, a potent opioid agonist, has many characteristics that make it useful for the treatment of pain when continuous opioid analgesia is indicated.
Although available for decades, its use has gained renewed interest due to its low cost and potential activity in neuropathic pain syndromes.
, methadone is a racemic mix; one stereoisomer acts as a NMDA receptor antagonist, the other is a mu-agonist opioid. The NMDA mechanism plays an important role in the prevention of opioid tolerance, potentiation of opioid effects, and efficacy for neuropathic pain syndromes, although this latter impression is largely anecdotal.
Methadone is highly lipophilic, with rapid GI absorption and onset of action. It has a large initial volume of distribution with slow tissue release. Oral bioavailability is high, ~ 80%. Unlike morphine, there are no active metabolites; biotransformation to an active drug is not required. The major route of metabolism is hepatic with significant fecal excretion; renal excretion can be enhanced by urine acidification (pH <6.0). Unlike morphine, no dose adjustment is needed in patients with renal failure since there are no active metabolites.
Methadone is available in tablet, liquid, and injectable forms; oral preparations can be used rectally. Parenteral routes include IV bolus dosing or continuous infusion.
Compared to morphine, methadone is inexpensive, may provide improved analgesia in neuropathic pain and will provide a longer duration of action.
Unlike morphine, hydromorphone
, methadone has an extended terminal half-life, up to 190 hours. This half-life does not match the observed duration of analgesia (6-12 hours) after steady state is reached. This long half-life can lead to increased risk for sedation and respiratory depression, especially in the elderly or with rapid dose adjustments.
Rapid titration guidelines for other opioids do not apply to methadone.
Its apparent potency, compared to other opioids, varies with the the patient’s current exposure to other opioids.
See below for a suggested dosing guide for opioids tolerant patients.
Daily oral morphine dose equivalents. Conversion ratio of oral morphine to oral methadone
< 100 mg = 3:1 (i.e., 3 mg morphine = 1 mg methadone)
101-300 mg = 5:1
301-600 mg = 10:1
601-800 mg = 12:1
801-1000 mg = 15:1
> 1001 mg = 20:1
Due to incomplete cross-tolerance, it is recommended that the initial dose is 50-75% of the equianalgesic dose.
See also Instructions and conversion table
and Opioid dose conversions
Adapted from Gazelle G and Fine PG. Palliative Care Network of Wisconsin. Fast facts and concepts #75. Methadone for the treatment of pain. Internet. Accessed on January 25, 2016.