A systematic review of opioid conversion ratios used with methadone for the treatment of pain

Pain Medicine

Volumn 9, Issue 5, 2008, Pages 595-612

  Weschules, Douglas J ^a   Bain, Kevin T ^a  

^a excelleRx Inc   (United States)

Author keywords

Conversion Ratio; Equianalgesic Ratio; Methadone; Opioid Ratio; Opioid Rotation; Pain

Indexed keywords

DELTA OPIATE RECEPTOR; DEXAMETHASONE; FENTANYL; HYDROMORPHONE; LEVOMEPROMAZINE; LEVORPHANOL; METHADONE; MORPHINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NARCOTIC ANALGESIC AGENT; OXYCODONE;

ADULT; ADVERSE DRUG REACTION; ANALGESIA; CANCER PAIN; CANCER PATIENT; COMPETITIVE INHIBITION; CONTINUOUS INFUSION; CORRELATION ANALYSIS; CORRELATION COEFFICIENT; DRUG ANTAGONISM; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE REGIMEN; DRUG DOSE TITRATION; DRUG MEGADOSE; DRUG SUBSTITUTION; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DYSPHORIA; EQUIANALGESIC RATIO; FEMALE; HUMAN; INTERMETHOD COMPARISON; MAJOR CLINICAL STUDY; MALE; NEUROPATHIC PAIN; OPOID CONVERSION RATIO; PAIN; REVIEW; SEDATION; SIDE EFFECT; STATISTICAL ANALYSIS; SYSTEMATIC REVIEW; TOXICITY; TRANSDERMAL DRUG ADMINISTRATION; UNSPECIFIED SIDE EFFECT;

ADULT; ANALGESICS, OPIOID; CHRONIC DISEASE; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; METHADONE; MIDDLE AGED; PAIN; PALLIATIVE CARE; STATISTICS AS TOPIC;

EID: 48449090970     PISSN: 15262375     EISSN: 15264637     Source Type: Journal    
DOI: 10.1111/j.1526-4637.2008.00461.x     Document Type: Review

References (99)

1. 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):165-8.
2. Laurel Gorman A, Elliott KJ, Inturrisi CE. The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-d-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett 1997;223(1):5-8.
3. Codd EE, Shank RP, Schupsky JJ, Raffa RB. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: Structural determinants and role in antinociception. J Pharmacol Exp Ther 1995;274(3):1263-70.
4. Liu J, Liao X, Gong Z, Qin B. The difference between methadone and morphine in regulation of [delta]-opioid receptors underlies the antagonistic effect of methadone on morphine-mediated cellular actions. Eur J Pharmacol 1999;373(2-3):233-9.
5. Bruera E, Watanabe S, Fainsinger RL, et al. Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain. Pain 1995;62(2):141-6.
6. Lawlor PG, Turner KS, Hanson J, Bruera ED. Dose ratio between morphine and methadone in patients with cancer pain. Cancer 1998;82(6):1167-73.
7. Mercadante S, Bianchi M, Villari P, et al. Opioid plasma concentration during switching from morphine to methadone: Preliminary data. Support Care Cancer 2003;11(5):326-31.
8. Mercadante S, Casuccio A, Calderone L. Rapid switching from morphine to methadone in cancer patients with poor response to morphine. J Clin Oncol 1999;17(10):3307-12.
9. Mercadante S, Casuccio A, Fulfaro F, et al. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: A prospective study. J Clin Oncol 2001;19(11):2898-904.
10. Morley JS, Watt JWG, Wells JC, et al. Methadone in pain uncontrolled by morphine. Lancet 1993;342(81):1243.
11. Nauck F, Ostgathe C, Dickerson EDA. German model for methadone conversion. Am J Hosp Palliat Care 2001;18(3):200-2.
12. 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.
13. Ripamonti C, Groff L, Brunelli C, et al. Switching from morphine to oral methadone in treating cancer pain: What is the equianalgesic dose ratio? J Clin Oncol 1998;16(10):3216-21.
14. Scholes CF, Gonty N, Trotman IF. Methadone titration in opioid-resistant cancer pain. Eur J Cancer Care 1999;8(1):26-9.
15. Wheeler W, Dickerson E. Clinical applications of methadone. Am J Hosp Palliat Care 2000;17(3):196-203.
16. 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.
17. Bruera E, Sweeney C. Methadone use in cancer patients with pain: A review. J Palliat Med 2002;5(1):127-38.
18. Layson-Wolf C, Goode JV, Small RE. Clinical use of methadone. J Pain Palliat Care Pharmacother 2002;16(1):29-59.
19. Fishman SM, Wilsey B, Mahajan G, Molina P. Methadone reincarnated: Novel clinical applications with related concerns. Pain Med 2002;3(4):339-48.
20. Manfredi PL, Houde RW. Prescribing methadone, a unique analgesic. J Support Oncol 2003;1(3):216-20.
21. Soares L. Methadone for cancer pain: What have we learned from clinical studies? Am J Hosp Palliat Med 2005;22(3):223-7.
22. Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician 2005;71(7):1353-8.
23. Manfredonia JF. Prescribing methadone for pain management in end-of-life care. J Am Osteopath Assoc 2005;105(suppl 3):18S-21.
24. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996;17(1):1-12.
25. Gordon DB, Stevenson KK, Grieffie J, et al. Opioid equianalgesic calculations. J Palliat Med 1999;2(2):209-18.
26. Gammaitoni A, Fine P, Alvarez N, McPherson M, Bergmark S. Clinical application of opioid equianalgesic data. Clin J Pain 2003;19(5):286-97.
27. aaiPharma. Methadone injection CII. Manufactured by AAI Development Services in Charleston, SC; Distributed by aaiPharma in Wilmington, NC 2004.
28. Jacox A, Carr DB, Payne R, et al. Management of cancer pain. Clinical guideline number 9. Rockville, MD: Agency for Health Care Policy and Research, U.S. Department of Health and Human Services, Public Health Service; 1994 Mar. Report No.: AHCPR Publication No. 94-0592.
29. Jacox A, Carr DB, Payne R. New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med 1994;330(9):651-5.
30. Rapp CJ, Gordon DB. Understanding equianalgesic dosing. Orthop Nurs 2000;19(3):65-70. quiz 70-2.
31. Brant JM. Opioid equianalgesic conversion: The right dose. Clin J Oncol Nurs 2001;5(4):163-5.
32. FDA. Patient information: Duragesic® (fentanyl transdermal system). Manufactured by ALZA Corporation; Distributed by Janssen Pharmaceutica Products, L.P. 2003.
33. Levy M. Pharmacologic management of cancer pain. Semin Oncol 1994;21(6):718-39.
34. Donner B, Zenz M, Tryba M, Strumpf M. Direct conversion from oral morphine to transdermal fentanyl: A multicenter study in patients with cancer pain. Pain 1996;64(3):527-34.
35. Hagen NA, Wasylenko E. Methadone: Outpatient titration and monitoring strategies in cancer patients. J Pain Symptom Manage 1999;18(5):369-75.
36. Hernansanz S, Gutierrez C, Rubiales AS, Flores LA, del Valle ML. Opioid rotation to methadone at home. J Pain Symptom Manage 2006;31(1):2-4.
37. Fredheim OM, Kaasa S, Dale O, et al. Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: A nine-month follow-up study. Palliat Med 2006;20(1):35-41.
38. Auret K, Roger Goucke C, Ilett KF, et al. Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain. Ther Drug Monit 2006;28(3):359-66.
39. Crews J, Sweeney N, DD D. Clinical 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):2266-72.
40. Eugenio KR. Profound morphine tolerance following high-dose methadone therapy. J Pain Palliat Care Pharmacother 2004;18(4):47-54.
41. Hays H, Woodroffe MA. Use of methadone in treating chronic noncancer pain. Pain Res Manage 1999;4(1):23-7.
42. Fitzgibbon DR, Ready LB. Intravenous high-dose methadone administered by patient controlled analgesia and continuous infusion for the treatment of cancer pain refractory to high-dose morphine. Pain 1997;73(2):259-61.
43. Gagnon B, Bruera E. Differences in the ratios of morphine to methadone in patients with neuropathic pain versus non-neuropathic pain. J Pain Symptom Manage 1999;18(2):120-25.
44. Gebhardt R, Kinney MAO. Conversion from intrathecal morphine to oral methadone. Reg Anesth Pain Med 2002;27(3):319-21.
45. Leng G, Finnegan M. Successful use of methadone in nociceptive cancer pain unresponsive to morphine. Palliat Med 1994;8:153-55.
46. Sabatowski R, Kasper SM, Radbruch L. Patient-controlled analgesia with intravenous L-methadone in a child with cancer pain refractory to high-dose morphine. J Pain Symptom Manage 2002;23(1):3-5.
47. Tse D, Sham M, Ng D, Ma H. An 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):206-11.
48. Bruera E, Pereira J, Watanabe S, et al. Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer 1996;78(4):852-7.
49. Gardner-Nix JS. Oral methadone for managing chronic nonmalignant pain. J Pain Symptom Manage 1996;11(5):321-28.
50. Hunt G, Bruera E. Respiratory depression in a patient receiving oral methadone for cancer pain. J Pain Symptom Manage 1995;10(5):401-4.
51. Manfredi PL, Borsook D, Chandler SW, Payne R. Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: Clinical observations. Pain 1997;70(1):99-101.
52. Oneschuk D, Bruera E. Case report: Respiratory depression during methadone rotation in a patient with advanced cancer. J Palliat Care 2000;16(2):50-4.
53. Thomas Z, Bruera E. Use of methadone in a highly tolerant patient receiving parenteral hydromorphone. J Pain Symptom Manage 1995;10(4):315-7.
54. ViganóA, Fan D, Bruera E. Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators. Pain 1996;67(1):115-19.
55. Watanabe S, Belzile M, Kuehn N, Hanson J, Bruera E. Capsules and suppositories of methadone for patients on high-dose opioids for cancer pain: Clinical and economic considerations. Cancer Treat Rev 1996;22(suppl 1):131-6.
56. Zimmermann C, Seccareccia D, Booth C, Cottrell W. Rotation to methadone after opioid dose escalation: How should individualization of dosing occur? J Pain Palliat Care Pharmacother 2005;19(2):25-31.
57. Mercadante S, Ferrera P, Villari P, Casuccio A. Rapid switching between transdermal fentanyl and methadone in cancer patients. J Clin Oncol 2005;23(22):5229-34.
58. Benítez-Rosario MA, Feria M, Salinas-Martín A, Martínez-Castillo LP, Martín-Ortega JJ. Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain. Cancer 2004;101(12):2866-73.
59. Santiago-Palma J, Khojainova N, Kornick C, et al. Intravenous methadone in the management of chronic cancer pain: Safe and effective starting doses when substituting methadone for fentanyl. Cancer 2001;92(7):1919-25.
60. Moulin DE, Palma D, Watling C, Schulz V. Methadone in the management of intractable neuropathic noncancer pain. Can J Neurol Sci 2005;32(3):340-3.
61. Säwe J, Hansen J, Ginman C, et al. Patient-controlled dose regimen of methadone for chronic cancer pain. BMJ 1981;282(6266):771-3.
62. Mercadante S, Arcuri E. Hyperalgesia and opioid switching. Am J Hosp Palliat Med 2005;22(4):291-4.
63. Mironer YE, Chapple IJC, et al. Successful use of methadone in neuropathic pain: A multicenter study by the national forum of independent pain clinicians. Pain Digest 1999;9(3):191-3.
64. Moryl N, Santiago-Palma J, Kornick C, et al. Pitfalls of opioid rotation: Substituting another opioid for methadone in patients with cancer pain. Pain 2002;96(3):325-8.
65. Bhimji K. Opioid rotation from methadone: Fraught with difficulties. J Pain Symptom Manage 2005;29(4):334-5.
66. Mercadante S, Bruera E. Opioid switching: A systematic and critical review. Cancer Treat Rev 2006;32(4):304-15.
67. Quigley C. Opioid switching to improve pain relief and drug tolerability. Cochrane Database Syst Rev 2004;(3):CD004847.
68. National Hospice and Palliative Care Organization. NHPCO's facts and figures-2005 findings. 2006 Nov. Available at: http://www.nhpco.org/ files/public/2005-facts-and-figures.pdf (accessed December 15, 2006).
69. Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: Implications for the treatment of opioid dependence. Clin Pharmacokinet 2002;41(14):1153-93.
70. DeConno F, Groff L, Brunelli C, et al. Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients. J Clin Oncol 1996;14(10):2836-42.
71. ViganóA, Bruera E, Suarez-Almazor ME. Age, pain intensity, and opioid dose in patients with advanced cancer. Cancer 1998;83(6):1244-50.
72. Hall S, Gallagher RM, Graceley E, Knowlton CH, Weschules DJ. The terminal cancer patient: Effects of age, gender, and primary tumor site on opioid dose. Pain Med 2003;4(2):125-34.
73. Mercadante S, Casuccio A, Pumo S, Fulfaro F. Opioid responsiveness-primary diagnosis relationship in advanced cancer patients followed at home. J Pain Symptom Manage 2000;20(1):27-34.
74. Mercadante S, Casuccio A, Pumo S, Fulfaro F. Factors influencing the opioid response in advanced cancer patients with pain followed at home: The effects of age and gender. Support Care Cancer 2000;8:123-30.
75. Bertilsson L, Lou YQ, Du YL, et al. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin. Clin Pharmacol Ther 1992;51(4):388-97.
76. Ishizaki T, Eichelbaum M, Horai Y, et al. Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol 1987;23(4):482-5.
77. Lotsch J, Skarke C, Liefhold J, Geisslinger G. Genetic predictors of the clinical response to opioid analgesics: Clinical utility and future perspectives. Clin Pharmacokinet 2004;43(14):983-1013.
78. Lou YC, Ying L, Bertilsson L, Sjoqvist F. Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet 1987;2(8563):852-3.
79. Nakamura K, Goto F, Ray WA, et al. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 1985;38(4):402-8.
80. Weschules DJ, McMath JA, Gallagher R, Alt CJ, Knowlton CH. Methadone and the hospice patient: Prescribing trends in the home-care setting. Pain Med 2003;4(3):269-76.
81. Grond S, Radbruch L, Meuser T, et al. Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain 1999;79(1):15-20.
82. Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. Pain 1999;82(3):263-74.
83. Stute P, Soukup J, Menzel M, Sabatowski R, Grond S. Analysis and treatment of different types of neuropathic cancer pain. J Pain Symptom Manage 2003;26(6):1123-31.
84. U.S. Food and Drug Administration. FDA public health advisory. Methadone use for pain control may result in death and life-threatening changes in breathing and heart beat. Available at: http://www.fda.gov/cder/drug/ advisory/methadone.htm (accessed November 30, 2006).
85. Fisch MJ, Cleeland CS. Managing cancer pain. In: Sheet RT, ed. Handbook of Cancer Chemotheapy, 6th edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:663.
86. Ferrari A, Coccia CP, Bertolini A, Sternieri E. Methadone-metabolism, pharmacokinetics and interactions. Pharmacol Res 2004;50(6):551-9.
87. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 2005;19(4):13-24.
88. Weschules DJ, Bain KT, Richeimer S. Actual and potential drug interactions associated with methadone. Pain Med 2008;9(3):315-44.
89. Sims SA, Snow LA, Porucznik CA. Surveillance of methadone-related adverse drug events using multiple public health data sources. J Biomed Inform 2007;40(4):382-9.
90. Kornick CA, Kilborn MJ, Santiago-Palma J, et al. QTc interval prolongation associated with intravenous methadone. Pain 2003;105(3):499-506.
91. Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS. Dose-related effects of methadone on QT prolongation in a Series of patients with torsade de pointes. Pharmacother 2003;23(6):802-5.
92. Walker PW, Klein D, Kasza L. High dose methadone and ventricular arrhythmias: A report of three cases. Pain 2003;103(3):321-4.
93. Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med 2002;137(6):501-4.
94. Morgan OW, Johnson H, Rooney C, Seagroatt V, Griffiths C. Changes to the daily pattern of methadone-related deaths in England and Wales, 1993-2003. J Public Health (Oxf) 2006;28(4):318-23.
95. Gagajewski A, Apple FS. Methadone-related deaths in Hennepin County, Minnesota: 1992-2002. J Forensic Sci 2003;48(3):668-71.
96. Caplehorn JR, Drummer OH. Fatal methadone toxicity: Signs and circumstances, and the role of benzodiazepines. Aust N Z J Public Health 2002;26(4):358-62.
97. Ernst E, Bartu A, Popescu A, et al. Methadone-related deaths in Western Australia 1993-1999. Aust N Z J Public Health 2002;26(4):364-70.
98. Shah N, Lathrop SL, Landen MG. Unintentional methadone-related overdose death in New Mexico (USA) and implications for surveillance, 1998-2002. Addiction 2005;100(2):176-88.
99. Wolf BC, Lavezzi WA, Sullivan LM, Flannagan LM. Methadone-related deaths in Palm Beach County. J Forensic Sci 2004;49(2):375-8.