Cargando…
1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients
BACKGROUND: TDM of VRCZ might be useful, especially in Asian people because of CYP2C19 genetic polymorphisms. However, limited data are available because of the small sample size. METHODS: Patients who received VRCZ and had TDM were reviewed retrospectively at five institutions. Adequate VRCZ dosage...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810842/ http://dx.doi.org/10.1093/ofid/ofz360.1401 |
_version_ | 1783462337786675200 |
---|---|
author | Ueda, Takashi Takesue, Yoshio Hamada, Yukihiro Fukunaga, Keiko Ikegame, Kazuhiro Ebihara, Fumiya Kimura, Toshimi Nakajima, Kazuhiro Miyazaki, Taiga Nakada-Motokawa, Nana Nagao, Miki Kawamura, Hideki Shigemi, Akari Miyazaki, Yoshitsugu |
author_facet | Ueda, Takashi Takesue, Yoshio Hamada, Yukihiro Fukunaga, Keiko Ikegame, Kazuhiro Ebihara, Fumiya Kimura, Toshimi Nakajima, Kazuhiro Miyazaki, Taiga Nakada-Motokawa, Nana Nagao, Miki Kawamura, Hideki Shigemi, Akari Miyazaki, Yoshitsugu |
author_sort | Ueda, Takashi |
collection | PubMed |
description | BACKGROUND: TDM of VRCZ might be useful, especially in Asian people because of CYP2C19 genetic polymorphisms. However, limited data are available because of the small sample size. METHODS: Patients who received VRCZ and had TDM were reviewed retrospectively at five institutions. Adequate VRCZ dosage was defined as a loading dose of 5–6 ± 0.5 mg/kg twice daily followed by a maintenance dose of 3–4 ± 0.5 mg/kg twice daily. For prophylaxis, the loading dose was left to the physician’s discretion. Optimal timing of TDM was defined as 4–7 days after starting therapy. Patients with adequate dosing and optimal timing of TDM were evaluated for analysis of trough levels (Cmin). Target Cmin was set at 1–5 µg/mL. RESULTS: The study included 584 patients (treatment: 402; prophylaxis: 182). TDM was conducted on days 4–7 in 66.5% of patients (>7, 30.2%). A low adequate dosage (44.5%) was observed for treatment mainly because of a low performance of the loading dose (46.8%). Achievement of target Cmin was obtained in 62.7% (>5 µg/mL, 32.2%) in the treatment group and in 67.6% (11.0%) in the prophylaxis group. Seventy-one of 81 (81.7%) patients who required a dose reduction reached target Cmin by the second TDM. In 38 patients whose dose was not altered at oral switching, Cmin was significantly reduced from 2.5 ± 1.6 to 1.2 ± 1.3 μg/mL (P = 0.002), which indicated the necessity of TDM after oral switching. Hepatotoxicity occurred in 4.6% and visual symptoms in 7.9% of patients. Visual symptoms resolved without discontinuation of VRCZ in 73.9% of patients. Because of dosage adjustment based on TDM, high Cmin did not cause hepatotoxicity. However, the incidence of visual symptoms was significantly higher in patients with a high Cmin (12.7% vs. 5.4%, P = 0.002). CONCLUSION: One-third of Japanese patients who underwent VRCZ treatment with a loading dose showed high Cmin. Occurrence of hepatotoxicity was prevented with alteration of dosage in these patients (AMED, JP18fk0108045). DISCLOSURES: All authors: No reported disclosures. |
format | Online Article Text |
id | pubmed-6810842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68108422019-10-28 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients Ueda, Takashi Takesue, Yoshio Hamada, Yukihiro Fukunaga, Keiko Ikegame, Kazuhiro Ebihara, Fumiya Kimura, Toshimi Nakajima, Kazuhiro Miyazaki, Taiga Nakada-Motokawa, Nana Nagao, Miki Kawamura, Hideki Shigemi, Akari Miyazaki, Yoshitsugu Open Forum Infect Dis Abstracts BACKGROUND: TDM of VRCZ might be useful, especially in Asian people because of CYP2C19 genetic polymorphisms. However, limited data are available because of the small sample size. METHODS: Patients who received VRCZ and had TDM were reviewed retrospectively at five institutions. Adequate VRCZ dosage was defined as a loading dose of 5–6 ± 0.5 mg/kg twice daily followed by a maintenance dose of 3–4 ± 0.5 mg/kg twice daily. For prophylaxis, the loading dose was left to the physician’s discretion. Optimal timing of TDM was defined as 4–7 days after starting therapy. Patients with adequate dosing and optimal timing of TDM were evaluated for analysis of trough levels (Cmin). Target Cmin was set at 1–5 µg/mL. RESULTS: The study included 584 patients (treatment: 402; prophylaxis: 182). TDM was conducted on days 4–7 in 66.5% of patients (>7, 30.2%). A low adequate dosage (44.5%) was observed for treatment mainly because of a low performance of the loading dose (46.8%). Achievement of target Cmin was obtained in 62.7% (>5 µg/mL, 32.2%) in the treatment group and in 67.6% (11.0%) in the prophylaxis group. Seventy-one of 81 (81.7%) patients who required a dose reduction reached target Cmin by the second TDM. In 38 patients whose dose was not altered at oral switching, Cmin was significantly reduced from 2.5 ± 1.6 to 1.2 ± 1.3 μg/mL (P = 0.002), which indicated the necessity of TDM after oral switching. Hepatotoxicity occurred in 4.6% and visual symptoms in 7.9% of patients. Visual symptoms resolved without discontinuation of VRCZ in 73.9% of patients. Because of dosage adjustment based on TDM, high Cmin did not cause hepatotoxicity. However, the incidence of visual symptoms was significantly higher in patients with a high Cmin (12.7% vs. 5.4%, P = 0.002). CONCLUSION: One-third of Japanese patients who underwent VRCZ treatment with a loading dose showed high Cmin. Occurrence of hepatotoxicity was prevented with alteration of dosage in these patients (AMED, JP18fk0108045). DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6810842/ http://dx.doi.org/10.1093/ofid/ofz360.1401 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Abstracts Ueda, Takashi Takesue, Yoshio Hamada, Yukihiro Fukunaga, Keiko Ikegame, Kazuhiro Ebihara, Fumiya Kimura, Toshimi Nakajima, Kazuhiro Miyazaki, Taiga Nakada-Motokawa, Nana Nagao, Miki Kawamura, Hideki Shigemi, Akari Miyazaki, Yoshitsugu 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients |
title | 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients |
title_full | 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients |
title_fullStr | 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients |
title_full_unstemmed | 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients |
title_short | 1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients |
title_sort | 1537. multicenter study with therapeutic drug monitoring (tdm) of voriconazole (vrcz) in japanese patients |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810842/ http://dx.doi.org/10.1093/ofid/ofz360.1401 |
work_keys_str_mv | AT uedatakashi 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT takesueyoshio 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT hamadayukihiro 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT fukunagakeiko 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT ikegamekazuhiro 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT ebiharafumiya 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT kimuratoshimi 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT nakajimakazuhiro 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT miyazakitaiga 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT nakadamotokawanana 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT nagaomiki 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT kawamurahideki 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT shigemiakari 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients AT miyazakiyoshitsugu 1537multicenterstudywiththerapeuticdrugmonitoringtdmofvoriconazolevrczinjapanesepatients |