Application of PharmacoviApplication of Pharmacovigilance in post-marketing trgilance in post-marketing traditional Chinese medicineaditional Chinese medicine

Hua-Wen XinHua-Wen Xin

Wuhan General Hospital,Wuhan General Hospital,

Wuhan, ChinaWuhan, China

PharmacovigilancePharmacovigilance

The science and activities relating to the detection, assessment, understanding and prevention of

adverse effects or any other drug-related problems

Aims of PharmacovigilanceAims of Pharmacovigilance

To improve patient care and safety To improve public health and safety To contribute to the assessment of benefit,

harm, effectiveness and risk of medicines To promote education and clinical training To promote effective communication to the

public To promote rational and safe use of

medicines

Its concerns including:

herbals traditional and complementary medicine blood products biologicals medical devices vaccines

Traditional Chinese Medicine (TCM)Traditional Chinese Medicine (TCM)

>9000 kinds of TCM preparations have been approved to be sold.

58000 approval numbers have been granted.

Side effects and desired effects

Three groupsThree groups

raw herbal medicine(Zhong yao cai),

sliced herbal medicine(zhong yao yin p

ian),

patent medicine(zhong cheng yao)

Industrial output value of TCM during 2000-2007

uni t:100mi l l i on yuan

476 540775 796

9571186

1432

1772

0

500

1000

1500

2000

2000 2001 2002 2003 2004 2005 2006 2007

ADR caused by TCMADR caused by TCM

ADRs related to TCM were reported frequently in Chi

na

152,320 and 663 kinds of TCM were detected with AD

R in the year 2001,2002,2003.

The ADR due to TCM injections accounted for 77.2%

of all ADR caused by TCM.

The causes of ADRs by TCMThe causes of ADRs by TCM

Variability in active/toxic ingredients Use of inherent toxic herbs Overdose of herbs drug-herb interactions Coexisting diseases Idiosyncratic reactions

Manufacturing and quality problems: Adulteration Misidentification Substitution of one herb with another Variability in the amount of active

ingredients Improper processing and preparation contamination

The causes of ADRs by TCMThe causes of ADRs by TCM

546 kinds of Chinese patent medicine w

ere recorded in the Chinese Pharmacop

oeia issued in 2005.

But 235 kinds did not describe the item

s related to pharmacovigilance.

Number ADR Contraindications Precaution

Missing number

% Missing number

% Missing number

%

Capsule 25 21 84 17 68 12 45

tablet 24 19 79 18 75 4 17

Injection 24 11 46 8 33 6 25

Granules 8 7 88 7 88 2 25

Mixture 8 8 100 7 88 1 13

Powder 1 1 100 1 100 0 0

Pill 2 2 100 2 100 1 50

Missing items about pharmacovigilance in 92 label instruction of TCM

Efforts in PV about TCMEfforts in PV about TCM

SFDA has improved its regulations on herbal medicine to implement quality control systems

GAP GLP GMP

ADR monitoring in ChinaADR monitoring in China

Three Three stagesstages

Primal constructionPrimal construction

experimentation

developmentdevelopment

““Information bulletin for ADR Information bulletin for ADR monitoring”monitoring”

Hepatic lesion caused by Zhuanggu Guanjie pill

Renal damage by Longdan Xiegan pill Serious ADR (allergic reaction and so o

n) by Qingkailin injection,Shuanghuanglian injection,Shenmai injection, Yuxingcao injection, Lianbizhi injection

To ensure the safety and efficacy of TCM injection, in 2000, the state launched the “Improvement of Quality Standards of TCM Injections with the Production Permission and Work on Fingerprints Chromatogram” and issued the Technological Requirements of Fingerprint Chromatogram Research of TCM Injection.

Working hard to improve the safety and Working hard to improve the safety and quality controlquality control

Fix the production areas of crude drugs of TCM injection

Strictly control the quality of raw materials,intermediate production

Realize overall quality control for production and processing

Aristolochic acid causes serious renal damage

SFDA cancelled the pharmaceutical standards of some medicinal materials containing aristolochic acid.

All TCM preparations which contain Fructus Aristolochiae,…….would be managed strictly as prescribed drugs.

SFDA suspended accepting the application of these TCM preparations for variety protection, generic drug and new drug registration.

SFDA suspended using and approving Yuxingcao injection on 1 June 2006.

In May 2007,the national ADR monitorin

g centre informed timely some correlati

ve manufactures of the serious adverse

reactions caused by Xiangdan injection

and urged them to strengthen the resea

rch on the ADR.

The drug administration departments have revised the directions for puerarin, potassium de-hydroandrograpolide succinate( 穿琥宁 ) and andrographolide sodium bisulfite （穿心莲） injections.

Abolished the pharmaceutical standard for manchurian aristolochia stem.

Revoked the manufacturing permission for bimolane

In order to supervise the quality of TCM, the drug monitoring authority implements the market spot checks.

It is beneficial to punish the manufacturer and seller of quack and inferior drugs.

Cohort study is suggested to do in future so that a further relationship between TCM and ADR can be obtained.

ConclusionsConclusions

The establishment of risk assessment

Early-warning mechanism

The interaction of TCM and chemicals

The international exchange of safety

information

ReferencesReferences

Wang HN, et al. China Journal of Chinese Materia Medica,2008,33:612-614

Cheng F, et al. China Journal of Chinese Materia Medica,2009,34:1052-1054

Wang H, et al. Pharmacoepidemiology and drug safety,2009,18:357-361