title: Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland.
abstract: Many patients with cardiac arrhythmias require concomitant therapy with warfarin and amiodarone. Beyond the predictable pharmacokinetic drug-drug interaction requiring a significant warfarin dose reduction, the iodine-rich amiodarone affects the thyroid gland, causing overt hypothyroidism or thyrotoxicosis in 14%-18% of cases. In turn, thyroid disorders may affect warfarin sensitivity, with hypothyroidism and thyrotoxicosis resulting in increased or decreased warfarin requirements, respectively. We describe 3 patients on concomitant amiodarone and warfarin who developed amiodarone-induced thyrotoxicosis heralded by a significant decrease in warfarin requirements. We review the literature on the mechanisms of the complex drug-drug and drug-disease interactions within the thyroid gland, warfarin, and amiodarone triad. Given that significant thyroid disorders may be only mildly symptomatic and thus may escape clinical detection, we suggest that thyroid function should be tested in any patient with otherwise unexplained changes in warfarin dose requirements, particularly if concomitantly treated with amiodarone.
authors.affiliation: From Division of Clinical Pharmacology and Anticoagulation Clinic (DK, RL, HH), Department of Internal Medicine E (ZF), Department of Internal Medicine A (DE, DO), and Department of Endocrinology (DO), Chaim Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
authors.forename: Ronen
authors.initials: R
authors.lastname: Loebstein
authors.forename: Zvi
authors.initials: Z
authors.lastname: Farfel
authors.forename: David
authors.initials: D
authors.lastname: Ezra
authors.forename: Hillel
authors.initials: H
authors.lastname: Halkin
authors.forename: David
authors.initials: D
authors.lastname: Olchovsky
mesh_terms: D000328:Adult; D000638:Amiodarone / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013961:Thyroid Gland / Q000502:physiology; D013971:Thyrotoxicosis / Q000139:chemically induced*; D014859:Warfarin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D014859:Warfarin; D000638:Amiodarone