At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.
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http://dx.doi.org/10.1177/1078155220908948 | DOI Listing |
J Am Acad Dermatol
January 2025
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL.
Frontal Fibrosing Alopecia (FFA) poses a distinct dermatological challenge with epithelial-mesenchymal transition (EMT) at its core, driving follicular cell transformation and fibrotic changes. Genetic studies highlight significant associations, while environmental triggers, such as implicated cosmetic products (sunblock, personal hair care products, and moisturizers), introduce complexity. Managing FFA proves daunting due to its chronic and unpredictable nature.
View Article and Find Full Text PDFMol Ther
January 2025
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School; 30625 Hannover, NI, Germany. Electronic address:
Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B-cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.
View Article and Find Full Text PDFTher Drug Monit
February 2025
School of Pharmacy, University of Queensland, Brisbane, QLD, Australia.
Background: Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (C u ), total plasma (C p ), and whole-blood (C wb ) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices.
View Article and Find Full Text PDFTransplant Cell Ther
January 2025
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt - Universität zu Berlin, and Berlin Institute of Health, Department of Pediatric Oncology and Hematology, Berlin, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Hematology and Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Background: Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants for allogeneic HSCT success. The immunosuppressive agent, ciclosporin A, is most often used to prevent GVHD in pediatric patients, but is known to be nephrotoxic.
View Article and Find Full Text PDFEur J Pharm Sci
January 2025
Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Pharmacy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address:
Tacrolimus is extensively used for the prevention of graft rejection following solid organ transplantation in pregnant women. However, knowledge gaps in the dosage of tacrolimus for pregnant patients with different CYP3A5 genotypes and infection conditions have been identified. This study aimed to develop a pregnant physiologically based pharmacokinetic (PBPK) model to characterize the maternal and fetal pharmacokinetics of tacrolimus during pregnancy and explore and provide dosage adjustments.
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