Switching from methadone to a different opioid: What is the equianalgesic dose ratio?

8617 Background: Methadone (ME) is a highly effective opioid agonist used for difficult pain syndromes. However, the rotation from ME to another opioid may be difficult because of the absence of a uniformly accepted conversion ratio. Methods: We retrospectively reviewed consecutive medical records of Pts undergoing an opioid rotation from ME to an alternative opioid. For inclusion, Pts were required to have received ME for at least 3 days prior to the switch and reach a stable dose of the alternative opioid(s) during 7 days following. Stable dose was defined as a 30% or less change in opioid dose from one day to the next. For purposes of analysis, on the day before the switch, doses, were divided into ME doses and the oral morphine equivalent daily dose (MEDD), based on medication and route of all other opioids taken on that day, using standard equinalgesic tables. All doses after the switch were converted to the MEDD. For Pts receiving ME and a second opioid prior to the switch, the MEDD of the second opioid was subtracted from the MEDD calculated for the day when stable dose was reached. The remainder was used to calculate the equianalgesic raio with the previous ME dose. Results: Records on 39 Pts met inclusion criteria. Excluded from analysis were 5 Pts who were restarted on ME in < 8 days, 2 whose opioid dose markedly decreased of post switch, and 3 due to concerns about reliability of multiple routes used for fentanyl. Data from 29 Pts, 10 female, mean age 48 ±14.4 were evaluable. The ratio for: oral ME to MEDD was 1:4.7 (CL 3.0–6.5)(n=16), IV ME to MEDD was 1:13.5 (CL6.6–20.5)(n=13), p=0.06. ME dose is significantly correlated to stable MEDD after switching opioids for both ME IV and oral (Spearman=0.86,p=0.0001 and Spearman=0.72, p=0.0024, respectively. Mean day of achieving stable dose was on day 2.5 ±0.2 for IV ME and day 2.6±0.3 for oral ME. Conclusions: These dose ratios are new findings that will assist in switching Pts more safely to alternative opioids, when side effects or pain problems occur.An important difference in analgesic potency appears to exist between IV and oral ME. Further research with prospective studies is required. No significant financial relationships to disclose.

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The conversion ratio from intravenous (IV) hydromorphone to oral (PO) opioids in patients with cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.26_suppl.197 ◽

2016 ◽

Vol 34 (26_suppl) ◽

pp. 197-197

Author(s):

Akhila Sunkepally Reddy ◽

Sara Dost ◽

Marieberta Vidal ◽

Saneese Stephen ◽

Karen Baumgartner ◽

...

Keyword(s):

Palliative Care ◽

Linear Regression Analysis ◽

Oral Morphine ◽

Patient Characteristics ◽

Conversion Ratio ◽

Opioid Rotation ◽

Patients With Cancer ◽

Daily Dose ◽

Oral Morphine Equivalent ◽

Morphine Equivalent

197 Background: Inpatients with cancer frequently undergo conversions from IV to PO hydromorphone (HM) or opioid rotation (OR) from IV HM to another PO opioid prior to discharge. Currently used conversion ratios (CR) between IV and PO HM range from 2-5 and opioid rotation ratios (ORR) between IV HM and oral morphine equivalent daily dose (MEDD) range from 10-20. This large variation in ratios may lead to uncontrolled pain or overdosing. Our aim was to determine the accurate CR from IV to PO HM and ORR from IV HM to PO morphine and oxycodone (measured as MEDD). Methods: We reviewed records of 4745 consecutive inpatient palliative care consults in our institute during 2010-14 for patients who underwent conversion from IV to PO HM or OR from IV HM to PO morphine or oxycodone. Patient characteristics, symptoms and opioid doses were determined in patients successfully discharged on oral opioids without readmission within 1 week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV HM mg dose prior to conversion to PO and the oral opioid mg dose used in the 24 hours prior to discharge. Results: Among 394 eligible patients on IV HM, 147 underwent conversion to PO HM and 247 underwent OR to oral morphine (163) or oxycodone (84). Mean age was 54 years, 39% were male, and 95% had advanced cancer. Median time between conversion to PO and discharge was 2 days. In 147 patients the median CR (IQR) from IV to PO HM was 2.5 (2.1-2.7) and correlation of IV to PO dose of HM was .95 (P < .0001). The median CR was 2.5 in patients receiving < 30mg of IV HM/day and 2.1 in patients receiving ≥ 30mg of HM/day (P = .004). In 247 patients the median ORR (IQR) from IV HM to MEDD was 11.5 (10-13) and correlation of IV HM to MEDD was .93 (P < .0001). The median ORR was 11.5 in patients receiving < 30mg of IV HM/day and 9.9 in patients receiving ≥ 30mg of HM/day (P = .0004). ORR from IV HM to MEDDs obtained from morphine (11) and oxycodone (12.1) were significantly different (P = .0023). The CR and ORR were not significantly impacted by other variables. Conclusions: The median CR from IV to PO HM is 2.5 and ORR from IV HM to MEDD is 11.5. This implies that 1 mg IV HM is equivalent to 2.5 mg PO HM and 11.5 mg MEDD. HM may cause hyperalgesia at doses ≥ 30 mg/day and thereby requires a lower ORR to other opioids.

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Opioid rotation from transdermal fentanyl to continuous subcutaneous hydromorphone in a cachectic patient: A case report and review of the literature

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220929415 ◽

2020 ◽

pp. 107815522092941 ◽

Cited By ~ 1

Author(s):

Lawrence D Jackson ◽

Rachel Wortzman ◽

Debbie Chua ◽

Debbie Selby

Keyword(s):

Case Report ◽

Oral Morphine ◽

Metastatic Breast ◽

High Dose ◽

Transdermal Fentanyl ◽

Academic Medical Centre ◽

Opioid Rotation ◽

Transdermal Fentanyl Patch ◽

Oral Morphine Equivalent ◽

End Stage

Opioid rotation from transdermal fentanyl to an alternate opioid is often necessitated in advanced disease, but is fraught with uncertainty due to variable absorption from the patch in end-stage illness and the lack of a clearly established opioid rotation ratio. The manufacturer of transdermal fentanyl provides opioid rotation recommendations only for rotation from the oral morphine equivalent daily dose (MEDD) of opioid to the patch, not in the opposite direction. This is a case report of a single patient with cancer and cachexia admitted to the palliative care unit of a large academic medical centre in Canada. The patient is a 50-year-old female with widely metastatic breast cancer who developed opioid toxicity when maintenance transdermal fentanyl patch therapy (100 μg patch applied every 72 h) was rotated to subcutaneous hydromorphone infusion to improve pain control. Hydromorphone was initiated at a rate of 1 mg/h by continuous infusion based on an opioid rotation ratio for transdermal fentanyl (μg/h):MEDD (mg/day) of 1:2.4. Opioid toxicity eventually resolved with downward titration of hydromorphone to only 30% of the initially estimated equianalgesic dose. This case highlights the need for close follow-up of all patients undergoing opioid rotation from transdermal fentanyl and reinforces the need to reduce the initial dose of the new opioid by 30%–50% of the calculated MEDD, especially when rotating from a high dose of transdermal fentanyl, or if there are factors potentially impairing absorption from the patch such as age, cachexia and weight loss, or if rotation is performed for reasons other than uncontrolled pain.

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Evaluation of the Japanese opioid conversion ratio for switching to methadone for cancer pain control.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.26_suppl.196 ◽

2016 ◽

Vol 34 (26_suppl) ◽

pp. 196-196

Author(s):

Yoshinobu Matsuda ◽

Sachiko Okayama ◽

Yoshito Yoshikawa ◽

Yoshio Kobayashi

Keyword(s):

Cancer Pain ◽

Oral Morphine ◽

Conversion Ratio ◽

Dose Titration ◽

Rapid Progression ◽

Methadone Dose ◽

Opioid Dose ◽

Refractory Pain ◽

Starting Dose ◽

Oral Morphine Equivalent

196 Background: In Japan, oral administration of methadone was approved for patients with cancer pain in March 2013. As methadone exhibits complex pharmacokinetics with individual differences and rare but serious adverse effects, methadone is only prescribed as a fourth-line drug by cancer pain specialists, who must start methadone according to the following table and must not increase methadone dose within 7 days. Aims: To assess the validity of the Japanese opioid conversion ratio. Methods: The clinical characteristics of 60 patients who were prescribed oral methadone between April 2013 and March 2016 were analyzed. Results: The switch from other opioids to methadone was initiated due to refractory pain in the stop-and-go switching. According to the table in Japan, the starting dose of methadone ranged from 15-45mg/day, depending on the previous opioid dose. Fifty cases (11 outpatients, 39 inpatients) were successfully switched to methadone; although 10 cases subsequently exhibited rapid progression of illness and failed due to oral difficulty during the course of dose titration. At the outset, the average oral morphine equivalent daily dose before methadone administration was 155mg (range, 40-660mg) and the starting methadone dose was 10 mg in 2 cases (extremely old age and multi-drug taking), 15 mg in 35 cases, 30 mg in 11 cases and 45 mg in 2 cases. Upon completion of the dose titration according to the Japanese definition, the methadone dose was the same as the starting dose in 21 cases, and was decreased or increased from the starting dose in 5 and 24 cases, respectively. Conclusions: TheJapanese opioid conversion ratio might be better corrected in the near future. For example, it is good to be able to start with 10mg or 20 mg because minute changes might lead the performance of low dose titration in some cases. It should be possible to increase the dose of methadone after 3 or 4 days from the later change based upon the pain severity. [Table: see text]

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Percutaneous cervical cordotomy for cancer-related pain: prospective multimodal outcomes evaluation

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2019-002084 ◽

2020 ◽

pp. bmjspcare-2019-002084

Author(s):

Aimee Doyle ◽

Manohar Lal Sharma ◽

Manish Gupta ◽

Andreas Goebel ◽

Kate Marley

Keyword(s):

Quality Of Life ◽

Group Performance ◽

Breakthrough Pain ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Oral Morphine ◽

Opioid Dose ◽

Oral Morphine Equivalent ◽

Global Impression Of Change

BackgroundPercutaneous cervical cordotomy (PCC) offers pain relief to patients with unilateral treatment-refractory cancer-related pain. There is insufficient evidence about any effects of this intervention on patients’ quality of life.MethodComprehensive multimodal assessment to determine how PCC affects pain, analgesic intake and quality of life of patients with medically refractory, unilateral cancer-related pain.This study was set in a multidisciplinary, tertiary cancer pain service. Patient outcomes immediately following PCC were prospectively recorded. Patients were also followed up at 4 weeks.ResultsOutcome variables collected included: background and breakthrough pain numerical rating scores before PCC, at discharge and 4 weeks postprocedure; oral morphine equivalent opioid dose changes, Patient’s Global Impression of Change, Eastern Cooperative oncology group performance status and health related quality of life score, that is, EuroQol-5 dimension-5 level (EQ-5D).ConclusionsDespite significant improvement in pain and other standard outcomes sustained at 4 weeks, there was little evidence of improvement in EQ-5D scores. In patients with terminal cancer, improved pain levels following cordotomy for cancer-related pain does not appear to translate into improvements in overall quality of life as assessed with the generic EQ-5D measure.

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Implementation of a patient-specific tapering protocol at discharge decreases total opioid dose prescribed for 6 weeks after elective primary spine surgery

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-2020-101324 ◽

2020 ◽

Vol 45 (6) ◽

pp. 474-478

Author(s):

Sarah S Joo ◽

Oluwatobi O Hunter ◽

Mallika Tamboli ◽

Jody C Leng ◽

T Kyle Harrison ◽

...

Keyword(s):

Spine Surgery ◽

Joint Replacement ◽

Oral Morphine ◽

Hospital Length ◽

Opioid Consumption ◽

Hospital Length Of Stay ◽

Patient Specific ◽

Opioid Dose ◽

Before And After ◽

Primary Spine

Background and objectivesAt our institution, we developed an individualized discharge opioid prescribing and tapering protocol for joint replacement patients and implemented the same protocol for neurosurgical spine patients. We then tested the hypothesis that this protocol will decrease the oral morphine milligram equivalent (MME) dose of opioid prescribed postdischarge after elective primary spine surgery.MethodsIn this retrospective cohort study, we identified all consecutive elective primary spine surgery cases 1 year before and after introduction of the protocol. This protocol used the patient’s prior 24-hour inpatient opioid consumption to determine discharge opioid pill count and tapering schedule. The primary outcome was total opioid dose prescribed in oral MME from discharge through 6 weeks. Secondary outcomes included in-hospital opioid consumption in MME, hospital length of stay, MME prescribed at discharge, opioid refills, and rates of minor and major adverse events.ResultsEighty-three cases comprised the final sample (45 preintervention and 38 postintervention). There were no differences in baseline characteristics. The total oral MME (median (IQR)) from discharge through 6 weeks postoperatively was 900 (420–1440) preintervention compared with 300 (112–806) postintervention (p<0.01, Mann-Whitney U test), and opioid refill rates were not different between groups. There were no differences in other outcomes.ConclusionsThis patient-specific prescribing and tapering protocol effectively decreases the total opioid dose prescribed for 6 weeks postdischarge after elective primary spine surgery. Our experience also demonstrates the potential generalizability of this protocol, which was originally designed for joint replacement patients, to other surgical populations.

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Treatment of chronic noncancer pain in patients on opioid therapy in primary care: A retrospective cohort study

Canadian Pharmacists Journal / Revue des Pharmaciens du Canada ◽

10.1177/1715163519887766 ◽

2019 ◽

Vol 153 (1) ◽

pp. 52-58

Author(s):

Arden R. Barry ◽

Chantal E. Chris

Keyword(s):

Primary Care ◽

Cohort Study ◽

Back Pain ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Opioid Therapy ◽

Opioid Agonist ◽

Chronic Noncancer Pain ◽

Opioid Dose ◽

Noncancer Pain

Background: This study sought to characterize the real-world treatment of chronic noncancer pain (CNCP) in patients on opioid therapy in primary care. Methods: A retrospective cohort study from 2014-18 was conducted at a multidisciplinary primary care clinic in Chilliwack, British Columbia. Included were adults on daily opioid therapy for CNCP. Patients receiving palliative care or ≤1 visit were excluded. Outcomes of interest included use of opioid/nonopioid pharmacotherapy, number/frequency of visits and proportion of patients able to reduce/discontinue opioid therapy. Results: Seventy patients (mean age 53 years, 53% male, 51% back pain) were included. Median follow-up was 6 visits over 12 months. Sixty-two patients (89%) reduced their opioid dose, 6 patients had no change and 2 patients required a dose increase. Mean opioid dose was reduced from 183 to 70 mg morphine equivalents daily. Twenty-four patients (34%) discontinued opioid therapy, 6 patients (9%) transitioned to opioid agonist therapy and 6 patients (9%) breached their opioid treatment agreement. Nonopioid pharmacotherapy included nonsteroidal anti-inflammatory drugs (64%), gabapentinoids (63%), tricyclic antidepressants (56%) and nabilone (51%). Discussion: Over half of patients were no longer on opioid therapy by the end of the study. Most patients had a disorder (e.g., back pain) for which opioids are generally not recommended. Overall mean opioid dose was reduced from baseline by approximately 60% over 1 year. Lack of access to specialized pain treatments may have accounted for high nonopioid pharmacotherapy usage. Conclusions: This study demonstrates that treatment of CNCP and opioid tapering can successfully be achieved in a primary care setting. Can Pharm J (Ott) 2020;153:xx-xx.

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The Prevalence and Characteristics of Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain

Cancers ◽

10.3390/cancers13051058 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1058

Author(s):

Sebastiano Mercadante ◽

Marco Maltoni ◽

Domenico Russo ◽

Claudio Adile ◽

Patrizia Ferrera ◽

...

Keyword(s):

Pain Relief ◽

Cancer Pain ◽

Oral Morphine ◽

Epidemiological Data ◽

Low Doses ◽

Advanced Cancer Patients ◽

Breakthrough Cancer Pain ◽

Background Pain ◽

The Mean ◽

Oral Morphine Equivalent

The aim of this study was to assess the prevalence and characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain. A consecutive sample of advanced cancer patients receiving less than 60 mg/day of oral morphine equivalent (OME) was selected. Epidemiological data, background pain intensity, and current analgesic therapy were recorded. The presence of BTcP was diagnosed according to a standard algorithm. The number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, satisfaction with BTcP medication, and time to meaningful pain relief were collected. A total of 126 patients were screened. The mean intensity of background pain was 2.71 (1.57), and the mean OME was 28.5 mg/day (SD15.8). BTP episodes were recorded in 88 patients (69.8%). The mean number/day of BTP episodes was 4.1 (SD 7.1, range 1–30). In a significant percentage of patients, BTcP was both predictable and unpredictable (23%). The BTcP onset was less than 20 min in the majority of patients. The mean duration of untreated episodes was 47.5 (SD 47.6) minutes. The mean time to meaningful pain relief after taking a BTcP medication was >20 min in 44.5% of patients. The efficacy of BTcP medication was not considered good in more than 63% of patients. Gender (females) (OR = 4.16) and lower Karnofsky (OR = 0.92) were independently associated with BTcP. A higher number of BTcP episodes/day was associated with gender (females) (p = 0.036), short duration of BTcP (p = 0.005), poorer efficacy of BTcP medication (none or mild) (p = 0.001), and late meaningful pain relief (p = 0.024). The poor efficacy of BTcP medication was independently associated with a higher number of episodes/day (OR = 0.22). In patients who were receiving low doses of opioids, BTcP prevalence was 69.8%. Many patients did not achieve a sufficient level of satisfaction with BTcP medications, particularly with oral morphine. Data also suggest that better optimization of background analgesia, though apparently acceptable, may limit the number of BTcP episodes.

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Morphine-Methadone Opioid Rotation in Cancer Patients: Analysis of Dose Ratio Predicting Factors

Journal of Pain and Symptom Management ◽

10.1016/j.jpainsymman.2008.05.016 ◽

2009 ◽

Vol 37 (6) ◽

pp. 1061-1068 ◽

Cited By ~ 27

Author(s):

Miguel Angel Benítez-Rosario ◽

Antonio Salinas-Martín ◽

Armando Aguirre-Jaime ◽

Lina Pérez-Méndez ◽

Manuel Feria

Keyword(s):

Cancer Patients ◽

Dose Ratio ◽

Opioid Rotation ◽

Predicting Factors

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OP0088 INITIATING TNF INHIBITORS IN INFLAMMATORY ARTHRITIS DOES NOT DECREASE THE AVERAGE OPIOID ANALGESIC CONSUMPTION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2587 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 58.2-59

Author(s):

O. Palsson ◽

T. Love ◽

J. K. Wallman ◽

M. C. Kapetanovic ◽

P. S. Gunnarsson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Inflammatory Arthritis ◽

Opioid Analgesic ◽

Oral Morphine ◽

Undifferentiated Arthritis ◽

First Line ◽

The Mean ◽

Oral Morphine Equivalent ◽

Morphine Equivalent

Background:TNFα-inhibitor (TNFi) therapy is effective in controlling several rheumatic diseases and has been shown to reduce pain in patients with arthritis. Opioids are often prescribed for chronic pain, a common issue in inflammatory joint disease.Objectives:To explore the impact of the initiation of TNFi therapy as a first-line biologic disease-modifying anti-rheumatic drug (DMARD) on the prescription rates of opioids in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and undifferentiated arthritis (UA) in Iceland.Methods:All patients receiving biologic DMARD therapy for rheumatic diseases in Iceland are registered in a nationwide database (ICEBIO). The Icelandic Directorate of Health operates a Prescription Medicines Register that includes over 90% of all drug prescriptions in Iceland. The study group included patients with RA, PsA, AS, and UA registered in ICEBIO and for each of them five randomly selected comparators from the general population matched on age, sex, and calendar time. On February 1st2016 we extracted data on all filled opioid analgesic prescriptions two years before and two years after the date of TNFi initiation.Results:Data from 359 RA, 217 AS, 251 PsA and 113 UA patients and 4700 comparators were collected. In total, 75% of patients compared to 43% of comparators received ≥1 opiate prescription during the study period. The proportion of patients using opioids (regardless of dose) two years prior to TNFi initiation was 41%, increasing to 49% the following year. After TNFi initiation the proportion returned to 40% (Figure 1). Despite this, the mean yearly opiate dose used by the patients followed a rising trajectory throughout the study period (Figure 2). In total, patients were prescribed nearly 6 times more opioids than the comparators, corresponding to a bootstrapped mean (95% CI) dose of 818 (601-1073) mg MED per patient and year compared to 139 (111-171) mg for comparators.Figure 1.Percental distributions of opioid analgesic use by dose (according to dispensed prescriptions) among patients with inflammatory arthritis (A) and matched comparators (B). All doses are oral morphine equivalent dose (MED) in milligrams.Figure 2.Bootstrapped mean oral morphine equivalent dose per person per year for patients with inflammatory arthritis (above) and age and sex matched comparators (below). Box edges represent 25-75thpercentiles and whiskers 95% confidence intervals.Conclusion:Three out of four patients with inflammatory arthritis in Iceland use opioid analgesics in the two years prior to and/or after the initiation of TNFi therapy and the mean doses were significantly higher than in matched comparators. The proportion of patients receiving opioids increased before TNFi therapy and then decreased again to the previous level. The initiation of the first-line TNFi did not reduce opioid consumption by dose at the group level. On the contrary, there was a trend towards increasing doses over time in both patients and comparators, possibly reflecting the development of opiate tolerance.Table 1.Baseline demographic data. Mean ± SD unless specified. * defined from diagnosis to baselAll patientsRheumatoid arthritisPsoriatic arthritisAnkylosing spondylitisUndifferentiated arthritisTotal n (%)940 (100)359 (38)251 (27)217 (23)113 (12)Age (years)49 ± 1453 ± 1449 ± 1343 ± 1344 ± 15Disease duration (years)*7.8 ± 8.58.2 ± 8.27.4 ± 7.88.3 ± 10.26.3 ± 6.6Female58%73%59%34%52%Disclosure of Interests:Olafur Palsson: None declared, Thorvardur Love: None declared, Johan K Wallman Consultant of: Consultant for AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma., Meliha C Kapetanovic: None declared, Petur S Gunnarsson: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen

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