Int J Med Sci 2021; 18(15):3574-3580. doi:10.7150/ijms.61412 This issue

Research Paper

Polypharmacy Is Associated With Amiodarone-Induced Hypothyroidism

Satoshi Yokoyama, Yuki Tanaka, Kouichi Hosomi, Mitsutaka Takada

Division of Drug Informatics, School of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashiosaka City, Osaka 577-8502, Japan

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Yokoyama S, Tanaka Y, Hosomi K, Takada M. Polypharmacy Is Associated With Amiodarone-Induced Hypothyroidism. Int J Med Sci 2021; 18(15):3574-3580. doi:10.7150/ijms.61412. Available from

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Graphic abstract

Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH.

Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192).

Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84).

Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.

Keywords: polypharmacy, amiodarone, hypothyroidism, data-mining, sequence symmetry analysis