Risk Factors for Initial Low Voriconazole Trough Level in Routine Therapeutic Drug Monitoring

Ref ID: 19304

Author:

S-H. Kim, J-C. Kwon, H-J. Lee, S-Y. Cho, J-K. Choi, C. Park, D-G. Lee, S-M. Choi, J-H. Choi, J-H. Yoo

Author address:

Pohang Univ. of Sci. and Technology, Pohang, KOREA, REPUBLIC OF, Coll. of Med., The Catholic Univ. of Korea, Seoul, KOREA, REPUBLIC OF, Vaccine Bio Res. Inst., Coll. of Med., The Catholic Univ. of Korea, Seoul, KOREA, REPUBLIC OF, Catholic Res. Inst.

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Background: It is known that low voriconazole levels are related to treatment failure in patients with invasive aspergillosis. The purpose of this study is to identify risk factors for initial low voriconazole trough level in routine therapeutic drug monitoring (TDM). Methods: In this prospective observational study, we analyzed all consecutive adult patients with hematologic disease who received intravenous or oral voriconazole in recommended dosage for treatment of invasive aspergillosis between January 2011 and June 2012. Serum voriconazole trough levels were measured by liquid chromatography[[Unable to Display Character: 8210;]]tandem mass spectrometry method. Initial trough level of <0.5 mg/L was considered as low. Results: A total of 104 patients were consecutively enrolled. In regard to CYP2C19 genotype, patients consisted of 15 poor (14%), 50 heterozygous extensive (48%) and 39 extensive metabolizers (EM, 38%). Median age (interquartile range) was 54 years (45-62 years) and acute leukemia (73%) was the most common hematologic disease. Out of 104 patients, 11 patients (11%) showed initial low trough levels. Initial low trough level was not related to age, sex, body mass index, underlying hematologic disease, clinical characteristics of invasive aspergillosis and voriconazole doses. Oral route administration (82% vs. 46%, P=0.052), concomitant steroid therapy (64% vs. 28%; P=0.023) and CYP2C19 EM (64% vs. 28%; P=0.018) were associated with initial low trough level. In multivariate logistic regression analysis, oral route (adjusted odds ratio [aOR], 6.479; 95% confidence interval [CI], 1.153-36.413), concomitant steroid therapy (aOR, 6.118; 95% CI, 1.380-27.129) and CYP2C19 EM (aOR, 7.628; 95% CI, 1.599-36.399) were significant risk factors for initial low trough level. Conclusions: In patients with CYP2C19 EM or coadministration of steroid or when voriconazole therapy was started with oral regimen, higher voriconazole doses might be required for achieving appropriate drug exposure.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

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