Morphine and methadone use in cancer pain

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Editor, – Changing to methadone may be beneficial for some patients with cancer pain who are suffering the adverse effects of morphine. We are concerned that there is confusion about the dose of methadone to prescribe when making this change.

Methadone is a useful second-line analgesic for cancer pain but has its own problems. A report into methadone-related deaths in South Australia between 1984 and 1994 showed that while methadone used for drug dependence was relatively safe, this was not the case when methadone was used for pain.1 A potential danger is the view that the dose of methadone, required to produce the same analgesic effect, is identical to the dose of oral morphine.

The view that the dose ratio is 1:1 was mainly developed from single dose studies. Individual variation in the pharmacokinetics of methadone should raise concern about using this ratio when replacing morphine with methadone.2,3 Studies focusing on chronic opioid use in cancer pain have reported varying equianalgesic dose ratios. These reports suggest that:

  • the comparative pharmacology of morphine and methadone is incomplete
  • the equianalgesic dose ratio varies with the dose of morphine before the change to methadone (at higher morphine doses methadone is relatively more potent)4,5
  • for analgesia, the dose of methadone should be carefully titrated, preferably in hospital.6

We believe that there is currently no reliable morphine to methadone equianalgesic dose ratio. There is little evidence to support any protocols for starting methadone. The safest way to replace morphine with methadone is therefore by individual titration over a number of days, preferably in a hospital setting. Furthermore, we suggest that this titration should only be carried out by a clinician experienced in prescribing methadone.

If the titration takes place in hospital the patient's general practitioner must be informed of the possibility of late onset adverse effects (half-life may vary from 40 to 600 hours).

Mary Brooksbank
Director, Palliative Care
Guy Bannick
Fellow in Palliative Care
Michael Briffa
Fellow in Palliative Care
Palliative Care Unit
Royal Adelaide Hospital


  1. Williamson PA, Foreman KJ, White JM, Anderson G. Methadone-related overdose deaths in South Australia, 1984-1994. How safe is methadone prescribing?. Med J Aust 1997;166:302-5.
  2. Inturrisi CE, Colburn WA, Kaiko RF, Houde RW, Foley KM. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol Ther 1987;41:392-401.
  3. Meresaar U, Nilsson MI, Holmstrand J, Anggard E. Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Eur J Clin Pharmacol 1981;20:473-8.
  4. Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F. Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? [see comments in J Clin Oncol 1998;16:3213-5]. J Clin Oncol 1998;16:3216-21.
  5. Bruera E, Pereira J, Watanabe S, Belzile M, Kuehn N, Hanson J. Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer 1996;78:852-7.
  6. Ripamonti C, Zecca E, Bruera E. An update on the clinical use of methadone for cancer pain [see comments in Pain 1997;73:114-5]. Pain 1997;70:109-15.