Opioid rotation for cancer pain: rationale and clinical aspects

Cancer. 1999 Nov 1;86(9):1856-66. doi: 10.1002/(sici)1097-0142(19991101)86:9<1856::aid-cncr30>3.0.co;2-g.


Background: Some patients with cancer pain may develop uncontrolled adverse effects, including generalized myoclonus, delirium, nausea and emesis, or severe sedation before achieving adequate analgesia during opioid dose titration. Sequential therapeutic trials should be considered to determine the most favorable drug.

Methods: Recent literature was taken into account when reviewing the rationale and potential of opioid rotation.

Results: When aggressive attempts to prevent adverse effects fail, drug rotation should be considered, because sequential therapeutic trials can be useful in identifying the most favorable 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 a clinical setting.

Conclusions: When pain is relieved inadequately by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them, treatment with the same opioid by an alternative route or with an alternative opioid administered by the same route should be considered. Opioid rotation may be useful in opening the therapeutic window and for establishing a more advantageous analgesia/toxicity relationship. By substituting opioids and using lower doses than expected according to the equivalency conversion tables, it is possible in the majority of cases to reduce or relieve the symptoms of opioid toxicity in those patients who were highly tolerant to previous opioids while improving analgesia and, as a consequence, the opioid responsiveness.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use
  • Analgesics, Opioid / toxicity
  • Fentanyl / administration & dosage
  • Fentanyl / therapeutic use
  • Fentanyl / toxicity
  • Humans
  • Hydromorphone / administration & dosage
  • Hydromorphone / therapeutic use
  • Hydromorphone / toxicity
  • Methadone / administration & dosage
  • Methadone / therapeutic use
  • Methadone / toxicity
  • Morphine / administration & dosage
  • Morphine / therapeutic use
  • Morphine / toxicity
  • Narcotics / administration & dosage*
  • Narcotics / therapeutic use
  • Narcotics / toxicity
  • Neoplasms / complications*
  • Pain / drug therapy*


  • Analgesics, Opioid
  • Narcotics
  • Morphine
  • Hydromorphone
  • Methadone
  • Fentanyl