Serial Monitoring of Plasma Voriconazole Levels in Lung Transplant Recipients: Results From a Single Centre Experience

PurposeVoriconazole is used to treat fungal infections after lung transplantation, a correlation between clinical outcomes and voriconazole levels has been shown with a lack of response to voriconazole levels <1mcg/ml. The aim of this study was to evaluate variability in voriconazole levels over time in individuals.MethodsAll lung transplant recipients who received voriconazole for at least 7 days and had at least 2 trough levels measured May 2010-2012 using high performance liquid chromatography with mass detection were included. Treatment was commenced with a loading dose of 400mg twice daily for 24 hours then 200mg twice daily orally thereafter; trough levels were measured at a minimum of 3 days after commencing treatment, and repeated (max. twice weekly). A therapeutic level was defined as >1mcg/ml (range 1-5mcg/ml), the dose was adjusted as required. The percentage of time in therapeutic range (%TTR) over the treatment course was determined using the Rosendaal method. Those commencing treatment within the first month of transplant were compared with those treated later; also cystic fibrosis (CF) patients were compared with non-CF.ResultsSixty five lung transplant recipients were included in the study (33 CF, 37 male), voriconazole commenced at a median of 1.2 months after lung transplantation (range 0.1-259) with a median length of treatment of 48 days (range 7-713).ConclusionThere was intra-subject variability over time in patients receiving voriconazole orally. Those with CF or who received voriconazole within the first month after transplantation had significantly lower TTR. We conclude that serial monitoring of plasma voriconazole levels is required to avoid sub-therapeutic periods in lung transplant recipients; however, further studies are required to determine clinical outcomes.Tabled 1Median TTR(IQR,%) and Time below range (IQR,%) in lung transplant patients receiving voriconazoleAll patientsTTR*76(53-98)CFn=33Non-CFn=32P valueTTR*65(44-87)91(60-100)0.029Time below range*32(11-56)9(0-37)0.039Within 1 monthn=32More than 1 monthn=33TTR*61(44-85)89(60-100)0.027Time below range*31(8-54)11(0-41)ns Open table in a new tab PurposeVoriconazole is used to treat fungal infections after lung transplantation, a correlation between clinical outcomes and voriconazole levels has been shown with a lack of response to voriconazole levels <1mcg/ml. The aim of this study was to evaluate variability in voriconazole levels over time in individuals. Voriconazole is used to treat fungal infections after lung transplantation, a correlation between clinical outcomes and voriconazole levels has been shown with a lack of response to voriconazole levels <1mcg/ml. The aim of this study was to evaluate variability in voriconazole levels over time in individuals. MethodsAll lung transplant recipients who received voriconazole for at least 7 days and had at least 2 trough levels measured May 2010-2012 using high performance liquid chromatography with mass detection were included. Treatment was commenced with a loading dose of 400mg twice daily for 24 hours then 200mg twice daily orally thereafter; trough levels were measured at a minimum of 3 days after commencing treatment, and repeated (max. twice weekly). A therapeutic level was defined as >1mcg/ml (range 1-5mcg/ml), the dose was adjusted as required. The percentage of time in therapeutic range (%TTR) over the treatment course was determined using the Rosendaal method. Those commencing treatment within the first month of transplant were compared with those treated later; also cystic fibrosis (CF) patients were compared with non-CF. All lung transplant recipients who received voriconazole for at least 7 days and had at least 2 trough levels measured May 2010-2012 using high performance liquid chromatography with mass detection were included. Treatment was commenced with a loading dose of 400mg twice daily for 24 hours then 200mg twice daily orally thereafter; trough levels were measured at a minimum of 3 days after commencing treatment, and repeated (max. twice weekly). A therapeutic level was defined as >1mcg/ml (range 1-5mcg/ml), the dose was adjusted as required. The percentage of time in therapeutic range (%TTR) over the treatment course was determined using the Rosendaal method. Those commencing treatment within the first month of transplant were compared with those treated later; also cystic fibrosis (CF) patients were compared with non-CF. ResultsSixty five lung transplant recipients were included in the study (33 CF, 37 male), voriconazole commenced at a median of 1.2 months after lung transplantation (range 0.1-259) with a median length of treatment of 48 days (range 7-713). Sixty five lung transplant recipients were included in the study (33 CF, 37 male), voriconazole commenced at a median of 1.2 months after lung transplantation (range 0.1-259) with a median length of treatment of 48 days (range 7-713). ConclusionThere was intra-subject variability over time in patients receiving voriconazole orally. Those with CF or who received voriconazole within the first month after transplantation had significantly lower TTR. We conclude that serial monitoring of plasma voriconazole levels is required to avoid sub-therapeutic periods in lung transplant recipients; however, further studies are required to determine clinical outcomes.Tabled 1Median TTR(IQR,%) and Time below range (IQR,%) in lung transplant patients receiving voriconazoleAll patientsTTR*76(53-98)CFn=33Non-CFn=32P valueTTR*65(44-87)91(60-100)0.029Time below range*32(11-56)9(0-37)0.039Within 1 monthn=32More than 1 monthn=33TTR*61(44-85)89(60-100)0.027Time below range*31(8-54)11(0-41)ns Open table in a new tab There was intra-subject variability over time in patients receiving voriconazole orally. Those with CF or who received voriconazole within the first month after transplantation had significantly lower TTR. We conclude that serial monitoring of plasma voriconazole levels is required to avoid sub-therapeutic periods in lung transplant recipients; however, further studies are required to determine clinical outcomes.