Methadone Reincarnated: Novel Clinical Applications with Related Concerns

Abstract

Methadone has numerous advantages as an analgesic, which have supported its recent increase in use. However, methadone also has a pharmacological profile as an opioid that differentiates it from other, better known or more widely used opioids. It also has unusual pharmacodynamics, pharmacokinetics, and metabolism that must be considered for safe use of methadone as an analgesic. This review looks at the history of methadone use as an analgesic and its properties that distinguish it as an unusual, and potentially, unstable opioid.

Bioavailabilities of rectal and oral methadone in healthy subjects

“…There is an increasing interest in the use of methadone in palliative care, particularly in the context of opioid rotation [9,10,26]. Methadone has favourable characteristics, both with respect to pharmacodynamics (faster onset of effect, long duration of action, incomplete cross tolerance towards morphine, and possible effects on NMDA receptors) and pharmacokinetics (faster absorption, long half-life, no active or toxic metabolites and little dependence on metabolite renal excretion) compared to morphine [9].…”

“…Methadone has favourable characteristics, both with respect to pharmacodynamics (faster onset of effect, long duration of action, incomplete cross tolerance towards morphine, and possible effects on NMDA receptors) and pharmacokinetics (faster absorption, long half-life, no active or toxic metabolites and little dependence on metabolite renal excretion) compared to morphine [9]. Methadone is therefore often preferred when morphine fails, either due to lack of adequate analgesia or intolerable sideeffects.…”

“…Morphine is the WHO opioid of choice for Step 3 therapy [1]. However, methadone has attracted an increasing interest in palliative care [2][3][4][5][6][7][8][9][10]. The usefulness of the latter for patients that are not properly managed with morphine, either due to adverse effect or inadequate pain relief, is documented in several reports underlining the pharmacological differences between the two opioids [9][10][11][12][13][14][15].…”

The use of methadone “as needed”, is it justified?

“…8 Although there is little data on clear dosing schedules for analgesia with methadone, most experts in the field suggest every 8 hours as a means for initiating therapy. 9 It must be strongly emphasized that there are significant inter-patient variations that can make any dosing schedule dangerous if patients are not monitored closely. Bioavailability can range from 41 to 99 percent.…”

“…7 Recommendations for the dosing of methadone have been outlined in other publications, specifically Fishman's 2002 article. 9 I would add the following:…”