Korean J Pediatr Infect Dis.  2014 Apr;21(1):9-21.

Voriconazole Therapeutic Drug Monitoring is Necessary for Children with Invasive Fungal Infection

• Kang HM
• Kang SY
• Cho EY
• Yu KS
• Lee JW
• Kang HJ
• Park KD
• Shin HY
• Ahn HS
• Lee H
• Choi EH
• Lee HJ

Abstract

PURPOSE
To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population.
METHODS
Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end.
RESULTS
Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1%) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P=0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P=0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P=0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration.
CONCLUSION
Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.

Keyword

Therapeutic drug monitoring; Voriconazole; Child; Invasive aspergillosis; Invasive fungal infection

MeSH Terms

Alanine Transaminase
Aspartate Aminotransferases
Child*
Drug Monitoring*
Humans
Retrospective Studies
Alanine Transaminase
Aspartate Aminotransferases

Figure

• 

  Fig. 1 Distribution of 143 voriconazole serum trough levels from 14 patients. With the therapeutic range set at 1.0-5.5 mg/L, 18 (12.6%) samples were in the toxic range (>5.5 mg/L), 49 (34.3%) samples were below therapeutic range (<1.0 mg/L), leaving 76 (53.1%) samples within therapeutic range.

• 

  Fig. 2 The initial voriconazole concentration of 13 patients and the day it was taken after initiation of the drug. One patient's initial voriconazole concentration was taken 52 days after initiation of therapy therefore is not included in the graph.

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