Effects of Amiodarone, Thyroid Hormones and CYP2C9 and VKORC1 Polymorphisms on Warfarin Metabolism: A Review of the Literature.

Objective: To review the literature regarding the interaction between amiodarone therapy, thyroid hormones and warfarin metabolism.Methods: A 73-year-old man with type 2 amiodarone induced thyrotoxicosis (AIT) who experienced a severe rise in the International Normalized Ratio (INR) values after starting warfarin therapy, owing to an unusual combination of an excess of thyroid hormones, amiodarone therapy and a genetic abnormality in warfarin metabolism.Results: The genetic analysis showed that the patient was CYP2C9*2 wild-type, CYP2C9*3/*3 homozygous mutant and VKORC1*3/*3 homozygous mutant. Review of the literature revealed that booth mutations can independently affect warfarin metabolism. In addition amiodarone therapy and the presence of thyrotoxicosis, per se, can affect warfarin metabolism and reduce the warfarin dose needed to maintain the INR in the therapeutic range. The association of the two genetic polymorphisms in a patient with AIT is extremely rare and strongly impairs warfarin metabolism, exposing the patient to a high risk of overtreatment.Conclusions: In patients with AIT, warfarin therapy should be gradually introduced, starting with a very low dose, because of the significant risk of a warfarin overtreatment. However, whether the genetic analysis of CYP2C9 and VKORC1 polymorphisms should be routinely performed in AIT patients remains conjectural.