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

Mikyung Kim; Kim, Mikyung

doi:10.13048/jkm.24011

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

Original Article

The Journal of Korean Medicine 2024; 45(1): 163-179.

Published online: March 1, 2024

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

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

Mikyung Kim

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 January 23, 2024 Revised February 12, 2024 Accepted February 16, 2024

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

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
Category	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

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