From OncoLog, September 2013, Vol. 58, No. 9

Opioid Rotation Can Improve Pain Control and Reduce Neurotoxicity for Cancer Patients

By Markeda Wade 

Opioids are a mainstay in the relief of pain—especially the chronic cancer-related pain often encountered in the palliative care setting. However, extended opioid use can result in tolerance, dependence, and opioid-induced neurotoxicity.

The symptoms of neurotoxicity—which include excessive sedation, confusion, hallucinations, and myoclonus—result from a buildup of the metabolites of opioids in the brain. Thus, when tolerance develops and pain is no longer controlled, simply increasing the opioid dose, as was commonly done in times past, may result in neurotoxicity.

In 1995, Eduardo Bruera, M.D., who was then a professor at the University of Alberta and is now a professor in and chair of the Department of Palliative Care and Rehabilitation Medicine at The University of Texas MD Anderson Cancer Center, proposed the notion of opioid rotation. In opioid rotation, the no-longer-effective opioid is replaced with a new one—but at a much lower dose, thereby minimizing the potential for toxicity. This is important because the most common indication for opioid rotation is opioid-induced neurotoxicity. “The cause of toxicity is the opioid, so that opioid needs to go,” said Akhila Reddy, M.D., an assistant professor in the Department of Palliative Care and Rehabilitation Medicine.

Opioid rotation is carried out using an equianalgesic table (these are published by numerous sources, including pharmaceutical companies) in which the morphine-equivalent daily dose of the original opioid is calculated and then decreased by 30%–50%.

Although opioid rotation was originally met with resistance by many clinicians—who were skeptical about cross-tolerance, which is common in patients treated with opioid analgesics—in the past decade, opioid rotation has become standard practice in the inpatient setting and is usually successful. For example, in a recent Italian study, 96 of 103 opioid substitutions were successful. This success is attributable to the daily monitoring of pain in inpatients, enabling rapid titration of drug doses.

Indications for Opioid Rotation

Although uncontrolled pain and opioid-induced neurotoxicity are the most common indications for opioid rotation, the procedure can be valuable for addressing other situations, such as the need to change the route by which a particular medication is administered. For example, in patients with head and neck cancer who have radiation-induced dysphagia and thus trouble taking pills, solid medications can be switched to a long-lasting liquid form. Moreover, in patients who have renal failure, morphine can be switched to methadone. And in a non-medical but perhaps equally significant situation, opioid rotation can be implemented when a drug is not covered by a patient’s insurance.

Increasingly, opioid rotation is also being considered for use in the outpatient setting. Recently, Dr. Reddy and her colleagues reported a retrospective review of all outpatients seen in 1 year in MD Anderson’s Supportive Care Clinic. Of those who were receiving strong opioids (morphine, hydromorphone, oxycodone, methadone, or fentanyl), 31% underwent opioid rotation, and the rotation was successful in 65% of those cases. Of the patients who required opioid rotation, 83% did so for uncontrolled pain and 12% for opioid-induced neurotoxicity. In the Supportive Care Clinic at MD Anderson, nurses and pharmacists follow up by phone with outpatients who have undergone opioid rotation to ensure the rotation went smoothly.

In addition, physicians schedule all outpatients for follow-up within a week of the opioid rotation. The close monitoring via nurse calls and the short intervals to follow-up increase the likelihood that the opioid rotation will be successful and help prevent both overdosing and underdosing.

Dr. Reddy recommended that a patient’s support system and likelihood of compliance be considered in the decision whether to use opioid rotation in an outpatient clinic. “Outpatients who do not follow up after opioid rotation and those who have unsuccessful opioid rotation have shorter survival times,” she said.

Opioid rotation has its limits for managing cancer pain in outpatients. Patients who have a poor performance status benefit more from opioid rotation in an inpatient setting, where they can be assessed more frequently than outpatients.

In any instance, Dr. Reddy advised, opioid rotation can be dangerous if performed by someone who is inexperienced. In the management of cancer pain, because of the high drug doses needed in some patients, imprecise opioid rotation could lead to overdose or even death. A palliative care or pain service consultation is advisable for patients requiring an opioid rotation.


de Stoutz ND, Bruera E, Suarez-Almazor M. Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage. 1995;10:378–384.

Reddy A, Yennurajalingam S, Pulivarthi K, et al. Frequency, outcome, and predictors of success within 6 weeks of an opioid rotation among outpatients with cancer receiving strong opioids. Oncologist. 2013;18:212–220.

For more information, contact Dr. Akhila Reddy at 13-792-6085 or asreddy@mdanderson.org.


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