Influence of azole antifungal drugs on blood tacrolimus levels after switching from intravenous tacrolimus to once‐daily modified release tacrolimus in patients receiving allogeneic hematopoietic stem cell transplantation
Summary What is known and objective Azole antifungal drugs are often co‐administered with tacrolimus after allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of azole antifungal drugs on variation in tacrolimus pharmacokinetics when switching from intravenous tacrolimu...
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| Veröffentlicht in: | Journal of clinical pharmacy and therapeutics 2019-08, Vol.44 (4), p.565-571, Article jcpt.12834 |
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| creator | Mimura, Akira Yamaori, Satoshi Ikemura, Noriaki Katsuyama, Yoshihiko Matsuzawa, Naoki Ohmori, Shigeru |
| description | Summary
What is known and objective
Azole antifungal drugs are often co‐administered with tacrolimus after allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of azole antifungal drugs on variation in tacrolimus pharmacokinetics when switching from intravenous tacrolimus (Tac‐iv) to once‐daily modified release tacrolimus (Tac‐MR) remains to be elucidated. This study was performed to evaluate the effects of oral azole antifungal drugs on variation in tacrolimus pharmacokinetics after conversion to Tac‐MR in HSCT patients.
Methods
Patients concomitantly receiving fluconazole (FLCZ) or voriconazole (VRCZ) along with tacrolimus were evaluated retrospectively. Blood tacrolimus concentrations before and after changing to oral administration were compared between FLCZ and VRCZ groups.
Results and discussion
A total of 52 patients (34 FLCZ and 18 VRCZ) were included in the analysis. There were no significant differences in the most recent daily dose (Div) and blood level (Civ) of Tac‐iv, Civ/Div, and ratio of daily dose of tacrolimus on the first to second day after changing to Tac‐MR (Dpo1‐2) to Div between FLCZ and VRCZ groups (P > 0.2). The trough levels of tacrolimus on the first to second day after switching to Tac‐MR (Cpo1‐2) and on the third to fifth day after the switch (Cpo3‐5) were significantly higher in the VRCZ group than the FLCZ group (P |
| doi_str_mv | 10.1111/jcpt.12834 |
| format | Article |
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What is known and objective
Azole antifungal drugs are often co‐administered with tacrolimus after allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of azole antifungal drugs on variation in tacrolimus pharmacokinetics when switching from intravenous tacrolimus (Tac‐iv) to once‐daily modified release tacrolimus (Tac‐MR) remains to be elucidated. This study was performed to evaluate the effects of oral azole antifungal drugs on variation in tacrolimus pharmacokinetics after conversion to Tac‐MR in HSCT patients.
Methods
Patients concomitantly receiving fluconazole (FLCZ) or voriconazole (VRCZ) along with tacrolimus were evaluated retrospectively. Blood tacrolimus concentrations before and after changing to oral administration were compared between FLCZ and VRCZ groups.
Results and discussion
A total of 52 patients (34 FLCZ and 18 VRCZ) were included in the analysis. There were no significant differences in the most recent daily dose (Div) and blood level (Civ) of Tac‐iv, Civ/Div, and ratio of daily dose of tacrolimus on the first to second day after changing to Tac‐MR (Dpo1‐2) to Div between FLCZ and VRCZ groups (P > 0.2). The trough levels of tacrolimus on the first to second day after switching to Tac‐MR (Cpo1‐2) and on the third to fifth day after the switch (Cpo3‐5) were significantly higher in the VRCZ group than the FLCZ group (P < 0.05). The values of (Civ/Div)/(Cpo1‐2/Dpo1‐2) and (Civ/Div)/(Cpo3‐5/Dpo3‐5) in the VRCZ group were significantly lower compared with those in the FLCZ group (P < 0.05). Furthermore, individual values of (Civ/Div)/(Cpo3‐5/Dpo3‐5) in the FLCZ group varied widely.
What is new and conclusion
Voriconazole increased blood tacrolimus level more markedly than FLCZ after switching to Tac‐MR, whereas FLCZ caused a large variation in tacrolimus blood level. These results suggest that therapeutic monitoring of tacrolimus after the switch may need to be performed carefully considering that orally co‐administered VRCZ and FLCZ exhibit different change in blood tacrolimus level just after the switch.
VRCZ increased blood tacrolimus level more markedly than FLCZ after switching to Tac‐MR, whereas FLCZ caused a large variation in tacrolimus blood level. These results suggest that therapeutic monitoring of tacrolimus after the switch may need to be performed carefully considering that orally co‐administered VRCZ and FLCZ exhibit different change in blood tacrolimus level just after the switch.</description><identifier>ISSN: 0269-4727</identifier><identifier>EISSN: 1365-2710</identifier><identifier>DOI: 10.1111/jcpt.12834</identifier><identifier>PMID: 30950099</identifier><language>eng</language><publisher>England: Hindawi Limited</publisher><subject>administration route ; Administration, Intravenous ; Adult ; Antifungal agents ; Antifungal Agents - therapeutic use ; azole antifungal drugs ; Azoles - therapeutic use ; Blood levels ; Drug dosages ; drug interaction ; Female ; Fluconazole ; Fluconazole - therapeutic use ; Fungicides ; hematopoietic stem cell transplantation ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic stem cells ; Humans ; Immunosuppressive agents ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Intravenous administration ; Male ; Middle Aged ; Nose ; Oral administration ; Pharmacokinetics ; Retrospective Studies ; Stem cell transplantation ; Stem cells ; Tacrolimus ; Tacrolimus - administration & dosage ; Tacrolimus - blood ; Tacrolimus - pharmacokinetics ; Transplantation ; Variation ; Voriconazole ; Voriconazole - therapeutic use ; Young Adult</subject><ispartof>Journal of clinical pharmacy and therapeutics, 2019-08, Vol.44 (4), p.565-571, Article jcpt.12834</ispartof><rights>2019 John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons Ltd.</rights><rights>Copyright © 2019 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3934-fe02c3e340561717cebb8e761a952a9903db9aa61c310d5087a71a4e3b7ca3103</citedby><cites>FETCH-LOGICAL-c3934-fe02c3e340561717cebb8e761a952a9903db9aa61c310d5087a71a4e3b7ca3103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjcpt.12834$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjcpt.12834$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30950099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mimura, Akira</creatorcontrib><creatorcontrib>Yamaori, Satoshi</creatorcontrib><creatorcontrib>Ikemura, Noriaki</creatorcontrib><creatorcontrib>Katsuyama, Yoshihiko</creatorcontrib><creatorcontrib>Matsuzawa, Naoki</creatorcontrib><creatorcontrib>Ohmori, Shigeru</creatorcontrib><title>Influence of azole antifungal drugs on blood tacrolimus levels after switching from intravenous tacrolimus to once‐daily modified release tacrolimus in patients receiving allogeneic hematopoietic stem cell transplantation</title><title>Journal of clinical pharmacy and therapeutics</title><addtitle>J Clin Pharm Ther</addtitle><description>Summary
What is known and objective
Azole antifungal drugs are often co‐administered with tacrolimus after allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of azole antifungal drugs on variation in tacrolimus pharmacokinetics when switching from intravenous tacrolimus (Tac‐iv) to once‐daily modified release tacrolimus (Tac‐MR) remains to be elucidated. This study was performed to evaluate the effects of oral azole antifungal drugs on variation in tacrolimus pharmacokinetics after conversion to Tac‐MR in HSCT patients.
Methods
Patients concomitantly receiving fluconazole (FLCZ) or voriconazole (VRCZ) along with tacrolimus were evaluated retrospectively. Blood tacrolimus concentrations before and after changing to oral administration were compared between FLCZ and VRCZ groups.
Results and discussion
A total of 52 patients (34 FLCZ and 18 VRCZ) were included in the analysis. There were no significant differences in the most recent daily dose (Div) and blood level (Civ) of Tac‐iv, Civ/Div, and ratio of daily dose of tacrolimus on the first to second day after changing to Tac‐MR (Dpo1‐2) to Div between FLCZ and VRCZ groups (P > 0.2). The trough levels of tacrolimus on the first to second day after switching to Tac‐MR (Cpo1‐2) and on the third to fifth day after the switch (Cpo3‐5) were significantly higher in the VRCZ group than the FLCZ group (P < 0.05). The values of (Civ/Div)/(Cpo1‐2/Dpo1‐2) and (Civ/Div)/(Cpo3‐5/Dpo3‐5) in the VRCZ group were significantly lower compared with those in the FLCZ group (P < 0.05). Furthermore, individual values of (Civ/Div)/(Cpo3‐5/Dpo3‐5) in the FLCZ group varied widely.
What is new and conclusion
Voriconazole increased blood tacrolimus level more markedly than FLCZ after switching to Tac‐MR, whereas FLCZ caused a large variation in tacrolimus blood level. These results suggest that therapeutic monitoring of tacrolimus after the switch may need to be performed carefully considering that orally co‐administered VRCZ and FLCZ exhibit different change in blood tacrolimus level just after the switch.
VRCZ increased blood tacrolimus level more markedly than FLCZ after switching to Tac‐MR, whereas FLCZ caused a large variation in tacrolimus blood level. These results suggest that therapeutic monitoring of tacrolimus after the switch may need to be performed carefully considering that orally co‐administered VRCZ and FLCZ exhibit different change in blood tacrolimus level just after the switch.</description><subject>administration route</subject><subject>Administration, Intravenous</subject><subject>Adult</subject><subject>Antifungal agents</subject><subject>Antifungal Agents - therapeutic use</subject><subject>azole antifungal drugs</subject><subject>Azoles - therapeutic use</subject><subject>Blood levels</subject><subject>Drug dosages</subject><subject>drug interaction</subject><subject>Female</subject><subject>Fluconazole</subject><subject>Fluconazole - therapeutic use</subject><subject>Fungicides</subject><subject>hematopoietic stem cell transplantation</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Immunosuppressive agents</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Intravenous administration</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nose</subject><subject>Oral administration</subject><subject>Pharmacokinetics</subject><subject>Retrospective Studies</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tacrolimus</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - blood</subject><subject>Tacrolimus - pharmacokinetics</subject><subject>Transplantation</subject><subject>Variation</subject><subject>Voriconazole</subject><subject>Voriconazole - therapeutic use</subject><subject>Young Adult</subject><issn>0269-4727</issn><issn>1365-2710</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi1ERZfChQdAlrghpbXjJI6PaAW0qBIcyjmaOJOtV44dbGer5cQj8IZIfRK8bEE94Yvl8TffaPQT8oqzc57PxVbP6ZyXraiekBUXTV2UkrOnZMXKRhWVLOUpeR7jljHWyFI8I6eCqZoxpVbk15Ub7YJOI_Ujhe_eIgWXzLi4DVg6hGUTqXe0t94PNIEO3pppidTiDm2kMCYMNN6ZpG-N29Ax-IkalwLs0PnMPWpJPps03v_4OYCxezr5wYwGBxrQIkR8zBpHZ0gGXYr5W6PZHexgrd-gQ6PpLU6Q_OwNpvyKCSeq0VqaJ7s427xDbvfuBTkZwUZ8-XCfka8f3t-sL4vrzx-v1u-uCy2UqIoRWakFiorVDZdcauz7FmXDQdUlKMXE0CuAhmvB2VCzVoLkUKHopYZcEmfkzdE7B_9twZi6rV-CyyO7sqyrtlaVbDP19kjlPWMMOHZzMBOEfcdZd8iyO2TZ_ckyw68flEs_4fAP_RteBvgRuDMW9_9RdZ_WX26O0t_9PrJf</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Mimura, Akira</creator><creator>Yamaori, Satoshi</creator><creator>Ikemura, Noriaki</creator><creator>Katsuyama, Yoshihiko</creator><creator>Matsuzawa, Naoki</creator><creator>Ohmori, Shigeru</creator><general>Hindawi Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope></search><sort><creationdate>201908</creationdate><title>Influence of azole antifungal drugs on blood tacrolimus levels after switching from intravenous tacrolimus to once‐daily modified release tacrolimus in patients receiving allogeneic hematopoietic stem cell transplantation</title><author>Mimura, Akira ; Yamaori, Satoshi ; Ikemura, Noriaki ; Katsuyama, Yoshihiko ; Matsuzawa, Naoki ; Ohmori, Shigeru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3934-fe02c3e340561717cebb8e761a952a9903db9aa61c310d5087a71a4e3b7ca3103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>administration route</topic><topic>Administration, Intravenous</topic><topic>Adult</topic><topic>Antifungal agents</topic><topic>Antifungal Agents - therapeutic use</topic><topic>azole antifungal drugs</topic><topic>Azoles - therapeutic use</topic><topic>Blood levels</topic><topic>Drug dosages</topic><topic>drug interaction</topic><topic>Female</topic><topic>Fluconazole</topic><topic>Fluconazole - therapeutic use</topic><topic>Fungicides</topic><topic>hematopoietic stem cell transplantation</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Immunosuppressive agents</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Intravenous administration</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nose</topic><topic>Oral administration</topic><topic>Pharmacokinetics</topic><topic>Retrospective Studies</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tacrolimus</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - blood</topic><topic>Tacrolimus - pharmacokinetics</topic><topic>Transplantation</topic><topic>Variation</topic><topic>Voriconazole</topic><topic>Voriconazole - therapeutic use</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mimura, Akira</creatorcontrib><creatorcontrib>Yamaori, Satoshi</creatorcontrib><creatorcontrib>Ikemura, Noriaki</creatorcontrib><creatorcontrib>Katsuyama, Yoshihiko</creatorcontrib><creatorcontrib>Matsuzawa, Naoki</creatorcontrib><creatorcontrib>Ohmori, Shigeru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Journal of clinical pharmacy and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mimura, Akira</au><au>Yamaori, Satoshi</au><au>Ikemura, Noriaki</au><au>Katsuyama, Yoshihiko</au><au>Matsuzawa, Naoki</au><au>Ohmori, Shigeru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of azole antifungal drugs on blood tacrolimus levels after switching from intravenous tacrolimus to once‐daily modified release tacrolimus in patients receiving allogeneic hematopoietic stem cell transplantation</atitle><jtitle>Journal of clinical pharmacy and therapeutics</jtitle><addtitle>J Clin Pharm Ther</addtitle><date>2019-08</date><risdate>2019</risdate><volume>44</volume><issue>4</issue><spage>565</spage><epage>571</epage><pages>565-571</pages><artnum>jcpt.12834</artnum><issn>0269-4727</issn><eissn>1365-2710</eissn><abstract>Summary
What is known and objective
Azole antifungal drugs are often co‐administered with tacrolimus after allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of azole antifungal drugs on variation in tacrolimus pharmacokinetics when switching from intravenous tacrolimus (Tac‐iv) to once‐daily modified release tacrolimus (Tac‐MR) remains to be elucidated. This study was performed to evaluate the effects of oral azole antifungal drugs on variation in tacrolimus pharmacokinetics after conversion to Tac‐MR in HSCT patients.
Methods
Patients concomitantly receiving fluconazole (FLCZ) or voriconazole (VRCZ) along with tacrolimus were evaluated retrospectively. Blood tacrolimus concentrations before and after changing to oral administration were compared between FLCZ and VRCZ groups.
Results and discussion
A total of 52 patients (34 FLCZ and 18 VRCZ) were included in the analysis. There were no significant differences in the most recent daily dose (Div) and blood level (Civ) of Tac‐iv, Civ/Div, and ratio of daily dose of tacrolimus on the first to second day after changing to Tac‐MR (Dpo1‐2) to Div between FLCZ and VRCZ groups (P > 0.2). The trough levels of tacrolimus on the first to second day after switching to Tac‐MR (Cpo1‐2) and on the third to fifth day after the switch (Cpo3‐5) were significantly higher in the VRCZ group than the FLCZ group (P < 0.05). The values of (Civ/Div)/(Cpo1‐2/Dpo1‐2) and (Civ/Div)/(Cpo3‐5/Dpo3‐5) in the VRCZ group were significantly lower compared with those in the FLCZ group (P < 0.05). Furthermore, individual values of (Civ/Div)/(Cpo3‐5/Dpo3‐5) in the FLCZ group varied widely.
What is new and conclusion
Voriconazole increased blood tacrolimus level more markedly than FLCZ after switching to Tac‐MR, whereas FLCZ caused a large variation in tacrolimus blood level. These results suggest that therapeutic monitoring of tacrolimus after the switch may need to be performed carefully considering that orally co‐administered VRCZ and FLCZ exhibit different change in blood tacrolimus level just after the switch.
VRCZ increased blood tacrolimus level more markedly than FLCZ after switching to Tac‐MR, whereas FLCZ caused a large variation in tacrolimus blood level. These results suggest that therapeutic monitoring of tacrolimus after the switch may need to be performed carefully considering that orally co‐administered VRCZ and FLCZ exhibit different change in blood tacrolimus level just after the switch.</abstract><cop>England</cop><pub>Hindawi Limited</pub><pmid>30950099</pmid><doi>10.1111/jcpt.12834</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0269-4727 |
| ispartof | Journal of clinical pharmacy and therapeutics, 2019-08, Vol.44 (4), p.565-571, Article jcpt.12834 |
| issn | 0269-4727 1365-2710 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | administration route Administration, Intravenous Adult Antifungal agents Antifungal Agents - therapeutic use azole antifungal drugs Azoles - therapeutic use Blood levels Drug dosages drug interaction Female Fluconazole Fluconazole - therapeutic use Fungicides hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Humans Immunosuppressive agents Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Intravenous administration Male Middle Aged Nose Oral administration Pharmacokinetics Retrospective Studies Stem cell transplantation Stem cells Tacrolimus Tacrolimus - administration & dosage Tacrolimus - blood Tacrolimus - pharmacokinetics Transplantation Variation Voriconazole Voriconazole - therapeutic use Young Adult |
| title | Influence of azole antifungal drugs on blood tacrolimus levels after switching from intravenous tacrolimus to once‐daily modified release tacrolimus in patients receiving allogeneic hematopoietic stem cell transplantation |
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