Arathi A Lambrix1, Hope D Swanson2, Jennifer L Pauley3, Allison W Bragg2, Delia C Carias2, Melissa S Bourque2, Yinmei Zhou4, Cheng Cheng4, William L Greene2, Gabriela Maron5. 1. Department of Pharmacy, Primary Children's Hospital, Salt Lake City, UT, USA. 2. Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, TN, USA. 3. Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA. 4. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA. 5. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
Abstract
BACKGROUND: Posaconazole exhibits broad-spectrum antifungal activity. An IV formulation became available in 2014. Few studies describing the use of this formulation exist in patients under the age of 18 years. This study describes our experience using IV posaconazole in paediatric and young adult cancer patients. METHODS: This single-centre retrospective chart review evaluated patients who received IV posaconazole and had at least one posaconazole plasma concentration obtained after five or more days with a consistent dosage. Relationships between doses required to achieve a plasma concentration of ≥1 µg/mL and patient age, weight and body surface area (BSA) were evaluated. The clinical record was reviewed to identify descriptions of any adverse events. RESULTS: Twenty-five patients were analysed, with a median age of 10.5 years (range 1.9-22.9 years; 92% were <18 years). All patients were able to achieve a posaconazole plasma concentration ≥1 µg/mL during their treatment course. The daily mg/kg/day dose required to achieve the target concentration decreased significantly with increasing age of the patient (P = 0.018). Assessment of dosage based on BSA suggested a requirement of 225 mg/m2/day across all age groups <18 years. Adverse events documented in the clinical record were consistent with those described with the oral formulations. No CNS toxicities were observed with use of IV posaconazole. CONCLUSIONS: Concentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients <18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations.
BACKGROUND: Posaconazole exhibits broad-spectrum antifungal activity. An IV formulation became available in 2014. Few studies describing the use of this formulation exist in patients under the age of 18 years. This study describes our experience using IV posaconazole in paediatric and young adult cancer patients. METHODS: This single-centre retrospective chart review evaluated patients who received IV posaconazole and had at least one posaconazole plasma concentration obtained after five or more days with a consistent dosage. Relationships between doses required to achieve a plasma concentration of ≥1 µg/mL and patient age, weight and body surface area (BSA) were evaluated. The clinical record was reviewed to identify descriptions of any adverse events. RESULTS: Twenty-five patients were analysed, with a median age of 10.5 years (range 1.9-22.9 years; 92% were <18 years). All patients were able to achieve a posaconazole plasma concentration ≥1 µg/mL during their treatment course. The daily mg/kg/day dose required to achieve the target concentration decreased significantly with increasing age of the patient (P = 0.018). Assessment of dosage based on BSA suggested a requirement of 225 mg/m2/day across all age groups <18 years. Adverse events documented in the clinical record were consistent with those described with the oral formulations. No CNS toxicities were observed with use of IV posaconazole. CONCLUSIONS: Concentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients <18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations.
Authors: Valeria A Bernardo; Shane J Cross; Kristine R Crews; Patricia M Flynn; James M Hoffman; Katherine M Knapp; Jennifer L Pauley; Alejandro R Molinelli; William L Greene Journal: Ann Pharmacother Date: 2013-06-04 Impact factor: 3.154
Authors: Jenna R Nickless; Kathryn E Bridger; Surabhi B Vora; Adam W Brothers Journal: J Pediatric Infect Dis Soc Date: 2019-09-25 Impact factor: 3.164