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Adverse event reports of tonifying herbal medicine products

Article information

J Korean Med. 2024;45(3):54-64
Publication date (electronic) : 2024 September 1
doi : https://doi.org/10.13048/jkm.24037
Yujin Choiorcid_icon, Jee-youn Jungorcid_icon, Hyeun-kyoo Shinorcid_icon
KM Science Research Division, Korea Institute of Oriental Medicine
Correspondence to: Hyeun-kyoo Shin, KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daejeon 34054, Republic of Korea, Tel: +82-42-868-9464, E-mail：hkshin@kiom.re.kr
Received 2024 June 11; Revised 2024 August 20; Accepted 2024 August 20.

Abstract

Objectives

Tonifying herbal medicines are used to nourish and balance the body’s qi, blood, yin, and yang, targeting deficiencies. They are the second most frequently used category by consumers visiting Korean medicine clinics, following prescriptions for back pain. This study aimed to analyze the adverse events associated with herbal medicine products classified as tonics through a national pharmacovigilance database.

Methods

We investigated 11 types of tonifying herbal medicine products (466 product codes) in the Korea Adverse Event Reporting System (KAERS) database from 2012 to 2021. Extracted adverse event reports were analyzed based on information of reports, patient demographics, classification of adverse events, reported herbal medicine products, and causality assessment results.

Results

A total of 31 individual case safety reports were identified, covering 33 adverse events. The annual number of reports has increased over the study period. Most reports were filed by physicians and pharmacists, with the majority of patients being adults or elderly. Gastrointestinal disorders were the most frequently reported adverse events, accounting for 48.5% of cases. Of the 33 adverse events, 93.9% were classified as non-serious, while 6.1% were classified as serious. The most frequently reported herbal medicine products were Bojungikgi-tang, Yukmijihwang-tang, and Palmijihwang-tang.

Conclusions

Although the study found that adverse events associated with tonifying herbal medicine products are generally not serious, it highlights the importance of systematic monitoring and reporting. The findings underscore the need for improved adverse event reporting systems within traditional Korean medicine to ensure patient safety and guide future research.

Keywords: Traditional herbal medicine; Side effect; adverse effect; Pharmacovigilance; KAERS DB
Fig. 1

Annual number of individual case safety reports associated with tonifying herbal medicine products

Basic Information of 31 ICSRs

Characteristics of 33 Adverse Events.

Reported Adverse Events

Characteristics of 31 Reported Herbal Medicine Products

Causality Assessment Results for 33 Combinations of Herbal Medicine Products and Adverse Events

References

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Article information Continued

Fig. 1

Fig. 1

Annual number of individual case safety reports associated with tonifying herbal medicine products

Table 1

Basic Information of 31 ICSRs

Information of reports n (%)
Original reporter
 Doctors, dentists, Korean medicine doctors 12 (38.7)
 Pharmacists, Korean medicine pharmacists 14 (45.2)
 Other medical professionals 1 (3.2)
 Consumers, non-medical professionals 1 (3.2)
 Unknown 3 (9.7)
Reporter
 Pharmaceutical company 0 (0.0)
 Medical experts (e.g., hospitals, pharmacies) 4 (12.9)
 Regional pharmacovigilance center 26 (83.9)
 Others (e.g., distributors) 1 (3.2)
 Patients, consumers 0 (0.0)
Report type
 Voluntary reporting 28 (90.3)
 Reporting in trials/research 0 (0.0)
 Others 1 (3.2)
 Unknown 2 (6.5)
Patient demographics
 Age at the time of occurrence
  0–27 days 0 (0.0)
  28 days to 1 year 0 (0.0)
  2–11 years 0 (0.0)
  12–18 years 0 (0.0)
  19–64 years 13 (41.9)
  65 years ~ 18 (58.1)
 Sex
  Male 15 (48.4)
  Female 16 (51.6)
Drugs
 Herbal medicine only 16 (51.6)
 Combination with other medications 15 (48.4)

Table 2

Characteristics of 33 Adverse Events.

Adverse events classified by System Organ Class n (%)
 Gastrointestinal disorders 16 (48.5)
 Investigations* 9 (27.3)
 General disorders and administration site conditions 2 (6.1)
 Skin and subcutaneous tissue disorders 2 (6.1)
 Eye disorders 1 (3.0)
 Musculoskeletal and connective tissue disorders 1 (3.0)
 Nervous system disorders 1 (3.0)
 Vascular disorders 1 (3.0)
Duration of adverse events
 −1 day 0 (0.0)
 2–5 days 8 (24.2)
 6–10 days 1 (3.0)
 11–50 days 1 (3.0)
 50 days ~ 1 (3.0)
 (Missing) 22 (66.7)
Results of adverse events
 Recovered or resolved 16 (48.5)
 Recovering or resolving 2 (6.1)
 Not Recovered or not resolved 3 (9.1)
 Recovered or resolved with sequelae 2 (6.1)
 Fetal 0 (0.0)
 Unknown 10 (30.3)
Serious adverse event (SAE)
 SAE 2 (6.1)
 Non-SAE 31 (93.9)
*

Investigations: Weight increased, Blood glucose increased, ALT increased, AST increased, Blood pressure increased, Weight decreased

Table 3

Reported Adverse Events

System Organ Class Adverse event (Preferred Term) n
Gastrointestinal disorders Diarrhoea 9
Gastrointestinal disorders Dyspepsia 4
Investigations Weight increased 3
Gastrointestinal disorders Constipation 2
Investigations Blood glucose increased 2
Skin and subcutaneous tissue disorders Urticaria 2
Eye disorders Periorbital oedema 1
Gastrointestinal disorders Gastric haemorrhage 1
General disorders and administration site conditions Chest discomfort 1
General disorders and administration site conditions Drug ineffective 1
Investigations Alanine aminotransferase increased 1
Investigations Aspartate aminotransferase increased 1
Investigations Blood pressure increased 1
Investigations Weight decreased 1
Musculoskeletal and connective tissue disorders Muscle spasms 1
Nervous system disorders Headache 1
Vascular disorders Hypertension 1

Table 4

Characteristics of 31 Reported Herbal Medicine Products

Causality of each drug n (%)
 Suspected drug 25 (80.6)
 Concomitant drug 6 (19.4)
 Interacting drug 0 (0.0)
Administration period
 up to 1 day 0 (0.0)
 2–5 days 4 (12.9)
 6–10 days 3 (9.7)
 11–50 days 1 (3.2)
 50 days ~ 3 (9.7)
 (Missing) 20 (64.5)
Action taken
 Drug withdrawn 18 (58.1)
 Dose not changed 4 (12.9)
 Not applicable 1 (3.2)
 (Missing) 8 (25.8)
Herbal medicine products*
 Bojungikgi-tang 11 (35.5)
 Yukmijihwang-tang 8 (25.8)
 Palmijihwang-tang 5 (16.1)
 Samryeongbaekchul-san 4 (12.9)
 Palmul-tang 2 (6.5)
 Samul-tang 1 (3.2)

Table 5

Causality Assessment Results for 33 Combinations of Herbal Medicine Products and Adverse Events

Causality assessment result n (%)
Certain 0 (0.0)
Probable/likely 9 (27.3)
Possible 10 (30.3)
Unlikely 1 (3.0)
Conditional/unclassified 3 (9.1)
Unassessable/unclassifiable 0 (0.0)
Not applicable 0 (0.0)
(Missing) 10 (30.3)