Analysis of Herbal-drug-associated Adverse Drug Reactions Using Data from Spontaneous Reporting System in Electronic Medical Records

Article information

J Korean Med. 2015;36(1):45-60

doi : https://doi.org/10.13048/jkm.15005

¹Research Institute of Oriental Medicine, Dongguk University

²Dept. of Internal Medicine, College of Korean Medicine, Dongguk University

Correspondence to : 한창호 (Chang-ho Han), 780-714 경상북도 경주시 동대로 123 동국대학교 한의과대학 내과학교실, Tel : +82-54-770-1257, FAX : +82-54-770-1500, E-mail : hani@dongguk.ac.kr

Received 2015 March 19; Revised 2015 March 25; Accepted 2015 March 25.

Abstract

Objectives:

The purpose of this study was to understand the status of reporting and characteristics of adverse drug reactions (ADRs) induced by herbal drugs and to make a suggestion for the domestic pharmacovigilance system on herbal medicine.

Methods:

We carried out a hospital-based observational study at Dongguk University Ilsan Oriental Hospital from April 2012 to December 2014. We reviewed all the herbal-drug-associated ADRs reports registered to the spontaneous ADR reporting system in electronic medical records of the hospital in the period.

Results:

We found out 101 reports including 163 herbal-drug-associated ADRs from 97 patients. Females (69.3%) outnumbered males and the most frequent age group was the 50s (44, 27.0%). No serious adverse event was observed. The most commonly reported ADR was gastro-intestinal system disorders (68, 41.5%) followed by skin-related disorders (42, 25.8%). Diarrhea (29, 17.8%) was the most frequently referred clinical manifestation. Most ADRs were induced by internal medicines (160, 98.2%) including manufactured (36, 22.1%) and self-prepared decoction (160, 76.1%). The pairs of Igi-hwan-diarrhea, gamiboa-tang-vomiting, and Magnoliae Flos-gastro-intestinal-system-related ADRs were observed twice each and the others appeared only once.

Conclusions:

We propose Korean government to take an initiative in national pharmacovigilance system for herbal medicine. To perform the surveillance on herbal drugs, the Association of Korean Medicine (AKOM) should set up a nationwide network by designating centers connecting the Korean medical hospitals, local Korean medicine clinics, and the public health centers. The government and AKOM should also educate and encourage them to understand the pharmacovigilance system and report the ADRs actively.

Keywords: side effects; adverse drug reaction; ADR reporting system; herbal-drug-associated ADR; pharmacovigilance; herbal medicine; Korean medicine

Table 1.

Between-group Comparison of the WHO-UMC Causality Assessment.

Table 2.

Number of the Cases with No Available Information to Score Each Category of Korean Algorithm for ADR Causality Assessment version 2.0.

Table 3.

Destribution of Adverse Drug Reactions by Gender and Age groups.

Table 4.

Types of Clinical Manifestations of Adverse Drug Reactions.

Table 5.

Status of Concomitant Drug Administration.

Table 6.

Demographic Data from the ADR^*s associated with Manufactured Herbal Drug.

Table 7.

Numbers of Clinical Manifestations of ADR^*s Due to Manufactured Herbal Drug.

Table 8.

Repeated Occurrence of the ADR^*s with the Same Drug – SOC Pairs.

Table 9.

Demographic Data from the ADR^*s associated with Herbal Decoction.

Table 10.

Numbers of Clinical Manifestations of ADR^*s Due to Herbal Decoction.

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Article information Continued

Table 1.

Between-group Comparison of the WHO-UMC Causality Assessment.

Rater Group	Certain	Probable	Possible	Unlikely	Unclassified	Not done
RPVC^*	0 (0.0)	6 (3.4)	97 (54.8)	1 (0.6)	2 (1.1)	71 (40.1)
Authors ^†	0 (0.0)	17 (9.6)	146 (82.5)	14 (7.9)	0 (0.0)	0 (0.0)

Raters of Regional Pharmacovigilance Center in Dongguk University Ilsan Hospital,

^†

Authors who are Korean Medical doctors

Table 2.

Number of the Cases with No Available Information to Score Each Category of Korean Algorithm for ADR Causality Assessment version 2.0.

Categories	Number (%)
Chronologic relationship	2 (1.1)
Dose reduction or stop	129 (72.9)
Past history of ADR	169 (95.5)
Combined medication	173 (97.7)
Drug-unrelated cause	118 (66.7)
Any unveiled information of drugs	173 (97.7)
Re-challenge	166 (93.8)
Specific Tests	177 (100.0)

Table 3.

Destribution of Adverse Drug Reactions by Gender and Age groups.

	Total (%)	Male (%)	Female (%)
Number	163 (100.0)	50 (30.7)	113 (69.3)
Age	49±20.8	41±24.0	52±18.3
0–9	10 (6.1)	8 (4.9)	2 (1.2)
10–19	10 (6.1)	6 (3.7)	4 (2.5)
20–29	8 (4.9)	3 (1.8)	5 (3.1)
30–39	20 (12.3)	2 (1.2)	18 (11.0)
40–49	20 (12.3)	8 (4.9)	12 (7.4)
50–59	44 (27.0)	12 (7.4)	32 (19.6)
60–69	30 (18.4)	7 (4.3)	23 (14.1)
70–79	11 (6.75)	4 (2.5)	7 (4.3)
80+	10 (6.1)	0 (0.0)	10 (6.1)

Table 4.

Types of Clinical Manifestations of Adverse Drug Reactions.

Clinical Manifestations	Number	SOC^*	Number (%)
PRURITUS	17	Skin and appendages disorders	42 (25.8)
RASH	12
URTICARIA	8
SWEATING INCREASED	2
RASH FOLLICULAR	2
ACNE	1

MYALGIA	1	Musculo-skeletal system disorders	1 (0.6)

DIZZINESS	5	Central & peripheral nervous system disorders	6 (3.7)
HYPERTONIA	1

PALPITATION	6	Autonomic nervous system disorders	6 (3.7)

INSOMNIA	3	Psychiatric disorders	3 (1.8)

VOMITING	5	Gastro-intestinal system disorders	68 (41.5)
DIARRHEA	29
DYSPEPSIA	20
ABDOMINAL PAIN	10
NAUSEA	2
FLATULENCE	2

HEPATIC ENZYMES INCREASED	7	Liver and biliary system disorders-	7 (4.2)

HYPERGLYCAEMIA	1	Metabolic and nutritional disorders	3 (1.8)
OEDEMA DEPENDENT	1
WEIGHT INCREASE	1

ARRHYTHMIA	1	Heart rate and rhythm disorders	1 (0.6)

DYSPNEA	2	Respiratory system disorders	2 (1.2)

DYSURIA	1	Urinary system disorders	1 (0.6)

HEADACHE	10	Body as a whole - general disorders	20 (12.3)
TEMPERATURE CHANGED SENSATION	4
CHEST PAIN	2
FEVER	2
ASTHENIA	1
OEDEMA PERIORBITAL	1

APPLICATION SITE REACTION	3	Application site disorders	3 (1.8)

System-Organ Classes

Table 5.

Status of Concomitant Drug Administration.

Single administration (%)	Concomitant administration (%)
84 (51.5)	79 (48.5)

	HD^*	WD ^†	HD+WD
	15 (9.2)	44 (27.0)	20 (12.3)

Herbal drug,

^†

Western drug

Table 6.

Demographic Data from the ADR^*s associated with Manufactured Herbal Drug.

	Total (%)	Male (%)	Female (%)
Number	36 (100.0)	11 (30.6)	25 (69.4)
Age	45± 19.8	44±25.1	47±17.3

Adverse drug reactions

Table 7.

Numbers of Clinical Manifestations of ADR^*s Due to Manufactured Herbal Drug.

Clinical Manifestations	Number	SOC ^†	Number (%)
PRURITUS	3	Skin and appendages disorders	6 (16.7)
SWEATING INCREASED	1
RASH FOLLICULAR	2

DIZZINESS	3	Central & peripheral nervous system disorders	5 (13.9)
HEADACHE	2

PALPITATION	3	Autonomic nervous system disorders	3 (8.3)

VOMITING	2	Gastro-intestinal system disorders	17 (47.2)
DIARRHEA	6
DYSPEPSIA	4
ABDOMINAL PAIN	4
NAUSEA	1

HEPATIC ENZYMES INCREASED	2	Liver and biliary system disorders-	2 (5.6)

TEMPERATURE CHANGED SENSATION	1	Body as a whole - general disorders	3 (8.3)
CHEST PAIN	1
OEDEMA PERIORBITAL	1

Adverse drug reactions,

^†

System-Organ Classes

Table 8.

Repeated Occurrence of the ADR^*s with the Same Drug – SOC Pairs.

Drug Type	Drug	Clinical Manifestation	SOC ^†
HD ^‡	Gamiboa-tang4 (加味補兒湯4)	PRURITUS, RASH	Skin and appendages disorders
HD	Gamisamhwang-tang1 (加味三黃湯1)	PRURITUS, URTICARIA, RASH
HD	Gamiwon-tang2 (加味元湯2)	PRURITUS, URTICARIA
HD	Gamicheongyeol-tang1 (加味淸熱湯1)	PRURITUS, RASH
HD	Gosamhoma-san1 (苦蔘胡麻散1)	PRURITUS, URTICARIA
HD	Gwibi-tang1 (歸脾湯1)	PRURITUS, RASH
HD	Gwibi-tang3 (歸脾湯3)	PRURITUS, RASH
HD	Danggwisu-san1 (當歸鬚散1)	PRURITUS, RASH
HD	Saenghwa-tang2 (生化湯2)	PRURITUS, URTICARIA, RASH
HD	Untitled decoction2 (任意處方2)	PRURITUS, RASH
HD	Jagamcho-tang1 (炙甘草湯1)	PRURITUS, URTICARIA, RASH
HD	Cheongsimyeonja-tang2 (淸心蓮子湯2)	URTICARIA, RASH
HD	Hyangsayuggunja-tang1 (香砂六君子湯1)	PRURITUS, URTICARIA
MHD^§	Socheonglyong-tang (小靑龍湯)	PRURITUS, RASH FOLLICULAR

MHD	Samchulgeonbi-tang (蔘朮健脾湯)	DIARRHEA, DYSPEPSIA	Gastro-intestinal system disorders
MHD	Gamiseogyeong-hwan (加味舒經丸)	ABDOMINAL PAIN, DYSPEPSIA
MHD	Sodo-hwan (消導丸)	ABDOMINAL PAIN, DIARRHEA, DYSPEPSIA
MHD	Bangpungtongseong-san (防風通聖散)	ABDOMINAL PAIN, DIARRHEA
MHD	Igi-hwan (理氣丸)	ABDOMINAL PAIN, DIARRHEA, DIARRHEA^‖
HD	Gamiwon-tang1 (加味元湯1)	ABDOMINAL PAIN, DIARRHEA
HD	Gamiboa-tang2 (加味補兒湯2)	DYSPEPSIA, FLATULENCE
HD	Gamiboa-tang5 (加味補兒湯5)	VOMITING, VOMITING^‖
HD	Gamiwon-tang2 (加味元湯2)	DIARRHEA, DYSPEPSIA
HD	Bangpungtongseong-san2 (防風通聖散2)	DIARRHEA, DYSPEPSIA
HD	Boyanghwano-tang1 (補陽還五湯1)	ABDOMINAL PAIN, DIARRHEA
HD	Bojungiggi-tang3 (補中益氣湯3)	DIARRHEA, DYSPEPSIA
HD	Sihosogan-tang1 (柴胡疎肝湯1)	VOMITING, DYSPEPSIA
HD	Eom’s tonggyu-bang1 (嚴氏通竅方1)	DIARRHEA, DYSPEPSIA
HD	Untitled decoction6 (任意處方6)	DIARRHEA, DYSPEPSIA
HD	Cheongsimyeonja-tang (淸心蓮子湯1)	DIARRHEA, FLATULENCE
HD	Taeeumincheonghyeolganggi-tang1 (太陰人淸血降氣湯1)	ABDOMINAL PAIN, DYSPEPSIA

Adverse Drug Reactions,

^†

System-Organ Classes,

^‡

Herbal Decoction,

^§

Manufactured Herbal Drug,

^‖

^{bold letters} the same drug-clinical manifestation pairs

Table 9.

Demographic Data from the ADR^*s associated with Herbal Decoction.

	Total (%)	Male (%)	Female (%)
Number	124 (100.0)	39 (31.5)	85 (68.5)
Age	50± 21.3	40±23.8	54±18.5

Adverse drug reactions

Table 10.

Numbers of Clinical Manifestations of ADR^*s Due to Herbal Decoction.

Clinical Manifestations	Number	SOC ^†	Number (%)
PRURITUS	14	Skin and appendages disorders	36 (29.0)
RASH	12
URTICARIA	8
SWEATING INCREASED	1
ACNE	1

MYALGIA	1	Musculo-skeletal system disorders	1 (0.8)

DIZZINESS	2	Central & peripheral nervous system disorders	3 (2.4)
HYPERTONIA	1

PALPITATION	3	Autonomic nervous system disorders	3 (2.4)

INSOMNIA	3	Psychiatric disorders	3 (2.4)

DIARRHEA	23	Gastro-intestinal system disorders	51 (41.1)
DYSPEPSIA	16
ABDOMINAL PAIN	6
VOMITING	3
FLATULENCE	2
NAUSEA	1

HEPATIC ENZYMES INCREASED	5	Liver and biliary system disorders-	5 (4.0)

HYPERGLYCAEMIA	1	Metabolic and nutritional disorders	3 (2.4)
OEDEMA DEPENDENT	1
WEIGHT INCREASE	1

ARRHYTHMIA	1	Heart rate and rhythm disorders	1 (0.8)

DYSPNEA	2	Respiratory system disorders	2 (1.6)

DYSURIA	1	Urinary system disorders	1 (0.8)

HEADACHE	8	Body as a whole - general disorders	15 (12.1)
TEMPERATURE CHANGED SENSATION	3
FEVER	2
ASTHENIA	1
CHEST PAIN	1

Adverse drug reactions, ,

^†

System-Organ Classes