Patterns of adverse event reporting for long-acting benzodiazepines

초록

Background: While benzodiazepines (BDZ) are effective as anxiolytic drug, BDZ is also known to cause more dangerous adverse events (AEs) in long-acting BDZ. Objectives: To compare patterns of AE reports including long-acting BDZ with short-acting BDZ. Methods: Among the Individual Case Safety Reports (ICSRs) reported to the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2016 and 2020, ICSRs containing BDZ drugs were selected. BDZ were categorized into two groups (long-acting and short-acting) based on their elimination half-life. Drugs that has a longer half-life (≥24 h) were considered long-acting BDZ and those with a shorter half-life (<24 h) were considered short-acting BDZ. Suspected AEs were coded with the WHO Adverse Reaction Terminology (WHO-ART) codes – Preferred Term (PT). For comparing patterns of reported AEs, we adopted the criteria of signal detection: PRR (PRR≥2, cases>2, chi-square≥4), ROR (ROR≥2, cases>2, chi-square≥4) and IC (IC_low>0). For the AEs that showing significance, we reviewed literatures and label information. Results: Among total of 3 722 851 ICSRs in KIDS-KD, the number of ICSRs for long-acting BDZ users was 10 920 (0.29%) and short-acting BDZ users was 25 596 (0.69%). Reports for average of age in long-acting BDZ users and short-acting BDZ users were 59 and 60 years old. The number of aged over 65 years old for long-acting BDZ and short-acting BDZ was 4229(0.11%) and 9665(0.26%), respectively. Cramps legs (PRR, 6.25), delusion (PRR, 3.13), dementia (PRR, 3.32), gait abnormal (PRR, 2.9), hypotonia (PRR, 2.75), malaise (PRR, 2.04) and vertigo (PRR, 2.41) were significantly reported higher in long-acting BDZ. Conclusions: We confirmed that AEs including cognitive impairment and ataxia showed higher reporting ratios in long-acting BDZ compared with short-acting BDZ. Therefore, caution is required in using long-acting BDZ.