The package insert of the antithrombotic agent warfarin warns users of its interaction with azole antifungals. However, information on the frequency or degree of these interactions is limited. In particular, the time to onset of azole-mediated prothrombin time prolongation, expressed as the international normalized ratio (INR), is poorly characterized. Therefore, we retrospectively examined the INR in 29 patients administered warfarin with fluconazole (FLCZ), voriconazole (VRCZ), or itraconazole (ITCZ). INRs in 18 patients taking FLCZ and in 5 patients taking VRCZ significantly increased from 1.40 to 2.94 and from 1.95 to 2.89, respectively. The warfarin sensitivity index (WSI), calculated as INR/daily warfarin dose, also significantly increased from 1.06 to 1.89 with FLCZ and showed an upward trend from 1.13 to 2.23 with VRCZ. ITCZ had no influence on the INR or WSI in 6 patients. The INRs observed when warfarin was coadministered with azoles (Y) correlated significantly with those observed in the absence of azoles (X): FLCZ, Y=4.94X-3.96, r(2)=0.80; VRCZ, Y=2.13X-1.27, r(2)=0.93. Moreover, in all 8 patients with closely monitored INRs, the WSI increased within 1 week of FLCZ or VRCZ coadministration. In conclusion, FLCZ and VRCZ augmented the anticoagulant activity of warfarin. The INR should be closely monitored within 1 week of initiating FLCZ or VRCZ coadministration with warfarin, especially in patients with high INRs.
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http://dx.doi.org/10.1248/bpb.b14-00564 | DOI Listing |
Jpn J Ophthalmol
May 2022
Institute of Medical Mycology, Teikyo University, Tokyo, Japan.
Purpose: To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan.
Study Design: Multicenter prospective observational study.
Methods: Eighteen isolates of yeast-like fungi and 22 isolates of filamentous fungi collected by the Multicenter Prospective Observational Study of Fungal Keratitis in Japan were studied.
Clin Biochem
January 2022
Department of Clinical Pharmacy, Oita University Hospital, Yufu-shi, Oita, Japan.
Objectives: For patients with hematological malignancy, triazole antifungal agents such as fluconazole (FLCZ), itraconazole (ITCZ), voriconazole (VRCZ), posaconazole (PSCZ) and isavuconazole (ISCZ) are often used for prophylaxis of deep mycosis. Since these azoles exhibit large pharmacokinetic variability, dose adjustment by therapeutic drug monitoring is recommended for some azoles. This study aimed to develop and validate a novel method for simultaneous determination of plasma concentrations of FLCZ, ITCZ, VRCZ, PSCZ, ISCZ and ITCZ-OH, an active metabolite of ITCZ, using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS).
View Article and Find Full Text PDFIDCases
July 2021
Department of Hematology and Oncology, Mie University Graduate School of Medicine/Faculty of Medicine, Tsu, Japan.
Antifungal prophylaxis is crucial for successful hematopoietic stem cell transplantation (HSCT). Maintenance therapy with fluconazole (FLCZ) is generally prescribed as secondary prophylaxis in patients with human immunodeficiency virus infection and non-immunocompromised hosts. However, previous reports have revealed that FLCZ is insufficient as a secondary prophylaxis for cryptococcal infection in HSCT cases.
View Article and Find Full Text PDFInt Med Case Rep J
October 2020
Department of Microbiology, Toyooka Hospital, Toyooka City, Hyogo 668-0065, Japan.
Background: spp. are rare human pathogens, and only three cases of keratitis have been reported. They were treated with anti-fungal drugs and surgical excision.
View Article and Find Full Text PDFMed Mycol J
August 2020
Department of Veterinary Pathobiology, Nihon University College of Bioresouce Sciences.
Ravuconazole (RVCZ) is a newly available human azole drug in Japan since 2018 and is a broad-spectrum antifungal agent that exhibits excellent activity against Candida albicans and Cryptococcus neoformans (formerly: Cryptococcus grubii). The drug is also highly active against isolates that are resistant to fluconazole (FLCZ). In the present study, the in vitro susceptibility to ravuconazole (RVCZ) of Japanese clinical isolates and multi-azole-resistant strains of C.
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