A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction

Abstract Background Warfarin, a widely used anticoagulant, interacts with various agents used in palliative care, such as oxycodone, morphine, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs); however, there are no reports of its interaction with methadone. We report a case of a pat...

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Main Authors: Kaoru Yoshioka, Katsuya Ohmori, Soshi Iwasaki, Kazunobu Takahashi, Akemi Sato, Hiromasa Nakata, Atsushi Miyamoto, Michiaki Yamakage
Format: Article
Language:English
Published: SpringerOpen 2017-06-01
Series:JA Clinical Reports
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40981-017-0092-7
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author Kaoru Yoshioka
Katsuya Ohmori
Soshi Iwasaki
Kazunobu Takahashi
Akemi Sato
Hiromasa Nakata
Atsushi Miyamoto
Michiaki Yamakage
author_facet Kaoru Yoshioka
Katsuya Ohmori
Soshi Iwasaki
Kazunobu Takahashi
Akemi Sato
Hiromasa Nakata
Atsushi Miyamoto
Michiaki Yamakage
author_sort Kaoru Yoshioka
collection DOAJ
description Abstract Background Warfarin, a widely used anticoagulant, interacts with various agents used in palliative care, such as oxycodone, morphine, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs); however, there are no reports of its interaction with methadone. We report a case of a patient receiving warfarin when methadone was introduced for pain control with monitoring of the prothrombin time-international normalized ratio (PT-INR) and deduced the pharmacological background. Case presentation A 60-year-old male was emergently admitted to our university hospital for the sudden onset of severe back pain. Abdominal CT imaging revealed that the vertebral body of the ninth thoracic vertebra was occupied by bone metastasis and crushed, which caused his back pain. He received warfarin 3.5 mg/day for atrial fibrillation and tapentadol 100 mg p.o. daily for pain relief. The prothrombin time-international normalized ratio (PT-INR) was maintained at >2.2. The patient’s history included diabetes mellitus and hypertension, but his laboratory test was unremarkable with the exception that his eGFR was 34 ml/min. Initially, a fentanyl dermal patch was used instead of tapentadol to avoid interactions with warfarin. We started concomitant administration of oxycodone and 2.4 g/day of acetaminophen while monitoring the PT-INR because acetaminophen increased the PT-INR to 2.93. A continuous intravenous infusion of oxycodone was introduced, in increments of the dose, resulting in an increase of the PT-INR to 3.41, which is required to reduce the dose of warfarin to 1.5 mg. Because of the lack of effective pain relief, methadone was introduced and the dose was gradually increased. The PT-INR was not changed and the dose of warfarin was not changed. An infusion of oxycodone and oral methadone was used to allow the patient to walk in his room, and he was later transferred to the palliative hospital. Conclusions In an oral warfarinized patient, methadone seemed to undergo different metabolism than oxycodone. When warfarin and methadone are used together, we have to consider their interaction by comparing the competitive inhibition of CYP2C9 to the induction of CYP3A4 by methadone, because CYP3A4 metabolize various drugs including oxycodone.
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spelling doaj.art-a699a451c3b24d3184f8f6e6b4337c9b2022-12-21T19:48:46ZengSpringerOpenJA Clinical Reports2363-90242017-06-01311410.1186/s40981-017-0092-7A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introductionKaoru Yoshioka0Katsuya Ohmori1Soshi Iwasaki2Kazunobu Takahashi3Akemi Sato4Hiromasa Nakata5Atsushi Miyamoto6Michiaki Yamakage7Division of Hospital Pharmacy, Sapporo Medical UniversityDivision of Hospital Pharmacy, Sapporo Medical UniversityDepartment of Anesthesiology, Sapporo Medical UniversityDepartment of Anesthesiology, Sapporo Medical UniversityDepartment of Nursing, Sapporo Medical UniversityDivision of Hospital Pharmacy, Sapporo Medical UniversityDivision of Hospital Pharmacy, Sapporo Medical UniversityDepartment of Anesthesiology, Sapporo Medical UniversityAbstract Background Warfarin, a widely used anticoagulant, interacts with various agents used in palliative care, such as oxycodone, morphine, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs); however, there are no reports of its interaction with methadone. We report a case of a patient receiving warfarin when methadone was introduced for pain control with monitoring of the prothrombin time-international normalized ratio (PT-INR) and deduced the pharmacological background. Case presentation A 60-year-old male was emergently admitted to our university hospital for the sudden onset of severe back pain. Abdominal CT imaging revealed that the vertebral body of the ninth thoracic vertebra was occupied by bone metastasis and crushed, which caused his back pain. He received warfarin 3.5 mg/day for atrial fibrillation and tapentadol 100 mg p.o. daily for pain relief. The prothrombin time-international normalized ratio (PT-INR) was maintained at >2.2. The patient’s history included diabetes mellitus and hypertension, but his laboratory test was unremarkable with the exception that his eGFR was 34 ml/min. Initially, a fentanyl dermal patch was used instead of tapentadol to avoid interactions with warfarin. We started concomitant administration of oxycodone and 2.4 g/day of acetaminophen while monitoring the PT-INR because acetaminophen increased the PT-INR to 2.93. A continuous intravenous infusion of oxycodone was introduced, in increments of the dose, resulting in an increase of the PT-INR to 3.41, which is required to reduce the dose of warfarin to 1.5 mg. Because of the lack of effective pain relief, methadone was introduced and the dose was gradually increased. The PT-INR was not changed and the dose of warfarin was not changed. An infusion of oxycodone and oral methadone was used to allow the patient to walk in his room, and he was later transferred to the palliative hospital. Conclusions In an oral warfarinized patient, methadone seemed to undergo different metabolism than oxycodone. When warfarin and methadone are used together, we have to consider their interaction by comparing the competitive inhibition of CYP2C9 to the induction of CYP3A4 by methadone, because CYP3A4 metabolize various drugs including oxycodone.http://link.springer.com/article/10.1186/s40981-017-0092-7MethadoneWarfarinCYP2C9CYP3A4CYP2D6CYP2B6
spellingShingle Kaoru Yoshioka
Katsuya Ohmori
Soshi Iwasaki
Kazunobu Takahashi
Akemi Sato
Hiromasa Nakata
Atsushi Miyamoto
Michiaki Yamakage
A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction
JA Clinical Reports
Methadone
Warfarin
CYP2C9
CYP3A4
CYP2D6
CYP2B6
title A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction
title_full A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction
title_fullStr A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction
title_full_unstemmed A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction
title_short A case of a warfarinized renal cancer patient monitored for prothrombin time-international normalized ratio during methadone introduction
title_sort case of a warfarinized renal cancer patient monitored for prothrombin time international normalized ratio during methadone introduction
topic Methadone
Warfarin
CYP2C9
CYP3A4
CYP2D6
CYP2B6
url http://link.springer.com/article/10.1186/s40981-017-0092-7
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