Methadone

Methadone is a synthetic mu-opioid agonist, similar to morphine. Methadone is used in the treatment opioid use disorder, but prolonged use of methadone itself may also result in dependence.

Pharmacokinetics

Absorption and Bioavailability Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%.
Volume of Distribution 1 to 8 L (mostly in plasma and blood)
Metabolism Hepatic, via cytochrome P450 enzymes. Primarily CYP3A4, CYP2B6, and CYP2C19. Lesser extent CYP2C9 and CYP2D6.
Excretion Excreted mainly in the urine

In patients using methadone for treatment of chronic pain, the methadone dose can be split into a BID dose for better pain control.

Methadone has depressant action on the cough center and can be given to control intractable cough associated with terminal lung cancer.

  • Do not co-prescribe with naltrexone

Avoid Prescribing Benzodiazepines!

The concomitant use of opioids with benzodiazepines or other central nervous system depressants such as alcohol can cause profound sedation, respiratory depression, coma, and even death.
  • Avoid highly serotonergic SSRIs such as citalopram and escitalopram (instead, use sertraline, fluoxetine, or venlafaxine)
  • Fluvoxamine can increase blood levels of methadone
  • Methadone increases the QT interval!