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Support Care Cancer. 2010 Feb;18(2):235-42. doi: 10.1007/s00520-009-0649-8. Epub 2009 May 7.

Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study.

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  • 1Department of Hematology and Oncology, ABC Foundation School of Medicine, Av. Príncipe de Gales, n. 821, anexo 3, Santo André, São Paulo, ZIP 09060-650, Brazil.



This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and/or to improve the level of pain control in oncologic patients.


Fifty patients on stable doses of morphine for 1 week were switched to methadone using a "stop-start" strategy and randomized in a double-blind fashion to receive either acetaminophen (750 mg PO every 6 hours) or placebo for a 7-day period. We collected data regarding level of pain, side effects, and quality of life.


Substitution of morphine for methadone resulted in a significant reduction in constipation (p < 0.001) and xerostomia (p = 0.03). There was also an improvement in the numeric pain scale (p = 0.03) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 questionnaire. Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced. At the end of the study, most patients (70.8%, p = 0.001) preferred methadone to morphine.


Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia, allowing for a comfortable dosing regimen. In this scenario, the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone.

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