Time-to-onset analysis of amiodarone-associated thyroid dysfunction.

Area of Science:

• Pharmacovigilance
• Endocrinology
• Clinical Pharmacology

Background:

• Amiodarone (AMD) is frequently associated with thyroid dysfunction.
• The precise relationship between AMD dosage, treatment duration, and the development of thyroid dysfunction remains incompletely understood.

Purpose of the Study:

• To investigate the onset profiles of amiodarone-associated thyroid dysfunction.
• To analyze the time-to-onset for amiodarone-induced hyperthyroidism and hypothyroidism using a spontaneous adverse drug reaction database.

Main Methods:

• Utilized data from the US Food and Drug Administration Adverse Event Reporting System (FAERS).
• Employed signal detection methods including reporting odds ratio (ROR) and information component (IC).
• Assessed cumulative incidences and time-to-onset profiles using Kaplan-Meier analysis and the Weibull shape parameter (WSP) test.

Main Results:

• The median time-to-onset for amiodarone-associated hyperthyroidism was significantly longer (720.0 days) compared to other drugs (101.5 days).
• No significant difference was observed in the median time-to-onset for amiodarone-associated hypothyroidism (183.0 days) versus other drugs (153.0 days).
• Weibull shape parameter analysis indicated a wear-out failure profile for AMD-associated hyperthyroidism and early failure profiles for both AMD-associated hypothyroidism and hyperthyroidism from other drugs.

Conclusions:

• Amiodarone-associated hyperthyroidism exhibits a distinct, widely distributed onset profile necessitating sustained vigilance.
• Amiodarone-associated hypothyroidism presents an early failure-type onset profile, similar to other drugs, warranting focus on initial treatment stages.
• These findings highlight the need for tailored monitoring strategies for different types of amiodarone-induced thyroid dysfunction.