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[Pharmacology](https://durgical.com/en/pharmacology/) · [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

# Methadone

A long-acting opioid for opioid use disorder and chronic pain. It accumulates, prolongs the QT interval and its respiratory depression peaks late.

Updated 2026-11-01

- Class: [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)
- Receptor: μ-opioid receptor
- ATC code: N07BC02
- WHO Model List of Essential Medicines

## ⚠ High-alert medication

An error with this medicine can cause serious harm: double checks and protocols are used.

◎**μ-opioid receptor**Methadone

ⓘ The figure shows morphine in the μ receptor; methadone, from another chemical family, occupies the same site. There is no structure of methadone in the receptor.

**Target in 3D:** μ-opioid receptor. PDB structure 8EF6 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8EF6) · Drag to rotate · pinch to zoom

## Mechanism of action

Methadone is a synthetic, orally active, long-acting μ agonist; its pain relief comes almost entirely from the levorotatory isomer. Its long, variable half-life avoids the peaks and troughs of short-acting opioids, so one daily dose suppresses withdrawal for a long time; for the same reason it accumulates over the first days.

- Activates the μ receptor in a sustained way
- Steady blood levels: no peaks of euphoria or troughs of withdrawal
- Suppresses craving and withdrawal in opioid use disorder
- Builds up in tissues: respiratory depression may come late

## Pharmacokinetics

**Absorption**
Effective by mouth.

**Metabolism**
Liver, by N-demethylation through several CYPs (3A4, 2B6, 2C19, 2C9, 2D6): many interactions.

**Half-life**
Long and highly variable, about 15 to 40 hours; it accumulates over the first days.

## Indications

- Detoxification and maintenance treatment of opioid use disorder, with medical and social support
- Severe chronic pain that needs a continuous opioid

## Adverse effects

### Common

- Dizziness and lightheadedness
- Sedation
- Nausea and vomiting
- Sweating
- Constipation

### Serious (rare, important)

- Life-threatening respiratory depression, above all at the start or after a dose increase
- Addiction, abuse and misuse, with risk of overdose and death
- Neonatal opioid withdrawal syndrome with prolonged use in pregnancy
- Adrenal insufficiency with prolonged use
- Severe hypotension
- QT prolongation and torsades de pointes
- Overdose in the first days from accumulation

## Contraindications

- Significant respiratory depression
- Acute or severe bronchial asthma without monitoring or resuscitation equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to the drug

## Key interactions

**Inhibitors of CYP3A4, 2B6, 2C19, 2C9 or 2D6, or stopping inducers**
Can raise methadone levels and cause a fatal overdose.

**Drugs that prolong the QT interval**
Add to the risk of serious arrhythmia.

**Benzodiazepines, alcohol and other central nervous system depressants**
Add up to profound sedation, respiratory depression, coma and death.

**CYP3A4, 2B6, 2C19 or 2C9 inducers, or stopping inhibitors**
Lower methadone levels and can precipitate withdrawal.

## What is monitored

- ECG (QT) at the start and when the dose changes in patients at risk
- Respiratory rate and sedation, above all in the first days
- A complete medicine list because of interactions

## Administration and safety

- Its peak effect on breathing comes later and lasts longer than its pain relief: the risk is highest in the first week.
- For opioid use disorder it is dispensed in licensed programmes, often with supervised dosing.
- Cross-tolerance with other opioids is incomplete: switching to methadone from another opioid calls for great caution.
- Controlled medicine: the order is verified, every dose recorded and leftovers kept secure.

## Nursing care

- Before each dose: respiratory rate, oxygen saturation and sedation level; hold the dose and report excessive sedation or slow breathing.
- Keep naloxone at hand and teach the family to recognise an overdose.
- Watch sedation and breathing more closely in the first days: methadone accumulates.
- Ask about palpitations, fainting or marked dizziness (long QT).
- Check every new medicine for CYP interactions.

## Pregnancy and breastfeeding

It is used in pregnancy to treat opioid use disorder; the newborn may develop neonatal opioid withdrawal syndrome, which is expected and treatable.

## Memory aid

METHADONE = «METHodical and DONE slowly»: it arrives slowly and leaves slowly. It accumulates, lengthens the QT, and breathing falls after the pain has gone.

## Test yourself

Think of the answer, then tap the question to see it.

## Why do most methadone deaths happen in the first days of treatment?

Its half-life is long and variable: it accumulates in tissues, and its respiratory depressant effect peaks later and lasts longer than the pain relief.

## Which cardiac effect of methadone calls for ECG monitoring?

QT prolongation, with a risk of torsades de pointes.

## Why is methadone useful for maintenance treatment of opioid use disorder?

It is orally active and long-acting: steady levels suppress withdrawal and craving without the euphoric peaks of short-acting opioids.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/methadone/)

## Related drugs

- [Buprenorphine](https://durgical.com/en/pharmacology/buprenorphine/)
- [Naltrexone](https://durgical.com/en/pharmacology/naltrexone/)
- [Morphine](https://durgical.com/en/pharmacology/morphine/)

[← Back to the class: Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Methadone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682134.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [METHADONE HYDROCHLORIDE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c54baaee-8ea4-45f5-a5c8-bb84cf86832f) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 23 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N07BC02) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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