Skip to main content Accessibility help

Consensus guideline on parenteral methadone use in pain and palliative care

  • Lauren Shaiova (a1), Ann Berger (a2), Craig D. Blinderman (a3), Eduardo Bruera (a4), Mellar P. Davis (a5), Susan Derby (a6), Charles Inturrisi (a7), Jill Kalman (a8), Davendra Mehta (a9), Marco Pappagallo (a10) and Eugene Perlov (a11)...


Once used only as third-line therapy for chronic pain management, methadone is now being used as first- and second-line therapy in palliative care. The risks and stigma associated with methadone use are known, but difficulties with dosing methadone and lack of an established conversion protocol from other opiates have limited the access for patient populations who could potentially benefit from this medication. For palliative care patients, the benefits of methadone can far outweigh its risks. This article provides an overview and specific recommendations on the use of parenteral methadone in pain and palliative care, with a focus on the transition from hospital to home/hospice care. The goal of this consensus guideline is to assist clinicians who are providing chronic pain management in acute care hospital and nonhospital settings (i.e., hospice, long-term care facilities, and community) for patients with life-limiting illnesses, where the goals of care are focused on comfort (i.e., palliative care). The recommendations in this article intend to promote a standard of care involving the use of intravenous methadone with the aim of reaching a broader population of patients for whom this drug would provide important benefits.


Corresponding author

Address correspondence and reprint requests to: Lauren Shaiova, Department of Pain Medicine and Palliative Care, Metropolitan Hospital Center, Health and Hospital Corporation of New York City; 1901 First Ave. New York, NY 10029. E-mail: or


Hide All
Al-Khatib, S.M., LaPointe, N.M., Kramer, J.M., et al. (2003). What clinicians should know about QT interval. Journal of the American Medical Association, 289, 21202127.
Anderson, M.E., Al-Khatib, S.M., Roden, D.M., et al. (2002). Cardiac repolarization: Current knowledge, critical gaps, and new approaches to drug development and patient management. American Heart Journal, 144, 769781.
Auret, K., Roger Goucke, C., Ilett, K.F., et al. (2006). Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain. Therapeutic Drug Monitoring, 28, 359366.
Centeno, C. & Vara, F. (2005). Intermittent subcutaneous methadone administration in the management of cancer pain. Journal of Pain Palliative Care Pharmacotherapy, 19(2), 712.
Derby, S., Chin, J., & Portenoy, R.K. (1998). Systemic opioid therapy for chronic cancer pain: Practical guidelines for converting drugs and routes of adminsistration. CNS Drugs, 9, 99109.
Drug Facts and Comparisons. (2007), p. 1082. St. Louis: Wolters-Kluwer Health.
Dyer, K.R. & White, J.M. (1997). Patterns of symptoms complaints in methadone maintenance patients. Addiction, 92, 14451455.
Ehret, G.B., Voide, C., Gex-Fabry, M., et al. (2006). Drug-induced long QT syndrome in injection drug users receiving methadone: High frequency in hospitalized patients and risk factors. Archives of Internal Medicine, 166, 12801287.
Fitzgibbon, D.R. & Ready, L.B. (1997). Intravenous high-dose methadone administered by patient controlled analgesia and continuous infusion for the treatment of cancer pain refractory to high-dose morphine. Pain, 73, 259261.
Garson, A. (1993). How to measure the QT interval—What is normal. American Journal of Cardiology, 72, 14B16B.
Kornick, C.A., Kilborn, M.J., Santiago-Palma, J., et al. (2003). QTc interval prolongation associated with intravenous methadone. Pain, 105, 499506.
Krantz, M.J. & Mehler, P.S. (2006) QTc prolongation: Methadone's efficacy-safety paradox. Lancet, 368, 556557.
Lawlor, P.G., Turner, K.S., Hanson, J., et al. (1998). Dose ratio between morphine and methadone in patients with cancer pain: A retrospective study. Cancer, 82, 11671173.
Makin, M.K. (2000). Subcutaneous methadone in terminally-ill patients [letter]. Journal of Pain and Symptom Management, 19, 237238.
Manfredi, P.L., Borsook, D., Chandler, S.W., et al. (1997). Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: Clinical observations. Pain, 70, 99101.
Manfredi, P.L. & Houde, R.W. (2003). Prescribing methadone, a unique analgesic. Journal of Supportive Oncology, 1, 216220.
Mathew, P. & Storey, P. (1999). Subcutaneous methadone in terminally ill patients: Manageable local toxicity. Journal of Pain and Symptom Management, 18, 4952.
Mercadante, S., Casuccio, A., & Calderone, L. (1999). Rapid switching from morphine to methadone in cancer patients with poor response to morphine. Journal of Clinical Oncology, 17, 16.
Morley, J.S. & Makin, M.K. (1998). The use of methadone in cancer pain poorly responsive to other opioids. Pain Reviews, 5, 5158.
Moss, A.J., Zareba, W., Benhorin, J., et al. (2001). ISHNE guidelines for electrocardiographic evaluation of drug-related QT prolongation and other alterations in ventricular repolarization: Task force summary. A report of the Task Force of the International Society for Holter and Noninvasive Electrocardiology (ISHNE), Committee on Ventricular Repolarization. Annals of Noninvasive Electrocardiology, 6, 333341.
Payne, R. & Inturrisi, C.E. (1985). CSF distribution of morphine, methadone and sucrose after intrathecal injection. Life Sciences, 37, 11371144.
Ripamonti, C., De Conno, F., Groff, L., et al. (1998). Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: Comparison of two clinical experiences. Annals of Oncology, 9, 7983.
Roden, D.M. (2004). Drug-induced prolongation of the QT interval. New England Journal of Medicine, 350, 10131022.
Santiago-Palma, J., Khojainova, N., Kornick, C., et al. (2001). Intravenous methadone in the management of chronic cancer pain: Safe and effective starting doses when substituting methadone for fentanyl. Cancer, 92, 1919–1925.
Sekine, R., Eugenia, A.M.T., Coyle, N., et al. (2007). The successful use of parenteral methadone in a patient with a prolonged QTc interval. Journal of Pain and Symptom Management, 34, 566569.
Shaiova, L. (2006). The role of methadone in the treatment of moderate to severe cancer pain. Supportive Cancer Therapy, 2, 15.


Related content

Powered by UNSILO

Consensus guideline on parenteral methadone use in pain and palliative care

  • Lauren Shaiova (a1), Ann Berger (a2), Craig D. Blinderman (a3), Eduardo Bruera (a4), Mellar P. Davis (a5), Susan Derby (a6), Charles Inturrisi (a7), Jill Kalman (a8), Davendra Mehta (a9), Marco Pappagallo (a10) and Eugene Perlov (a11)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.