Opioid rotation in cancer pain

Abstract

Some patients with cancer pain may develop uncontrolled adverse effects, including generalized myoclonus, delirium, nausea and vomiting, or severe sedation before achieving adequate analgesia during opioid dose titration. When aggressive attempts to provide prophylaxis against adverse effects fail, drug rotation should be considered, because sequential therapeutic trials can identify the most favorable drug. Experiences are accumulating demonstrating that opioid responsiveness to difficult pain syndromes should not be based on the results obtained by a single drug. Different mechanisms, including receptor activity, the asymmetry in cross-tolerance among different opioids, different opioid efficacies, and accumulation of toxic metabolites can explain the differences in analgesic or adverse effect responses among opioids in the clinical setting. Opioid rotation may be useful in opening the therapeutic window and establishing a more advantageous analgesia-toxicity relationship. By substituting opioids and using lower doses it is possible in most cases to reduce or relieve the symptoms of opioid toxicity and to manage highly tolerant patients with previous opioids while improving analgesia and, as a consequence, the opioid responsiveness. Conversion to alternative opioids poses some problems because previous conversion tables may be misleading. Because methadone is much more potent than previously described, any change should start at a lower equivalent dose. Different approaches have been proposed to avoid the problems caused by methadone’s long half-life and possible accumulation. This review will examine the rationale and the clinical aspects of opioid rotation on the basis of recent research.