Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain

Moksnes, Kristin; Kaasa, Stein; Paulsen, Ørnulf; Rosland, Jan Henrik; Spigset, Olav; Dale, Ola

doi:10.1007/s00228-012-1228-3

Cited by 16 publications

(9 citation statements)

References 37 publications

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“…Current practice recommends switching if patients fail to respond to an opioid, however, there is no evidence that one switch is better than another. Some switches are more complex than others [28], [29]. Switching opioids or combining them requires skilled clinicians who are aware of the latest evidence regarding appropriate doses, as well a carefully monitoring during the switch [26].…”

Section: Discussionmentioning

confidence: 99%

Managing Cancer Pain at the End of Life with Multiple Strong Opioids: A Population-Based Retrospective Cohort Study in Primary Care

et al. 2014

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BackgroundEnd-of-life cancer patients commonly receive more than one type of strong opioid. The three-step analgesic ladder framework of the World Health Organisation (WHO) provides no guidance on multiple opioid prescribing and there is little epidemiological data available to inform practice. This study aims to investigate the time trend of such cases and the associated factors.MethodsStrong opioid prescribing in the last three months of life of cancer patients were extracted from the General Practice Research Database (GPRD). The outcome variable was the number of different types of prescribed non-rescue doses of opioids (1 vs 2–4, referred to as a complex case). Associated factors were evaluated using prevalence ratios (PR) derived from multivariate log-binomial model, adjusting for clustering effects and potential confounding variables.ResultsOverall, 26.4% (95% CI: 25.6–27.1%) of 13,427 cancer patients (lung 41.7%, colorectal 19.1%, breast 18.6%, prostate 15.5%, head and neck 5.0%) were complex cases. Complex cases increased steadily over the study period (1.02% annually, 95%CI: 0.42–1.61%, p = 0.048) but with a small dip (7.5% reduction, 95%CI: −0.03 to 17.8%) around the period of the Shipman case, a British primary care doctor who murdered his patients with opioids. The dip significantly affected the correlation of the complex cases with persistent increasing background opioid prescribing (weighted correlation coefficients pre-, post-Shipman periods: 0.98(95%CI: 0.67–1.00), p = 0.011; 0.14 (95%CI: −0.85 to 0.91), p = 0.85). Multivariate adjusted analysis showed that the complex cases were predominantly associated with year of death (PRs vs 2000: 1.05–1.65), not other demographic and clinical factors except colorectal cancer (PR vs lung cancer: 1.24, 95%CI: 1.12–1.37).ConclusionThese findings suggest that prescribing behaviour, rather than patient factors, plays an important role in multiple opioid prescribing at the end of life; highlighting the need for training and education that goes beyond the well-recognised WHO approach for clinical practitioners.

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Section: Discussionmentioning

confidence: 99%

Managing Cancer Pain at the End of Life with Multiple Strong Opioids: A Population-Based Retrospective Cohort Study in Primary Care

et al. 2014

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“…Fifty (55.6%) and forty (44.4%) patients were switched to methadone via the 3-day switch (3DS) and stop and go (SAG) strategies, respectively. In the case of SAG, the current opioid is immediately substituted with methadone [ 23 , 24 ], while for 3DS, the dose of the current opioid is substituted stepwise with methadone over three days [ 25 , 26 ]. Univariate analysis revealed that switching via the 3DS strategy significantly improved the rate of successful switching (OR = 3.37, 95% CI: 1.30–8.76, p = 0.013) compared with switching via the SAG strategy.…”

Section: Resultsmentioning

confidence: 99%

Methadone switching for refractory cancer pain

et al. 2022

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Background Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone in the treatment of refractory cancer pain. Methods A retrospective study was conducted in patients who used methadone for refractory cancer pain from April 2016 to December 2020 at a cancer specialized hospital. Pain control, evaluated via pain score and breakthrough pain frequency, and adverse events of methadone were compared with analgesic regimens prior to methadone administration. The factors potentially affecting the switching outcome were analyzed via multivariate analysis. Moreover, the cost of pain control was estimated. Results Ninety patients received methadone for poor pain control (74.4%), intolerable adverse events (10.0%), or both (15.6%) after prior opioid treatments. Sixty-four patients (71.1%) were successfully switched to methadone with median pain score significantly decreased from 4.0 to 2.0 (p < 0.001) and median daily frequency of breakthrough pain from 3.0 to 0.0 (p < 0.001) at a maintained median conversion ratio of 6.3 [interquartile range (IQR): 4.0–10.0] to prior opioid treatment. Similar adverse event profiles of constipation, nausea, vomiting, and dizziness were observed between methadone and prior opioid regimens. The median daily cost of analgesic regimens was significantly reduced from $19.5 (IQR: 12.3–46.2) to $10.8 (IQR: 7.1–18.7) (p < 0.01) after switching to methadone. The 3-day switch method significantly improved the rate of successful switching compared with the stop and go method (odds ratio = 3.37, 95% CI: 1.30–8.76, p = 0.013). Conclusion Methadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain.

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“…11 A final potential limitation is that the data were collected during a three-day period 12 after switching, whereas the half-life of methadone ranges from three to five days. Although some authors recommend monitoring patients for up to five days after adjusting the methadone dose, 31 we believe that, for this study, such a long period would be excessive in stable patients with good symptom control who are candidates for hospital discharge. However, patients with a strong opioid tolerance might not develop toxicity in the first 72 hours after switching but could do so later.…”

Section: Study Strengths and Limitationsmentioning

confidence: 91%

“…30 Clinical trials in these populations should be multi-institutional to recruit sufficient patient numbers in a short period. 31 Another limitation is that some patients received subcutaneous methadone, while others received intravenous methadone. This was permitted to facilitate patient recruitment, and because, in the published literature, switching ratios for intravenous to subcutaneous methadone are considered the same (1:1).…”

Section: Study Strengths and Limitationsmentioning

confidence: 99%

Switching Ratio from Parenteral to Oral Methadone 1:1.2 Is Safer Compared with Ratio 1:2 in Patients with Controlled Cancer Pain: A Multicenter Randomized-Controlled Trial (RATIOMTD-010810)

González‐Barboteo

Porta-Sales

Nabal-Vicuña

et al. 2021

Journal of Palliative Medicine

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Background: The most commonly used switching ratio from parenteral to oral methadone is 1:2. Methadone is highly bioavailable and a lower ratio might result in similar analgesia with less toxicity. Objective: To compare success and side effects with two ratios from parenteral to oral methadone: 1:2 versus 1:1.2 in hospitalized patients with cancer pain. Design: A multicenter double-blind randomized clinical trial. Settings/Particiants: Inpatients with well-controlled cancer pain with parenteral methadone requiring rotation to the oral route. Measurements: Outcomes included pain intensity (Brief Inventory Pain), opioid toxicity (Common Toxicology Criteria for Adverse Events), and methadone dose. Success was defined as no toxicity with good pain control at 72 hours. Results: Thirty-nine of forty-four randomized patients were evaluable: 21 in ratio 1:2 and 18 in ratio 1:1.2. Seventyone percent male. Median age 65 years. No significant differences in basal clinical characteristics between both groups. Median methadone dose pre/post switching was 24.5 mg-13.5 and 49 mg-27.3 for ratio 1:2, versus 23.3 mg-9.4 (p: not significant) and 28 mg-11.3 (p < 0.01) for ratio 1:1.2. Pain was well controlled without differences between both ratios. Drowsiness at day +1 (p < 0.017) and myoclonus at day +3 (p < 0.019) were more prevalent in group 1:2. Success was observed in 12 patients in ratio 1:2 versus 18 in ratio 1:1.2 (p < 0.001). Methadone side effects were observed in 12 patients in ratio 1:2 (mainly neurotoxicity symptoms) versus 2 in ratio 1:1.2 (p < 0.005). Conclusion: Ratio 1:1.2 when changing from parenteral to oral methadone resulted in lower toxicity and no difference in analgesia. More conservative dose adjustment during methadone route change should be considered. European Clinical Trials Register (EudraCT No. 2010-024092-39).

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Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain

Cited by 16 publications

References 37 publications

Managing Cancer Pain at the End of Life with Multiple Strong Opioids: A Population-Based Retrospective Cohort Study in Primary Care

Managing Cancer Pain at the End of Life with Multiple Strong Opioids: A Population-Based Retrospective Cohort Study in Primary Care

Methadone switching for refractory cancer pain

Switching Ratio from Parenteral to Oral Methadone 1:1.2 Is Safer Compared with Ratio 1:2 in Patients with Controlled Cancer Pain: A Multicenter Randomized-Controlled Trial (RATIOMTD-010810)

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