Methadone for cancer pain

Abstract

There is evidence to suggest that methadone is an analgesic with similar efficacy to morphine and a comparable side effect profile. However, the majority of studies involved single dose comparisons or short term use. This methodology fails to reproduce clinical practice. Therefore there is a very significant danger that the effects of methadone accumulation leading to delayed onset of adverse effects which occurs with chronic administration has not been represented. Fixed interval dosing schedules conducted over several days are associated with a high risk of serious morbidity and mortality. There is no trial evidence to support the proposal that methadone has a particular role in neuropathic pain of malignant origin. Conclusions have been limited by the variations in trial design, dosing regimens and limited presentation of primary outcome data. The complex and highly individual pharmacokinetics of methadone require that experienced clinicians take responsibility for initiating, titrating and monitoring this drug.

Methods of Rotation From Another Strong Opioid to Methadone for the Management of Cancer Pain: A Systematic Review of the Available Evidence

“…12,13 Methadone is a unique synthetic opioid with activity at both m-receptors, and N-methyl-D-aspartate receptors, 14 which are implicated in the development of neuropathic pain. Two systematic reviews 15,16 have examined the use of methadone for cancer-related pain. Four studies that compared methadone to other oral or transdermal strong opioids 17e20 found that methadone provides similarly effective analgesia as morphine sulfate, oxycodone, and hydromorphone and is associated with no more side effects than these opioids.…”

Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain

“…Morphine is metabolized to morphine-3-glucuronide (M3G) and the active morphine-6-glucuronide (M6G) via UGT2B7 [6]. It is commonly cited that the interindividual variability of the pharmacokinetics of methadone is larger than for other opioids [7].…”

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

“…In recent years, its demonstrated clinical efficacy and cost-effectiveness have made methadone an increasingly prescribed opioid, particularly in treating moderate-to-severe pain (211,212). Methadone consists of a racemic mix of R-and S-methadone (213), though the Risomer is believed to account for its opioid effects (214).…”