Eunah Cho1, Holly Chan2, Huan Mark Nguyen3,4, Sepideh Shayani2, Ryotaro Nakamura5, Doreen Pon2,3. 1. Department of Pharmacy, Sharp HealthCare, San Diego, California. 2. Department of Pharmacy, City of Hope National Medical Center, Duarte, California. 3. College of Pharmacy, Western University of Health Sciences, Pomona, California. 4. Department of Pharmacy, St. Mary Medical Center, Long Beach, California. 5. Department of Hematology and Hematopoietic Stem Cell Transplantation, City of Hope National Medical Center, Duarte, California.
Abstract
STUDY OBJECTIVE: To determine an appropriate empiric oral sirolimus dose adjustment when given concurrently with posaconazole oral suspension in patients who undergo hematopoietic stem cell transplant (HSCT). DESIGN: Retrospective cohort study. SETTING: Comprehensive cancer center in the United States. SUBJECTS: Seventy five allogeneic HSCT patients who received posaconazole oral suspension and oral sirolimus concurrently between 2009 and 2011. MEASUREMENTS AND MAIN RESULTS: Sirolimus concentrations were recorded at baseline and for up to 28 days after posaconazole initiation. The sirolimus concentration/dose (C/D) ratio was determined for each sirolimus concentration obtained. Following analysis of patient data and based on the initial empiric sirolimus dose reduction, patients were stratified into two groups: ≥50% sirolimus dose reduction (Group 1) and <50% sirolimus dose reduction (Group 2). The mean sirolimus C/D ratio was 2.29 ng/mL/mg prior to posaconzole initiation. Coadministration of posaconazole and sirolimus resulted in an increase in the steady state sirolimus C/D ratio to 6.24 ng/mL/mg, which occurred approximately 17-20 days after initiation of posaconazole. The mean maximum sirolimus concentration was significantly higher in Group 2 compared to Group 1 (12.64 ng/mL vs. 9.24 ng/mL, p=0.001). Significantly more patients in Group 2 than Group 1 experienced at least one sirolimus concentration >15 ng/mL (27% vs. 2.6%, p=0.003). CONCLUSION: Coadministration of posaconazole oral suspension with oral sirolimus increases the sirolimus C/D ratio by approximately 2.7-fold in HSCT patients. An initial empiric oral sirolimus dose reduction between 50% and 65% may be recommended for most clinically stable patients with close sirolimus concentration monitoring for at least 3 weeks following posaconazole initiation.
STUDY OBJECTIVE: To determine an appropriate empiric oral sirolimus dose adjustment when given concurrently with posaconazole oral suspension in patients who undergo hematopoietic stem cell transplant (HSCT). DESIGN: Retrospective cohort study. SETTING: Comprehensive cancer center in the United States. SUBJECTS: Seventy five allogeneic HSCT patients who received posaconazole oral suspension and oral sirolimus concurrently between 2009 and 2011. MEASUREMENTS AND MAIN RESULTS:Sirolimus concentrations were recorded at baseline and for up to 28 days after posaconazole initiation. The sirolimus concentration/dose (C/D) ratio was determined for each sirolimus concentration obtained. Following analysis of patient data and based on the initial empiric sirolimus dose reduction, patients were stratified into two groups: ≥50% sirolimus dose reduction (Group 1) and <50% sirolimus dose reduction (Group 2). The mean sirolimus C/D ratio was 2.29 ng/mL/mg prior to posaconzole initiation. Coadministration of posaconazole and sirolimus resulted in an increase in the steady state sirolimus C/D ratio to 6.24 ng/mL/mg, which occurred approximately 17-20 days after initiation of posaconazole. The mean maximum sirolimus concentration was significantly higher in Group 2 compared to Group 1 (12.64 ng/mL vs. 9.24 ng/mL, p=0.001). Significantly more patients in Group 2 than Group 1 experienced at least one sirolimus concentration >15 ng/mL (27% vs. 2.6%, p=0.003). CONCLUSION: Coadministration of posaconazole oral suspension with oral sirolimus increases the sirolimus C/D ratio by approximately 2.7-fold in HSCT patients. An initial empiric oral sirolimus dose reduction between 50% and 65% may be recommended for most clinically stable patients with close sirolimus concentration monitoring for at least 3 weeks following posaconazole initiation.
Authors: R Greco; M C Barbanti; M T Lupo Stranghellini; F Giglio; M Morelli; C Messina; A Forcina; C Oltolini; S Piemontese; P Scarpellini; S Marktel; A Assanelli; M Carrabba; L Vago; C Corti; M Bernardi; J Peccatori; F Ciceri Journal: Bone Marrow Transplant Date: 2016-04-25 Impact factor: 5.483