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JKM > Volume 45(1); 2024 > Article
Kim: 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

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.

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
jkm-45-1-163f1a.gif
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)
jkm-45-1-163f1b.gif
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)
jkm-45-1-163f2a.gif
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
jkm-45-1-163f2b.gif
Fig. 3
Number of Reports by System of Organ Class (SOC)
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
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
jkm-45-1-163f3.gif
Table 1
Herbal Medicines Searched for in This Study
한글명 초오 천오 부자 백부자 천남성 반하 낭독 감수 속수자 파두 보두 마전자 아마인
漢子 草烏 川烏 附子 白附子 天南星 半夏 狼毒 甘遂 續隨子 巴豆 寶豆 馬錢子 亞麻仁
Latin name Aconiti Ciliare Tuber Aconiti Radix Aconiti Iateralis Preparata Radix Typhonii Rhizoma Typhonium giganteum Engl Arisamatis Rhizoma Pinelliae Rhizoma Euphorbiae Fischerianae Radix Euphorbiae Kansui Radix Euphorbiae Lathyridis Semen Crotonis Semen Strychni Ignatii Semen Strychni semen Lini Semen
Scientific name Aconitum kusnezoffii REICHB., Aconitum ciliare DC Aconitum carmichaeli Debx Aconitum carmichaeli Debx Aconiti Koreani Tuber Aconitum koreanum Raymond Arisaema amurense Maximowicz, Arisaema erubescens Schott, Arisaema heterophyllum Blume, Arisaema japonicum BI. Pinellia ternata (Thunb.) Breitenbach Euphorbia fischeriana Steudel, Stellera chamaejasme L., Euphorbia ebiacteolata Hayata Euphorbia kansui Liou ex Wang Euphorbia lathyris Linné Croton tiglium Linné Strychnos ignatii Bergius Strychons nux-vomica Linné Linum usitatissim um Linné
Appendix I
Frequency of Adverse Event Terms Reported in Individual Case Safety Reports for Each Materia Medica
Category Ranunculaceae Araceae Euphorbiaceae Loganiaceae Linaceae
Aconitum spp. Arisaema spp Pinellia spp. Euphorbia spp. Codiaeum spp. Strychnos spp. Linum
Name of herbal medicine 草烏 (Aconiti Ciliare Tuber) 川烏 (Aconiti Radix), 附子 (Aconiti lateralis Preparata Radix) 天南星(Arisa ematis Rhizoma) 半夏 (Pinelliae Rhizoma) 續隨子 (Euphorbiae Lathyridis Semen) 巴豆 (Crotonis Fructus) 寶豆 (Strychni Ignatii Semen) 馬錢子 (Strychni semen) 亞麻仁 (Lini Semen)
Reported frequency/Search term Aconitum ciliare (n=2) Aconitum carmichaeli (n=13) Arisaema japonicum (n=3) Pinellia ternata (n=17) Euphorbiae Lathyridis (n=1) Croton tiglium (n=1) Strychni Ignatii (n=26) Strychnons nux-vomica (n=39) Linum usitatissimum (n=137)
10 diarrhea
9 drug interaction
7 vomiting, fatigue, dyspnea
6 blood cholesterol increased, headache
respiratory disroder
5 ALT increased
AST increased
Vertigo
abdominal pain
constipation
dyspepsia
muscle spasms
dizziness
4 Asthenia
drug ineffective
migraine
somnolence
pruritus
hypertension
3 ALT increased
AST increased
dizziness diarrhoea vomiting anaemia
nausea
hepatitis
drug hypersensitivity
decreased appetit
tremor
cough
2 dizziness palpitation
dyspepsia
burning sensation
diarrhoea
dyspepsia
nausea
chills
headache
supraventricular
tachycardia
vertigo
abdominal pain upper
nausea
fatigue
malaise
dizziness
dyspnoea
rash
skin reaction
cataract
mydriasis
visual impairment
abdominal pain upper
gastrointestinal haemorrhage
glossodynia
condition aggravated
drug withdrawal syndrome
face oedema
feeling cold
food interaction
influenza like illness
malaise
pyrexia
therapeutic response decreased
pneumonia
contusion
prothrombin time prolonged
weight decreased
musculoskeletal stiffness
myalgia
dysuria
hyperhidrosis
rash
rash erythematous
thrombosis
1 asthenia
ALT
increase
AST
increase
sensory
disturbance
dyspnoea
ventricular
tachycardia
abdominal
discomfort
pyrexia
dizziness
facial paralysis
headache
syncope
rash1 hot flush
Hepatotoxicity
Blood bilirubin increased
abdominal
pain
gastritis
nausea
pancreatitis
acute
vomiting
haematuria
dysphonia
pruritus
rash
urticaria
diarrhoea
syncopee
abdominal
pain
diarrhoea
haematochezia
pyrexia
palpitation
ear pain
tinnitus
abdominal pain
abdominal pain upper
constipation
diarrhoea
faeces pale
gastric dilatation
gastrointestinal disorder
pancreatitis acute
tongue discomfort
vomiting
asthenia
chest pain
drug intolerance
fatigue
feeling abormal
feeling drunk
malaise
pyrexia
swelling
hepatic failure
hepatitis
hypersensitivity
blood potassium
decreased
blood TSH increased
INR decreased
decreased appetite
muscle atrophy
muscle spasms
myalgia
amnesia
burning sensation
dizziness
generalised tonic-clonic
seizure
loss of consciousness
paraesthesia
paralysis
tremor
product odour abnormal
product taste abnormal
anger
anxiety
sleep disorder
urinary retention
throat irritation
blister
cold sweat
dermatitis bullous
hair disorder
pruritus
rash
skin burning sensation
hot flush
anaemia
neutropenia
tachycardia
ventricular tachycardia
visual impairment
abdominal pain
constipation
dyspepsia
eructation
faeces hard
flatulence
frequent bowel
movements
functional
gastrointestinal disorder
pancreatitis
retching
condition aggravated
death
feeling abnormal
pyrexia
choestatis
hepatic cytolysis
liver injury
drug hypersensitivity
oral fungal infection
fall
overdose
ALT increased
AST increased
blood glucose increased
blood TSH increased
GGT increased
INR decreased
weight increased
hyponatraemia
arthralgia
growth retardatation
joint swelling
musculoskeletal
stiffness
myalgia
dysgeusia
dyskinesia
headache
seizure
serotonin syndrome
somnolence
tremor
product complaint
product taste abnormal
bradyphrenia
delirium
listless
nervousness
micturition disorder
pollaiuria
oropharyngeal pain
throat irritation
angioedema
eczema asteatotic
rash macular
skin mass
urticaria
loss of employment
hypotension
thrombosis
hypercoagulation
leukopenia
thrombocytopenia
atrioventricular block
complete
bradycardia
cardiac failure
cardiovascular disorder
extrasystoles
left ventricular dysfunction
tachycardia
thyroditis
diplopia
eye irritation
lacrimation increased
ocular hyperaemia
papilloedema
photophobia
photopsia
abdominal dyscomfort
dry mouth
duodenal ulcer
dysphagia
flatulence
haematochezia
irritable bowel syndrome
lip oedema
malabsorption
peptic ulcer haemorrhage
rectal haemorrhage
salivary hypersecretion
tongue oedema
application site erythema
application site pain
chest discomfort
chest pain
drug interlerance
feeling abnormal
feeling hot
feeling jittery
gait disturbance
herbal interaction
infusion site erythema
infusion site pain
infusion site reaction
infusion site swelling
oedema
pain
therapeutic product effect
decreased
Budd-Chiari syndrome
hepatic filure
hepatic function abnormal
hepatic pain
hepatitis cholestatic
hepatitis fulminant
hepatitis ftoxic
hepatocellular injury
jaundice cholestatic
portal vein thrombosis
abscess
candida infection
diverticulitis
eye infection viral
herpes simplex
herpes zoster
nasopharyngitis
urinary tract infection
accidental exposure to product
inappropriate schedule of
product administration
limb injury
medication error
scar
vascular injury
ALT increased
AST increased
bleeding time prolonged
blood aldosterone decreased
blood iron decreased
blod potassium increased
blood TSH abnormal
blood TSH decreased
blood urine present
carbohydrate antigen 125
increased
chest X-ray abnormal
coagulation time prolonged
cortisol decreased
drug level below therapeutic
full blood count
heart rate increased
HDL decreased
INR decreased
INR fluctuation
lipids increased
liver function test increased
LDL increased
RBC count
thyroid function test abnormal
WBC count decreased
diabetes mellitus
hypercholesterolaemia
hyperglycaemia
hypokalaemia
lactose intolerance
overweight
weight loss poor
arthralgia
back pain
breast cancer
prostate cancer
burning sensation
cerebral venous sinus
thrombosis
cerebral venous thrombosis
coordination abnormal
diabetic neuropathy
disturbance in attention
dysgeusia
generalised tonic-clonic
seizure
haemorrhagic stroke
hypoaesthesia
loss of consciousness
memory impairment
movement disorder
neuropathy peripheral
sedation
seizure
premature labour
device breakage
device kink
device occlusion
product formulation issue
agitation
behaviour disorder
confusional state
fear
hallucination
insomnia
irritability
poor quality sleep
acute kidney injury
crystal nephropathy
renal impairment
renal pain
urinary incontinence
breast pain
heavy menstrual bleeding
vaginal haemorrhage
oropharyngeal pain
respiratory distress
rhinorrhoea
tachypnoea
throat irritation
blister
dermatitis contact
dry skin
nail ridging
pain of skin
prosriasis
purpura
rash papular
skin fissures
skin irritation
urrticaria
social problem
stent placement
blood pressure fluctuation
flushing
hot flush
hypotension

Bold font and underline: serious adverse event, italic and underline: liver injury

참고문헌

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
crossref pmid pmc

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
crossref

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
crossref pmid pmc

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
crossref

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 al2022; 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
crossref

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
crossref

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
crossref

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
crossref pmid

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
crossref pmid

25. Kim M., Woo Y., Han C-h2021; 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
crossref pmid pmc

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
crossref

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
crossref pmid

28. van Hunsel F., van de Koppel S., Skalli S., Kuemmerle A., Teng L., Wang J. B., et al2019; 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
pmid pmc

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
crossref pmid

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