PLASMA POSACONAZOLE CONCENTRATION DURING CONCOMITANT TREATMENT WITH PROTON PUMP INHIBITHOR OMEPRAZOLE IN ADOLESCENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANT.
(Abstract release date: 05/19/16)
EHA Library. Ribersani M. 06/09/16; 134794; PB1894
Dr. Michela Ribersani
Contributions
Contributions
Abstract
Abstract: PB1894
Type: Publication Only
Background
Posaconazole (PCZ) is a broad-spectrum triazole approved for primary antifungal prophylaxis in patients (pts) with acute myeloid leukaemia or myelodisplastic syndrome during chemotherapy, in pts who develop a graft versus host disease (GVHD) after allogeneic stem cell transplant (allo-SCT) and for salvage therapy of pts with invasive fungal diseases (IFD). Concomitant use of PCZ suspension (PCZ-susp) and proton pump inhibitors (PPIs) has been associated with a significant reduction in the bioavailability of the antifungal drug, however, whether and in what extent this reduction affects the probability in reaching the target levels should be defined. Furthermore, few data are available in the paediatric population.
Aims
Omeprazole is a PPI often prescribed to allo-SCT recipients who receive steroids for prophylaxis or treatment of GVHD, therefore concomitant PPI and PCZ-susp are commonly administered. In this study the impact of omeprazole on plasma PCZ concentration (PPC) in 4 adolescents who received PCZ-susp after allo-SCT was evaluated.
Methods
This study represents a sub-analysis of a large, prospective, multicenter trial which included adult and paediatric allo-SCT pts. The trial was approved by Ethic Committee, written informed consent was obtained from each parent prior to any study-related activity. They were 3 males and 1 female (aged 11-13-16 and 17 years) and they were affected by sickle cells disease and β-thalassemia (2 pts each) and underwent allo-SCT from related donors. Two pts received PCZ-susp for second line therapy of proven Aspergillus Terreus infection and possible IFD respectively, and other 2 pts received PCZ-susp for primary prophylaxis during GVHD. PCZ-susp was administered at standard dose (600 mg/die or 12 mg/Kg regard to the weight). Plasma samples were stored at -80°C. The PPC was measured by high-pressure liquid chromatography at a reference pharmacology laboratory in Florence. All pts received concomitant treatment with omeprazole during the entire PCZ-susp therapy. At steady state (after 5 days of treatment) 0.7 mcg/ml was considered the therapeutic cut-off value.
Results
Overall, 2, 2, 3 and 6 samples were obtained, respectively. In two pts PPC was always above the cut-off value (mean 2.34 and 1.19 mcg/ml respectively), while in two pts the first PPC was inadequate (0,27 and 0,49 mcg/ml respectively) but reached higher values at a second evaluation (0,50 and 2,05 mcg/ml respectively), without changing the dosage of the drug. The patient with persistent sub-therapeutic PPC suffered of gastro-intestinal GVHD with diarrhoea.
Conclusion
PPC monitoring is considered a standard good practice in pts treated with PCZ-susp. However, considering that a timely PPC monitoring is difficult to perform in several centers, clinical conditions which may impact on the bioavailability of the drug can be considered for the safe use of PCZ-susp without PPC monitoring. This small experience in adolescent SCT pts doesn’t seem to show a significant impact of omeprazole in the bioavailability of PCZ-susp. In the only patient with inadequate PPC, diarrhoea, and not concomitant PPI, presumably was the cause of reduced absorption. While diarrhoea has been associated to impaired intestinal absorption in several experiences, concomitant use of PPI doesn’t seem to significantly impact on PPC and doesn’t seem to be considered an absolute indication to PPC monitoring.
Session topic: E-poster
Type: Publication Only
Background
Posaconazole (PCZ) is a broad-spectrum triazole approved for primary antifungal prophylaxis in patients (pts) with acute myeloid leukaemia or myelodisplastic syndrome during chemotherapy, in pts who develop a graft versus host disease (GVHD) after allogeneic stem cell transplant (allo-SCT) and for salvage therapy of pts with invasive fungal diseases (IFD). Concomitant use of PCZ suspension (PCZ-susp) and proton pump inhibitors (PPIs) has been associated with a significant reduction in the bioavailability of the antifungal drug, however, whether and in what extent this reduction affects the probability in reaching the target levels should be defined. Furthermore, few data are available in the paediatric population.
Aims
Omeprazole is a PPI often prescribed to allo-SCT recipients who receive steroids for prophylaxis or treatment of GVHD, therefore concomitant PPI and PCZ-susp are commonly administered. In this study the impact of omeprazole on plasma PCZ concentration (PPC) in 4 adolescents who received PCZ-susp after allo-SCT was evaluated.
Methods
This study represents a sub-analysis of a large, prospective, multicenter trial which included adult and paediatric allo-SCT pts. The trial was approved by Ethic Committee, written informed consent was obtained from each parent prior to any study-related activity. They were 3 males and 1 female (aged 11-13-16 and 17 years) and they were affected by sickle cells disease and β-thalassemia (2 pts each) and underwent allo-SCT from related donors. Two pts received PCZ-susp for second line therapy of proven Aspergillus Terreus infection and possible IFD respectively, and other 2 pts received PCZ-susp for primary prophylaxis during GVHD. PCZ-susp was administered at standard dose (600 mg/die or 12 mg/Kg regard to the weight). Plasma samples were stored at -80°C. The PPC was measured by high-pressure liquid chromatography at a reference pharmacology laboratory in Florence. All pts received concomitant treatment with omeprazole during the entire PCZ-susp therapy. At steady state (after 5 days of treatment) 0.7 mcg/ml was considered the therapeutic cut-off value.
Results
Overall, 2, 2, 3 and 6 samples were obtained, respectively. In two pts PPC was always above the cut-off value (mean 2.34 and 1.19 mcg/ml respectively), while in two pts the first PPC was inadequate (0,27 and 0,49 mcg/ml respectively) but reached higher values at a second evaluation (0,50 and 2,05 mcg/ml respectively), without changing the dosage of the drug. The patient with persistent sub-therapeutic PPC suffered of gastro-intestinal GVHD with diarrhoea.
Conclusion
PPC monitoring is considered a standard good practice in pts treated with PCZ-susp. However, considering that a timely PPC monitoring is difficult to perform in several centers, clinical conditions which may impact on the bioavailability of the drug can be considered for the safe use of PCZ-susp without PPC monitoring. This small experience in adolescent SCT pts doesn’t seem to show a significant impact of omeprazole in the bioavailability of PCZ-susp. In the only patient with inadequate PPC, diarrhoea, and not concomitant PPI, presumably was the cause of reduced absorption. While diarrhoea has been associated to impaired intestinal absorption in several experiences, concomitant use of PPI doesn’t seem to significantly impact on PPC and doesn’t seem to be considered an absolute indication to PPC monitoring.
Session topic: E-poster
Abstract: PB1894
Type: Publication Only
Background
Posaconazole (PCZ) is a broad-spectrum triazole approved for primary antifungal prophylaxis in patients (pts) with acute myeloid leukaemia or myelodisplastic syndrome during chemotherapy, in pts who develop a graft versus host disease (GVHD) after allogeneic stem cell transplant (allo-SCT) and for salvage therapy of pts with invasive fungal diseases (IFD). Concomitant use of PCZ suspension (PCZ-susp) and proton pump inhibitors (PPIs) has been associated with a significant reduction in the bioavailability of the antifungal drug, however, whether and in what extent this reduction affects the probability in reaching the target levels should be defined. Furthermore, few data are available in the paediatric population.
Aims
Omeprazole is a PPI often prescribed to allo-SCT recipients who receive steroids for prophylaxis or treatment of GVHD, therefore concomitant PPI and PCZ-susp are commonly administered. In this study the impact of omeprazole on plasma PCZ concentration (PPC) in 4 adolescents who received PCZ-susp after allo-SCT was evaluated.
Methods
This study represents a sub-analysis of a large, prospective, multicenter trial which included adult and paediatric allo-SCT pts. The trial was approved by Ethic Committee, written informed consent was obtained from each parent prior to any study-related activity. They were 3 males and 1 female (aged 11-13-16 and 17 years) and they were affected by sickle cells disease and β-thalassemia (2 pts each) and underwent allo-SCT from related donors. Two pts received PCZ-susp for second line therapy of proven Aspergillus Terreus infection and possible IFD respectively, and other 2 pts received PCZ-susp for primary prophylaxis during GVHD. PCZ-susp was administered at standard dose (600 mg/die or 12 mg/Kg regard to the weight). Plasma samples were stored at -80°C. The PPC was measured by high-pressure liquid chromatography at a reference pharmacology laboratory in Florence. All pts received concomitant treatment with omeprazole during the entire PCZ-susp therapy. At steady state (after 5 days of treatment) 0.7 mcg/ml was considered the therapeutic cut-off value.
Results
Overall, 2, 2, 3 and 6 samples were obtained, respectively. In two pts PPC was always above the cut-off value (mean 2.34 and 1.19 mcg/ml respectively), while in two pts the first PPC was inadequate (0,27 and 0,49 mcg/ml respectively) but reached higher values at a second evaluation (0,50 and 2,05 mcg/ml respectively), without changing the dosage of the drug. The patient with persistent sub-therapeutic PPC suffered of gastro-intestinal GVHD with diarrhoea.
Conclusion
PPC monitoring is considered a standard good practice in pts treated with PCZ-susp. However, considering that a timely PPC monitoring is difficult to perform in several centers, clinical conditions which may impact on the bioavailability of the drug can be considered for the safe use of PCZ-susp without PPC monitoring. This small experience in adolescent SCT pts doesn’t seem to show a significant impact of omeprazole in the bioavailability of PCZ-susp. In the only patient with inadequate PPC, diarrhoea, and not concomitant PPI, presumably was the cause of reduced absorption. While diarrhoea has been associated to impaired intestinal absorption in several experiences, concomitant use of PPI doesn’t seem to significantly impact on PPC and doesn’t seem to be considered an absolute indication to PPC monitoring.
Session topic: E-poster
Type: Publication Only
Background
Posaconazole (PCZ) is a broad-spectrum triazole approved for primary antifungal prophylaxis in patients (pts) with acute myeloid leukaemia or myelodisplastic syndrome during chemotherapy, in pts who develop a graft versus host disease (GVHD) after allogeneic stem cell transplant (allo-SCT) and for salvage therapy of pts with invasive fungal diseases (IFD). Concomitant use of PCZ suspension (PCZ-susp) and proton pump inhibitors (PPIs) has been associated with a significant reduction in the bioavailability of the antifungal drug, however, whether and in what extent this reduction affects the probability in reaching the target levels should be defined. Furthermore, few data are available in the paediatric population.
Aims
Omeprazole is a PPI often prescribed to allo-SCT recipients who receive steroids for prophylaxis or treatment of GVHD, therefore concomitant PPI and PCZ-susp are commonly administered. In this study the impact of omeprazole on plasma PCZ concentration (PPC) in 4 adolescents who received PCZ-susp after allo-SCT was evaluated.
Methods
This study represents a sub-analysis of a large, prospective, multicenter trial which included adult and paediatric allo-SCT pts. The trial was approved by Ethic Committee, written informed consent was obtained from each parent prior to any study-related activity. They were 3 males and 1 female (aged 11-13-16 and 17 years) and they were affected by sickle cells disease and β-thalassemia (2 pts each) and underwent allo-SCT from related donors. Two pts received PCZ-susp for second line therapy of proven Aspergillus Terreus infection and possible IFD respectively, and other 2 pts received PCZ-susp for primary prophylaxis during GVHD. PCZ-susp was administered at standard dose (600 mg/die or 12 mg/Kg regard to the weight). Plasma samples were stored at -80°C. The PPC was measured by high-pressure liquid chromatography at a reference pharmacology laboratory in Florence. All pts received concomitant treatment with omeprazole during the entire PCZ-susp therapy. At steady state (after 5 days of treatment) 0.7 mcg/ml was considered the therapeutic cut-off value.
Results
Overall, 2, 2, 3 and 6 samples were obtained, respectively. In two pts PPC was always above the cut-off value (mean 2.34 and 1.19 mcg/ml respectively), while in two pts the first PPC was inadequate (0,27 and 0,49 mcg/ml respectively) but reached higher values at a second evaluation (0,50 and 2,05 mcg/ml respectively), without changing the dosage of the drug. The patient with persistent sub-therapeutic PPC suffered of gastro-intestinal GVHD with diarrhoea.
Conclusion
PPC monitoring is considered a standard good practice in pts treated with PCZ-susp. However, considering that a timely PPC monitoring is difficult to perform in several centers, clinical conditions which may impact on the bioavailability of the drug can be considered for the safe use of PCZ-susp without PPC monitoring. This small experience in adolescent SCT pts doesn’t seem to show a significant impact of omeprazole in the bioavailability of PCZ-susp. In the only patient with inadequate PPC, diarrhoea, and not concomitant PPI, presumably was the cause of reduced absorption. While diarrhoea has been associated to impaired intestinal absorption in several experiences, concomitant use of PPI doesn’t seem to significantly impact on PPC and doesn’t seem to be considered an absolute indication to PPC monitoring.
Session topic: E-poster
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