Gary D Peksa1, Kathryn Schultz2, Henry C Fung3. 1. Department of Pharmacy, Rush University Medical Center, Chicago, IL, USA gary_d_peksa@rush.edu. 2. Department of Pharmacy, Rush University Medical Center, Chicago, IL, USA. 3. Division of Hematology, Oncology and Stem Cell Transplant, Rush University Medical Center, Chicago, IL, USA.
Abstract
BACKGROUND: Allogeneic hematopoietic stem cell transplant patients are at risk of invasive fungal infections and prophylaxis with azole agents is common practice. The concomitant use of these agents with sirolimus and tacrolimus for the prevention of graft-versus-host disease may result in excessive immunosuppression or toxicity. METHODS: This retrospective study identified hospitalized patients who underwent allogeneic hematopoietic stem cell transplantation between August 2009 and April 2011 at Rush University Medical Center. From this group, patients who underwent concomitant tacrolimus, sirolimus, and azole therapy were included for evaluation. The immunosuppression dosing in conjunction with azole use at discharge was analyzed to develop a dosing algorithm dependent on whether fluconazole, posaconazole, or voriconazole was used. RESULTS: A total of 36 patients were screened for inclusion, of which 8 were excluded due to acute renal failure and/or hemolysis. The remaining patients were stratified by the azole they were concomitantly taking with tacrolimus and sirolimus. The fluconazole arm required the lowest magnitude of dose reductions, while voriconazole required the greatest. CONCLUSION: Dose reductions of 50-75% for both sirolimus and tacrolimus, in combination with standard dosing of azole antifungal agents, were necessary to achieve therapeutic drug concentrations for immunosuppressants and potentially avoid toxicities.
BACKGROUND: Allogeneic hematopoietic stem cell transplant patients are at risk of invasive fungal infections and prophylaxis with azole agents is common practice. The concomitant use of these agents with sirolimus and tacrolimus for the prevention of graft-versus-host disease may result in excessive immunosuppression or toxicity. METHODS: This retrospective study identified hospitalized patients who underwent allogeneic hematopoietic stem cell transplantation between August 2009 and April 2011 at Rush University Medical Center. From this group, patients who underwent concomitant tacrolimus, sirolimus, and azole therapy were included for evaluation. The immunosuppression dosing in conjunction with azole use at discharge was analyzed to develop a dosing algorithm dependent on whether fluconazole, posaconazole, or voriconazole was used. RESULTS: A total of 36 patients were screened for inclusion, of which 8 were excluded due to acute renal failure and/or hemolysis. The remaining patients were stratified by the azole they were concomitantly taking with tacrolimus and sirolimus. The fluconazole arm required the lowest magnitude of dose reductions, while voriconazole required the greatest. CONCLUSION: Dose reductions of 50-75% for both sirolimus and tacrolimus, in combination with standard dosing of azole antifungal agents, were necessary to achieve therapeutic drug concentrations for immunosuppressants and potentially avoid toxicities.
Authors: Francisco M Marty; Colleen M Lowry; Corey S Cutler; Bonnie J Campbell; Karen Fiumara; Lindsey R Baden; Joseph H Antin Journal: Biol Blood Marrow Transplant Date: 2006-05 Impact factor: 5.742
Authors: Andrew J Ullmann; Jeffrey H Lipton; David H Vesole; Pranatharthi Chandrasekar; Amelia Langston; Stefano R Tarantolo; Hildegard Greinix; Wellington Morais de Azevedo; Vijay Reddy; Navdeep Boparai; Lisa Pedicone; Hernando Patino; Simon Durrant Journal: N Engl J Med Date: 2007-01-25 Impact factor: 91.245
Authors: Corey Cutler; Haesook T Kim; Ephraim Hochberg; Vincent Ho; Edwin Alyea; Stephanie J Lee; David C Fisher; David Miklos; Jesse Levin; Stephen Sonis; Robert J Soiffer; Joseph H Antin Journal: Biol Blood Marrow Transplant Date: 2004-05 Impact factor: 5.742
Authors: M A Slavin; B Osborne; R Adams; M J Levenstein; H G Schoch; A R Feldman; J D Meyers; R A Bowden Journal: J Infect Dis Date: 1995-06 Impact factor: 5.226
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
Authors: Thomas F Patterson; George R Thompson; David W Denning; Jay A Fishman; Susan Hadley; Raoul Herbrecht; Dimitrios P Kontoyiannis; Kieren A Marr; Vicki A Morrison; M Hong Nguyen; Brahm H Segal; William J Steinbach; David A Stevens; Thomas J Walsh; John R Wingard; Jo-Anne H Young; John E Bennett Journal: Clin Infect Dis Date: 2016-06-29 Impact factor: 9.079
Authors: Kathryn T Maples; Molly Maloy; Sean Devlin; Andrew Lin; Lauren DeRespiris; Meagan Griffin; Carmen Lau; Anthony J Proli; Genovefa A Papanicolaou; Susan K Seo; Juliet N Barker; Miguel-Angel Perales; Sergio A Giralt; Valkal Bhatt Journal: Bone Marrow Transplant Date: 2020-01-14 Impact factor: 5.483