QT prolongation after the combined use of haloperidol and contraindicated drugs: A case/non-case study using Korea adverse event reporting system (KAERS) database, 2016-2020

초록

Background: QT prolongation can lead to sudden cardiac death following ventricular arrhythmia, and Torsade de Points (TdP). Haloperidol, a typical antipsychotic, can prolong QT interval by blocking the inward potassium rectifier channel in ventricular muscle. QT prolongation is enhanced when there are other risk factors such as co-administration with QT-prolonging drugs. Objectives: To detect a signal of QT prolongation after the combined use of haloperidol and contraindications using the national spontaneous adverse event reports in Korea. Methods: We conducted a case/non-case study using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2016 and 2020. Cases were defined by Standardized MedDRA Queries (SMQ) ‘TdP/QT prolongation', and all reports other than TdP/QT prolongation were defined as non-cases. The Medical Dictionary for Regulatory Activities (MedDRA) and World Health Organization Adverse Reactions Terminology (WHO-ART) were mapped. We selected the list of drugs contraindicated in combined use with haloperidol due to QT prolongation. For comparison, a list of drugs that are not contraindicated in combined use with haloperidol due to QT prolongation was also selected. Reporting odds ratios (ROR) and 95% confidence intervals (CI) were calculated through logistic regression analyzes. It was considered as a signal if ROR > 2 and the lower bound of 95% CI > 1. Results: During the study period, QT prolongation-related reports defined as cases have been consistently reported at an annual average of about 1700 reports. Among cases including haloperidol, the combined use of haloperidol and contraindicated drugs existed the most (23 out of 31). Of those 23 cases, 15 reports were from male patients aged 65 years or older. Among 23 cases above, the most frequently reported combined use with haloperidol was levofloxacin (21 reports, 91%). The ROR (95% CI) of haloperidol-levofloxacin was 60.19 (26.02–139.23). In addition, the ROR (95% CI) of haloperidol-amiodarone and haloperidol-moxifloxacin were 3.84 (0.44–33.8), and 2.39 (0.29–19.66), respectively. Conclusions: The combined use of haloperidol-levofloxacin was detected as a signal. However, because other factors including demographics and comorbidities may affect AEs, cautious interpretation was required.