Serum Concentration of Fentanyl During Conversion From Intravenous to Transdermal Administration to Patients With Chronic Cancer Pain

Nomura, Motoo; Inoue, Kōichi; Matsushita, Shoko; Takahari, Daisuke; Kondoh, Chihiro; Shitara, Kohei; Umemura, Takashi; Hayashi, Kenji; Kojima, Hiroyuki; Kamata, Minoru; Tatematsu, M; Hosoda, Renko; Sawada, Satoshi; Oka, Hisao; Muro, Kei

doi:10.1097/ajp.0b013e318266f6a5

Cited by 22 publications

(23 citation statements)

References 14 publications

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“…It was reported previously that albumin levels and BMI interfered with the ORR to TDF . However, in our study, the ORR from MEDD to TDF did not significantly change in patients who had lower albumin and BMI.…”

Section: Discussioncontrasting

confidence: 72%

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients

Reddy

Tayjasanant

Haider

et al. 2015

Cancer

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BACKGROUND: Transdermal fentanyl (TDF) is 1 of the most common opioids prescribed to patients with cancer. However, the accurate opioid rotation ratio (ORR) from other opioids to TDF is unknown, and various currently used methods result in wide variation of the ORR. The objective of this study was to determine the ORR of the oral morphine equivalent daily dose (MEDD) to the TDF dose when correcting for the MEDD of breakthrough opioids (the net MEDD) in cancer outpatients. METHODS: The records of 6790 consecutive patients were reviewed at the authors' supportive care center from 2010 to 2013 to identify those who underwent rotation from other opioids to TDF. Data regarding Edmonton Symptom Assessment Scale scores and MEDDs were collected for patients who returned for a follow-up visit within 5 weeks. Linear regression analysis was used to estimate the ORR between the TDF dose and the net MEDD (the MEDD before opioid rotation [OR] minus the MEDD of the breakthrough opioid used along with TDF after OR). RESULTS: In total, 129 patients underwent OR from other opioids to TDF. The mean patient age was 56 years, 59% were men, and 88% had advanced cancer. Uncontrolled pain (80%) was the most frequent reason for OR. In 101 patients who underwent OR and had no worsening of pain at follow-up, the median ORR from net MEDD to TDF (in mg per day) was 0.01 (range, 20.02 to 0.04), and the correlation coefficient of the TDF dose to the net MEDD was 0.77 (P <.0001). The ORR was not significantly impacted by body mass index or serum albumin. The ORR of 0.01 suggests that an MEDD of 100 mg is equivalent to 1 mg TDF daily or approximately 40 micrograms per hour of TDF (1000 micrograms/24 hours). CONCLUSIONS: The median ORR from MEDD to TDF in mg per day was 0.01. These results warrant further studies Cancer 2016;122:149-56. V C 2015 American Cancer Society.KEYWORDS: cancer pain, cancer patients, conversion ratio, fentanyl transdermal, morphine equivalent daily dose, opioid rotation, supportive care. INTRODUCTIONA large majority of patients with cancer experience pain. 1 Opioids are the preferred medications to treat cancer-related pain. 2,3 Chronic use of opioids may result in accumulation of the parent opioid and its metabolites, resulting in opioidinduced neurotoxicity (OIN), characterized by symptoms such as excessive sedation, delirium, hallucinations, myoclonus, and seizures. 4 The preferred treatment for OIN and refractory pain involves opioid rotation (OR), which is substituting 1 opioid by another using equianalgesic tables. [5][6][7][8][9][10][11][12] The lack of accurate OR ratios (ORRs) from 1 opioid to another can result in uncontrolled pain, overdosing, or even fatal outcomes. 13,14 Moreover, there are several published equianalgesic tables involving inconsistent ORRs, 13 and most of the evidence supporting the ratios are studies involving a single-dose administration rather than chronic opioid administration. 15 Almost 33% of cancer patients receiving opioids will require OR. 16,17 Apart from uncontrolled pain and OIN...

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Section: Discussioncontrasting

confidence: 72%

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients

Reddy

Tayjasanant

Haider

et al. 2015

Cancer

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“…Comparison of patients whose serum albumin levels were ≥3.0 g/dL with those whose levels were <2.5 g/dL with respect to pain control based on NRS scores showed that a higher percentage of patients responded to fentanyl in the former group. Nomura et al 16) administered transdermal fentanyl to patients with low or normal serum albumin levels and assessed the changes in serum fentanyl concentrations. They found no significant difference between the 2 groups up to 6 h after patch application.…”

Section: Discussionmentioning

confidence: 99%

“…14,15) Nomura et al 16) studied the association between the serum albumin level and serum fentanyl concentration after transdermal administration of fentanyl. They classified 18 cancer patients into the following 2 groups according to their serum albumin levels: a normal albumin group (≥3.5 g/dL) and a low albumin group (<3.5 g/dL).…”

Section: Influence Of Serum Albumin Levels During Opioid Rotation Fromentioning

confidence: 99%

Influence of Serum Albumin Levels during Opioid Rotation from Morphine or Oxycodone to Fentanyl for Cancer Pain

Hayashi

Ikehata

Matsuzaki

et al. 2014

Biological & Pharmaceutical Bulletin

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Morphine, oxycodone, and fentanyl are commonly used to control cancer pain. Because these drugs have differences in receptor affinity or pharmacokinetic parameters, changing the opioid formulation may result in an unexpected outcome, depending on the patient's condition. This study investigated whether low serum protein levels influence the effectiveness of opioid rotation by determining the impact of serum albumin levels on the analgesic effect before and after opioid rotation from morphine or oxycodone to fentanyl in cancer patients. The patients were classified into 3 groups according to their serum albumin levels before opioid rotation: group 1, <2.5 g/dL; group 2, from 2.5 g/dL to <3.0 g/dL; and group 3, ≥3.0 g/dL. There was no significant change in the percentage of patients with good pain control after rotation in group 1 or group 2; however, the percentage of patients with good pain control increased significantly in group 3. When the percentage of patients whose numerical rating scale scores increased, were unchanged, or decreased after rotation were compared, a significant difference in the percentage of those showing improvement was noted among the 3 groups and between groups 1 and 3. These findings suggest that monitoring serum albumin levels during fentanyl therapy is useful for pain management, and that the effectiveness of opioid rotation to fentanyl in patients with serum albumin levels of <2.5 g/dL should be carefully evaluated after rotation.

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“…The patients with an albumin <3.5 g dl À1 had significantly reduced doseadjusted serum fentanyl concentrations at 9-24 h after application of the patch compared to patients with an albumin >3.5 g dl À1 . The authors suggest lower absorption from the patch in patients with low plasma albumin concentrations [61]. Barrett et al showed no clinically relevant influence of albumin on fentanyl plasma concentrations in a large crosssectional study in patients using transdermal fentanyl [21].…”

Section: Patient-related Factorsmentioning

confidence: 98%

“…albumin, alpha-1-acid glycoprotein). The Variability in fentanyl pharmacokinetics effect of hypoalbuminemia was studied in two studies with a different design, both in patients using a fentanyl patch [21,61].…”

Section: Patient-related Factorsmentioning

confidence: 99%

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

Kuip

Zandvliet

Koolen

et al. 2016

Brit J Clinical Pharma

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Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter-and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side-effects and increasing its efficacy. British Journal of Clinical PharmacologyBr J Clin Pharmacol (2017) 83 294-313 294

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Serum Concentration of Fentanyl During Conversion From Intravenous to Transdermal Administration to Patients With Chronic Cancer Pain

Abstract: Our study demonstrated that the dose-adjusted serum fentanyl concentrations remained relatively stable, and pain intensity and the number of rescue events remained stable during conversion. Hypoalbuminemia was strongly associated with poor absorption of transdermally administered fentanyl.

Cited by 22 publications

References 14 publications

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients

Influence of Serum Albumin Levels during Opioid Rotation from Morphine or Oxycodone to Fentanyl for Cancer Pain

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

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