PHARMACOVIGILANCE

OF
HERBAL DRUGS

-Towards safety of herbal medication

PHARMACOVIGILANCE
"Pharmacovigilance =( Pharmakon -drug )

+ (Vigilance

keep watch)

The science and activities relating to the detection,

evaluation, understanding and prevention of
adverse drug reactions or any other drug-related
problems

AIMS & SCOPE

Patient
Care

Risk

To improve patient care & safety in

relation to
medicines & all medical & paramedical
interventions

Publi

To improve public health & safety in

relation to

Heal
th

the use of medicines

To contribute to the assessment of benefit,

Benefit

harm,

Assessme

effectiveness and risk of medicines

To promote understanding, clinical training

nt
Communicati
on

&
effective communication to health
professionals

Pharmacovigilance in India: A
Brief History

NEED FOR PHARMACOVIGILANCE

Humanitarian concern
ADR May cause sudden death
Promoting rational use of medicines
and adherence
Ethics:
To know of something that is

harmful to another person who does not know,

and not telling, is unethical.

ADRs: 4th Leading Cause of

Death

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)
(Bizarre)
(Continuous)
(Delayed)
(Ending of Use)
(Failure of Efficacy)

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)

Herbalism
Herbalism("herbology"or"herbal medicine") is use
of plants for medicinal purposes, and the study of such use.
Plants have been the basis for
medical treatments through much
of human history, and such
traditional medicineis still widely
practiced today.
The World Health Organization
estimates that 80 % of the population
of some Asian and African countries
presently use herbal medicine for some
aspect of primary health care.

Prevalence of use
The use of herbal remedies is more
prevalent in patients with chronic
diseases such as cancer, diabetes,
asthma and end-stage renal disease.
Multiple factors such as gender, age,
ethnicity, education and social class
are also shown to have association
with prevalence of herbal remedies
use.

In India the herbal remedy is so popular that the

government of India has created a separate
departmentAYUSHunder 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.

Herbal preparations
Herbal teas, or tisanes, are the resultant liquid of extracting herbs into
water, though they are made in a few different ways.
Infusions are hot water extracts of herbs, such aschamomile or mint,
through steeping.
Decoctions are the long-term boiled extracts, usually of harder
substances like roots or bark.
Maceration is the old infusion of plants with high mucilage-content,
such as sage, thyme, etc.
Tinctures are alcoholic extracts of herbs, which are generally stronger
than herbal teas. Usually obtained by combining 100% pure with the
herb.
Extracts include liquid extracts, dry extracts, and nebulisates. Liquid
extracts are liquids with a lower ethanol % than tinctures. Dry extracts
are extracts of plant material that are evaporated into a dry mass.

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.

Examples of highly toxic herbs include:

Poison hemlock and nightshade.They are not marketed to the public as
herbs, because the risks are well known, partly due to a long and colorful
history in Europe, associated with "sorcery", "magic" and intrigue.
A case of major potassium depletion has been attributed to chronic licorice
ingestion., and consequently professional herbalists avoid the use of licorice
Black cohosh has been implicated in a case of liver failure.
Examples of herbs where a high degree of confidence of a risk long term
adverse effects can be asserted include ginseng, which is unpopular among
herbalists for this reason, the endangered herb goldenseal, milk thistle, senna,
against which herbalists generally advise and rarely use, aloe vera juice,
buckthorn bark and berry, cascara sagrada bark, saw palmetto, valerian, kava,
which is banned in the European Union, St. John's wort, Khat, Betel nut, the
restricted herb Ephedra, and Guarana.

Herbal Pharmacovigilance
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).

The safety of herbal medicines has

become an issue for the regulatory
authorities, as serious effects have
been reported, including
hepatotoxicity, renal failure and
allergic reactions

Systematic pharmacovigilance is
essential to build up reliable
information on the safety of herbal
medicines for the development of
appropriate guidelines for safe
effective use.

Herbal medicines are

traditionally considered
harmless since these belong to
natural sources. However, this is
not true as there are several case
reports of adverse reactions of
herbal drugs mentioned in
published literature.

The World Health Organisation,

recognising the growing importance
of the use of herbal medicines
worldwide developed guidelines for
the monitoring of herbal safety
within the existing
pharmacovigilance framework.

Herbs with suspected or known adverse effects

HERBAL DRUGS
Ginkgo biloba
St. John's wort

ADVERSE EFFECTS
Bleeding
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(
Piper methysticum)

Sedation, oral and lingual

dyskinesia,torticollis, oculogyric
crisis,exacerbation of Parkinson's
disease,painful twisting movements of
thetrunk, rash

Herbs with Adverse Drug Interactions

Herb

Drug

Adverse Effects

Ginkgo biloba

Drugs like Aspirin,

With aspirin -retards

warfarin, ticlopidine,

aspirin absorption

clopidogrel,
dipyridamole, garlic,
vitamin E
Psylliumseed

Coumarinderivates

Retards absorption of
drug

Ephedra

Feverfew

Caffeine,

May be additive in

decongestants,

nature

stimulants
Aspirin

Additiveeffects

Problems encountered with the use of herbal

medicines and products.
Some herbal products were found to contain 0.1 to 0.3 mg of
betamethasone per capsule after some patients developed corticosteroidlike side effects.
Owing to misidentification of the medicinal plant species, plant materials
containing aristolochic acid were used for manufacturing herbal products,
which caused severe kidney failure in patients in several countries.
Reports have been received by drug safety monitoring agencies of
prolonged prothrombin times, increased coagulation time, subcutaneous
hematomas, and intracranial hemorrhage associated with the use of Ginkgo
biloba.
One of the most well-known traditionally used herbal medicines caused
severe, sometimes fatal cases of interstitial pneumonia, when used in
conjunction with interferon.

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

Importance of Herbal Pharmacovigilance

Some countries accept traditional, experience based evidence
while others consider herbal remedies as dangerous or of
questionable value. Medicinal herbs as potential source of
therapeutics aids has attained a significant role in health care
system all over the world for human beings not only in the
diseased condition but also as potential material for maintaining
proper health
A major factor impeding the development of the medicinal plant
based industries in developing countries has been the lack of
information on the social and economic benefits that could be
derived from the industrial utilization of medicinal plants.
The monitoring the safety ofherbal medicinal products, in the
market or in the pipeline, will definitely go a long way in restoring
the confidence of their safety

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

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.

ADR REPORTING

Why report ADRs?

To prevent drug-induced human

suffering

To avoid financial risks associated with

unexpected risks

ADR Monitoring System

Reports
Reports
from
from
Private
Participating
Practitioners
Hospitals

Report
from
Drug Mfr.
Traders/
Outlets

Reports
on
Clinical
Investigations

Reports
from
Regulatory
Authorities

Reports
from
Intl
ADR
Centers

BFAD ADR UNIT

NADRAC
Director - BFAD
Secretary of
Health - DOH

WHO Collaborating Center

REPORTING SCHEME
CASE
Reporter Fills Out a
Form
Hospital
Therapeutic
Committees
ADRMP Office
(Central Database)

WHO

NADRAC
(Trend Analysis)

WHO

How do we report ADRs?

STEP 1 : Fill out the RED ALERT CARDS
PGH FORM # P 60170

PGH ADVERSE DRUG SURVEILLANCE

ALERT CARD
(Clip this on chart front cover)

Name of patient:___________________________________
Ward & Bed No.:__________________________________
Name of suspect drug:______________________________
Manufacturer:_____________________________________
Lot/ Code No.:__________ (Retain empty vial or container)
Describe the reaction:_______________________________
________________________________________________
________________________________________________
__
Reporter:
_________________________________________
(Please Print)
PLEASE NOTIFY: CENTRAL BLOCK PHARMACY
Loc. 3163 / 3170

How do we report ADRs?

STEP 2: Complete the ADR REPORT FORM
The Resident - in - charge of
the patient shall
complete the
necessary report of ADR
circumstances.

How do we report ADRs?

STEP 3: Submit the red alert card and the
ADR report form to the Central Block
Pharmacy for proper referral.
STEP 4: The Pharmacy will then compile
the reports for review of the ADR
Subcommittee and submission to the
Bureau of Food and Drugs (BFAD).

Pharmacist

The WHO international drug monitoring program

Under the WHO International Drug Monitoring Program, national

pharmacovigilance centers designated by the competent health
authorities are responsible for the collection, processing, and evaluation
of case reports of suspected adverse reactions supplied by health care
professionals (mainly spontaneous reporting by physicians of reactions
associated with the use of prescribed medicines). The Program is
described in two publications: Safety monitoring of medicinal products:
guidelines for setting up and running a pharmacovigilance center.

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

THANK YOU