Pharmacology · 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
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.
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
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.
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.
Related drugs
← Back to the class: 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 (MedlinePlus (U.S. National Library of Medicine), 2026); METHADONE HYDROCHLORIDE tablet (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 (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.