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| |  Increased Liver Abnormalities With Voriconazole Prophylaxis Against Aspergillus in Lung Transplant Patients: Presented at ATS By Jill Stein SAN DIEGO, C.A. -- May 24, 2006 -- Voriconazole is associated with an increase in abnormal liver function tests in most lung transplant (LT) recipients receiving prophylaxis against aspergillus infection, investigators reported here at the International Conference of the American Thoracic Society (ATS). Their results also demonstrate that normalization in liver function occurs when the voriconazole dose is reduced or the drug is stopped. Deborah J. Levine, MD, assistant professor, division of pulmonology, University of Texas Health Sciences Center, San Antonio, Texas, reported the results of a retrospective review of 52 consecutive LT recipients over a recent 16-month period. Overall, 26 patients were treated with itraconazole 200 mg orally BID for 3 months, and 26 patients were treated with voriconazole 200 mg orally BID for 3 months plus inhaled AmBisome 10 mg BID for 2 weeks. "Lung transplant recipients are particularly susceptible to aspergillus infection secondary to impaired local defenses, immunosuppression, ischemic airway injury, and altered alveolar phagocytic function, and there is a 6% to 8% incidence of aspergillus infection after LT," Dr. Levine said during her presentation on May 23rd. "While 80% of LT centers prophylax against aspergillus infection, no guidelines exist on how best to prevent this infection," she pointed out. Results showed no significant elevations in liver function tests in the itraconazole group while 38% of 26 patients in the voriconazole group had significant elevations in 1 or more liver function values. Of these, 8% had a mean aspartate aminotransferase (AST) of 229 ± 179 IU/L, and 15% had a mean alanine aminotransferase (ALT) of 187 ± 109 IU/L. Eight percent had a mean alkaline phosphatase (ALP) of 388 ± 54 IU/L, and 26% had a mean bilirubin level of 3 ± 1.3 mg/dL. Aspergillus was isolated in 19% of patients in the itraconazole group and 23% of patients in the voriconazole/inhaled AmBisome group. There was no evidence of invasive aspergillus in either group. There were no significant differences between the 2 groups in their use of concurrent medications that may cause elevated liver function levels, including trimethoprim-sulfametoxazole, statins, amiodarone, cyclosporine, macrolides, digoxin, and proton pump inhibitors. Dr. Levine noted that the incidence of increased liver function levels in the present study is higher than that reported in the literature. This may be due to a variation in genetic factors, pharmacokinetics, enzyme inhibition/induction by concurrent medication, age, and volume of distribution, he said. If voriconazole is used as prophylaxis against aspergillus in LT patients, serum levels and liver function should be monitored closely because of interpatient variability in its serum concentrations and the nonlinear kinetics of the drug, she said. Finally, she emphasized that more studies are needed to identify the optimal prophylactic regimen for aspergillus infection post-LT.
[Presentation title: Liver Function Abnormalities in Lung Transplants Recipients Receiving Voriconazole Versus Itraconazole for Aspergillus Prophylaxis. Abstract 711]
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