There was no evidence to support the superiority of one method of rotation to methadone over another. Patients may be successfully rotated to methadone despite discrepancies between rotation ratios initially used and those associated with stabilization. Further research is needed to identify patient-level factors that may explain the wide variance in successful methadone rotations.
Objective. To identify and characterize methadone-related drug interactions, as well as factors accounting for the variability in manifesting these interactions clinically.Design. Systematic review of the primary literature.Methods. Over 200 articles, reports of clinical trials, and case reports were reviewed. Studies and case reports were included if they revealed either quantitative or qualitative methods to identify, evaluate severity of, or compare methadone-related drug interactions.Results of Data Synthesis. The evidence base associated with methadone drug interactions is underdeveloped in general, as the majority of references found were case reports or case series. Most of the studies and reports focused on inpatients receiving methadone maintenance treatment (MMT) that were between 20 and 60 years of age, taking 200 mg/day of methadone or less. Evidence supporting the involvement of lesser known cytochrome P450 enzymes such as 2B6 is emerging, which may partially explain the inconsistencies previously found in studies looking specifically at 3A4 in vitro and in vivo . Genetic variability may play a role in the pharmacokinetics and pharmacodynamics of many medications, including methadone.Conclusions. Drug interactions associated with methadone and their clinical significance are still poorly understood in general. Many tertiary drug information references and review articles report interactions associated with methadone in a general sense, much of which is theoretical and not verified by case reports, much less well-designed clinical trials. The majority of drug interaction reports that do exist were performed in the MMT population, which may differ significantly from chronic pain or cancer pain populations.
There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved.
Despite its potential clinical and economic benefits, methadone is not commonly prescribed for the hospice patient in the home-care setting. Clinicians may be more aware of the usefulness of methadone in the treatment of neuropathic pain.
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