Background: Voriconazole is an azole antifungal utilized for the prevention or treatment of systemic fungal infections in hematologic malignancies and hematopoietic stem cell transplantation. Voriconazole has a non-linear pharmacokinetics with wide inter-patient variability, which makes dosing challenging. Previous studies have revealed decreased efficacy and increased toxicity with subtherapeutic <1 mcg/mL and supratherapeutic >4 mcg/mL levels respectively. The VDMG was introduced at Yale New Haven Hospital in July 2014 that was based on a retrospective pooled analysis.(Table 1) The objective of this prospective study was to validate the VDMG.
Methods: This study included patients with a history of hematological malignancies who received voriconazole from July 2014 and February 2016. Eligible adult patients initiating voriconazole for prophylaxis or treatment with at least one voriconazole trough level were included. Age, gender, race, body mass index (BMI), proton pump inhibitor use, primary diagnosis, primary reason for admission, indication for voriconazole, adverse effects and breakthrough infections were documented.
Results: One hundred twenty eight patients with 250 admissions were initiated on voriconazole during the study period. Voriconazole use was categorized into new start, new start with loading dose and continuation from home. The median first levels were 1.5, 3.5, and 1.7 mg/mL with 62% (73/119), 55% (6/11), and 60% (71/120) within the therapeutic range. Using the VDMG, an additional 68% were within goal by the 3rd level. The median number of dose changes in all three groups to achieve therapeutic goal level was one. In patient specific characteristics, age <30 and BMI <25 kg/m2 had higher rates of subtherapeutic levels in the new starts cohorts (p=0.043 & p=0.01). A total of 7.5% experienced an adverse effect with neurologic/psychological being the most common. 8.5% had a presumed or documented breakthrough fungal infection while on voriconazole.
Conclusion: Using the VDMG, we improved the number of patients reaching goal from 36% to 68% by the 3rd level (p=0.007). This guideline has been validated to optimize achieving therapeutic levels in a timely manner.
D. Mcmanus, None
S. Perreault, None
M. Ruggero, None
J. Topal, None
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