Commentary (Moryl/Foley)-Opioid Rotation in Cancer Patients: Pros and Cons

April 1, 2005

The use of sequential therapeutictrials to determine the optimaldrug for a given patienthas become a standard strategy in painmanagement. We appreciate Estfanand colleagues’ thoughtful and practicalreview of the advantages and disadvantagesof opioid rotation in cancerpain management.[1] Their commentson the need for individualization ofopioid dose and ongoing monitoring,opioid choice in renal and liver insufficiency,compliance, and cost reductionare particularly important.

The use of sequential therapeutic trials to determine the optimal drug for a given patient has become a standard strategy in pain management. We appreciate Estfan and colleagues' thoughtful and practical review of the advantages and disadvantages of opioid rotation in cancer pain management.[1] Their comments on the need for individualization of opioid dose and ongoing monitoring, opioid choice in renal and liver insufficiency, compliance, and cost reduction are particularly important. Concerns About Methadone
We wish to highlight further the need for caution when switching to methadone. Estfan and coauthors[1] refer to the dose-dependent ratio between the initial opioid and methadone. This becomes especially important in opioid-naive patients and patients highly tolerant to opioids. Also, methadone potency with chronic use has recently been found to be 3 to 10 times higher than it was thought 5 to 7 years ago. One can come across a wide range of recommended methadone dose ratios (from the American Pain Society, Agency for Health Care Policy and Research, and others) and should seek the most updated equianalgesic tables. If a patient is being considered for a rotation to methadone, conservative dose calculation should be used and liberal rescue methadone doses (prn) should be provided. Close clinical monitoring should be provided for the first 2 to 5 days. For example, in anticipation of potential dose accumulation, methadone dose should be decreased by half if the patient reports complete pain relief 24 hours after rotation to the agent, to avoid overdose. If these conditions cannot be met on an outpatient basis, rotation in an inpatient setting should be strongly considered. Undirectionality of opioid ratios, especially in the case of methadone, should be remembered.[2] In our experience, rotation off methadone should be done in a monitored setting-often on an inpatient basis- to avoid pain flare and/or opioid withdrawal symptoms. Further Considerations
We also wish to point out that a long-acting formulation of hydromorphone (Palladone) is now available in the United States. This formulation is based on a controlled-release melt extrusion technology in which pellets containing hydromorphone HCl and comelted excipients release the active ingredient significantly more slowly and for a longer period than an immediate- release product. It is designed to provide controlled delivery of hydromorphone over 24 hours.[3-5] The evidence to support the practice of opioid rotation is based on observational and uncontrolled studies. Randomized controlled trials, are needed to confirm the effectiveness of this clinical practice, and to determine which opioid should be used in first- or second-line treatment. Standardized conversion ratios need to be further described.


The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.


1. Estfan B, LeGrand S, Walsh D, et al: Opioid rotation in cancer patients: Pros and cons. Oncology 19:511-516, 2005.
2. Moryl N, Santiago-Palma J, Kornick C, et al: Pitfalls of opioid rotation: Substituting another opioid for methadone in patient s with cancer pain. Pain 96:325-328, 2002.
3. Palangio M, Northfelt DW, Portenoy RK, et al: Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain. J Pain Symptom Manage 23:355-368, 2002.
4. Wright C, Colonnese C: Efficacy and safety of an oral 24-hour extended-release hydromorphone formulation for the relief of persistent nonmalignant pain. Poster presented at Annual Meeting of the American Academy of Pain Medicine; Orlando, Fla; March 3-7, 2004.
5. Weinstein SM, Grosset AL, Roberts MS, et al: Two double-blind randomized trials of once-a-day controlled release oral hydromorphone (Palladone XL) compared to immediate release hydromorphone dosed QID. Poster presented at 18th Annual Scientific Meeting of the American Pain Society; Fort Lauderdale, Fla; October 21-24, 1999.