Status of reports of adverse events related to botanical herbal medicines with toxic precautions officially managed by Korean government: A descriptive analysis from WHO VigiAccess

Article information

J Korean Med. 2024;45(1):163-179

Publication date (electronic) : 2024 March 1

doi : https://doi.org/10.13048/jkm.24011

Department of Internal Medicine, Dongguk University Ilsan Oriental Medicine Hospital

Correspondence to：Mikyung Kim, Dongguk University Ilsan Oriental Medicine Hospital, 27, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Tel: +82-31-961-9045, E-mail: 01mkkim@gmail.com

Received 2024 January 23; Revised 2024 February 12; Accepted 2024 February 16.

Abstract

Objectives

This study was aimed to review the global status of adverse event (AE) reports and the characteristics of the reported AEs of plants managed as herbal medicines (HMs) with toxic precautions in Korea.

Methods

This is a cross-sectional quantitative study that analyzed information available through VigiAccess, a website that provides summarized statistical information from the WHO’s global AE database to the public. VigiAccess was searched in 8 Jan, 2024. Information on the total number of reports, number of reports by year and continent, and the age and gender of patients were obtained, and the types of frequently reported AEs were also reviewed.

Results

Data on the status of report submissions were obtained for a total of 9 HMs including Aconitum ciliare, Aconitum carmichaeli, Arisaema japonicum, Pinellia ternata, Euphorbiae Lathyridis, Croton tiglium, Strychni Ignatii, Strychnons nux-vomica, and Linum usitatissimum. The number of reports per HM was from 1 to 137. The most commonly reported type of AEs were gastrointestinal disorders in most of the HMs, followed by neurological disorders. Serious adverse events were reported only in Strychni Ignatii, Strychnons nux-vomica, and Linum usitatissimum, including one case of death.

Conclusions

This study shows the status of reported AEs of botanicals considered as HMs with toxic precautions in Korea based on real world data. However, when interpreting the findings of this study, readers should consider the significant limitations of this study mainly because of the characteristics of the data source.

Keywords: adverse drug reaction; adverse effect; side effect; spontaneous reporting; pharmacovigilance; VigiBase

Fig. 1(A)

Number of annual reports for each herbal medicine

X-axis: reported year, Y-axis: number of annual reports

A. ciliare: Aconitum ciliare, A. carmichaeli: Aconitum carmichaeli, AJ: Arisaema japonicum, PT: Pinellia ternata, EL: Euphorbiae Lathyridis, CT: Croton tiglium, SI: Strychni Ignatii, SN: Strychnons nux-vomica, and LU: Linum usitatissimum

Fig. 1(B)

Distribution of individual case safety reports by continent

X-axis: number of cumulative reports for each herbal medicine

A. ciliare: Aconitum ciliare (n=2), A. carmichaeli: Aconitum carmichaeli (n=13), AJ: Arisaema japonicum (n=3), PT: Pinellia ternate (n=17), EL: Euphorbiae Lathyridis (n=1), CT: Croton tiglium (n=1), SI: Strychni Ignatii (n=26), SN: Strychnons nux-vomica (n=39), and LU: Linum usitatissimum (n=137)

Fig. 2(A)

Gender distribution of patients

X-axis: total number of cumulative reports for each herbal medicine

A. ciliare: Aconitum ciliare (n=2), A. carmichaeli: Aconitum carmichaeli (n=13), AJ: Arisaema japonicum (n=3), PT: Pinellia ternate (n=17), EL: Euphorbiae Lathyridis (n=1), CT: Croton tiglium (n=1), SI: Strychni Ignatii (n=26), SN: Strychnons nux-vomica (n=39), and LU: Linum usitatissimum (n=137)

Fig. 2(B)

Age distribution of patients

X-axis: age range, Y-axis: number of reports for each herbal medicine

A. ciliare (n=2): Aconitum ciliare, A. carmichaeli (n=13): Aconitum carmichaeli, AJ (n=3): Arisaema japonicum, PT (n=17): Pinellia ternata, EL (n=1): Euphorbiae Lathyridis, CT (n=1): Croton tiglium, SI (n==26): Strychni Ignatii, SN (n=39): Strychnons nux-vomica, and LU (n=137): Linum usitatissimum

d: day, m: month, y: year

Fig. 3

Number of Reports by System of Organ Class (SOC)

BL: Blood and lymphatic system disorders; CA: Cardiac disorders; EA: Ear and labrinth disorders; EN: Endocrine disorders; EY: Eye disorders; GA: Gastrointestinal disorders; GE: General disorders and administration site conditions; HE: Hepatobiliary disorders; IM: Immune system disorders; INF: Infections and infestations; INJ: Injury, poisoning and procedural complications; INV: Investigations; ME: Metabolism and nutrition disorders; MU: Musculoskeletal and connective tissue disorders; NEO: Neoplasms benign, malignant and unspecified; NER: Nervous system disorders; PRE: Pregnancy, puerperium and perinatal conditions; PRO: Product issues; PS: Psychiatric disorders; REN: Renal and urinary disorders; REP: Reproductive system and breast disorders; RES: Respiratory, thoracic and mediastinal disorders; SK: Skin and subcutaneous tissue disorders; SO: Social circumstances; SU: Surgical and medical procedures; VA: Vascular disorders

Table 1

Herbal Medicines Searched for in This Study

Appendix I

Frequency of Adverse Event Terms Reported in Individual Case Safety Reports for Each Materia Medica

References

1. Ministry of Food and Drug Safety. [administrative regulations]. Herbal medicine safety and quality control regulations 2016. [cited 2024 7 Feb]; Available from: https://www.law.go.kr/admRulLsInfoP.do?admRulSeq=2100000043697.

2. Faculty of Internal Medicine of Liver System of Korean Medicine. 2016. Textbook of Internal Medicine of Liver System in Korean Medicine Seoul: Book Publisher Nadoh. p. 871–889.

3. Federation of Herbal Formula Professors of Colleges of Korean Medicine. 2019. Textbook of Herbal Formula Seoul: Yeonglimsa.

4. Kwon D.. 2008. [Research project report] Studies on control and management of medicinal herbs for poisonous concern Korea Food and Drug Administration.

5. World Health Organization. 2023. Programmed for International Drug Monitoring [cited 2024 Jan 21]. Available from: https://www.who.int/teams/regulation-prequalification/regulation-and-safety/pharmacovigilance/networks/pidm.

6. World Health Organization. 2024. [cited 2024 Jan 21]. Available from: https://www.vigiaccess.org/.

7. Yamoah P., Mensah K. B., Attakorah J., Padayachee N., Oosthuizen F., Bangalee V.. Adverse events following immunization associated with coronavirus disease 2019 (COVID-19) vaccines: A descriptive analysis from VigiAccess. Human Vaccines & Immunotherapeutics 2022;18(6):2109365.

8. Pandey D., Mehta G., Sachdeva M., Tripathi R.. 2022;Adverse Event Following Immunization (AEFI) in Children: An Analysis of Reporting in VigiAccess. Drug Research (Stuttgart) 72(8):435–440. https://doi:10.1055/a-1852-5335. Epub 2022 Jun 20.

9. Li M., You R., Su Y., Zhou H., Gong S.. 2023;Characteristic analysis of adverse reactions of five anti-TNFα agents: a descriptive analysis from WHO-VigiAccess. Frontiers in Pharmacology 14:1169327. https://doi:10.3389/fphar.2023.1169327.eCollection2023.

10. He M., Zhou J., Yang T., Li X., Wang R.. 2023;Real-world study of antifibrotic drugs-related adverse events based on the United States Food and Drug Administration Adverse Event Reporting System and VigiAccess databases. Authorea https://doi/full/10.22541/au.168672965.58074889/v1.

11. Sun W., Zhang W., Cai Y., Huang R., Gong S.. 2023;Characteristic Analysis of Adverse Reactions of Five PD-1/PD-L1 Anti-cancer Monoclonal Antibodies Based on WHO-VigiAccess. HERALD OF MEDICINE 42(6):851–858. https://doi:10.3870/j.issn.1004-0781.2023.06.012.

12. Ko Y., Yun S., Kim M., Song Y., Shin B.. 2005;Literatural Study on Toxicity of Herbs used in <Bangyakhappyeon>. Journal of Physiology & Pathology in Korean Medicine 19(05):1120–1128.

13. Kim J., Lee G., Choi G., Kim Y., Lee S., Kim H.. 2021;Review on the mechanism for the reduction of raphide-induced toxicity via processing of Pinelliae Tuber and Arisaematis Rhizoma. The Korea Journal of Herbology 36(5):15–27. http://dx.doi.org/10.6116/kjh.2021.36.5.15.

14. Kim J., Lee J., Song G., Park S., Kim Y., Ha H.. 2022. [Research project report] Studies on liver toxicities induced by traditional herbal administrations Korea Food and Drug Administration.

15. Jang I., Yang C., Lee S., Han C.. 2007;A Review of Herbal Medicinal Products Associated with Toxic Events in Korea. The Journal of Korean Oriental Internal Medicine 1:67–74.

16. Zhang A., Li Z., Qi G., Xu Z., Liu X., Ma J., et al. 2022;Study of Pinelliae Rhizoma hepatotoxicity based on complex network algorithm improvement. bioRxiv 2022;11(29):518337. https://doi.org/10.1101/2022.11.29.518337.

17. Song X., Yang D., Wang Y., Liu W., Wang Y., Zhu J.. 2019;Pharmacokinetic, acute toxicity, and pharmacodynamic studies of Semen Strychni total alkaloid microcapsules. Tropical Journal of Pharmaceutical Research 18(9):1985–1992. https://doi:10.4314/tjpr.v18i9.29.

18. Korea Institute of Oriental Medicine. OASIS Encyclopedia of Medicinal Products [cited 2024 21 Jan]; Available from: https://oasis.kiom.re.kr/oasis/herb/monoSearch.jsp?srch_menu_nix=87Z2RM16.

19. Carraro J. C. C., Dantas M., Ide S., Espeschit A. C. R., Martino H. S. D. M., Ribeiro S. M. R.. 2012;Flaxseed and human health: reviewing benefits and adverse effects. Food Reviews International 28(2):203–230. https://doi.org/10.1080/87559129.2011.595025.

20. Kim M., Han C.. 2017;Adverse drug reactions in Korean herbal medicine: A prospective cohort study. European Journal of Integrative Medicine 9:103–9. https://doi.org/10.1016/j.eujim.2016.11.016.

21. Park Y., Park H. M., Lee S.. 2011;Inducible Mechanisms for Hepatotoxicity caused by Traditional Korean Medicines in a View of Toxicology. Journal of Korean Medicine 32(4):48–67.

22. Edwards I. R., Aronson J. K.. 2000;Adverse drug reactions: definitions, diagnosis, and management. The Lancet 356(9237):1255–1259. https://doi:10.1016/S0140-6736(00)02799-9.

23. World Health Organization. How UMC detects signals 2022. [cited 2024 21 Jan]; Available from: https://who-umc.org/signal-work/signal-detection/.

24. van Puijenbroek E. P., Bate A., Leufkens H. G., Lindquist M., Orre R., Egberts A. C.. 2002;A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiology and drug safety 11(1):3–10. https://doi:10.1002/pds.668.

25. Kim M., Woo Y., Han C-h. 2021;Current status of the spontaneous reporting and classification/coding system for herbal and traditional medicine in pharmacovigilance. Integrative Medicine Research 10(1):100467. https://10.1016/j.imr.2020.100467.

26. Kim M.. 2020;Effect of A Pharmacovigilance Practice Training Course for Future Doctors of Korean Medicine on Knowledge, Attitudes and Self Efficacy. Journal of Korean Medicine 41(1):21–44. https://doi.org/10.13048/jkm.20003.

27. Jordan S. A., Cunningham D. G., Marles R. J.. 2010;Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicology and Applied Pharmacology 243(2):198–216. https://doi.org/10.1016/j.taap.2009.12.005.

28. van Hunsel F., van de Koppel S., Skalli S., Kuemmerle A., Teng L., Wang J. B., et al. 2019;Analysis of Hepatobiliary Disorder Reports Associated With the Use of Herbal Medicines in the Global Suspected ADR Database Vigibase. Frontiers in Pharmacology 10:1326. https://doi:10.3389/fphar.2019.01326.

29. Hsieh S. C., Lai J. N., Chen P. C., Chen H. J., Wang J. D.. 2006;Development of active safety surveillance system for traditional Chinese medicine: an empirical study in treating climacteric women. Pharmacoepidemiology and Drug Safety 15(12):889–899. https://doi:10.1002/pds.1340.

Article information Continued