Methadone is a potent synthetic opioid agonist which is well absorbed orally and has a long, although variable, plasma half life. The effects of methadone are qualitatively similar to those of morphine and other opiates.

Methadone is effective in the treatment of heroin dependence as it:

  • substitutes for heroin, prevents the emergence of opioid withdrawal symptoms and reduces cravings for heroin;
  • is well absorbed orally but does not produce rapid intoxication;
  • has a long half life and is taken in a single daily dose;
  • binds to various body tissues and is very slowly released enabling the patient to be maintained in a stable state; and
  • diminishes the euphoric effects of additional opioids.
Other relevant properties:
  • Onset of effects - 30 minutes
  • Peak effects - Approx 3 hours
  • Half life (in Methadone Maintenance Treatment) - Approx 24 hours
  • Time to reach stabilisation - 3-10 days
  • Metabolised in the liver via the cytochrome P450 enzyme system.
  • Eliminated principally in the urine and faeces.
Withdrawal syndrome
Side effects
Drug interactions
Safety

Withdrawal syndrome

The withdrawal syndrome from methadone tends to emerge later and be more prolonged than with short acting opioids (eg heroin). Signs and symptoms usually begin 36 to 48 hours after the last dose. The duration of methadone withdrawal is typically 5 to 21 days with some features lasting for a prolonged period characterised by a general feeling of reduced well-being.
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Side effects

  • Most dependent opioid users will experience few side effects from methadone.
  • Once on a stable dose, tolerance develops until cognitive skills and attention are not impaired.
  • Symptoms of constipation, sexual dysfunction and occasionally increased sweating can continue to be troubling for the duration of treatment.

Drug interactions

  • Other sedatives (eg. alcohol and benzodiazepines) in combination with methadone can result in respiratory depression, coma and death.
  • Cytochrome P450 inducing drugs can increase the metabolism of methadone and cause a withdrawal syndrome if administered to patients maintained on methadone.
  • CYP 3A inhibitors can decrease the metabolism of methadone and cause overdose.
  • Opioid antagonists (eg naltrexone, naloxone) will precipitate withdrawal in opioid dependent patients.
  • SSRI, MAOI, tricyclic antidepressants and some antibiotics may raise plasma methadone levels and increase the effects of methadone.
The full list of drugs which interact with methadone appears at Appendix 1 of the unabridged Clinical guidelines for the use of methadone in the maintenance treatment of opioid dependence.

Safety

  • The long term side effects of methadone taken orally in controlled doses are few;
  • Overdose is the main risk;
  • Overdose risk is increased:
    • In the first two weeks of induction to methadone maintenance treatment;
    • When methadone is used in combination with other sedative drugs.
  • Toxic effects of overdose may become life threatening several hours after ingestion due to the slow onset of action and long half life of methadone.