652. Can Therapeutic Drug Monitoring Reduce Voriconazole Adverse Events?
Session: Poster Abstract Session: Pharmacokinetics and Adverse Drug Reactions
Friday, October 21, 2011
Room: Poster Hall B1
Background: 

Recent data suggest that therapeutic drug monitoring (TDM) for voriconazole may improve efficacy and safety outcomes. However, there is no randomized controlled trial to evaluate whether routine voriconazole TDM can reduce drug adverse events.

Methods: 

We conducted a prospective randomized assessor-blinded controlled trial in a single tertiary care hospital (South Korea) from Oct. 2008. Adult patients receiving voriconazole (6 mg/kg q12h twice followed by 4 mg/kg q12h) were randomly assigned into the TDM or the non-TDM group. Four days after starting voriconazole, voriconazole trough blood level was measured using high performance liquid chromatography-tandem mass spectrometry. Voriconazole dosage was adjusted with a target range (1-5.5 mg/L) in the TDM group, while routine dosage was maintained in the non-TDM group. Severe adverse events were defined according to the criteria of the National Cancer Institute.

Results: 

Of 90 patients, 44 were randomized into the TDM group and 46 into the non-TDM group. The median age was 60 years, 64 (71%) were male and 66 (73%) had hematologic diseases. Sixty-six (73%) had proven or probable fungal infection and 12% (11/74) were homozygous poor metabolizers by CYP2C19 genotype. In the TDM group, initial concentration of voriconazole was higher than target level in 16 (38%) and lower in 4 (10%). Overall adverse events developed in 20 (46%) in the TDM group vs. in 19 (41%) in the non-TDM group (p=0.832) and severe adverse events developed in 6 (14%) in the TDM group vs. in 3 (7%) in the non-TDM group (p=0.310). Median time to severe adverse events was 6 days (range 1-16 days). Voriconazole was discontinued due to adverse events in 1 (2%) in the TDM group vs. 8 (17%) in the non-TDM group (p=0.030).

Conclusion: 

Voriconazole TDM can reduce drug discontinuation due to adverse events, although it may not reduce adverse events because most of them develop too early to adjust the blood level. (ClinicalTtrials.gov number, NCT00890708)


Subject Category: J. Clinical practice issues

Wan Beom Park, MD, PhD1, Nak-Hyun Kim, MD1, SeungHwan Lee2, Kye-Hyung Kim, MD1, Na Ra Yun, MD3, Kyung-Sang Yu4, Nam Joong Kim, MD5, In-Jin Jang4 and Myoung-don Oh, MD, PhD6, (1)Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea, (2)Seoul National Univesity Hospital, Seoul, South Korea, (3)Seoul National University Hospital, Seoul, Korea, Republic of, (4)Seoul National University College of Medicine, Seoul, South Korea, (5)Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of, (6)Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea

Disclosures:

W. B. Park, None

N. H. Kim, None

S. Lee, None

K. H. Kim, None

N. R. Yun, None

K. S. Yu, None

N. J. Kim, None

I. J. Jang, None

M. D. Oh, None

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