Associate Professor College of Pharmacy, Chung-Ang University, Korea, Republic of Korea
Background: The potential risk of QT prolongation, which can lead to ventricular arrhythmia, Torsade de Points (TdP), and sudden cardiac death, associated with haloperidol has been reported. Extended use of haloperidol for diverse conditions necessitates monitoring for QT prolongation, especially under the use of intravenous administration and potential drug interactions.
Objectives: To evaluate QT prolongation associated with haloperidol and according to the route of administration of haloperidol, and to identify association between QT prolongation and drug-drug interaction of haloperidol and concomitant drugs 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. We calculated adjusted reporting odds ratios (RORs) and 95% confidential intervals (CIs) for haloperidol, intravenous haloperidol, and potential drug interactions. After identified all concomitant drugs in all reports containing haloperidol, and the concomitant drugs with 3 or more cases reported were classified by therapeutic classes. All adjusted RORs and 95% CIs were calculated through logistic regression analyses adjusted for age, sex, and number of drugs in the report.
Results: During the study period, QT prolongation-related reports have been consistently reported at an annual average of about 1,700 reports. QT prolongation cases were more common in men and aged 65 years and older, respectively. The adjusted ROR (95% CI) of haloperidol and intravenous haloperidol were 10.52 (8.01-13.81) and 35.14 (23.91-51.64), respectively. In addition, we found that in more than half of the cases of QT prolongation including haloperidol, haloperidol was used with concomitant drugs (31 out of 58). The adjusted ROR (95% CI) of haloperidol+antibacterials for systematic use was 36.29 (16.72-78.79).
Conclusions: Significant ROR values support the association of haloperidol with QT prolongation. The association of QT prolongation according to the route of administration of haloperidol and of QT prolongation with drug-drug interaction of haloperidol and concomitant drugs, suggests that cautious monitoring should be required. However, because other factors including demographics and comorbidities may affect AEs, cautious interpretation was required.
