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Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients
Background Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that...
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| Published in: | Transplant infectious disease 2018-12, Vol.20 (6), p.e12979-n/a |
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| cites | cdi_FETCH-LOGICAL-c4199-60581b6821b656fefaaf0a208743c854f3468a757999dcfdc43464aee3e966043 |
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| container_issue | 6 |
| container_start_page | e12979 |
| container_title | Transplant infectious disease |
| container_volume | 20 |
| creator | Laub, Melissa R. Crow, Stacy A. Personett, Heather A. Dierkhising, Ross Boilson, Barry Razonable, Raymund |
| description | Background
Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.
Methods
To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.
Results
The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR −52.3%, −30.9%). Five cases of allograft rejection were observed.
Conclusion
In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation. |
| doi_str_mv | 10.1111/tid.12979 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2089857748</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2140795054</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4199-60581b6821b656fefaaf0a208743c854f3468a757999dcfdc43464aee3e966043</originalsourceid><addsrcrecordid>eNp1kE9LwzAYh4Mobk4PfgEpeNHDtqRNm-Yoc_6BgQfnOWTpG5fRNTNJkfnpzdbpQTCHJLw8PPzeH0KXBI9IPONgqhFJOeNHqE8yzocZLtLj_b8cpinLeujM-xXGhHHKT1EvwyTFZZH30etUa1DBJ1YnqrbBmbX8sjUkwVm1hDhvkiCVs7VZtz6prDfNe2KaZAnShUjJxm9q2YTEgTIbA03w5-hEy9rDxeEdoLeH6XzyNJy9PD5P7mZDRUkMWeC8JIuiTOOVFxq0lBrLmIvRTJU51RktSslyxjmvlK4UjQMqATLgRYFpNkA3nXfj7EcLPoi18QrqGAds60VU8TJnjJYRvf6DrmzrmphOpIRixnOc74S3HRX39d6BFptdH24rCBa7pkVsWuybjuzVwdgu1lD9kj_VRmDcAZ-mhu3_JjF_vu-U3zXch0w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2140795054</pqid></control><display><type>article</type><title>Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Laub, Melissa R. ; Crow, Stacy A. ; Personett, Heather A. ; Dierkhising, Ross ; Boilson, Barry ; Razonable, Raymund</creator><creatorcontrib>Laub, Melissa R. ; Crow, Stacy A. ; Personett, Heather A. ; Dierkhising, Ross ; Boilson, Barry ; Razonable, Raymund</creatorcontrib><description>Background
Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.
Methods
To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.
Results
The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR −52.3%, −30.9%). Five cases of allograft rejection were observed.
Conclusion
In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.</description><identifier>ISSN: 1398-2273</identifier><identifier>EISSN: 1399-3062</identifier><identifier>DOI: 10.1111/tid.12979</identifier><identifier>PMID: 30120865</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Administration, Oral ; Antifungal agents ; Antifungal Agents - pharmacology ; Candidiasis ; Candidiasis, Oral - immunology ; Candidiasis, Oral - prevention & control ; Clotrimazole ; Clotrimazole - pharmacology ; Dosage ; Drug Interactions ; Enzymatic activity ; Enzyme activity ; Female ; Fungicides ; Graft rejection ; Graft Rejection - epidemiology ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; heart transplant ; Heart transplantation ; Heart Transplantation - adverse effects ; Humans ; Immunosuppression ; Immunosuppression - adverse effects ; Immunosuppression - methods ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacology ; Intestine ; Male ; Middle Aged ; Prophylaxis ; Retrospective Studies ; Tacrolimus ; Tacrolimus - administration & dosage ; Tacrolimus - blood ; Tacrolimus - pharmacology ; thrush ; Transplantation ; Transplants & implants ; Treatment Outcome</subject><ispartof>Transplant infectious disease, 2018-12, Vol.20 (6), p.e12979-n/a</ispartof><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4199-60581b6821b656fefaaf0a208743c854f3468a757999dcfdc43464aee3e966043</citedby><cites>FETCH-LOGICAL-c4199-60581b6821b656fefaaf0a208743c854f3468a757999dcfdc43464aee3e966043</cites><orcidid>0000-0002-6251-9153</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30120865$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laub, Melissa R.</creatorcontrib><creatorcontrib>Crow, Stacy A.</creatorcontrib><creatorcontrib>Personett, Heather A.</creatorcontrib><creatorcontrib>Dierkhising, Ross</creatorcontrib><creatorcontrib>Boilson, Barry</creatorcontrib><creatorcontrib>Razonable, Raymund</creatorcontrib><title>Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients</title><title>Transplant infectious disease</title><addtitle>Transpl Infect Dis</addtitle><description>Background
Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.
Methods
To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.
Results
The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR −52.3%, −30.9%). Five cases of allograft rejection were observed.
Conclusion
In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.</description><subject>Administration, Oral</subject><subject>Antifungal agents</subject><subject>Antifungal Agents - pharmacology</subject><subject>Candidiasis</subject><subject>Candidiasis, Oral - immunology</subject><subject>Candidiasis, Oral - prevention & control</subject><subject>Clotrimazole</subject><subject>Clotrimazole - pharmacology</subject><subject>Dosage</subject><subject>Drug Interactions</subject><subject>Enzymatic activity</subject><subject>Enzyme activity</subject><subject>Female</subject><subject>Fungicides</subject><subject>Graft rejection</subject><subject>Graft Rejection - epidemiology</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>heart transplant</subject><subject>Heart transplantation</subject><subject>Heart Transplantation - adverse effects</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>Immunosuppression - adverse effects</subject><subject>Immunosuppression - methods</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Intestine</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prophylaxis</subject><subject>Retrospective Studies</subject><subject>Tacrolimus</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - blood</subject><subject>Tacrolimus - pharmacology</subject><subject>thrush</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><issn>1398-2273</issn><issn>1399-3062</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kE9LwzAYh4Mobk4PfgEpeNHDtqRNm-Yoc_6BgQfnOWTpG5fRNTNJkfnpzdbpQTCHJLw8PPzeH0KXBI9IPONgqhFJOeNHqE8yzocZLtLj_b8cpinLeujM-xXGhHHKT1EvwyTFZZH30etUa1DBJ1YnqrbBmbX8sjUkwVm1hDhvkiCVs7VZtz6prDfNe2KaZAnShUjJxm9q2YTEgTIbA03w5-hEy9rDxeEdoLeH6XzyNJy9PD5P7mZDRUkMWeC8JIuiTOOVFxq0lBrLmIvRTJU51RktSslyxjmvlK4UjQMqATLgRYFpNkA3nXfj7EcLPoi18QrqGAds60VU8TJnjJYRvf6DrmzrmphOpIRixnOc74S3HRX39d6BFptdH24rCBa7pkVsWuybjuzVwdgu1lD9kj_VRmDcAZ-mhu3_JjF_vu-U3zXch0w</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Laub, Melissa R.</creator><creator>Crow, Stacy A.</creator><creator>Personett, Heather A.</creator><creator>Dierkhising, Ross</creator><creator>Boilson, Barry</creator><creator>Razonable, Raymund</creator><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6251-9153</orcidid></search><sort><creationdate>201812</creationdate><title>Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients</title><author>Laub, Melissa R. ; Crow, Stacy A. ; Personett, Heather A. ; Dierkhising, Ross ; Boilson, Barry ; Razonable, Raymund</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4199-60581b6821b656fefaaf0a208743c854f3468a757999dcfdc43464aee3e966043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Administration, Oral</topic><topic>Antifungal agents</topic><topic>Antifungal Agents - pharmacology</topic><topic>Candidiasis</topic><topic>Candidiasis, Oral - immunology</topic><topic>Candidiasis, Oral - prevention & control</topic><topic>Clotrimazole</topic><topic>Clotrimazole - pharmacology</topic><topic>Dosage</topic><topic>Drug Interactions</topic><topic>Enzymatic activity</topic><topic>Enzyme activity</topic><topic>Female</topic><topic>Fungicides</topic><topic>Graft rejection</topic><topic>Graft Rejection - epidemiology</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - prevention & control</topic><topic>heart transplant</topic><topic>Heart transplantation</topic><topic>Heart Transplantation - adverse effects</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>Immunosuppression - adverse effects</topic><topic>Immunosuppression - methods</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Intestine</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prophylaxis</topic><topic>Retrospective Studies</topic><topic>Tacrolimus</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - blood</topic><topic>Tacrolimus - pharmacology</topic><topic>thrush</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laub, Melissa R.</creatorcontrib><creatorcontrib>Crow, Stacy A.</creatorcontrib><creatorcontrib>Personett, Heather A.</creatorcontrib><creatorcontrib>Dierkhising, Ross</creatorcontrib><creatorcontrib>Boilson, Barry</creatorcontrib><creatorcontrib>Razonable, Raymund</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplant infectious disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laub, Melissa R.</au><au>Crow, Stacy A.</au><au>Personett, Heather A.</au><au>Dierkhising, Ross</au><au>Boilson, Barry</au><au>Razonable, Raymund</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients</atitle><jtitle>Transplant infectious disease</jtitle><addtitle>Transpl Infect Dis</addtitle><date>2018-12</date><risdate>2018</risdate><volume>20</volume><issue>6</issue><spage>e12979</spage><epage>n/a</epage><pages>e12979-n/a</pages><issn>1398-2273</issn><eissn>1399-3062</eissn><abstract>Background
Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.
Methods
To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.
Results
The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR −52.3%, −30.9%). Five cases of allograft rejection were observed.
Conclusion
In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30120865</pmid><doi>10.1111/tid.12979</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-6251-9153</orcidid></addata></record> |
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| subjects | Administration, Oral Antifungal agents Antifungal Agents - pharmacology Candidiasis Candidiasis, Oral - immunology Candidiasis, Oral - prevention & control Clotrimazole Clotrimazole - pharmacology Dosage Drug Interactions Enzymatic activity Enzyme activity Female Fungicides Graft rejection Graft Rejection - epidemiology Graft Rejection - immunology Graft Rejection - prevention & control heart transplant Heart transplantation Heart Transplantation - adverse effects Humans Immunosuppression Immunosuppression - adverse effects Immunosuppression - methods Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacology Intestine Male Middle Aged Prophylaxis Retrospective Studies Tacrolimus Tacrolimus - administration & dosage Tacrolimus - blood Tacrolimus - pharmacology thrush Transplantation Transplants & implants Treatment Outcome |
| title | Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients |
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