Monitoring plasma voriconazole levels may prevent subtheraputic dosing in pediatric stem cell transplant (SCT) patients

Abstract

7105 Background: Voriconazole is frequently used for prophylaxis and treatment of fungal infections during hematopoeitic stem cell transplant (SCT). Clinical studies demonstrate a poorer outcome when voriconazole concentrations are ≤0.5mcg/ml. Pediatric dosing schedules to achieve trough concentrations >0.5mcg/ml are not established. Methods: Retrospective analysis of voriconazole levels in 16 pediatric allogeneic SCT patients recieving fungal prophylaxis with oral or iv voriconazole. Ages ranged from 0.5 to 16 years, median 8 years. Serum levels were measured by high-performance liquid chromatography. Samples were obtained 5 to 7 days after start or change of voriconazole therapy. Ninety-eight total levels were evaluated. Results: Eight patients (50%) achieved a trough level > 0.5mcg/ml on the majority of samples tested at doses ranging from 3.5 to 10 mg/kg po q 12 hours. At constant dose there was a significant intra-patient variability in trough levels over time. Most patients failing to achieve adequate trough levels were below the median age (see table ). Changing to iv therapy in 3 patients with low trough levels after oral therapy did not improve the trough levels. Multi-time point measurements were > 0.5mcg/ml at 2 to 6 hours after oral dose, but fell to < 0.2mcg/ml by 12 hours in 3 patients tested. Of 98 voriconazole levels, 52 were ≤ 0.5mcg/ml and 74 were < 1.0 mcg/ml. Conclusions: Unlike reports in adult patients, we found that frequent monitoring of voriconazole levels was necessary in pediatric SCT patients due to intra-patient variability. Younger pediatric SCT patients may require more frequent dosing schedules to achieve trough levels. No significant financial relationships to disclose. [Table: see text]