1622. How common is Subsequent Central Nervous System (CNS) Toxicity in Patients (pts) with Hematologic Malignancy (HM) and Supra-therapeutic Voriconazole (VRC) Serum Levels?
Session: Poster Abstract Session: Mycology - There's a Fungus Among Us: Treatment
Friday, October 28, 2016
Room: Poster Hall
Background: VRC is a mold-active triazole used extensively for treatment and prophylaxis of invasive fungal infections (IFI) in pts with HM. In view of the significant inter-patient and intra-patient variability of VRC metabolism, therapeutic drug monitoring is recommended to optimize its efficacy and avoid adverse effects. Specifically, a correlation between an elevated VRC level > 5.5mcg/mL and CNS toxicity has been reported. However, the frequency of subsequent CNS toxicity in pts with elevated VRC levels and no clinically evident toxicity at the time the level was obtained are unclear in routine practice.

Methods: We retrospectively reviewed the records of adult pts with HM who had a random VRC level > 5.5mcg/mL at MD Anderson Cancer Center (January 2010 to December 2015). VRC was used for IFI prophylaxis or treatment. Pts with any documented CNS neurotoxicity at the time the VRC level was obtained were excluded. The neurologic status was assessed using neurotoxicity NCI grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity.

Results: We identified 320 patients (mean age 57 ± 15 y; 63% male). 67.2% had acute leukemia, 33.1% had prior hematopoietic stem cell transplant and 73.1% were receiving VRC for treatment of an IFI. Median follow up was 103 days (IQR 36-314 days). Subsequent CNS toxicity was documented in only 16 patients (5.0%). The most common CNS toxicities were visual disturbances (56.3%), depressed level of consciousness (37.5%) and cognitive disturbance (18.8%). Pts with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p = 0.08). The use of one or more concomitant neurotoxic drugs was comparable in pts with developed new CNS toxicity than those without (87.5% vs. 79.3%, p = 0.43).

Conclusion: The development of subsequent CNS toxicity is uncommon in pts with supra-therapeutic VRC serum levels who had no evidence of toxicity at the time VRC level was obtained. Automatic VRC dose reduction for the concern for impending CNS toxicity might not be justified in such pts.

Sang Taek Heo, M.D. PhD.1,2, Samuel L. Aitken, PharmD3, Frank P. Tverdek, PharmD3 and Dimitrios P. Kontoyiannis, MD, ScD, FIDSA1, (1)Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, (2)Internal Medicine, Jeju National University School of Medicine, Jeju Special-Governing Province, South Korea, (3)Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX


S. T. Heo, None

S. L. Aitken, Astellas: Scientific Advisor , Consulting fee

F. P. Tverdek, Astellas: Scientific Advisor , Consulting fee

D. P. Kontoyiannis, •: Advisory Board , Research support
Pfizer: Research grant , Research support
Gilead: Invited lecturer , Speaker honorarium
Astellas: Consultant , Research support and Speaker honorarium
F2G: Consultant , Consulting fee
T2 Biosystems: Invited lecturer , Speaker honorarium
Mylan Inc: Invited lecturer , Speaker honorarium

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