Universität zu Köln

Cornely, Oliver A., Boehme, Angelika, Schmitt-Hoffmann, Anne and Ullmann, Andrew J. (2015). Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study. Antimicrob. Agents Chemother., 59 (4). S. 2078 - 2086. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-6596

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Abstract

Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n = 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n = 12). The mean +/- standard deviation plasma isavuconazole areas under the concentration- time curves for the dosing period on day 7 were 60.1 +/- 22.3 mu g.h/ml and 113.1 +/- 19.6 mu g.h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n = 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehme, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt-Hoffmann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullmann, Andrew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-408848
DOI:	10.1128/AAC.04569-14
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	59
Number:	4
Page Range:	S. 2078 - 2086
Date:	2015
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-6596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INVASIVE FUNGAL-INFECTIONS; STEM-CELL TRANSPLANT; TRIAZOLE BAL4815; FLUCONAZOLE; VORICONAZOLE; PRODRUG; CANDIDA; POSACONAZOLE; BAL8557; ASPERGILLOSIS Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40884