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Analysis of Dose Changing Pattern for Voriconazole and Recommendation
J. Kor. Soc. Health-syst. Pharm. 2018;35:292-309
Published online August 31, 2018
© 2018 Korean Society of Health-System Pharmacists

Jae-Eun Leea, Seoung-Lan Kima, Ye-Jee Kimb, Hee-Se Kima and Jae-Youn Kima,†

Department of Pharmacy, Asan Medical Centera
Department of Clinical Epidemiology and Biostatistics, Asan Medical Centerb
43 Olympic-ro, Songpa-gu, Seoul, 05505, Republic of Korea
Correspondence to: 김재연 Tel:02-3010-5191
Received October 16, 2017; Revised February 1, 2018; Accepted June 22, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background : Voriconazole is a first-line agent for treatment of invasive aspergillosis. However, the relationship between dose and serum concentration of voriconazole is non-linear, making it very difficult to predict changes in serum level of voriconazole upon dosage change. Here, we reviewed and analyzed cases of changing dose of voriconazole when its serum concentration was not within therapeutic range.
Methods : We retrospectively analyzed medical records of adult patients who were hospitalized in Asan Medical Center from January 2010 to December 2015. We excluded cases whose voriconazole level was not in a steady state, those who were administered incompatible drugs, and those who were diagnosed with liver cirrhosis. The number of hospitalization was the unit of analysis. Patients were classified by their initial serum concentration of voriconazole as follows: Group 1 (G1) (TDM1; 1st level 0.5 ㎍/ml), G2 (0.5≤TDM1 1 ㎍/ml), G3 (1≤TDM1 5.5 ㎍/ml (therapeutic range)), G4 (5.5 ≤TDM1 10 ㎍/ml) and G5 (TDM1≥10 ㎍/ml). Chi-square test and Fisher’s exact test were used to test if there were statistical differences between groups. This study was approved by our Institutional Review Board (No. S2016-1134-0001).
Results : A total of 574 cases were analyzed and classified into five groups. We found that 93%, 82%, 87% and 76% of G1, G2, G4 and G5, respectively, reached therapeutic range of voriconazole when their dosages were changed as follows: increased by >2 mg/kg/day, increased by >0.5 mg/kg/day, decreased by ≥1 mg/kg/day and decreased by ≥2 mg/kg/day, respectively.
Conclusions : The following dose changing regimen would be more reasonable when serum level of voriconazole is not within therapeutic range: G1, increase by 2-5 mg/kg/day; G2, increase by 0.5-2.5 mg/kg/day; G4, decrease by 1.5-4 mg/kg/day; G5, skip one dose and decrease by 2.5-4 mg/kg/day.
Keywords : Voriconazole, Therapeutic Drug Monitoring, Pharmacokinetics