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

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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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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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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Intravenous Methadone for Severe Cancer Pain: A Presentation of 10 Cases

ISRN Pain ◽

10.1155/2013/452957 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4

Author(s):

D. Lossignol ◽

I. Libert ◽

B. Michel ◽

C. Rousseau ◽

M. Obiols-Portis

Keyword(s):

Cancer Pain ◽

Pain Syndrome ◽

Oral Formulation ◽

Opioid Agonist ◽

Refractory Pain ◽

Day Range ◽

Starting Dose ◽

Reduction Of Pain ◽

Few Data ◽

Strong Opioids

Purpose. Methadone, a synthetic opioid agonist, is an effective alternative to strong opioids (morphine, hydromorphone, oxycodone, and buprenorphine) and is widely available as an oral formulation. Few data have been published so far on the use of intravenous (i.v.) methadone for the management of severe or refractory cancer pain. Methods. We followed 10 consecutives cancer patients with severe pain, treated with IV methadone. All had advanced disease and had already received strong opioids, some in association with ketamine. Pain was assessed at T0, T24 hours, and at the end of the treatment. Results. All patients benefited from the switch to IV methadone with a reduction of pain on VAS after 24 hours (median: 4/10; range 0–5) until the end of the treatment (all cases <3/10). The median starting dose was 100 mg/day (range 20–400) and the final dose remained stable with a median of 100 mg/day (range 27–700). The median duration of IV methadone was 11 days (range 2–59). No cardiac toxicity had been observed. Conclusions. IV methadone is an effective pain relieving alternative for the treatment of severe cancer pain, especially in refractory pain syndrome. Moreover, we did not observe any toxicity (neurological or cardiac) or any other major side effects and the treatment was overall well tolerated. More extensive comparative studies should be planned.

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Spinal analgesia for severe cancer pain: A retrospective analysis of 60 patients

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2017.04.073 ◽

2017 ◽

Vol 16 (1) ◽

pp. 140-145 ◽

Cited By ~ 7

Author(s):

Lauri Kiehelä ◽

Katri Hamunen ◽

Tarja Heiskanen

Keyword(s):

Cancer Pain ◽

Oral Morphine ◽

Common Adverse Effect ◽

Lower Limbs ◽

University Hospital ◽

Spinal Analgesia ◽

Intrathecal Catheter ◽

Opioid Dose ◽

Academic Center ◽

Spinal Administration

AbstractBackground and aimsPain is highly prevalent in advanced cancer, and in some patients refractory to conventional opioid treatment. For these patients, invasive methods of pain relief should be considered. Spinal administration of opioids has been shown to be an effective alternative in refractory cancer pain. The aim of this retrospective study was to collect information on the use of spinal analgesia for cancer pain in Helsinki University Hospital.MethodsA retrospective patient chart study of all cancer patients with spinal analgesia, either intrathecal or epidural, in a single academic center during a five year period (n = 60).ResultsForty-four patients were treated with intrathecal (IT) and sixteen with epidural (EP) technique. The most common indication for spinal analgesia was pain refractory to systemic analgesics. Good analgesia was achieved in 50% and 70% of the patients in the EP and IT groups, respectively. The median daily systemic opioid doses prior to spinal analgesia were 874.5 mg and 730.5 mg as oral morphine equivalents in the IT and EP groups, respectively. The systemic opioid could be discontinued or significantly reduced in 83% of the patients. Morphine was used in all IT infusions and most EP infusions, mostly combined with bupivacaine 10mg (IT) or 66mg (EP). The median starting doses of morphine were 3 mg/day (IT) and 19 mg/day (EP) and were increased during titration 27% to 3.8 mg/day (IT) and 91% to 36.2 mg/day (EP). Clonidine (median 0.015 mg/day IT and 0.15 mg/day EP) and/or ketamine were used as adjuvants. The average titration time to stable analgesia was 7–9 days. Numbness in lower limbs was reported by 24% of the IT group. On average, catheters were placed 98 and 61 days before death in IT and EP groups, respectively. No serious complications occurred. Catheter dislocation occurred in 27% of all sixty patients during follow-up. Treatment was discontinued in 10 patients because of catheter dislocation (n =7) or local infection (n = 3).Conclusions and implicationsSpinal administration of opioids is a safe and effective method of pain management in patients with severe cancer pain and can greatly reduce the need of systemic opioids. We are implementing closer collaboration with oncologists to provide spinal analgesia to more patients and earlier to reduce suffering. Catheter dislocation led to discontinuation of spinal analgesia in 17% of the patients and we are evaluating new ways to prevent catheter dislocation. The initial median spinal opioid dose was too low in both groups, and we are now using higher initial doses. A common adverse effect was numbness of the lower limbs, regardless of the relatively low doses of spinal bupivacaine. We now use lower doses and introduce the intrathecal catheter higher at L1–2 to reduce motor blockade at the level of conus.As an initial intrathecal infusions we suggest: morphine dose calculated using an oral to intrathecal ratio of 1:100 (unless the patient is elderly or already drowsy), clonidine dose 30μg/day and bupivacaine dose 7.5 mg/day.

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Oramorph - two liquid morphine formulations

Drug and Therapeutics Bulletin ◽

10.1136/dtb.27.18.71 ◽

1989 ◽

Vol 27 (18) ◽

pp. 71-72

Keyword(s):

Aqueous Solution ◽

Cancer Pain ◽

Community Pharmacy ◽

Initial Dose ◽

Slow Release ◽

Oral Morphine ◽

Morphine Sulphate ◽

Dose Titration

Oral morphine is the standard analgesic for severe opioid-responsive cancer pain.1 It is traditionally used as an aqueous solution, prepared as needed by the hospital or community pharmacy, and although slow-release morphine sulphate tablets (MST-Continus) are now widely used many doctors still prescribe an aqueous solution for initial dose titration, for top-up use, “as needed” use and for patients who dislike tablets.2

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The current clinical use of adjuvant analgesics for refractory cancer pain in Japan: a nationwide cross-sectional survey

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa147 ◽

2020 ◽

Vol 50 (12) ◽

pp. 1434-1441

Author(s):

Keita Tagami ◽

Hiromichi Matsuoka ◽

Keisuke Ariyoshi ◽

Shunsuke Oyamada ◽

Yusuke Hiratsuka ◽

...

Keyword(s):

Palliative Care ◽

Cancer Pain ◽

Online Survey ◽

Cord Compression ◽

Dose Titration ◽

Pathophysiological Mechanism ◽

Cross Sectional Survey ◽

Cross Sectional ◽

First Response ◽

Starting Dose

Abstract Background Although adjuvant analgesics are used to treat opioid-refractory cancer pain, there is insufficient evidence to support this practice and limited data to guide the choice depending on cancer pain pathophysiology, dose titration and starting dose. This survey aimed to clarify the current use of adjuvant analgesics for treating opioid-refractory cancer pain. Methods In this cross-sectional study, we sent an online survey questionnaire to 208 certified palliative care specialists. Primary outcomes were (i) effective pathophysiological mechanism of cancer pain and (ii) initiating doses and time period to the first response to each adjuvant analgesic therapy. Results In total, 87 (42%) palliative care specialists responded. Of all patients with cancer pain, 40% of patients (median) with refractory cancer pain were prescribed adjuvant analgesics. Additionally, 94.3, 93.1 and 86.2% of palliative care specialists found dexamethasone/betamethasone effective for neuropathic pain caused by tumor-related spinal cord compression, pregabalin effective for malignant painful radiculopathy and dexamethasone/betamethasone effective for brain tumor or leptomeningeal metastases-related headache, respectively. The median starting dose of pregabalin, dexamethasone/betamethasone, lidocaine and ketamine were 75, 4, 200, and 50 mg/day, respectively, and the median time to the first response of those medications were 5, 3, 2 and 3 days, respectively. Conclusions Many palliative care specialists select adjuvant analgesics depending on the pathophysiological mechanism of cancer pain in each case. They used such adjuvant analgesics in low doses for cancer pain with short first-response periods.

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Lack of correlation between the effective dose of fentanyl sublingual spray for breakthrough cancer pain and the around-the-clock opioid dose

Journal of Opioid Management ◽

10.5055/jom.2014.0212 ◽

2014 ◽

Vol 10 (4) ◽

pp. 247 ◽

Cited By ~ 6

Author(s):

Srinivas R. Nalamachu, MD ◽

Neha Parikh ◽

Larry Dillaha, MD ◽

Richard Rauck, MD

Keyword(s):

Pain Relief ◽

Cancer Pain ◽

Effective Dose ◽

Rank Correlation ◽

Dose Titration ◽

Open Label ◽

Double Blind ◽

Breakthrough Cancer Pain ◽

Opioid Dose ◽

Titration Phase

Objective: To examine the relationship between the dose of fentanyl sublingual spray needed to control breakthrough cancer pain (BTCP) and the dose of around-the-clock (ATC) opioid used to control background pain.Design: Analysis was based on the open-label, dose-titration phase (up to 26 days) of a randomized, double-blind, placebo-controlled trial.Patients: Opioid-tolerant cancer patients (aged ≥18 years) with chronic pain of ≤moderate severity in the 24 hours before screening while receiving stable doses of scheduled ATC opioid therapy for ≥1 week and 1 to 4 episodes of BTCP per day.Interventions: Fentanyl sublingual spray was initiated at 100 μg. Dose titration proceeded until a dose was reached that provided adequate pain relief for two consecutive BTCP episodes without intolerable adverse effects (AEs).Results: Overall, 98/130 (75.4 percent) patients completed the dose-titration phase and achieved pain relief, and 73.5 percent of those who completed the titration period attained an effective dose of ≥600 μg (median effective dose, 800 μg). No clinically relevant correlation was found between effective doses of fentanyl sublingual spray for the treatment of BTCP and the ATC opioid doses used to control persistent pain (Spearman rank correlation [rs ] = 0.351, n = 98). Sixty percent of patients reported ≥1 AE during the dose-titration phase. The most common AEs considered related to study treatment were nausea (6.2 percent), somnolence (4.6 percent), dizziness (3.8 percent), and vomiting (3.8 percent).Conclusions: These findings highlight the importance of titrating the dose of fentanyl sublingual spray to optimize dosing for individual patients.

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

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.8617 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 8617-8617

Author(s):

P. W. Walker ◽

E. Bruera ◽

B. Pei ◽

G. Kaur ◽

K. Zhang ◽

...

Keyword(s):

Oral Morphine ◽

Dose Ratio ◽

Opioid Agonist ◽

Opioid Rotation ◽

Stable Dose ◽

Opioid Dose ◽

Pain Syndromes ◽

New Findings ◽

Multiple Routes ◽

Oral Morphine Equivalent

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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