Methadone Analgesia Safety Overview & Patient Instructions Handout

By: Stewart B. Leavitt, MA, PhD, October 2006.

PDF available PDF available here for download: Methadone_Safety_Overview&Handout.pdf (685 KB; 14 pp)

Methadone SafetyThis Overview document provides essential background information and serves as a gateway to the several evidence-based documents created by Pain Treatment Topics that can guide healthcare providers in more safely and effectively prescribing methadone analgesia. A special handout for patients and their families or caretakers (at the end of the Overview) offers vital instructions for treatment compliance and safety.

Oral methadone has demonstrated an excellent record of effectiveness and safety during the more than 60 years since its development. It is suitable for treatment of even the most severe acute or chronic pain. Although millions of patients have been successfully treated daily with the medication, reports of methadone-associated overdoses and fatalities continue to appear in sensational news headlines, describing methadone as a widely abused and dangerous drug. This has caused apprehension among healthcare providers and patients alike and, consequently, has burdened methadone with an unwarranted tarnished reputation.

Yet, when properly prescribed and used, oral methadone can provide effective and economical pain relief even when other analgesics – opioid or non-opioid – fail to do so. Most of the tragedies surrounding the misuse and abuse of oral methadone, typically in tablet form, could be prevented by a greater understanding of prescribing the medication among healthcare providers and by better education of patients – those are the objectives of this report.

Methadone Dosing for Chronic Pain in Ambulatory Patients: A Clinician's Perspective

By: James D. Toombs, MD, February 2006.

PDF available PDF available here for download: Methadone_Dosing_Chronic_Pain_2006.pdf (260 KB; 12 pp)

Methadone DosingMethadone is emerging as a good choice for the management of chronic non-cancer pain both as a first line medication and as a replacement opioid. Particular cautions must be observed as methadone's pharmacokinetics and pharmacodynamics are unique among opioids. Milligram for milligram, methadone is much more powerful than morphine; however, there is significant interindividual variability in the response to methadone. In the initiation of chronic opioid therapy with methadone or the transition from a different opioid, careful day-to-day monitoring is essential. Furthermore, methadone has potential to interact with a large number of medications, and drug-drug interactions must be considered. Finally, compared with other opioids, methadone can offer a very significant cost advantage.

This paper discusses these issues and provides guidance for methadone analgesia dosing in daily clinical practice. 

Methadone-Drug* Interactions (*Medications, illicit drugs, & other substances)

By: Stewart B. Leavitt, MA, PhD, January 2006.

PDF available PDF available here for download: Methadone-Drug_Intx_2006.pdf (700 KB; 33 pp)

Drug InteractionsEach year in the U.S. there are innumerable adverse drug reactions, broadly defined as any unexpected, unintended, undesired, or excessive response to a medicine. Such reactions may require discontinuing or changing medication therapy. Furthermore, greater than 2 million of those are serious reactions resulting in hospitalization and/or permanent disability, and there are more than 100,000 deaths annually attributed to reactions involving prescribed medications.

Three-fourths of those adverse reactions relate to drug interactions, which occur when the amount or action of a drug in the body is altered – usually increased or decreased – by the presence of another drug or multiple drugs. Avoiding these can be difficult and, as the tables in this document indicate, there are more than100 substances – medications, illicit drugs, OTC products, etc. – that can interact in some fashion to affect a patient's response to methadone.

During extensive clinical study and use, oral methadone analgesia has proven to be a well-tolerated medication with minimal adverse reactions when prescribed appropriately. However, potential methadone-drug interactions sometimes can be difficult to predict. Such interactions may be potentially harmful and/or can lead to treatment failures; although, they can usually be avoided or minimized.


Methadone Cardiac Concerns

By: Stewart B. Leavitt, MA, PhD; Mori J. Krantz, MD, FACC - from Addiction Treatment Forum, October 2003.

PDF available PDF available here for download: Methadone_Cardiac_Concerns.pdf (200 KB; 6 pp)

Cardiac ConcernsSome patients with chronic pain may have conditions associated with increased risks of arrhythmia, including: cardiovascular disease, electrolyte imbalances, and prescribed medications or abuse of cardiotoxic substances that may foster cardiac repolarization disturbances. Furthermore, studies of patients in methadone maintenance therapy (MMT) for opioid addiction suggest that in some individuals methadone – alone or, more commonly, in combination with other drugs and/or cardiac risk factors – can prolong the QT interval, which may contribute to the development of the serious arrhythmia torsade de pointes (TdP) in susceptible patients.

Current evidence, however, does not support altering methadone analgesia dosing practices or requiring electrocardiograms (ECGs) for all patients beginning methadone therapy and should not deter the appropriate use of methadone. The relatively small potential risk of adverse cardiac events with methadone should be weighed against the significant benefits of this analgesic. This paper briefly summarizes the published research concerning methadone effects on cardiac repolarization and TdP. Clinical suggestions are offered for identifying individual patient cardiac risk factors and for optimizing cardiac safety during methadone therapy.

Methadone-Associated Mortality – U.S. Government Reports

From: CSAT (Center for Substance Abuse Treatment), SAMHSA (Substance Abuse and Mental Health
           Services Administration), 2004.

A National Assessment of Methadone-Associated Mortality: Background Briefing Report
PDF available PDF available here for download: CSAT_Methadone_Briefing.pdf (658 KB; 77 pp)

Methadone-Associated Mortality: Report of a National Assessment
PDF available PDF available here for download: CSAT_Methadone_Report.pdf (422 KB; 60 pp)

SAMHSA LogoDuring 2002 and 2003, articles appeared in prominent newspapers describing methadone as “widely abused and dangerous.” These alarming reports arose from apparent increases in methadone-associated mortality. However, determining methadone’s role in such deaths was complicated by inconsistencies in methods of determining and reporting causes of death, the coinciding presence of other CNS drugs, and the absence of information about the decedent’s antemortem physical or mental condition and level of opioid tolerance.

In response to the concerns, SAMHSA’s Center for Substance Abuse Treatment convened a large multidisciplinary group of experts for a National Assessment of Methadone-Associated Mortality in May 2003. In preparation for this meeting, a “Background Briefing Report” was issued, containing research data and other information to help establish a common understanding of the problem. The findings and recommendations of the assessment group itself were summarized in a “Report of the National Assessment.” Together, the documents, published in 2004, provide a vital source of information regarding methadone, as well as expert analysis of both anecdotal and statistical reports of methadone-associated mortality.

Managing Opioid-Induced Constipation in Ambulatory-Care Patients

By: Clyde R. Goodheart, MD, MBA, MS; Stewart B. Leavitt, MA, PhD, August 2006.

PDF available PDF available here for download: Managing_Opioid-Induced_Constipation.pdf (180 KB; 9 pp)

Opioid-Induced_ConstipationConstipation is a frequent side effect of opioid therapy since these agents decrease peristaltic activity in the gastrointestinal tract. Because of the mechanisms involved in opioid-induced constipation, some treatments that may be applicable for common, functional constipation are inappropriate for ambulatory-care patients prescribed opioid analgesics.

The distress of constipation in these patients may add to the discomfort already present from pain, and they might decrease or discontinue opioid therapy to avoid constipation. So, motivating such patients to comply with their opioid regimen also requires a special approach for managing constipation.

Certain popular beliefs about treating constipation have little or no evidence to support them. For example, adding fluids or fiber to the diet, and increasing activity, may be unhelpful in patients with opioid-induced constipation. In most cases, laxative therapy will be needed for prevention or for treatment of existing constipation.

Opioid Tapering: Safely Discontinuing Opioid Analgesics

By: Lee A. Kral, PharmD, BCPS, March 2006.

PDF available PDF available here for download: Safely_Tapering_Opioids.pdf (140 KB; 7 pp)

Medication TaperingThere are many reasons for considering opioid analgesic tapering, both from healthcare-provider and patient perspectives. Whereas, guidance for starting opioid analgesics can be obtained from product package inserts and reference sources, it is much more difficult to find reliable information about switching or stopping these medications. Some practitioners have their own protocols for managing conversions or tapers; although, there is no single strategy that can be applied to all patients and each situation must be handled on an individual basis.

This paper discusses the many factors to consider when discontinuing opioid analgesics, and it presents specific and practical clinical guidance for establishing protocols that maximize patient safety and comfort during the process. Important advice for patients regarding emergency tapering – such as following natural disasters or other crises when medication is inaccessible – also is provided.

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Pain Treatment Topics and its associates do not endorse any medications, products, services, or treatments described, mentioned, or discussed in any of the resources in this section. Nor are any representations made concerning efficacy, appropriateness, or suitability of any such medications, products, services, or treatments for particular patients.

In view of the possibility of human error or advances in medical knowledge, Pain Treatment Topics and its associates do not warrant the information contained in the above Addiction Topics contents is in every respect accurate or complete, and they are not responsible nor liable for any errors or omissions made by the original sources or for results obtained from the use of this information.

Posted 10-26-06