For the past 20 years, methadone has been experiencing resurgence in the palliative care community as a second-line opioid for the treatment of cancer pain. The advantages of using methadone for refractory pain in patients with cancer or in those who could not tolerate the side effects of other opioids such as morphine are well cited in recent literature. Advantages of methadone over other opioids include dual elimination without active metabolites, allowing safe use with renal and liver failure, N-methyl-D-aspartate (NMDA) and delta receptor activity in addition to mu receptor agonism, multiple routes of administration, rapid onset of action, long half-life, low cost, and fewer adverse effects. Despite the abundance of recent case reports and literature reviews demonstrating the effective use of methadone in patients with cancer, there is a lack of consensus for an appropriate method for converting morphine (and by extension, other opioids) to methadone. This article will review methadone pharmacology and multiple proposed conversion methods; a case report illustrating a popular method for high-dose conversion is also included.
Lawlor P., Turner K., Hanson J., Bruera EDDose ratio between morphine and methadone in patients with cancer pain: a retrospective study. Cancer. 1998;82(6):1167-1173.
2.
Mancini I., Lossignol D., Body JJOpioid switch to oral methadone in cancer pain. Curr Opin Oncol. 2000;12(4):308-313.
3.
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? J Clin Oncol. 1998;16(10):3216-3221.
4.
Tse DM, Sham MM, Ng DK, Ma HMAn ad libitum schedule for conversion of morphine to methadone in advanced cancer patients: an open uncontrolled prospective study in a Chinese population . Palliat Med. 2003;17(2):206-211.
Davis M., Walsh D.Methadone for relief of cancer pain: a review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Support Care Cancer. 2001;9(2): 73-83.
7.
Morley J., Makin M.The use of methadone in cancer pain poorly responsive to other opioids. Pain Rev. 1998;5(1):51-58.
8.
Auret K., Goucke R., Ilett KF, Page-Sharp M., Boyd F., Oh TEPharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain. Ther Drug Monit. 2006; 28(3):359-366.
9.
Sjogren P., Jensen N., Jensen TSDisappearance of morphine-induced hyperalgesia after discontinuing of substitituting morphine with other opioid agonists. Pain. 1994;59(2):313-316.
10.
Leng G., Finnegan MJSuccessful use of methadone in nociceptive cancer pain unresponsive to morphine . Palliat Med. 1994; 8(2):153-156.
11.
Crews J., Sweeney N., Denson DDClinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics. Cancer. 1993;72(7):2266-2272.
12.
Moryl N., Kogan M., Comfort C., Obbens E.Methadone in the treatment of pain and terminal delirum in advanced cancer patients. Palliat Support Care. 2005;3(4):311-317.
13.
Patanwala A. , Duby J., Waters D., Erstad BLOpioid conversions in acute care. Ann Pharmacother. 2007;41(2):255-266.
14.
Gammaitoni A., Fine P., Alvarez N., McPherson ML, Bergmark S.Clinical application of opioid equianalgesic data. Clin J Pain. 2003;19(5):286-297.
15.
Ripamonti C. , Zecca E., Bruera E.An update on the clinical use of methadone for cancer pain. Pain. 1997;70(2-3):109-115.
16.
Bruera E., Watanabe S., Fainsinger RL, Spachynski K., Suarez-Almazor M., Inturrisi C.Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain. Pain. 1995;62(2):141-146.
17.
Manfredi P., Borsook D., Chandler SW, Payne R.Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Pain. 1997;70(1):99-101.
18.
Mancini I., Lossignol D., Body JJOpioid switch to oral methadone in cancer pain. Curr Opin Oncol. 2000;12(4):308-313.
19.
Fisher K., Stiles C., Hagen NACharacterization of the early pharmacodynamic profile of oral methadone for cancer-related breatkthrough pain: a pilot study. J Pain Symptom Manage. 2004;28(6): 619-625.
20.
Ripamonti C., Groff L., Brunelli C., Polastri D., Stavrakis A., De Conno F.Switching from morphine to oral methadone in treating cancer: what is the equianalgesic dose ratio? J Clin Oncol. 1998 ; 16(10):3216-3221.
21.
Mercadante S. , Casuccio A., Agnello A., Serretta R., Calderone L., Barresi L.Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. J Clin Oncol . 1998;16(11):3656-3661.
22.
Zech D., Grond S., Lynch J., Hertel D., Lehmann KAValidation of World Health Organization Guidelines for cancer pain relief: a 10-year propspective study. Pain. 1995;63(1):65-76.
23.
Fainsinger R., Schoeller T., Bruera E.Methadone in the management of cancer pain: a review. Pain. 1993;52(2):137-147.
24.
de Stoutz N. , Bruera E., Suarez-Almazor M.Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage . 1995;10(5):378-384.
25.
Ebert B., Andersen S., Krogsgaard-Larsen P.Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate (NMDA) antagonists in the rat cortex and spinal cord. Neurosci Lett. 1995;187(3):165-168.
26.
Inturrisi CE , Colburn WA, Kaiko RF, Houde RW, Foley KMPharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clinical Pharmacol Ther. 1987; 41(4):392-401.
27.
Gourlay G., Cherry D., Cousins MJA comparative study of the efficacy and pharmacokinetic considerations of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain. 1986;25(3):297-312.
28.
De Conno F. , Groff L., Brunelli C., Zecca E., Ventafridda V., Ripamonti C.Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients. J Clin Oncol. 1996;14(10):2836-2842.
29.
Hagen N., Wasylenko E.Methadone: outpatient titration and monitoring strategies in cancer patients . J Pain Symptom Manage. 1999;18(5):369-375.
30.
Ripamonti C. , De Conno F., Groff L., et al. Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: comparison of two clinical experiences . Ann Oncol. 1998;9(1): 79-83.
