Effects of Amiodarone,Thyroid Hormones and CYP2C9 and VKORC1 Polymorphisms on Warfarin Metabolism: A Review of the Literature |
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| Institution: | 1. Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy;2. Division of Pharmacology, Department of Internal Medicine, University of Pisa, Pisa, Italy;3. Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy;4. Cardiology Unit, Hospital of Carrara, Carrara, Italy;5. Department of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts.;1. Department of Surgery, Jersey Shore University Medical Center, Neptune, New Jersey;2. Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania;3. Department of Pathology, Jersey Shore University Medical Center, Neptune, New Jersey;4. Department of Endocrinology, Jersey Shore University Medical Center, Neptune, New Jersey;5. Shore Endocrinology Associates, Pt. Pleasant, New Jersey;6. Southern Ocean Medical Center, Manahawkin, New Jersey;7. Atlantic Hematology Oncology, Manasquan, New Jersey;8. Hereditary Cancer Risk Program, Meridian Health System, Neptune, New Jersey.;1. UAB School of Medicine, University of Alabama at Birmingham;2. Center for Clinical and Translational Sciences, University of Alabama at Birmingham;3. Department of Pediatrics/Division of Pediatric Endocrinology and Metabolism, Children’s of Alabama, University of Alabama at Birmingham, Birmingham, Alabama.;1. Section of Endocrine Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.;2. Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, California. |
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| Abstract: | ObjectiveTo review the literature regarding the interaction among amiodarone therapy, thyroid hormone levels, and warfarin metabolism.Methods73-year-old male with type 2 after describing an unusual case of amiodarone-induced thyrotoxicosis (AIT) who experienced a severe rise in international normalized ratio (INR) values after initiating warfarin therapy due to an unusual combination of excessive thyroid hormones, amiodarone therapy, and a genetic abnormality affecting warfarin metabolism.ResultsGenetic analysis revealed that the patient was CYP2C9*2 wild-type, CYP2C9*3/*3 homozygous mutant, and VKORC1*3/*3 homozygous mutant. A review of the literature revealed that both mutations can independently affect warfarin metabolism. In addition, amiodarone therapy and the presence of thyrotoxicosis per se can affect warfarin metabolism and reduce the dose needed to maintain INR in the therapeutic range. The association of the 2 genetic polymorphisms in a patient with AIT is extremely rare and strongly impairs warfarin metabolism, exposing the patient to a high risk of overtreatment.ConclusionsIn patients with AIT, warfarin therapy should be gradually introduced, starting with a very low dose, because of the significant risk of warfarin overtreatment. Whether the genetic analysis of CYP2C9 and VKORC1 polymorphisms should be routinely performed in AIT patients remains conjectural. (Endocr Pract. 2013; 19:1043-1049) |
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