Methadone
Pronunciation: METH-uh-done.
- Generic name
- methadone hydrochloride
- Drug class
- Full mu-opioid receptor agonist (synthetic opioid); Schedule II/Schedule 8/Controlled Drug
- Form
- Tablet, oral solution/concentrate, and (in some markets) injectable solution
- Route
- Oral (tablet, oral solution/concentrate); also available as solution for injection in some markets (e.g. UK Physeptone) for specialist use
- Legal status
- Prescription-only, controlled substance in every market reviewed; opioid-use-disorder treatment dispensed only through certified/registered opioid treatment programs (42 CFR Part 8 in the United States)
Supply Rules Vary
Trade names by country: United States · United Kingdom · Canada · Australia · New Zealand
Australia: Biodone Forte (5), Physeptone (5) · Full directory
Boxed warning: Life-Threatening Respiratory Depression, Life-Threatening QT Prolongation, Accidental Ingestion, Abuse Potential, Interactions with Drugs Affecting Cytochrome P450 Isoenzymes, and Treatment for Opioid Addiction
Life-Threatening Respiratory Depression: Respiratory depression, including fatal cases, have been reported during initiation and conversion of patients to methadone, and even when the drug has been used as recommended and not misused or abused. Proper dosing and titration are essential and METHADOSE should only be prescribed by healthcare professionals who are knowledgeable in the use of methadone for detoxification and maintenance treatment of opioid addiction. Monitor for respiratory depression, especially during initiation of METHADOSE or following a dose increase. The peak respiratory depressant effect of methadone occurs later, and persists longer than the peak pharmacologic effect, especially during the initial dosing period. Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death. Reserve concomitant prescribing of benzodiazepines or other CNS depressants in patients in methadone treatment to those for whom alternatives to benzodiazepines or other CNS depressants are inadequate. Follow patients for signs and symptoms of respiratory depression and sedation. If the patient is visibly sedated, evaluate the cause of sedation and consider delaying or omitting daily methadone dosing. Life-Threatening QT Prolongation: QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction for changes in cardiac rhythm during initiation and titration of METHADOSE. Accidental Ingestion: Accidental ingestion of METHADOSE, especially by children, can result in fatal overdose of methadone. Misuse, Abuse, and Diversion of Opioids: METHADOSE contains methadone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. In addition, discontinuation of concomitantly used cytochrome P450 3A4, 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dosage reduction with any changes of concomitant medications that can result in an increase in methadone levels. Conditions for Distribution and Use of Methadone Products for the Treatment of Opioid Addiction: For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration. (1) (2)
What methadone hydrochloride is and how it works
Methadone is a long-acting, full mu-opioid receptor agonist. It has two genuinely distinct real uses: managing severe, chronic pain that requires daily, around-the-clock, long-term opioid treatment when other options are inadequate; and treating opioid addiction (to heroin or other morphine-like drugs) as part of a supervised detoxification or maintenance program, alongside social and medical support. (1) (2)
Methadone carries a serious, genuine, multi-part FDA boxed warning -- the strongest safety warning the FDA issues -- covering life-threatening respiratory depression, life-threatening heart-rhythm changes (QT prolongation and torsades de pointes), fatal accidental ingestion risk (especially in children), abuse potential, and dangerous interactions with many other medicines. Its effects build up more slowly and last much longer than most other opioids, which is exactly why the highest overdose risk happens when treatment is first started, when the dose is increased, or when someone is switched onto methadone from another opioid. When used to treat opioid addiction, methadone is dispensed only through a certified opioid treatment program, never as an ordinary retail prescription for that purpose. All dosing, and any change in dose, must be decided and supervised by the clinician or opioid treatment program managing your care -- never adjusted by yourself.
Mechanism of action: how methadone hydrochloride works
Methadone is a synthetic full mu-opioid receptor agonist with pharmacologic properties qualitatively similar to morphine. It has a long and highly variable elimination half-life, meaning its peak respiratory-depressant effect occurs later and persists longer than its peak analgesic/pharmacologic effect -- particularly during the initial dosing period -- and repeated dosing leads to hepatic accumulation that prolongs potential toxicity. Steady-state plasma concentrations are not reached until 3-5 days after initiation. Methadone also inhibits cardiac potassium (hERG) channels, prolonging the QT interval, an effect confirmed in both in vitro and in vivo studies. (1) (6)
What methadone hydrochloride is used for
Management of severe, chronic pain
Used for pain severe enough to require daily, around-the-clock, long-term opioid treatment, for which alternative treatment options (including immediate-release opioids) are inadequate. (2)
Detoxification treatment of opioid addiction
Used for supervised detoxification from opioid addiction (heroin or other morphine-like drugs), dispensed only by a certified opioid treatment program. (1) (6)
Maintenance treatment of opioid addiction
Used for longer-term maintenance treatment of opioid addiction, in conjunction with appropriate social and medical services, dispensed only by a certified opioid treatment program. (1) (6)
Before taking methadone hydrochloride
Do not take / not appropriate for
- Do not take if you have significant respiratory depression, or acute/severe bronchial asthma in an unmonitored setting or without resuscitation equipment available. (all countries) (1) (6)
- Do not take if you have a known or suspected gastrointestinal obstruction, including paralytic ileus. (all countries) (1)
- Do not take if you have a known hypersensitivity (including anaphylaxis) to methadone or any ingredient in the product. (all countries) (1)
- Do not take if you are taking, or have taken within the last 14 days, a monoamine oxidase inhibitor (MAOI). (New Zealand (and reflected as a caution elsewhere)) (6)
- Do not take if you have ulcerative colitis (risk of toxic colonic dilation/spasm), severe hepatic impairment (risk of hepatic encephalopathy), or acute alcoholism, head injury, and raised intracranial pressure. (New Zealand) (6)
Tell your clinician about
- Whether you have any heart problems, an irregular heartbeat, or a family history of QT prolongation, since methadone can affect heart rhythm.
- All other medicines and supplements you take, including benzodiazepines, sedatives, other opioids, alcohol, or any medicine that affects liver enzymes (CYP3A4, 2B6, 2C19, 2C9, or 2D6) -- these interactions can be genuinely dangerous.
- Whether you are pregnant, could become pregnant, or are breastfeeding.
- Whether you have any history of seizures, adrenal problems, low blood pressure, head injury, or increased pressure in the skull.
- Whether you are currently taking any other opioid, and at what dose, since switching to methadone requires careful, individualised, clinician-directed dosing -- never a standard conversion applied without close supervision.
How to take methadone hydrochloride
- Take methadone exactly as prescribed by your clinician or opioid treatment program -- never adjust your own dose, frequency, or route of administration.
- For opioid-use-disorder treatment, methadone is dispensed only through a certified/registered opioid treatment program, with the first doses typically given under direct supervision.
- Because methadone builds up in the body more slowly than most opioids, its full effect -- including its respiratory-depressant effect -- can take several days to become apparent; do not assume a dose is 'not working' and take more without your clinician's guidance.
- If you are being switched to methadone from another opioid, this conversion must be done gradually and individually by your prescriber -- standard opioid-conversion tables are not considered accurate for methadone and following one yourself could be fatal.
- Ask your prescriber about having an opioid overdose reversal medicine (such as naloxone) available, and make sure household members know how to recognize an overdose and use it.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5) (6) (7)
Missed dose
Contact your prescriber or opioid treatment program if you miss a dose -- do not take an extra dose to make up for it, and do not decide on your own how to adjust the next dose. Missing doses, especially several in a row, can change your tolerance, which affects how safe your usual dose is.
Overdose
Call 911 or get emergency medical help immediately for any known or suspected methadone overdose, even if you are not sure. Signs can include severe drowsiness, slow or stopped breathing, pinpoint pupils, or unresponsiveness. If an opioid overdose reversal medicine (such as naloxone) is available, it should be given while waiting for emergency help -- but emergency medical care is still required, since methadone's effects last much longer than naloxone's and repeated doses or ongoing monitoring may be needed. (1) (6)
Side effects
Side effects and their urgency vary; report severe, persistent, or concerning symptoms.
Lightheadedness, dizziness, and sedation.
What to notice: Lightheadedness, dizziness, and sedation.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Nausea, vomiting, and sweating.
What to notice: Nausea, vomiting, and sweating.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Constipation, dry mouth, and headache.
What to notice: Constipation, dry mouth, and headache.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Serious warnings
Life-threatening respiratory depression — boxed_warning
Symptoms: Slow, shallow, or stopped breathing; extreme drowsiness; unresponsiveness. Risk is greatest at treatment initiation, after a dose increase, or when switching from another opioid.
Action: Call 911 or get emergency medical help immediately. Give an opioid overdose reversal medicine (such as naloxone) if available while waiting for help. (1)
Life-threatening QT interval prolongation and torsades de pointes (abnormal heart rhythm) — boxed_warning
Symptoms: Fainting, palpitations, dizziness, or a racing/irregular heartbeat.
Action: Seek urgent medical attention. Your clinician may recommend an ECG (heart tracing) before starting treatment, at dose stabilisation, and before/after certain dose increases, particularly if you have heart risk factors. (1) (3)
Accidental ingestion by children or others — boxed_warning
Symptoms: Not applicable to the patient directly -- this is a household safety risk. Even a single dose can be fatal to a child.
Action: Store methadone in a locked, child-resistant container out of reach of children and anyone else it was not prescribed for. If accidental ingestion is suspected, call emergency services immediately. (1) (6)
Dangerous interaction with benzodiazepines, alcohol, or other CNS depressants — boxed_warning
Symptoms: Profound sedation, slowed or stopped breathing, confusion, or unresponsiveness when methadone is combined with these substances.
Action: Tell every prescriber about your methadone treatment before starting any new sedative, sleep, anxiety, or muscle-relaxant medicine, and never combine methadone with alcohol or unprescribed sedatives. Seek emergency help for any of the symptoms above. (1)
Serotonin syndrome (with other serotonergic medicines) — high caution
Symptoms: Agitation, hallucinations, confusion, fast heart rate, unstable blood pressure, fever, muscle twitching or stiffness, loss of coordination, nausea, vomiting, or diarrhoea.
Action: Seek prompt medical attention. Tell your clinician about all other medicines, including antidepressants, that affect serotonin. (1) (6)
Neonatal opioid withdrawal syndrome (if used during pregnancy) — high caution
Symptoms: In the newborn: irritability, poor feeding, tremors, or breathing problems appearing after birth.
Action: This is an expected, treatable risk of methadone use during pregnancy, and healthcare professionals will monitor the newborn for it. Discuss the risks and benefits of continuing or adjusting treatment during pregnancy with your prescriber -- this must be balanced against the real risks of untreated opioid addiction, and should never be a reason to stop treatment abruptly without medical guidance. (1)
Severe hypotension (including fainting) — high caution
Symptoms: Feeling faint or dizzy, especially on standing, or fainting.
Action: Tell your clinician, particularly during treatment initiation or dose changes -- monitoring may be needed. (1)
Interactions
- Benzodiazepines and other CNS depressants (including alcohol, sedatives, muscle relaxants, and other opioids): increased risk of profound sedation, respiratory depression, coma, and death. Management of this combination should be individualised with your prescriber -- opioid-use-disorder treatment should not be automatically withheld because of it. (1)
- Medicines that inhibit CYP3A4, 2B6, 2C19, 2C9, or 2D6 enzymes (e.g. certain macrolide antibiotics, azole antifungals, some protease inhibitors, some SSRIs): can raise methadone levels and cause potentially fatal respiratory depression. Stopping a CYP inducer can have the same effect. (1)
- Other medicines that can prolong the QT interval (e.g. sotalol, amiodarone, flecainide, certain antipsychotics such as thioridazine): increased risk of dangerous heart-rhythm changes. (3)
- Serotonergic medicines (e.g. SSRIs, SNRIs, tricyclic antidepressants, triptans, tramadol, certain muscle relaxants, MAO inhibitors): increased risk of serotonin syndrome. (1)
- Mixed opioid agonist/antagonist or partial agonist medicines (e.g. pentazocine, nalbuphine, butorphanol, buprenorphine): may precipitate withdrawal symptoms in patients taking methadone. (1)
Pregnancy, breastfeeding, kidney/liver function, age
Pregnancy
Methadone clearance may increase during pregnancy, and dose or dosing interval may need adjustment by your clinician. Neonatal opioid withdrawal syndrome is an expected, treatable outcome of prolonged opioid use during pregnancy; healthcare professionals will observe and manage the newborn for this. The real risks of treatment must be weighed against the real risks of untreated opioid addiction, which is associated with poorer pregnancy outcomes -- this decision should always be made with your prescriber. (1) (2) (3) (4) (5) (6) (7)
Breastfeeding
Discuss breastfeeding with your clinician. Breastfed infants should be monitored for increased drowsiness and breathing difficulties. (1) (2) (3) (4) (5) (6) (7)
Children
The fatal dose of methadone in children may be as low as 10-20 mg. Methadone must be stored safely out of reach of children at all times because of this real, serious accidental-ingestion risk. (1) (2) (3) (4) (5) (6) (7)
Elderly
Methadone's long plasma half-life may lead to drug accumulation, particularly if kidney function is reduced. Confusion can occur more often in this age group, so careful monitoring is advised. (1) (2) (3) (4) (5) (6) (7)
Hepatic_impairment
Methadone is metabolised more slowly in patients with impaired liver function. Where not contraindicated (severe hepatic impairment is a contraindication in some markets because of the risk of hepatic encephalopathy), a lower dose may be used, guided by clinical response. (1) (2) (3) (4) (5) (6) (7)
Renal_impairment
Use with caution in patients with reduced kidney function, since accumulation may occur, particularly in combination with age-related changes. (1) (2) (3) (4) (5) (6) (7)
Source_ids
US-DAILYMED-METHADOSE-FDA-2025,NZ-MEDSAFE-BIODONE-DATASHEET-2026 (1) (2) (3) (4) (5) (6) (7)
Monitoring
Before starting
- Assessment of prior opioid tolerance and current opioid use, to guide individualised starting dose.
- Baseline ECG for patients with recognised risk factors for QT prolongation, a history of cardiac conduction abnormalities, or those taking other QT-affecting medications.
- Review of all other medicines, including benzodiazepines, sedatives, and any medicine affecting cytochrome P450 enzymes.
During treatment
- Close monitoring for respiratory depression and sedation, especially during initiation and after any dose increase.
- ECG monitoring at dose stabilisation for at-risk patients; ECG before dose titration above 100 mg/day and again about 7 days after that titration for patients without recognised cardiac risk factors (per the UK SPC).
- Ongoing review for signs of serotonin syndrome, adrenal insufficiency, severe hypotension, and hypoglycemia.
- Regular reassessment of continued need for any concomitant benzodiazepine or CNS depressant.
Storage
Store in a secure, child-resistant container out of reach of children and anyone else it was not prescribed for, since even one accidental dose can be fatal to a child. Follow your treatment program's specific storage and disposal instructions for any unused medicine.
Professional information
Clinician-facing context only, sourced from the current live US DailyMed label (METHADOSE, Reference ID 5715751), the UK EMC Physeptone SPC, the Health Canada Metadol Product Monograph, and the New Zealand Medsafe Biodone data sheet; verify against the current full label before prescribing.
United States
Indication: Opioid-use-disorder detoxification/maintenance
Dose summary: Initial single dose 20-30 mg (not exceeding 30 mg); first-day total ordinarily not exceeding 40 mg; maintenance stability most commonly 80-120 mg/day, individualised.
Renal context: No standardised renal dose-adjustment table provided; use with caution and individualise based on clinical response. (1)
United Kingdom
Indication: Pain management and opioid substitution treatment
Dose summary: ECG monitoring recommended before starting treatment and at dose stabilisation for at-risk patients; before dose titration above 100 mg/day and 7 days after for others.
Renal context: Not specified in the sources reviewed; individualise dosing and monitor closely. (3)
New Zealand
Indication: Opioid substitution treatment
Dose summary: Initial doses 15-35 mg/day, never exceeding 40 mg; maintenance stabilisation usually 60-120 mg/day.
Renal context: Use with caution in renal dysfunction. (6)
Hepatic guidance
Metabolised more slowly in hepatic impairment; use a lower dose where not contraindicated, guided by clinical response. Severe hepatic impairment is a contraindication in some markets due to the risk of precipitating hepatic encephalopathy.
Overdose note
Overdose is a medical emergency requiring immediate care; opioid overdose reversal agents (e.g. naloxone) may be used but methadone's long duration of action means repeated dosing or prolonged monitoring may be required even after reversal-agent administration. (1) (6)
Frequently asked questions
Why is methadone's overdose risk described as especially high when starting treatment or changing dose?
Methadone builds up in the body much more slowly, and stays in the body much longer, than its pain-relieving or craving-suppressing effect suggests. This means the peak respiratory-depressant (breathing-slowing) effect happens later and lasts longer than the peak effect you feel -- so a dose that seems fine on day one can become dangerous a few days later as it accumulates. This is exactly why the FDA's boxed warning identifies treatment initiation, dose increases, and switching from another opioid as the highest-risk periods, and why dosing must always be decided by an experienced prescriber or opioid treatment program, never adjusted by the patient. (1)
Can I get methadone for opioid use disorder from a regular pharmacy prescription?
No. In the United States, methadone used for detoxification or maintenance treatment of opioid addiction may only be dispensed through an Opioid Treatment Program certified under 42 CFR Part 8 -- not a standard retail pharmacy prescription. Equivalent certified/registered opioid substitution treatment frameworks apply in the other markets reviewed (United Kingdom, European Union, Canada, Australia, New Zealand). Methadone prescribed for pain management follows standard controlled-substance prescribing rules instead. (1)
Why might I need an ECG (heart tracing) while taking methadone?
Methadone can prolong the QT interval, a measure of the heart's electrical cycle, and in rare cases this has led to a dangerous irregular heart rhythm called torsades de pointes. Regulators recommend ECG monitoring tied to specific timing: before starting treatment and at dose stabilisation if you have heart-risk factors, and before increasing your dose above certain thresholds (100 mg/day per the UK label) and again about a week afterward if you do not have known risk factors. Your prescriber will tell you if and when an ECG is needed for you. (1) (3)
Is it safe to take methadone with sleeping pills, anti-anxiety medicines, or alcohol?
Combining methadone with benzodiazepines, other sedatives, or alcohol significantly increases the risk of profound sedation, slowed or stopped breathing, coma, and death -- this is part of the FDA's boxed warning. That said, opioid-use-disorder treatment should not be automatically denied to someone taking these medicines; instead, your prescriber will work with you to manage the combination safely, which may include adjusting or gradually stopping the other medicine rather than stopping methadone. (1)
Was there ever a safety problem with methadone oral liquid formulations in Europe?
Yes, a real, historical, and now-resolved one. In 2014, European regulators (via the EMA and CMDh) suspended methadone oral solutions containing a specific excipient -- high molecular weight povidone (K90) -- after it was found that when the oral solution was misused by injecting it intravenously, the povidone accumulated inside cells of vital organs and caused serious harm, including anaemia and pathological fractures, in people who injected it. This was specific to that excipient in oral solutions, not a general risk of methadone tablets or of methadone taken as directed; low molecular weight povidone tablets remained available with updated labelling emphasising oral-only use. (7)
What is the mechanism of action of methadone hydrochloride?
Methadone is a synthetic full mu-opioid receptor agonist with pharmacologic properties qualitatively similar to morphine. It has a long and highly variable elimination half-life, meaning its peak respiratory-depressant effect occurs later and persists longer than its peak analgesic/pharmacologic effect -- particularly during the initial dosing period -- and repeated dosing leads to hepatic accumulation that prolongs potential toxicity. Steady-state plasma concentrations are not reached until 3-5 days after initiation. Methadone also inhibits cardiac potassium (hERG) channels, prolonging the QT interval, an effect confirmed in both in vitro and in vivo studies. (1) (6)
References
- METHADOSE (methadone hydrochloride) oral concentrate, CII -- full prescribing information (Reference ID 5715751)U.S. Food and Drug Administration (via DailyMed) · United States · dated 2025-12-01 · accessed 2026-07-31 · source 1
- DOLOPHINE (methadone hydrochloride) tablets -- pain-management indication labelingU.S. Food and Drug Administration (via DailyMed) · United States · accessed 2026-07-31 · source 2
- Physeptone (methadone hydrochloride) tablets/oral solution/injection -- Summary of Product Characteristics (SmPC)UK Medicines and Healthcare products Regulatory Agency (via the electronic Medicines Compendium, emc) · United Kingdom · accessed 2026-07-31 · source 3
- METADOL / METADOL-D (methadone hydrochloride) -- Health Canada Product MonographHealth Canada · Canada · accessed 2026-07-31 · source 4
- BIODONE FORTE (ARTG 64800) and PHYSEPTONE (ARTG 76083 tablets, 159750 injection, 381325 liquid) -- methadone hydrochloride productsTherapeutic Goods Administration (TGA) · Australia · accessed 2026-07-31 · source 5
- Biodone / Biodone Forte / Biodone Extra Forte (methadone hydrochloride 2/5/10 mg/mL oral solution) -- New Zealand Data SheetNew Zealand Medicines and Medical Devices Safety Authority (Medsafe) · New Zealand · accessed 2026-07-31 · source 6
- Methadone medicinal products for oral use containing (high molecular weight) povidone -- referral outcomeEuropean Medicines Agency (EMA) / CMDh, Article 107i referral · European Union / EEA · dated 2014-07-23 · accessed 2026-07-31 · source 7
Brand names by country
Single-ingredient methadone hydrochloride names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.
Priority countries
United States
- Methadone Hydrocloride dye-free, sugar-free, unflavored10 mg/mL · bryant ranch prepack
- METHADOSE10 mg/mL · specgx llc
- DISKETS40 mg · hikma pharmaceuticals usa inc.
- METHADOSE DISPERSIBLE40 mg · specgx llc
United Kingdom
- Physeptone (3)current authorised prescription medicine · 5 mg tablets, 1 mg/mL oral solution, 10 mg/mL and 50 mg/mL injection · Martindale Pharma (an Ethypharm Group company)
Canada
- METADOL
- METADOL-D
- METHADOSE
Australia
New Zealand
- Biodone / Biodone Forte / Biodone Extra Forte (6)current authorised prescription medicine · 2 mg/mL, 5 mg/mL, 10 mg/mL · See current Medsafe data sheet
View brands in additional countries.
European Union
Eptadone (7)