DETERMINING VORICONAZOLE (VOR) SERUM TROUGH CONCENTRATIONS ASSOCIATED WITH MICROBIOLOGIC FAILURE AND TOXICITY DURING PROPHYLAXIS: RESULTS FROM A PROSPECTIVE, OBSERVATIONAL STUDY OF THERAPEUTIC DRUG MONITORING (TDM) IN LUNG TRANSPLANT (LT) RECIPIENTS

D. Mitsani1, R. Shields1, M. Nguyen1, Y. Toyoda1, C. Clancy1*

Author address: 

1University of Pittsburgh Medical Center (UPMC)

Abstract: 

Purpose: VOR TDM has been advocated in patients (pts) treated for invasive fungal infections (IFI). Troughs of 1-2 μg/ml have been proposed as therapeutic. Data are less clear for pts receiving VOR prophylaxis (px). Methods: LT pts from Jan-Oct 2009 were followed with serum trough VOR TDM. All pts received 2 doses IV load (6 mg/kg) then 200 mg po BID. TDM was performed by HPLC. Results: 65 LT pts underwent TDM, 86% (56/65) of whom were serially tested. Pts were 20-74 yrs (median: 63). Underlying diseases were COPD (44%), IPF (34%) and CF (12%). 38% (25/65) of initial VOR levels were 8804; 1 μg/mL (3 undetectable, 10 between 0.2-0.5, 12 between 0.5-1.0), 18% (12/65) between 1-2, 10% (7/65) between 2-3, 14% (9/65) between 3-4, 9% (6/65) between 4-5, 3% (2/65) between 5-6, and 6% (4/65) >6. Patients > 60 yrs were more likely to have initial levels > 1 (p=0.03). Upon serial testing, 62.5% (35/56) had significant (>0.5) variation in levels. 27% (15/56) had persistent levels 8804; 1, including 12.5% (7/56) with persistent levels 8804; 0.5. 32% (13/40) of pts with initial levels > 1 had subsequent levels 8804; 1. 100% (5/5) of IFIs occurring during VOR px were tracheobronchitis caused by yeasts, and serum VOR levels were 1 included A. niger (2), Rhizopus (1), Penicillium (1), and Scedosporium (1). Nausea/vomiting requiring medical intervention was encountered in 11% (7/65), but only 43% (3/7) had VOR levels > 3; in 57%, VOR levels were 3. Pts with hepatotoxicity or neurotoxicity were significantly more likely to have VOR levels > 3 μg/mL (p=0.001). Conclusions: VOR levels 3 μg/mL were associated with breakthrough colonization/IFIs and hepato-/neurotoxicity during px, respectively. The therapeutic target for px is similar to that proposed for treatment of IFI. In order to assure that target levels are achieved and maintained, serial drug monitoring is necessary.
2010

abstract No: 

67

Full conference title: 

4th Advances Against Aspergillosis
    • AAA 4th (2010)