An update on the clinical use of methadone for cancer pain

Methadone is a synthetic opioid agonist considered a second choice drug in the management of cancer pain. Methadone has a number of unique characteristics including excellent oral and rectal absorption, no known active metabolites, high potency, low cost, and longer administration intervals, as well as an incomplete cross-tolerance with respect to other mu-opioid receptor agonist drugs. For these reasons, methadone has the potential of playing a major role in the treatment of cancer pain. However, its use is limited by the remarkably long and unpredictable half-life, large inter-individual variations in pharmacokinetics, the potential for delayed toxicity, and above all by the limited knowledge of correct administration intervals and the equianalgesic ratio with other opioids when administered chronically. Recent findings suggest that standard equianalgesic tables are unreliable for methadone titration in patients tolerant to high doses of opioid agonists and that switchovers should take place slowly and should be personalized. Future research has to better define the variation in both bioavailability and elimination of methadone in different patient populations, the interaction between methadone and the most commonly used drugs in cancer patients, the type and activity of potential methadone metabolites, and the equianalgesic doses between methadone and the most commonly used opioids.