A Retrospective Analysis for the Safety and Effectiveness of Voriconazole in a Medical Center in Taiwan
Date Issued
2010
Date
2010
Author(s)
Tseng, Yu-Ju
Abstract
Background:
Voriconazole is a new generation triazole antifungal agent. It was approved by FDA in 2002 and Department of Health in Taiwan in 2003. Its indications include invasive aspergillosis, candidemia, esophageal candidiasis, and other mold infections due to Scedosporium apiospermum and Fusarium spp. Voriconazole is generally considered well tolerated, however, some severe adverse events have been reported. It plays an important role in the drug-drug interactions due to being substrate and inhibitors of CYP2C19, CYP2C9 and CYP3A4. The interactions may interfere in the clinical response and safety of voriconazole.
Objective:
This retrospective study attempted to describe the prescribing pattern of voriconazole, eg., voriconazole dosage, administration route, and indications. The relationship between clinical response and prescribing pattern was evaluated. Adverse events (AEs) potential caused by voriconazole, and risk factors would be discussed.
Methods
The study was a retrospective chart review. Patients who were treated with voriconazole in the National Taiwan University Hospital (NTUH) during 01/01~12/31/2008 were included. Patients’ data were collected from medical records and the computerized databases in the hospital, including patients’ demographic data, risk factors of fungal infections, laboratory data, indication for voriconazole, dosing regimen, drug interactions, adverse events, etc. We evaluated the clinical response upon discontinuation of voriconazole and 8 weeks after. Furthermore, we discussed the association between clinical response and patients’ characteristics and prescribing pattern. We also reviewed voriconazole associated AEs and assessed the probability with Naranjo Scale. The statistical methods included Student’s t test, Mann-Whitney U Test, and χ2 test. The logistic regression model was used to identify the risk factors of poor response and adverse events.
Result
The study included 94 patients and there were 105 treatment courses. The average age was 44.3±21.12 years old. Male accounted for 56.4%. Almost 70% patients (64/94) had hematological malignancies, 2 patients didn’t have any underlying disease. Voriconazole was indicated for the treatment of proven, probable, possible invasive fungal infections in 16.2%, 30.4%, and 45.7% of patients, respectively. But 5 patients were treated with voriconazole without evidence of fungal infection. Voriconzole was used as primary therapy in 54.3% of patients. Among 34 patients (32.4%) treated with IV voriconazole as initial therapy, 5.9% of patients (2/34) didn’t receive the loading dose. Average maintenance doses were 3.8 ± 1.18 mg/kg (oral) and 3.7 ± 0.76 mg/kg (IV). The median course duration was 29 (1~701) days. In terms of response, 29.5%, 28.6%, 39% of patients had complete response, partial response, and no response to voriconazole respectively. One patient lost to follow up. One tenth of patients died during voriconazole therapy with fungal infections. AEs occurred in 41 treatment courses (39 %). Because some patients had ≧ 1 adverse events, there were a total of 55 adverse events. Three AEs were considered as definite, 24 AEs as probable and 28 AEs as possible. The most common side effect was liver function abnormality (28/105, 26.7%). However, adverse events had no association between patients’ characteristics and prescribing pattern. The most common potential drug-drug interaction was involved prednisolone (16/105, 15.2%). There were also 6 treatment courses combined the contraindicated drugs, such as carbamazepine, ergonovine and rifampin. Approximately 20% of AEs (21/105) might be associated with drug-drug medicines. There was no difference between indications and clinical response (p-value = 0.35). In the logistic regression, if patients were on foley catheter and without G-CSF therapy before voriconazole therapy, the risk of treatment failure would be increased.
Conclusion
In this retrospective study, majority patients had hematological malignancies. Voriconazole was usually indicated for possible invasive fungal infections (45.7%) and as a salvage therapy. Most of patients were treated with oral formulation. In general, the administration of voriconazole in this study was consistent with clinical recommendation. Approximately 58% of patients had good response to voriconazole and the most common adverse event was live enzymes abnormality (26%). There were also 6 treatment courses combined the contraindicated drugs. Approximately 20% of AEs might be associated with drug-drug interactions.
Subjects
voriconazole
invasive fungal infection
drug utilization evaluation
treatment response
adverse event
drug-drug interaction
Type
thesis
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