totally about phytopharmacovigilance for sem 8 pharmacy

1. Towards safety of herbal medication
Prepared by : Mrs Pooja Khanpara

2. PHARMACOVIGILANCE
"Pharmacovigilance” =( Pharmakon -drug ) + (Vigilance- t
watch)
The science and activities relating to the detection,
evaluation, understanding and prevention of
adverse drug reactions or any other drug-related
problems
Or
The study of the safety of marketed drug under the
practical conditions of clinical usage in large
communities

3. • To improve patient care & safety in
relation to medicines & all medical &
para-medical interventions
Patient
Care
• To improve public health & safety in relation
to the use of medicines
Public
Health
Risk Benefit
Assessment
• To contribute to the assessment of benefit,
harm,effectiveness and risk of medicines
• To promote understanding, clinical training &
effective communication to health professionals
& the public
Communication
AIMS & SCOPE

4. PhytoPharmacovigilance
Some unwanted reactions due to herbs can be :
(i) Side effects (usually detectable by pharmacodynamics and often
predictable)
(ii) Reactions occurring as a result of overdose, over duration,
tolerance, dependence-addiction (detectable either by
pharmacodynamics or pharmacovigilance)
(iii) Hypersensitivity, allergic and idiosyncratic reactions
(detectable by pharmacovigilance)
(iv) Mid-term and long-term toxic effects including liver, renal,
cardiac and neurotoxicity also genotoxicity and teratogenicity
(detectable by in vitro and in vivo toxicological studies or by
pharmacovigilance).

5. CHALLENGES IN MONITORING THE SAFETY OF
HERBAL MEDICINES:
Regulation
Quality assurance and control
Safety monitoring of herbal
medicines
Recording and coding the identity
of herbal medicines

6. Specific challenges
Unlike synthetic medicines, herbal medicines are
typically chemically rich and complex products and
not isolated single compounds.
A number of factors can influence the qualitative and
quantitative chemical profile including:
• Geographical origin – climate, soil, photoperiod.
• Genotype.
• Parts of the plant – leaves, stems, root, root bark, etc.
• Harvesting time (year, season, time of day) and
conditions.
• Storage, processing, extraction.
• Combinations of herbs and/or processing of the
combined herbs as medicines.

7. Herbal medicines & Dietary
Supplements
 Its different from different countries.
 EU classified as herbal medicines with
requirements for safety & quality standards. Some
herbs supplied as food supplement.
 In Europe H.M. registered under 2 directives,
either “well establish used” or ‘traditional herbal
medicinal products”
 In U.S. herbal products classified as dietary
supplement , not as medicine.
 Quality verifying through GMP , issued by the FDA
in 2007

8. Subtleties(detail) in legal differentiation
Food supplement
 it cant claim to treat or
prevent disease in human
beings.
 Don’t have legal
requirement for quality
control & GMP
Herbal medicine
 Any substance or
combinations of
substances presented as
having properties of
treating or preventing
disease in human beings
 GMP & safety must
require.

9. Nomenclature
 Names for medicinal herbs includes
 - Latin scientific names (used as synonyms , on
labeling in EU)
 - common or vernacular name (used for different
genera & species)
 - Pharmaceutical or pharmacopoeial name
 - specific herbal drug name (as used in TCM)
 In Europe & U.S. common name is used as reference.
 On labeling scientific name is used.
 If Pharmacopeial quality drug then will be define in
‘PhEur’.

10. Initiatives to address Nomenclature &
Quality Issue
 ‘International Code of Nomenclature of algae, fungi &
plant (ICN).
 ‘Medicinal Plant Names Index’ (MPNI) underway at the
Royal Botanic Gardens Kew will address the issue.
 One of this projects main aims to develop an
authoritative index to scientific plant names mapped to
frequently use vernacular, trade & pharmacopoeia names
in order to support the development of global, industry-
wide medicinal data standard.
 The UMC has worked with RBGK & Uppsala
University to develop appropriate standardization and
cross-referencing of herbal names for their ADRs.

12. Initiatives to address Nomenclature &
Quality Issue
 UMC developed the WHO Herbal dictionary an
international reference source of herbal product
designed to be used for coding and analysis of drug safety
data(pre & post marketing)
 Herbal monographs developed by all countries
Pharmacopoeia(British, European, India, U.S., China)
 Monographs define the standard for herb quality.
 IN Europe, All registered herbal product also require
GMP
 Its improve quality of herbal product available in market.

13. Source Users of Herbal medicine
 Self prescribed
 Herbal practitioner
 Health professional
 Orthodox medicinal professionals in Germany
 Consumer may not be aware that adverse effect of
product.
 Consumer are reluctant to admit to their physician
that they have been using herbal medicines.
 Training & practice standards vary from highly
trained professionals to untrained & unregulated.

14. Adverse Drug Reactions (ADRs)
Any response to a drug which is
noxious and unintended and
which occurs at doses used in
man for prophylaxis,
diagnosis or therapy
Six Classifications of ADR
Type A
Type B
Type C
Type D
Type E
Type F
(Augmented/acute)
(Bizarre/Idiosyncratic)
(Cumulative/chronic)
(Delayed Onset)
(Ending of Use)
(Failure of Efficacy)

15. Type A -
Type B -
Type C -
Type D -
Type E -
Type F -
(Augmented/acute) – dose related & explained by
pharmacology of herbs
- effect of herbs within hours or days
(Bizarre/Idiosyncratic) – not drug related &
predictable by Pharmacology within days or weeks
Rarely occur, may be serious of even fatal.
e.g. hepatotoxicity
(Cumulative/chronic) – Cumulative effect
- e.g. Aristolochic Acid Nephropathy(AAN) :
cumulative & renal symptoms show after stopping
drug for 2 years
(Delayed Onset) – Carcinogenic, geotoxic
(Ending of Use)
(Failure of Efficacy)

16. 78,095
56,231
4,667
*
1
4
7
C
E
2
5
8
%
3
6
/
9
0
+
=
STATISTICS
 5% of adults are allergic to one or more medications
 6 – 10% of ADRs result from a drug allergy
 3% of hospital admissions are due to ADRs
 28% of ADRs are preventable
 Drugs associated with ADRs: 29% analgesics, 10%
sedatives, 9% antibiotics, and 7% antipsychotics.
 PGH: Antibiotics (35%), anti-TB meds (34%),
anticonvulsants and ASA/NSAIDS (10% each)

17. In India the herbal remedy is so popular that the
government of India has created a separate
department—AYUSH—under the Ministry of
Health & Family Welfare. The National Medicinal
Plants Board was also established in 2000 by the
Indian government in order to deal with the herbal
medical system.

18. Safety
•A number of herbs are thought to be likely to cause adverse effects.
Datura stramonium is a highly
effective treatment for asthma
symptoms when smoked, because it
contains atropine, which acts as an
antispasmodic in the lungs. However,
datura is also an extremely powerful
hallucinogen and overdoses of the
tropane alkaloids in it can result in
hospitalization or death.

19. Herbs with suspected or known adverse effects
HERBALDRUGS ADVERSEEFFECTS
Ginkgo biloba Bleeding
St. John's wort Gastrointestinal disturbances, allergicreactions,
fatigue, dizziness,confusion, dry
mouth,photosensitivity
Ephedra (Ma Huang) Hypertension, insomnia,
arrhythmia,nervousness, tremor,
headache,seizure, cerebrovascular
event,myocardial infarction, kidney stones.
Kava(
Pipermethysticum)
Sedation, oral and lingual dyskinesia,torticollis,
oculogyric crisis,exacerbation of Parkinson's
disease,painful twisting movements of thetrunk,
rash

20. Pharmacovigilance method
 1) Spontaneous Reports
 2) Prescription event monitoring
 3)Herbal practicinors

21. 1) Spontaneous Reports
 Standardised forms are used for reporting suspected ADR
(purpose – safety of medicine)
 Authorised persons – Pharmacists, Physicians, nurses
 In U.S. reported – FDA MedWatch scheme.
 U.K. – ‘Yellow card’ scheme (20,000 – 100 herbal)
 Australia ‘blue card’
 Problems with S.R.:
 1) Lack of association B/W herbs & adverse effect.
 2) Patient stops using the herbal medicine when they feel
unwell.
 3) Physician/Patient unaware of use of herbal drug ADRs
should reported
 4) Physician dose not consider herbal & nutrient product to be
medicine and they dose not disclose use.

22. 1) Spontaneous Reports
 Quality of ADR reports improve by collaboration with
Pharmacognosy dpt., botanic gardens, other toxicologic
units.
 In U.K. the Chinese Medicine Advisory Service
assists with enquiries.
 Also with RBGK(Royal Botanic Garden Kew).
 IN Hong Kong the Hospital Authority Toxicology
Reference Laboratory at Princess Margret
Hospital also undertake multidispensory investigations
for herbal toxicology.
 Well establoshed product registerd under
THMPD(Traditional Herbal Medicinal Product
Directive)

23. 1) Spontaneous Reports
 Herbal product adultrants with Pharmaceutical
medicines for slimming, Inflammatory condition are
international problems.
 336 of 390 warnings issued by regulatory authorities
in U.K., U.S., Canada, Singapore, Hong Kong, &
Australia.
 By early 2011, 6 million drug and herbal report
identified in UMC.

24. 2) Prescription event monitoring
 There is a prescription that herbal medicines are safe,
even if taken at the same time as prescribed drug.
 It may be reduced side effect of treatment.
 Problems arise when orthodox & herbal medicines use
together.(cancer patient)
 Prescription event monitoring(PEM) is a non-
interventional hypothesis method for studying drug once
placed on the market.
 In Thiland, there is an extensive list of registered herbal
medicines are also used in hospital settings.
 In EU & U.S. there is a Poisons Control Centers(PCC)
available (mainly for dilatory supplements).
 Others , Case control & cohort(group) studies available.

25. 3) Herbal Practitioners
 Some Organization prepare Owen report scheme for
report ADRs.
 But trained herbal practitioners must be available.
 So they educate patients about herbal medicine
properly.
 Herbal prescriptions are routinely modified to
reduce side effects or improve response of patients.

26. Minimum requirement fir ADRs
 Patient demographics (Age, gender)
 Relevent medicinal history
 Symptoms
 Abnormal laboratory reports
 Drug identification
 Reason for use
 Dosage
 Time of course
 Detail of adverse events

27. Minimum requirement fir ADRs
 For manufacturer,
 Product name,
 Procrdure
 Batch no.
 Type & concentration of extract & standards
 Botanical identifications include,
 Latine scintific name
 Plant parts,
 preparation

30. List of the unapproved Ayurvedic
medicinal products
•Karela tablets, produced by Shriji Herbal Products, India
•Karela capsules, produced by Himalaya Drug, India
•Karela capsules, produced by Charantia, UK (specifically
batch #12011)
•Maha Sudarshan Churna powder, produced by Zandu Pharmaceuticals, Mumbai, India
•Maha Sudarshan Churna powder, D and K Pharmacy, Bhavnagar, India
•Maha Sudarshan Churna powder, produced by Chhatrisha, Lalpur, India
•Maha Sudarshan Churna powder, produced by Dabur India, New Delhi, India
•Safi liquid, produced by Hamdard-WAKF-Pakistan
•Safi liquid, produced by Hamdard-WAKF-India
•Yograj Guggul tablets, produced by Zandu Pharmaceuticals, Mumbai, India
•Sudarshan tablets, produced by Zandu Pharmaceuticals, Mumbai, India
•Shilajit capsules, produced by Dabur India, New Delhi, India

31. CONCLUSION
This project aims to provide a comprehensive and critical
overview of the current state of pharmacovigilance activities for
herbal medicines at the national and global levels. It will explore
in depth the challenges that pharmacovigilance of herbal
medicines presents, consider relevant emerging issues and what
steps could and should be taken to improve safety monitoring
for herbal medicines in the future