658. Serum Concentrations and Tolerability of Standard and Weight-Based Oral Dosing Regimens of Voriconazole
Session: Abstracts: Mycology
Friday, October 22, 2010
Background: Voriconazole (VOR) displays inter- and intra-patient variance in serum concentrations despite standardized dosing.  Intravenous (IV) VOR is weight-based; oral (PO) dosing is less defined. The indicated PO dose of 200 mg every (q) 12 hours (h) may lead to a lower PO than IV dose and has led some practitioners to utilize weight-based PO regimens. This study compared the rates of adverse effects (AEs) in patients (pts) receiving standard PO dosing (SD) of 200 mg q 12 h to those receiving weight based PO dosing (WD).

Methods: Medical records of pts who received PO VOR while hospitalized at University Hospital from 8/2003 to 5/2009 were reviewed including demographic data, VOR dosing and duration, VOR levels (if obtained), and adverse effects.  Pts who received less than 3 days of PO VOR were excluded. VOR levels were sorted into 3 ranges: subtherapeutic (<1 mcg/mL), therapeutic (1-6 mcg/mL), and possibly toxic (>6 mcg/mL).

Results: 90 hospital courses were included.  Most pts were either solid organ transplant recipients (29%) or had hematologic malignancies (42%).  39 received SD and 51 received WD.  Mean dosage for the SD group was 3.2 mg/kg q 12 h (range 1.5 - 5.7) vs 4.4 mg/kg q 12 h in the WD group (2.4 - 7.1).  In 14 SD pts, 19 levels were drawn: 3/19 (16%) were < 1, 16/19 (84%) 1-6, and none > 6. In 29 WD pts, 67 levels were drawn: 21/67 (31%) were <1, 35/67 (52%) 1-6, and 11/67 (16%) > 6.  Mean levels in the SD and WD groups were 2.1 mcg/ml (<0.2 - 4.52) and 3.2 (<0.2 – 12.24) respectively.    In the SD group, 5 of 39 (13%) had AEs vs 6 of 51 (12%) in the WD group.  AEs in the SD group consisted entirely of elevated liver function tests (LFTs). The WD group AEs were mostly elevated LFTs (4/6) but also included 3 pts with central nervous system (CNS) AEs.  All 3 Pts with CNS AEs had VOR levels > 6 mcg/mL while only 1 Pt with elevated LFTs had a level > 6 mcg/mL.

Conclusion: There was no difference in the rate of AEs between the SD and WD groups supporting tolerability of higher PO dosing.  However, variability of levels obtained in this cohort of pts even with weight-based dosing suggests that therapeutic drug monitoring should be used to avoid subtherapeutic or toxic levels.


Subject Category: M. Mycology including clinical and basic studies of fungal infections

Jason E. Bowling, MD , UTHSCSA & STVHCS, San Antonio, TX
James S. Lewis II, PharmD , University Health System&UTHSC-SA, San Antonio, TX
Thomas F. Patterson, MD , Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, San Antonio, TX


J. E. Bowling, None

J. S. Lewis II, Yes
Pfizer: Scientific Advisor, Consulting fee
Merck: Scientific Advisor, Consulting fee
Astellas: Scientific Advisor, Consulting fee and Speaker honorarium

T. F. Patterson, Yes
Pfizer: Data Review Committee, Grant Investigator and Scientific Advisor,
Merck: Grant Investigator,
Basilea: Data Review Committee, Grant Investigator and Scientific Advisor,

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