Signal detection of botulinum toxin type A (BoNT/A) using the Korea Adverse Event Reporting System Database, 1999 - 2016.

[OBJECTIVE] To detect signals of potential adverse events (AEs) after botulinum toxin (BTX) treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD).

[MATERIALS AND METHODS] The individual case safety reports (ICSRs) submitted to KIDS-KD from 1999 to 2016 were analyzed. To detect safety signals, disproportionality analysis was introduced, and the three indices (proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC)) were calculated based on the reported preferred terms (WHO-ART, preferred term (PT)). The signals detected were compared with drug labels from Korea and the USA.

[RESULTS] A total of 5,896 AE reports were collected in January 1999 - December 2016 in the Korea Adverse Event Reporting System (KAERS) databases. Among the total of 103,785 drug-AE pairs, 1,413 were attributed to BTX. The disproportionality analysis produced 44 PTs as safety signals and detected 7 unlabeled PTs that were not listed on the labels. After matching for age and sex (1 : 2), the adjusted ROR of ineffective medicine and depression in BTX was 21.60 (95% confidence interval (CI), 19.12 - 24.41) and 6.02 (95% CI, 3.41 - 10.64) respectively.

[CONCLUSION] The number of AE reports after BTX has increased, the majority of which were from females. Safety signals such as "medicine ineffective" and "concentration impaired" may be due to increasing off-label use, which warrants long-term surveillance, especially among females after BTX injection.