Opioid Rotation to Methadone: Proceed With Caution
Authors: Sharon Watanabe, Yoko Tarumi, Doreen Oneschuk, Peter Lawlor, Russell K. Portenoy, Rose Anne Indelicato
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.9.2409 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11981018 Opioid Rotation to Methadone: Proceed With Caution Sharon WatanabexSharon WatanabeSearch for articles by this author , Yoko TarumixYoko TarumiSearch for articles by this author , Doreen OneschukxDoreen OneschukSearch for articles by this author , Peter LawlorxPeter LawlorSearch for articles by this author Russell K. PortenoyxRussell K. PortenoySearch for articles by this author , Rose Anne IndelicatoxRose Anne IndelicatoSearch for articles by this author Show More University of Alberta, Edmonton, Alberta, CanadaBeth Israel Medical Center, New York, NY https://doi.org/10.1200/JCO.2002.20.9.2409 Full Text PDF Figures and Tables "Opioid Rotation to Methadone: Proceed With Caution." Journal of Clinical Oncology, 20(9), pp. 2409–2410© 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01052002In Reply to Daniell and Watanabe et al:We thank Dr Daniell and Dr Watanabe et al for their comments on our article.1 We strongly agree with the latter authors’ call for caution when switching to methadone from some other mu agonist opioid. As we discussed in our article,1 the d-isomer of methadone, which makes up half of the racemic methadone available in the United States, blocks the N-methyl-d-aspartate receptor. This action, which may produce independent analgesic effects and reverse analgesic tolerance, presumably explains the observation that methadone may be far more potent than suggested on published equianalgesic dose tables. Unexpectedly high potency and a long elimination half-life combine to increase the challenge in using methadone safely and effectively. However, with cautious dosing and appropriate monitoring, the drug can indeed be useful, and we would encourage oncologists to learn the guidelines for methadone administration that we1 and others2,3 have suggested.Dr Daniell’s comments highlight the potential for molecular biology and pharmacogenomic research to alter clinical practice. The observation that some patients—fewer than 10%—may be poorly responsive to codeine because of relatively limited activity at the cytochrome P-450 isoenzyme 2D6 (CYP 2D6) is well accepted.4 This understanding should be incorporated into the assessment of patient outcomes when codeine is used. We would encourage caution, however, in extrapolating biochemical data to the clinical setting when referring to other opioids. Although it is true that oxycodone and hydrocodone are metabolized to active opioid compounds, it has not been demonstrated that this effect has clinical relevance. A study of oxycodone in humans, which evaluated psychomotor and subjective effects,5 and several animal studies of hydrocodone6,7 did not confirm that the actions of these drugs are dependent on conversion to their active metabolites. Until we have better clinical data, it would be premature to conclude that change in the functioning of the CYP 2D6 isozyme induced by other drugs is a significant factor in the response to these opioids.1. Indelicato RA, Portenoy RK: Opioid rotation in the management of refractory cancer pain. J Clin Oncol 20:: 348,2002-352, Link, Google Scholar2. Mancini I, Lossignol DA, Body JJ: Opioid switch to oral methadone in cancer pain. Curr Opin Oncol 12:: 308,2000-313, Crossref, Medline, Google Scholar3. Ripamonti C, Groff L, Brunelli C, et al: Switching from morphine to oral methadone in treating cancer pain: What is the equianalgesic ratio? J Clin Oncol 16:: 3216,1998-3221, Link, Google Scholar4. Poulsen L, Brosen K, Arendt-Nielsen L, et al: Codeine and morphine in extensive and poor metabolizers of sparteine: Pharmacokinetics, analgesic effects and side effects. Eur J Clin Pharmacol 51:: 289,1996-295, Crossref, Medline, Google Scholar5. Heiskanen T, Olkkola KT, Kalso E: Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther 64:: 603,1998-611, Crossref, Medline, Google Scholar6. Tomkins DM, Otton SV, Hoharchi N, et al: Effect of cytochrome P450 2D1 inhibition on hydrocodone metabolism and its behavioral consequences in rats. J Pharmacol Exp Ther 280:: 1374,1997-1382, Medline, Google Scholar7. Lelas S, Wegert S, Otton SV, et al: Inhibitors of cytochrome P450 differentially modify discriminative-stimulus and antinociceptive effects of hydrocodone and hydromorphone in rhesus monkeys. Drug Alcohol Depend 54:: 239,1999-249, Crossref, Medline, Google Scholar