Analysis of Adverse Drug Reactions to First-Line Anti-Tuberculosis Drugs Using the Korea Adverse Event Reporting System.

Background: Adverse drug reactions (ADRs) to first-line anti-tuberculosis (TB) drugs are common; however, there have been few reports of nationwide epidemiologic studies on ADRs to anti-TB drugs in Korea. This study aimed to investigate the clinical characteristics of various ADRs to first-line anti-TB drugs using a nationwide database of ADRs.

Methods: We used the Korea Adverse Event Reporting System (KAERS) database (2009-2018). The study subjects were selected using the Korean Standard Classification of Diseases codes for pulmonary and extrapulmonary TB and electronic data interchange codes for isoniazid (INH), rifampicin (RIF), ethambutol (ETB), and pyrazinamide (PZA). The causality assessment of "possible," "probable," or "certain" by World Health Organization-Uppsala Monitoring Center System causality category was selected.

Results: A total of 1,562,024 ADRs were reported in the KIDS-KAERS database from 2009 to 2018, where ADRs to first-line anti-TB drugs were 17,843 cases (1.14%). The most common causative drugs were RIF (28.7%), INH (24.0%), ETB (23.4%), and PZA (23.9%) in that order. 48.5% of cases were reported in the older patients (≥ 60 years). According to organ system, gastro-intestinal system disorder was most common (32.0%), followed by skin and appendage (25.9%), liver and biliary system (14.2%). Nausea was the most common ADR (14.6%), followed by hepatic enzyme elevation (14.2%), rash (11.7%), pruritus (9.1%), vomiting (8.9%), and urticaria (4.2%). Most ADRs appeared within 1 month, but ADRs such as neuropathy, paresthesia, hematologic abnormalities, renal function abnormalities and liver enzyme abnormality were also often reported after 2 months.

Conclusion: Our data are clinically informative for recognizing and coping with ADRs of anti-TB drugs.