ABSTRACT
WHAT IS KNOWN AND OBJECTIVES: Enzalutamide package labeling recommends avoiding concurrent warfarin use due to potential reductions in warfarin concentrations via enzalutamide-associated hepatic enzyme induction. A case of successful management of this interaction via warfarin adjustments is reported. CASE DESCRIPTION: A 77-year-old Caucasian male, previously relatively stable on warfarin 42-45 mg weekly, reported to clinic after the recent start of enzalutamide and subsequent hospitalization with a subtherapeutic International Normalized Ratio (INR). A 50% increase in weekly warfarin dose resulted in a therapeutic INR. Enzalutamide was temporarily discontinued, and a 33% weekly warfarin dose decrease resulted in two therapeutic INRs. WHAT IS NEW AND CONCLUSION: This is the first case to highlight the clinical significance of this interaction, noting that patients taking enzalutamide may require approximately 30%-50% adjustment in their warfarin dosage to maintain a therapeutic INR.
Subject(s)
Anticoagulants/administration & dosage , Phenylthiohydantoin/analogs & derivatives , Warfarin/administration & dosage , Aged , Benzamides , Drug Interactions , Humans , Male , Nitriles , Phenylthiohydantoin/therapeutic useABSTRACT
BACKGROUND: Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of $1 billion per annum. Venous neointimal hyperplasia (VNH) characterized by stenosis and subsequent thrombosis accounts for the overwhelming majority of pathology resulting in polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem and the enormity of the cost ($1 billion), there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts. METHODS: Tissue samples were collected from the graft-vein anastomosis of stenotic PTFE grafts during surgical revision. Specimens were graded using standard light microscopy and immunohistochemistry for the magnitude of neointimal hyperplasia and for the expression of specific cell types, cytokines, and matrix proteins. RESULTS: VNH was characterized by the (1) presence of smooth muscle cells/myofibroblasts, (2) accumulation of extracellular matrix components, (3) angiogenesis within the neointima and adventitia, and (4) presence of an active macrophage cell layer lining the PTFE graft material. Platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were expressed by smooth muscle cells/myofibroblasts within the venous neointima, by macrophages lining both sides of the PTFE graft, and by vessels within the neointima and adventitia. CONCLUSIONS: Our results suggest that macrophages, specific cytokines (bFGF, PDGF, and VEGF), and angiogenesis within the neointima and adventitia are likely to contribute to the pathogenesis of VNH in PTFE dialysis grafts. Interventions aimed at these specific mediators and processes may be successful in reducing the very significant human and economic costs of vascular access dysfunction.
