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JKM > Volume 36(1); 2015 > Article
Kim and Han: Analysis of Herbal-drug-associated Adverse Drug Reactions Using Data from Spontaneous Reporting System in Electronic Medical Records

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.

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

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