Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio?
OBJECTIVE
To define the dose ratio between morphine and methadone in relation to the previous morphine dose and the number of days needed to achieve the same level of analgesia in a group of patients with advanced cancer with pain who switched from morphine to oral methadone.


METHODS
A cross-sectional prospective study of 38 consecutive cancer patients who switched from morphine to oral methadone was performed. The intensity of pain before, during, and after the switching period was assessed through a four-point verbal Likert scale. The relationship between previous morphine dose and the final equianalgesic methadone dose, dose ratio between morphine and methadone, and the number of days required to achieve equianalgesia have been examined by means of Pearson's correlation coefficient, scatter plots, and Cuzick's test for trend respectively.


RESULTS
Before the switch, the median oral equivalent daily dose of morphine was 145 mg/d; after the switch, the median equianalgesic oral methadone dose was 21 mg/d. A median time of 3 days (range, 1 to 7 days) was necessary to achieve the equianalgesia with oral methadone; the lower the preswitching morphine dose, the fewer days necessary to achieve equianalgesia with oral methadone (P < .001). Dose ratios ranged from 2.5:1 to 14.3:1 (median, 7.75:1), which indicated that, in most cases, the dose ratio was much higher than that suggested by the published equianalgesic tables. A strong linear positive relationship between morphine and methadone equianalgesic doses was obtained (Pearson's correlation coefficient, 0.91). The dose ratio increased with the increase of the previous morphine dose with a much higher increase at low morphine doses.


CONCLUSIONS
The results of our study confirm that methadone is a potent opioid, more potent than believed. Caution is recommended when switching from any opioid to methadone, especially in patients who are tolerant to high doses of opioids.
Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. tdpint@tin.it
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Ripamonti
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Groff
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Brunelli
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Polastri
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Stavrakis
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De Conno
D000284:Administration, Oral; D000368:Aged; D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy*; D011446:Prospective Studies; D013810:Therapeutic Equivalency; D013997:Time Factors
D000701:Analgesics, Opioid; D009020:Morphine; D008691:Methadone