title: Clotrimazole troches induce supratherapeutic blood levels of sirolimus and tacrolimus in an allogeneic hematopoietic cell-transplant recipient resulting in acute kidney injury.
abstract: Allogeneic hematopoietic cell transplantation is a potential curative treatment option for various malignant and nonmalignant hematologic disorders. Patients undergoing an allogeneic hematopoietic cell transplant are prescribed immune-suppressant therapies to facilitate hematopoietic donor-cell engraftment and prevent graft-versus-host disease. Drug-drug interactions may occur, owing to exposure to complex multidrug regimens with narrow therapeutic windows and high toxicity profiles. Here, we describe a unique case of a 65-year-old man with poor-risk acute myeloid leukemia who underwent a matched-sibling hematopoietic cell allograft. Sirolimus and tacrolimus were used for graft-versus-host disease prophylaxis. He developed oral thrush requiring treatment with clotrimazole troches, which subsequently resulted in serious renal toxicity attributed to supratherapeutic levels of sirolimus and tacrolimus. Patient renal function improved after temporarily holding both immune suppressants, and administering phenytoin to help induce sirolimus and tacrolimus metabolism. This case highlights sudden and serious toxicities that resulted from clotrimazole-sirolimus and clotrimazole-tacrolimus drug-drug interactions, even when administered topically.
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Jessica
authors.initials: J
authors.lastname: El-Asmar
authors.affiliation: Department of Pharmacy, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Department of Pharmacy, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bookout
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center/University of South Florida, Morsani College of Medicine, Tampa, FL, USA.
authors.forename: Asmita
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center/University of South Florida, Morsani College of Medicine, Tampa, FL, USA. Electronic address: Mohamed.Kharfan-Dabaja@Moffitt.org.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology*; D000368:Aged; D003022:Clotrimazole / Q000009:adverse effects* / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D020123:Sirolimus / Q000097:blood*; D016559:Tacrolimus / Q000097:blood*; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D003404:Creatinine; D003022:Clotrimazole; D020123:Sirolimus; D016559:Tacrolimus
keywords: Allogeneic hematopoietic cell transplantation; Clotrimazole; Sirolimus; Tacrolimus