A Disproportionality Analysis of the Adverse Effect Profiles of Methimazole and Propylthiouracil in Patients with Hyperthyroidism Using the Japanese Adverse Drug Event Report Database

• Published in: Thyroid (New York, N.Y.) Vol. 33; no. 7; p. 804
• Main Authors: Arai, Masanori, Tsuno, Takahiro, Konishi, Hiromi, Nishiyama, Kuniyuki, Terauchi, Yasuo, Inoue, Ryota, Shirakawa, Jun
• Format: Journal Article
• Language: English
• Published: United States 01-07-2023
• Subjects: Antithyroid Agents - adverse effects; Antithyroid Agents - therapeutic use; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; East Asian People; Female; Humans; Hyperthyroidism - chemically induced; Hyperthyroidism - drug therapy; Hyperthyroidism - epidemiology; Methimazole - adverse effects; Methimazole - therapeutic use; Propylthiouracil - adverse effects; Propylthiouracil - therapeutic use; Japanese Adverse Drug Event Report database; antithyroid drugs; adverse events; methimazole; pharmacovigilance; propylthiouracil
• ISSN: 1557-9077
• DOI: 10.1089/thy.2023.0030

Antithyroid drugs (ATDs) are frequently used to achieve euthyroidism in patients with hyperthyroidism. ATDs cause characteristic common and rare adverse events; however, comprehensive comparisons between methimazole (MMI) and propylthiouracil (PTU) in terms of adverse events are limited.
In this study, we thoroughly explored adverse events in association with MMI and PTU use with a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database and evaluated the prevalence of MMI and PTU prescriptions using the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. We analyzed 3271 cases of MMI use and 1029 cases of PTU use with respect to 9789 preferred terms (PTs) for adverse events registered in the JADER database by calculating and comparing reporting odds ratios (RORs).
We found that 8 PTs, including agranulocytosis (
 < 0.0001, 4.01-fold), aplasia cutis congenita (
 < 0.0001, 123.22-fold), and exomphalos (
 = 0.0002, 22.17-fold), demonstrated significantly higher RORs (more than 4-fold) for MMI use than for PTU use. Nineteen PTs, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (
 < 0.0001, 29.84), rapidly progressive glomerulonephritis (
 < 0.0001, 6.44), and pulmonary alveolar hemorrhage (
 < 0.0001, 7.77), had RORs for PTU use more than four times those for MMI use. NDB Open Data Japan showed more frequent PTU prescriptions than MMI prescriptions for women of reproductive age.
This large-scale study confirmed that a variety of congenital malformations were identified as having significantly high RORs for MMI use, while diseases related to ANCA-associated vasculitis were specific to PTU.