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Long-acting synthetic opioid Pregnancy: A careful risk/benefit assessment should be made before administration to pregnant women because of possible adverse effects on the foetus and neonate including respiratory depression, low birth weight, neonatal withdrawal syndrome and increased rate of stillbirths. Regular use during pregnancy may cause drug dependence in the foetus with neonatal withdrawal symptoms. Methadone should not be used in labour. Excreted in breast milk at low levels; if breastfeeding is considered the dose should be as low as possible and the infant monitored for sedation and breathing difficulties.

Methadone hydrochloride

Brand names: Physeptone

Methadone is a long-acting synthetic opioid agonist used in opioid substitution therapy for opioid dependence and also as an analgesic.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Opioid addiction: initially 10-20 mg per day, increasing by 10-20 mg per day until there are no signs of withdrawal or intoxication; usual dose 40-60 mg per day
Route: Oral (for oral administration only)
Frequency: Once daily (addiction); every 6 to 8 hours (pain)
Max: Not stated in SPC section 4.2
Addiction: dose is adjusted according to the degree of dependence, with the aim of gradual reduction. Pain (adults): usual single dose 5 to 10 mg orally; usual initial dose 5 to 10 mg 6 to 8 hourly, later adjusted to the degree of pain relief obtained; owing to its long plasma half-life, caution with repeated dosage should be observed in the very ill or elderly. Elderly: in the elderly or ill patients repeated doses should only be given with extreme caution. Children: not recommended / not suitable for children (SPC states serious risk of toxicity); US labelling states safety and effectiveness in patients below 18 years have not been established. Before initiating treatment a treatment strategy including treatment duration and treatment goals should be agreed with the patient in accordance with pain management guidelines; there should be frequent contact between physician and patient to evaluate the need for continued treatment. When therapy is no longer required it may be advisable to taper the dose gradually to prevent withdrawal symptoms. In absence of adequate pain control, consider hyperalgesia, tolerance and progression of underlying disease.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Respiratory depression, obstructive airways disease (use during an acute asthma attack is not recommended)
  • Acute alcoholism
  • Concurrent administration with MAO inhibitors, including moclobemide, or within 2 weeks of discontinuation
  • Patients dependent on non-opioid drugs
  • Use during labour is not recommended (prolonged duration of action increases risk of neonatal depression)
  • Not suitable for children (serious risk of toxicity)
  • Hypersensitivity to the active substance or to any of the excipients
  • Raised intracranial pressure or head injury
  • Phaeochromocytoma
  • Risk of paralytic ileus (including drug-induced gastrointestinal hypotonia)

Side effects

  • Nausea and vomiting (very common)
  • Respiratory depression - the most serious adverse effect, may emerge during the stabilisation phase; apnoea, shock and cardiac arrest have occurred
  • Constipation (common)
  • Sedation, fatigue, drowsiness (common)
  • Blurred vision, miosis, dry eyes (common)
  • Prolonged QT interval and torsade de pointes, bradycardia, palpitations (rare) - especially with high doses

Interactions

  • MAO inhibitors including moclobemide - contraindicated concurrently or within 2 weeks of discontinuation (SPC section 4.3)
  • Alcohol - acute alcoholism is a contraindication (SPC section 4.3)
  • Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9 or CYP2D6 - can increase methadone plasma concentration, causing increased or prolonged opioid effects and possible fatal overdose; consider dosage reduction and monitor for respiratory depression and sedation (US labelling)
  • Stopping a CYP3A4, CYP2B6, CYP2C19, CYP2C9 or CYP2D6 inhibitor - methadone plasma concentration can decrease, causing reduced efficacy or withdrawal in physically dependent patients (US labelling)

Clinical monograph

How it works

It is a full agonist at the mu-opioid receptor with a long half-life, providing sustained suppression of withdrawal and craving, and additionally has NMDA-receptor antagonist activity.

Prescribing in practice

  • Methadone carries a high risk of fatal respiratory depression, particularly during initiation, dose titration and in opioid-naive individuals, and overdose risk is increased by concomitant alcohol, benzodiazepines or other CNS depressants.
  • It prolongs the QT interval and can cause torsade de pointes, so an ECG and review of cardiac risk factors and interacting medicines is advised.
  • Supervised consumption is commonly required at the start of treatment because of accumulation risk from its long half-life.

Monitoring

Monitor for sedation and respiratory depression during titration, assess QT interval where cardiac risk factors exist, and review treatment response regularly.

Counselling the patient

  • Do not drink alcohol or take other sedating medicines with methadone, as the combination can be fatal.
  • Keep this medicine locked away and out of reach of children, as even one dose can be fatal to a child.
  • Do not take extra doses if you feel a dose is not holding you; contact your service instead.

Evidence & guidelines

Methadone maintenance is an established evidence-based treatment for opioid dependence supported by NICE guidance, and the MHRA has highlighted the risks of QT prolongation and respiratory depression.

Reference: NICE CG52; PHE/UK clinical guidelines on drug misuse; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

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