and spinal cord; and the hERG potassium channel of cardiac myocytes, which is where the boxed cardiac warning comes from
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

  • Its recorded molecular formula is C21H27NO•HCl, weighing 345.91.

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · 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 171 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Comparator

A comparator is whatever the treatment was measured against.

A picture of it, and where the picture fails

It is like the other runner in a race.

Where that stops being true. A race has one winner. A study can show both arms improved.

What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.

The control condition against which the experimental intervention is assessed.

Randomisation

Randomisation means chance decides who gets which treatment.

A picture of it, and where the picture fails

It is like a coin toss deciding the groups.

Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.

What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.

Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.

Absolute difference

An absolute difference is how many more people in a hundred were affected.

A picture of it, and where the picture fails

It is like counting heads in two rooms of a hundred.

Where that stops being true. Heads are easy to count. Study results carry a margin of error too.

What people get wrong. It is confused with a percentage change, which can look far larger.

The arithmetic difference in event rates between arms.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

What happened in peopleRead 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.

Retention in treatment and suppression of heroin use with methadone maintenance against treatments not using opioid replacement, in opioid dependence

The study showed what it set out to show

Who was studied
Cochrane CD002209 — 11 randomised trials of methadone maintenance
How many people
1969
Study design
Systematic review and meta-analysis of randomised clinical trials, two of them double-blind
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Heroin use RR 0.66 (95% CI 0.56 to 0.78) across 6 RCTs; retention significantly better; criminal activity RR 0.39 (0.12 to 1.25) and mortality RR 0.48 (0.10 to 2.39), neither statistically significant
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. Sequence generation was inadequate in one included study and unclear in several; allocation concealment was adequate in only three. The mortality analysis rests on four trials and its confidence interval spans a five-fold reduction to a two-fold increase — the outcome most often attributed to methadone is the one the randomised evidence is least able to resolve.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.

Interval reported. 95% CI 0

Written into the record, not signed off as a reviewed claim.

All-cause and overdose mortality per 1,000 person-years during and outside methadone treatment in people with opioid dependence

The study showed what it set out to show

Who was studied
Sordo et al., BMJ 2017;357:j1550 — pooled cohort mortality analysis
How many people
122885
Study design
Systematic review and multivariate random-effects meta-analysis of cohort studies
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
All-cause mortality 11.3 in against 36.1 out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% CI 2.65 to 3.86); overdose mortality 2.6 against 12.7 (4.80, 2.90 to 7.96)
Repeated elsewhere
Partially Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. These are cohort data, not randomised. The authors state that further research must properly account for potential confounding and selection bias, both between treatments and across periods in and out of treatment. All-cause mortality dropped sharply only over the first four weeks of methadone treatment, so induction is a period of elevated rather than reduced risk, as are the weeks immediately after leaving.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.

Interval reported. 95% CI 2

Written into the record, not signed off as a reviewed claim.

What we know
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 bodyRead 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.

Where a source records it acting

  • Brain: Mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involve the central nervous system

    US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27

  • Brainstem: Produces respiratory depression by direct action on brain stem respiratory centers

    US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27

  • Stomach: Causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum

    US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27

  1. Start

    Methadone

    What a person takes: Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8..

    The measurement behind this step

    Once-daily oral dosing is possible because of a terminal half-life the label reports between 8 and 59 hours, and that same range is why steady state is reached at an unpredictable time. Being lipophilic, methadone loads into liver and other tissue and releases slowly, which the label notes may prolong its action despite low plasma concentrations. Because it is a base of pKa 9.2, urinary pH alters its disposition.

  2. Getting in

    Not a poppy molecule at all

    Methadone looks nothing like morphine. It is a fully synthetic compound built from two benzene rings and a short chain, which happens to fold into the shape the opioid receptor recognises.

    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

    A diphenylheptanone, C21H27NO, with no morphinan ring system. Marketed as the racemate: R-methadone carries essentially all the mu agonism, S-methadone most of the hERG potassium channel block.

  3. Reaching the cell

    It goes into tissue and comes back out slowly

    Being fat-soluble, methadone loads into the liver and other tissues and leaks back out for days. That is why one dose lasts and why several doses stack up.

    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

    The label notes methadone is lipophilic and known to persist in liver and other tissues, and that slow release from those tissues may prolong its action despite low plasma concentrations. Terminal half-life 8 to 59 hours and apparent clearance 1.4 to 126 L/h across published studies; being a base of pKa 9.2, urinary pH alters disposition.

  4. What it acts on

    Steady occupancy of the mu receptor

    Instead of a peak and a crash, methadone holds the receptor at a steady level. No rush, no withdrawal, and enough occupancy that another opioid on top does much less.

    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

    Full mu agonism with a pharmacodynamic profile qualitatively similar to morphine; the label notes the withdrawal syndrome is slower in onset, longer in course and less severe in symptoms than morphine’s. Some data indicate NMDA receptor antagonism, whose contribution to efficacy the label states is unknown.

  5. The change it makes

    Five liver enzymes, and everything interacts

    Methadone is broken down by five different liver enzymes. Almost any new medicine can raise or lower its level, and the boxed warning names all five.

    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 to inactive EDDP by CYP3A4, CYP2B6, CYP2C19, CYP2C9 and CYP2D6. The boxed warning states that concomitant use with inhibitors of any of them may increase methadone concentrations and cause potentially fatal respiratory depression, and that inducers may reduce effect and precipitate withdrawal.

  6. What that does for a person

    And a potassium channel in the heart

    The same molecule blocks a channel that resets the heart’s electrical cycle. Lengthen that cycle enough and a lethal rhythm becomes possible.

    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

    hERG potassium channel block, more potent for S-methadone than R-methadone. Boxed warning for QT prolongation and torsades de pointes, most cases at large multiple daily analgesic doses but reported at maintenance doses too. The founding case series: 17 patients, mean daily dose 397 ± 283 mg, mean QTc 615 ± 77 ms.

  7. What that does for a person

    What treatment actually changes

    Randomised trials show people stay in treatment and use less heroin. The much larger observational record shows death rates roughly a third of those out of treatment — a finding its own authors flag for confounding.

    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 CD002209, 11 RCTs, 1,969 participants: heroin use RR 0.66 (95% CI 0.56 to 0.78); mortality RR 0.48 (0.10 to 2.39), not significant. Sordo BMJ 2017, 19 cohorts, 122,885 methadone patients: all-cause mortality 11.3 against 36.1 per 1,000 person-years in against out of treatment; overdose mortality 2.6 against 12.7.

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 unclearRead 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 in opioid maintenance or detoxification programmes, dispensed under a specific federal regulatory framework in the United States; and a much smaller number of people with severe chronic pain.

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, effectiveness, and pharmacokinetics of methadone in pediatric patients below the age of 18 years have not been established.”

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30

  • On older people, the label states: “Clinical studies of methadone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects.”

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30

  • On people who are pregnant, the label states: “Risk Summary The majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone.”

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30

  • On people who are breastfeeding, the label states: “Risk Summary Based on two small clinical studies, methadone was present in low levels in human milk, but the exposed infants in these studies did not show adverse reactions.”

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30

  • On people with reduced liver function, the label states: “Methadone pharmacokinetics have not been extensively evaluated in patients with hepatic insufficiency.”

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30

  • On people with reduced kidney function, the label states: “Methadone pharmacokinetics have not been extensively evaluated in patients with renal insufficiency.”

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30

Where the result stopped carrying

  • Mortality and criminal activity as randomised endpoints, neither reaching statistical significance across the available trials
  • Methadone as a cheap first-line long-acting analgesic, which CDC concluded should not be a drug of first choice for chronic non-cancer pain
  • The assumption that a long half-life is simply convenient, when the peak respiratory depressant effect arrives after the peak analgesic effect
  • Levacetylmethadol, a methadone derivative withdrawn from the European market after association with torsades de pointes, which is the fact the original QT case series opens with
  • 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 takeRead 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 takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Prescription only

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.

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

Once-daily oral dosing is possible because of a terminal half-life the label reports between 8 and 59 hours, and that same range is why steady state is reached at an unpredictable time.

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: Being lipophilic, methadone loads into liver and other tissue and releases slowly, which the label notes may prolong its action despite low plasma concentrations. 2, urinary pH alters its disposition.

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 takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Boxed warnings for life-threatening respiratory depression during initiation and conversion, including in patients using the drug as directed; life-threatening QT prolongation and torsades de pointes; fatal overdose from accidental ingestion, especially by children; abuse potential comparable to other opioid agonists; interactions with drugs affecting CYP3A4, CYP2B6, CYP2C19, CYP2C9 and CYP2D6; concomitant benzodiazepines and other CNS depressants; and the regulatory conditions for treatment of opioid addiction. The label states that the peak respiratory depressant effect occurs later and persists longer than the peak pharmacologic effect, especially during initial dosing — the single most important sentence on the document.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

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 unclearRead 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, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.

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

Being lipophilic, methadone loads into liver and other tissue and releases slowly, which the label notes may prolong its action despite low plasma concentrations. 2, urinary pH alters its disposition.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

What is recorded as being sold

  • 62 products list this as an active ingredient in the United States drug directory. 62 of them contain it and nothing else.

    FDA National Drug Code directory · 72865-120 · read 2026-08-29

  • They are sold as concentrate, injection, injection, solution, powder, solution and tablet, taken intramuscular, intravenous, oral and subcutaneous.

    FDA National Drug Code directory · 72865-120 · 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 · 72865-120 · read 2026-08-29

  • 36 published labels name it as an active ingredient. 36 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-29

  • 1 marketed supplement label lists this ingredient, classed as botanical with nutrients.

    NIH Dietary Supplement Label Database · 249075 · read 2026-08-29

  • Those labels carry all other and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.

    NIH Dietary Supplement Label Database · 249075 · read 2026-08-29

  • Methadone Hydrochloride is injection (multiple-dose vials) at 200 mg/20 mL (10 mg/mL), recorded as prescription opioid; fda label in effect 2025-12-31 in the United States.

    US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27

  • Recorded price in US: 0.16625–0.17521 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 19 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: 0.55399 USD per one millilitre, across 2 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 takeRead 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 Methadone 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 unclearRead 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 methadone maintenance has a demonstrated randomised mortality benefit — the point estimate favours it, the confidence interval does not exclude harm, and the case rests on cohort data

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 NMDA receptor antagonism gives methadone an advantage in neuropathic or opioid-tolerant pain, when the label states that contribution is unknown

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That a stated methadone dose corresponds to a predictable exposure, given a reported ninety-fold range in apparent clearance

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That the cohort comparison of methadone against buprenorphine mortality ranks the two drugs, when the populations were never randomised against each other

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 unclearRead 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 Methadone 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 peopleRead 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.

The randomised evidence shows retention, not survival
In plain words
Eleven randomised trials in nearly two thousand people found methadone kept more of them in treatment and cut heroin use. On deaths, and on crime, the difference did not reach statistical significance.
What was measured
Retention in treatment, heroin use, criminal activity and mortality, methadone maintenance against non-pharmacological treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mattick and colleagues included 11 randomised clinical trials, two of them double-blind, totalling 1,969 participants. Methadone was statistically significantly more effective than non-pharmacological approaches at retaining patients in treatment and at suppressing heroin use measured by self-report and urine or hair analysis (6 RCTs, RR 0.66, 95% CI 0.56 to 0.78). It was not statistically different on criminal activity (3 RCTs, RR 0.39, 95% CI 0.12 to 1.25) or on mortality (4 RCTs, RR 0.48, 95% CI 0.10 to 2.39). Sequence generation was inadequate in one study and unclear in several; allocation concealment was adequate in only three. The point estimates for crime and mortality both favour methadone substantially and both have confidence intervals crossing one, which is what four small trials look like when the outcome is rare. The reviewers’ conclusion states it precisely: methadone retains patients and decreases heroin use better than treatments without opioid replacement, and does not show a statistically significant superior effect on criminal activity or mortality.
Source
Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009;(3):CD002209
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
The mortality case is enormous, consistent, and observational
In plain words
Nineteen cohorts following almost 123,000 people on methadone found death rates roughly a third of those seen out of treatment. The authors themselves say further work is needed to account for confounding and selection, because people are not randomly assigned to be in or out of treatment.
What was measured
All-cause and overdose mortality per 1,000 person-years in and out of methadone treatment across 122,885 patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sordo and colleagues pooled 19 eligible cohorts following 122,885 people treated with methadone over 1.3 to 13.9 years and 15,831 treated with buprenorphine over 1.1 to 4.5 years. Pooled all-cause mortality was 11.3 per 1,000 person-years in methadone treatment and 36.1 out of it (unadjusted out-to-in rate ratio 3.20, 95% CI 2.65 to 3.86), and 4.3 against 9.5 for buprenorphine (2.20, 1.34 to 3.61). Pooled overdose mortality was 2.6 in and 12.7 out of methadone treatment (rate ratio 4.80, 2.90 to 7.96) and 1.4 against 4.6 for buprenorphine. In trend analysis, all-cause mortality dropped sharply over the first four weeks of methadone treatment and rose in the two weeks after leaving treatment; on buprenorphine it remained stable during induction. The authors state that these findings are potentially important but that further research must properly account for potential confounding and selection bias in comparisons of mortality risk between treatments and across periods in and out of them. The inference this supports is that retention is associated with far lower mortality. The inference it does not license, on its own, is a causal effect size, or a head-to-head ranking of methadone against buprenorphine.
Source
Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ 2017;357:j1550
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
A few per cent of prescriptions, a third of the deaths
In plain words
When methadone was widely prescribed as a cheap long-acting painkiller, it accounted for a small share of opioid prescribing and about a third of prescription opioid overdose deaths.
What was measured
Share of opioid pain reliever overdose deaths involving methadone against its share of opioids distributed, 13 states, 2009-2010
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
CDC analysed fatal methadone overdoses and sales nationally over 1999 to 2010 and overdose death rates in 13 states for 2009. Methadone overdose deaths and sales rates peaked in 2007. In 2010 methadone accounted for between 4.5% and 18.5% of the opioids distributed by state. It was involved in 31.4% of opioid pain reliever deaths in the 13 states and accounted for 39.8% of single-drug opioid pain reliever deaths, with an overdose death rate significantly greater than that of other opioid pain relievers for both multidrug and single-drug deaths. The mechanism is in the label: the peak respiratory depressant effect occurs later and persists longer than the peak analgesic effect, and terminal half-life ranges from 8 to 59 hours across studies, so a patient titrating by feel accumulates. CDC concluded that methadone should not be used for mild pain, acute pain, breakthrough pain or on an as-needed basis, and that for chronic non-cancer pain it should not be considered a drug of first choice by prescribers or insurers. That last clause names the actual driver: methadone was being selected on formularies because it was cheap.
Source
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal Wkly Rep 2012;61(26):493-497
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
It blocks a cardiac potassium channel, and the label says so in a box
In plain words
Methadone lengthens the heart’s electrical recovery and can trigger a lethal rhythm. The case series that established this reported seventeen patients with an average corrected QT of 615 milliseconds — well over the usual danger threshold.
What was measured
Corrected QT interval and daily methadone dose in 17 patients who developed torsades de pointes
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Krantz and colleagues reported a retrospective case series of 17 methadone-treated patients from United States maintenance programmes and a Canadian pain centre who developed torsades de pointes. Mean daily methadone dose was 397 ± 283 mg and mean corrected QT interval was 615 ± 77 ms. Fourteen had a predisposing risk factor for arrhythmia, 14 received a defibrillator or pacemaker, and all 17 survived. The paper opens by noting that a methadone derivative, levacetylmethadol, had already been withdrawn from the European market after association with torsades. The current methadone label carries this as a boxed warning: QT interval prolongation and serious arrhythmia have occurred during treatment, most cases involving patients treated for pain with large multiple daily doses, although cases have been reported at doses commonly used for maintenance treatment of opioid addiction. Mechanistically the racemate’s S-enantiomer is the more potent blocker of the hERG potassium channel while the R-enantiomer carries the opioid effect, so the cardiac liability travels with a component that is not doing the therapeutic work.
Source
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med 2002;137(6):501-504; methadone hydrochloride United States prescribing information, boxed warning and Warnings and Precautions 5.3
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
The NMDA story is on the label, and the label says its value is unknown
In plain words
Methadone is often described as uniquely useful in nerve pain because it also blocks a second receptor called NMDA. The prescribing information states that some data indicate it does, and that what that contributes to the drug’s effect is unknown.
What was measured
That NMDA receptor antagonism gives methadone a clinical advantage in neuropathic or opioid-tolerant pain — a mechanism the label acknowledges and whose contribution to efficacy it states is unknown
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 12.1 of the methadone label reads: "Methadone hydrochloride is a mu-agonist; a synthetic opioid with multiple actions qualitatively similar to those of morphine... Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown." The clinical claim built on that sentence — that methadone succeeds in neuropathic pain, or in opioid-tolerant patients, where other opioids fail, because of NMDA blockade — is a mechanism-to-outcome inference the regulator declines to make. It also sits awkwardly with the enantiomer picture: the NMDA antagonism is generally attributed to S-methadone, the same enantiomer that carries most of the hERG liability and little of the opioid agonism. Whether the marketed racemate delivers enough NMDA blockade at clinical concentrations to matter is the question, and the label’s position is that it is unanswered.
Source
Methadone hydrochloride United States prescribing information, Clinical Pharmacology 12.1
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
A half-life the label cannot give a single number for
In plain words
The prescribing information reports that methadone’s terminal half-life ranged from eight to fifty-nine hours across published studies, and its clearance from 1.4 to 126 litres per hour. That is a ninety-fold spread in clearance for a drug with a narrow safety margin.
What was measured
Reported range of apparent plasma clearance (1.4 to 126 L/h) and terminal half-life (8 to 59 hours) across published multiple-dose studies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label states that after multiple-dose administration, published reports put apparent plasma clearance between 1.4 and 126 L/h and terminal half-life between 8 and 59 hours in different studies. It adds that methadone is a base with pKa 9.2 so urinary pH alters its plasma disposition, and that it is lipophilic enough to persist in the liver and other tissues, with slow release from those tissues potentially prolonging its action despite low plasma concentrations. Hepatic N-demethylation runs through five cytochrome P450 isoforms — CYP3A4, CYP2B6, CYP2C19, CYP2C9 and CYP2D6 — each with its own inhibitors and inducers, which is why the boxed warning names all five. The practical consequence is that steady state is reached at a time nobody can predict for an individual patient, that the peak respiratory depressant effect arrives after the peak analgesic effect, and that a dose which felt too weak on the first day may be lethal on the fourth. This is a pharmacokinetic failure mode rather than a trial failure, and it is the mechanism behind the mortality figures on this page.
Source
Methadone hydrochloride United States prescribing information, Clinical Pharmacology 12.3 and boxed warning
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim

How many documents were read

  • 36 documents were read for this substance.

    RNAWiki source record

Where else this substance is registered

FDA substance identifier (UNII)
229809935B
CAS registry number
76-99-3
PubChem compound
4095
RxNorm concept
218337

Checks this page had to pass

  • Passed

    Identity resolved

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  • 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 unclearRead 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.

What the approval register records

  • 34 approved applications cover products containing this substance. The earliest was NDA021624, approved 19470813 to MYLAN INSTITUTIONAL.

    Drugs@FDA application register · NDA021624 · read 2026-08-29

  • Marketing status on the register: discontinued and prescription.

    Drugs@FDA application register · NDA021624 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 19730314.

    FDA National Drug Code directory · 72865-120 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

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.
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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 long-acting mu-agonist that in 11 randomised trials and 1,969 participants beat non-pharmacological treatment on retention and heroin use (RR 0.66, 95% CI 0.56 to 0.78) but not on mortality (RR 0.48, 95% CI 0.10 to 2.39) or crime — while 19 cohorts following 122,885 methadone patients found all-cause mortality of 11.3 per 1,000 person-years in treatment against 36.1 out of it — and whose terminal half-life its own label reports as ranging from 8 to 59 hours across studies, with a boxed warning for torsades de pointes.

Recorded evidence blocks (10)

On the Methadone label: indicated for what?


"Methadone hydrochloride tablets for oral suspension contain methadone, an opioid agonist indicated for the: Detoxification treatment of opioid addiction (heroin or other morphine-like drugs). Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and…": indications and usage on Methadone's label. DailyMed label · 544483e6-6f9d-4371-9e93-313e54e0ea05 · 2026-08-04

175 registered trials of Methadone — at which phases?


Registered studies posting no result
134 of 175

175 registered studies of Methadone: 53 phase4, 39 phase3, 34 phase1, 26 phase2, 17 na, 10 na or unstated, 4 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01

1670 with a PubMed record

Show the evidence
  • phase4
    53
  • phase3
    39
  • phase1
    34
  • phase2
    26
  • na
    17
  • na or unstated
    10
9 more recorded rows
  • early phase1
    4
  • completed
    104
  • terminated
    22
  • recruiting
    21
  • unknown
    13
  • withdrawn
    8
  • active not recruiting
    3
  • not yet recruiting
    3
  • enrolling by invitation
    1

recorded 2026-09-01 · last checked 2026-09-04

30 of Methadone's trials stopped: accrual/recruitment, funding/business, sponsor decision unspecified, other?


accrual/recruitment (15), funding/business (1), sponsor decision unspecified (1) and other (13): Methadone's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01

"Study terminated due to halt in funding; may resume recruiting in future"; 30 of 175 registered studies

Show the evidence

Trial

  • NCT00142727
    terminated; "Study terminated due to halt in funding; may resume recruiting in future"
  • NCT00279565
    terminated; "The trial was terminated because of deviations from the protocol."
  • NCT00558870
    terminated; "Low Accrual."
  • NCT00573937
    terminated; "Slow accrual."
  • NCT00634010
    terminated; "Slow Accrual"
  • NCT00723918
    withdrawn; "Withdrawal of pharmaceutical support from Novartis - no participants randomized"
14 further recorded trials
  • NCT00726830
    terminated; "Low Accrual."
  • NCT00863057
    terminated; "Due to slow rate of enrollment, which compromised the ability to meet study objectives in a timely manner."
  • NCT00930332
    terminated; "Poor accrual"
  • NCT01125059
    withdrawn; "Unable to fulfill recruitment"
  • NCT01205516
    terminated; "Funding agency withdrew funding due to slow recruitment"
  • NCT01430182
    terminated; "Shortages of study drug, difficulty enrolling patients"
  • NCT01677650
    withdrawn; "Investigator moved to new institution"
  • NCT02025855
    terminated; "PI no longer practicing at study institution."
  • NCT02252432
    terminated; "No enough recruitments, very slow enrollment over the years"
  • NCT02698098
    terminated; "1\) Policy change affecting C\&Cs; 2) interm analysis revealing overt differences"
  • NCT02747875
    terminated; "Drug Shortage"
  • NCT02989597
    terminated; "Due to personnel loss and logistical issues the study was unable to be completed as planned."
  • NCT03134703
    terminated; "Poor recruitment"
  • NCT03908944
    withdrawn; "PI- Dr. Jellish passed away. The study was terminated with the IRB"

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Methadone used Methadone HCl Inject 10 mg/ml (will require dilution) — over how long?


studies of Methadone used the recorded amount. ClinicalTrials.gov · 2026-09-01

5 recorded entries; human; IV, oral; also "Methadone HCl Inject 10 mg/ml (will require dilution)", "0.25mg/kg IV of racemic methadone", "Eptadone (1mg/ml) oral solution"

Show the evidence

human

  • NCT00715988
    Methadone HCl Inject 10 mg/ml (will require dilution)
  • NCT01205256
    IV; 0.25mg/kg IV of racemic methadone
  • NCT01836328
    oral; Eptadone (1mg/ml) oral solution
  • NCT05459402
    Methadone (100% dose)
  • NCT05459402
    Methadone (50% dose)

recorded 2026-09-01 · last checked 2026-09-04

Methadone's half-life is 8 to 59 hours — which schedules were studied?


8 to 59 hours, the half-life Methadone's label states: "Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.4 and 126 L/h, and the terminal half-life (T 1/2 ) was highly variable and ranged between 8 to 59 hours in different studies." DailyMed label · 544483e6-6f9d-4371-9e93-313e54e0ea05 · 2026-08-04

tmax 1 to 7.5 hours; bioavailability 36 to 100 %.

Show the evidence
  • half life pharmacokinetics
    8 to 59 hours; Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.4 and 126 L/h, and the terminal half-life (T 1/2 ) was highly variable and ranged between 8 to 59 hours in different studies.
  • tmax pharmacokinetics
    1 to 7.5 hours; Absorption Following oral administration the bioavailability of methadone ranges between 36 to 100% and peak plasma concentrations are achieved between 1 to 7.5 hours.
  • bioavailability pharmacokinetics
    36 to 100 %; Absorption Following oral administration the bioavailability of methadone ranges between 36 to 100% and peak plasma concentrations are achieved between 1 to 7.5 hours.
  • metabolism pharmacokinetics
    Elimination Metabolism : Methadone is primarily metabolized by N-demethylation to an inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene(EDDP).

recorded 2026-08-04 · last checked 2026-09-04

Which 68 trials of Methadone posted no result?


Posted no result
68 of 68 completed trials
Registrations
NCT00000788, NCT00000200, NCT00000800, NCT00000311, NCT00000906 and NCT00356083, and 62 more
Completion dates
oldest 1994-06; newest 2023-12-31
Show the evidence

Trial

  • NCT00000788
    1994-06
  • NCT00000200
    1998-01
  • NCT00000800
    1998-10
  • NCT00000311
    1999-02
  • NCT00000906
    2000-09
  • NCT00356083
    2005-03
14 further recorded trials
  • NCT00249587
    2005-09
  • NCT00000273
    2005-11
  • NCT00310934
    2006-03
  • NCT00292123
    2006-08
  • NCT00125294
    2007-01
  • NCT00268814
    2007-12
  • NCT00367302
    2008-01
  • NCT00204243
    2008-12
  • NCT00175357
    2009-04
  • NCT00184496
    2009-09
  • NCT00933283
    2009-12
  • NCT00915564
    2010-01
  • NCT01205256
    2010-04
  • NCT01099748
    2010-06

At the median, Methadone's trials enrolled 54 people — anything larger?


Median enrolment
54
Largest enrolment
27034
Registered trials counted
175

What do 4257 spontaneous reports say about Methadone — 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.

Methadone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4257 reaction mentions were counted: drug withdrawal syndrome neonatal 1034; toxicity to various agents 538; drug abuse 484; electrocardiogram qt prolonged 461. FAERS via Open Targets · CHEMBL1200825 · 2026-06-24

Show the evidence
  • drug withdrawal syndrome neonatal
    1034
  • toxicity to various agents
    538
  • drug abuse
    484
  • electrocardiogram qt prolonged
    461
  • somnolence
    351
  • drug interaction
    330
4 more recorded rows
  • coma
    324
  • torsade de pointes
    281
  • respiratory depression
    228
  • drug withdrawal syndrome
    226

recorded 2026-06-24 · last checked 2026-09-04

Which 10 reactions does Methadone's label not list?


coma, drug abuse and drug interaction and 7 more reported for Methadone, absent from its label. FAERS via Open Targets · CHEMBL1200825 · 2026-06-24

2 label terms; 10 reported and unlisted; 544483e6-6f9d-4371-9e93-313e54e0ea05

Show the evidence
  • coma
    count not stated
  • drug abuse
    count not stated
  • drug interaction
    count not stated
  • drug withdrawal syndrome
    count not stated
  • drug withdrawal syndrome neonatal
    count not stated
  • electrocardiogram qt prolonged
    count not stated
4 more recorded rows
  • respiratory depression
    count not stated
  • somnolence
    count not stated
  • torsade de pointes
    count not stated
  • toxicity to various agents
    count not stated

recorded 2026-06-24 · last checked 2026-09-04

Methadone and CYP3A4, CYP2B6 and CYP2C9: shared by which compounds?


CYP3A4, CYP2B6 and CYP2C9 appear in Methadone's recorded interaction sentences, 8 in all. DailyMed label · 544483e6-6f9d-4371-9e93-313e54e0ea05 · 2026-08-04

CYP2B6, CYP2B6, CYP2C19, CYP2C19, CYP2C9, CYP2C9; 9 shared nodes; drug_interactions

Show the evidence

Interaction statement

  • drug_interactions
    Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6.
  • drug_interactions
    The concomitant use of methadone hydrochloride tablets for oral suspension and CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors can increase the plasma concentration of methadone, resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone hydrochloride tablets for oral suspension is achieved.
  • drug_interactions
    After stopping a CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitor, as the effects of the inhibitor decline, the methadone plasma concentration can decrease [see Clinical Pharmacology ( 12.3 )] , resulting in decreased opioid efficacy or withdrawal symptoms in patients physically dependent on methadone.
  • drug_interactions
    If a CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitor is discontinued, follow patients for signs of opioid withdrawal and consider increasing the methadone hydrochloride tablets for oral suspension dosage until stable drug effects are achieved.
  • drug_interactions
    Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone hydrochloride tablets for oral suspension and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent on methadone.
  • drug_interactions
    After stopping a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer, as the effects of the inducer decline, the methadone plasma concentration can increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression, sedation, or death.
2 more recorded rows
  • Interaction statement drug_interactions
    If a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer is discontinued, consider methadone hydrochloride tablets for oral suspension dosage reduction and monitor for signs of respiratory depression and sedation.
  • Interaction statement drug_interactions
    Paradoxical Effects of Antiretroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranavir+ritonavir, has resulted in increased clearance or decreased plasma…

CYP2B6

  • FINGOLIMOD LAURYL SULFATE, TAFAMIDIS MEGLUMINE, Arimoclomol, Sofpironium, Bupropion, Golodirsen, Tinidazole, Naldemedine
  • FINGOLIMOD LAURYL SULFATE, TAFAMIDIS MEGLUMINE, Arimoclomol, Sofpironium, Bupropion, Golodirsen, Tinidazole, Naldemedine

CYP2C19

  • FINGOLIMOD LAURYL SULFATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Rasagiline, Golodirsen, Naldemedine, Etravirine
  • FINGOLIMOD LAURYL SULFATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Rasagiline, Golodirsen, Naldemedine, Etravirine

CYP2C9

  • FINGOLIMOD LAURYL SULFATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Rasagiline, Golodirsen, Tinidazole, Naldemedine
  • FINGOLIMOD LAURYL SULFATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Rasagiline, Golodirsen, Tinidazole, Naldemedine
  • CYP2D6
    FINGOLIMOD LAURYL SULFATE, Darunavir Propylene Glycolate, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Rasagiline, Sofpironium, Fluoxetine

CYP3A4

  • FINGOLIMOD LAURYL SULFATE, ERYTHROMYCIN LACTOBIONATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Beclometasone, Rasagiline, Sofpironium
  • FINGOLIMOD LAURYL SULFATE, ERYTHROMYCIN LACTOBIONATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Beclometasone, Rasagiline, Sofpironium

recorded 2026-08-04 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL1200825
PubChem CID
20055402
CAS number
15284-15-8
RxCUI
218337
InChIKey
USSIQXCVUWKGNF-UHFFFAOYSA-N
Also called
METHADONE HYDROCHLORIDE, Butalgin, Dolophine, Fenadone, Heptadon, Mecodin, Amidone, Diaminon, Dl-methadone, Dolophin, Heptadone, Metadona
Salt form
Adanon hydrochloride, Dolofin hydrochloride, Dolophine hydrochloride, Ketalgin hydrochloride, Methadone hcl, Methadone hydrochloride cii, Methadone hydrochloride intensol, Phenadone hydrochloride, Methadose / Dolophine / Methadone Hydrochloride Intensol
Development code
AN-148, NSC-19600, IDS-NM-002
Trade name
Eptadone, Martindale, Methadose, Metharose, Methex, Physeptone, Pinadone, Synastone, Westadone, Methadone Hydrocloride Dye-Free, Sugar-Free, Unflavored, DISKETS, METHADOSE DISPERSIBLE
Sources (6)

Sources

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

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • 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: 6 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
  • no raw internal fields: enforced by the copy-contract test over the rendered page

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