Methadone in cancer pain

Methadone is often considered as a second‐choice drug alternative to morphine in cancer pain treatment. A lack of information regarding methadone's pharmacokinetic/pharmacodynamic relationships has contributed to limitation in its use in analgesic treatments. However, it has been recently re‐evaluated in light of better knowledge of its pharmacological characteristics and wider experience. Concern about the safety of methadone therapy arising because of its long and unpredictable half‐life should not deter clinicians from its appropriate use. Methadone is a very useful drug in cancer pain because of its low cost, lack of known metabolites, high oral bioavailability, rapid onset and time to peak analgesic effect, and the long duration of activity which allows for longer intervals between doses. Moreover, methadone has been demonstrated to have a high receptor reserve and to exert some NMDA receptor antagonist effect. A shift from one opioid to methadone is recommended when the side‐effect/analgesic balance is unfavourable, as symmetrical patterns of cross‐tolerance of opioid agonists have been demonstrated. Different approaches, including the oral PCA, have been proposed to circumvent problems related to its pharmacokinetic properties.