PHARMACOVIGILANCE OF DRUGS OF NATURAL ORIGIN. WHO AND AYUSH GUIDELINES FOR SAFETY MONITORING OF NATURAL MEDICINE. SPONTANEOUS REPORTING SCHEMES FOR BIODRUG ADVERSE REACTIONS BIO DRUG-DRUG AND BIO DRUG-FOOD INTERACTIONS WITH SUITABLE EXAMPLES

1. Pharmacovigilance
of drugs of natural
origin
Kipa Pape
82/MPG/2021/DPSRU
Presented by :
Submittedto:
Dr.AjaySharma

2. Content Outline :
PHARMACOVIGILANCE OF
DRUGS OF NATURAL ORIGIN.
WHO AND AYUSH GUIDELINES FOR SAFETY MONITORI
NATURAL MEDICINE.
SPONTANEOUS REPORTING SCHEMES FOR
BIODRUG ADVERSE REACTIONS
BIO DRUG-DRUG AND BIO DRUG-FOOD
INTERACTIONS WITH SUITABLE EXAMPLES

3. INTRODUCTION
Herbal medicine are frequently used in
conjuction with other medicines , and it is
essential to understand the consequences
of such combined use and monitor
whether any adverse effect are rising.
In India, the herbal remedy is so
popular that the government of
India has created a separate
department- AYUSH- under the
ministry of Health and Family
welfare.
The National Medicinal Plants Board
(NMPB) was also established in 2000
by the Indian government in order
to deal with the herbal medicinal
system.

4. Drug interaction
Lack of GMPs
Lack of knowledge of
ADRs of herbal drugs
Patients dont take
herbal as drug
Multiple ingredient in one
preparation
Difficulty to identify
ingredients
False but attractive claims
by manufacturers

5. herbals
traditional and complementary medicines
blood products
biologicals
medicinal devices
vaccine
Recently, its concerns have been widened to include-
Pharmacovigilance is the science and activities relating to the detection , assessment,
understanding and prevention of adverse effects of drugs or any other possible drug-
related problems.

6. AIM OF PHARMACOVIGILANCE
RISK BENEFIT
ASSESSMENT
PATIENT CARE
To improve patient
care and safety in
relation to medicines
and all medical and
paramedical
interventions.
PUBLIC HEALTH
To improve public
health and safety in
relation to the use of
medicines.
Collect data for
ADR reports.
To create
awareness among
society
for Ayurvedic,
Siddha and Unani
drugs

7. NEED FOR PHARMACOVIGILANCE
ADR MAY CAUSE
SUDDEN DEATH
HUMANITARIAN
CONCERN
PROMOTING RATIONAL USE
OF MEDICINES AND
ADHERENCE

8. 1986 1998 2004-2008 2010
ADR
monitoring
system for
India
initiated
with 12
regional
centres.
India joined
WHO-ADR
monitoring
programme
based in
Uppsala, Sweden.
Launch of National
Pharmacovigilance
programme,
coordinated by
CDSCO with 2 zonzl,5
regional, 24
peripheral centres.
Renamed as the
Pharmacovigilance
Programme of India
PHARMACOVIGILANCE IN INDIA
HISTORY:

9. PHARMACOVIGILANCE PROGRAM IN
INDIA
The CDSCO, New Delhi initiated pharmacovigilance programme in july 2010, with the
AIIMS New Delhi as the National Coordinating Centre (NCC) for monitoring Adverse Drug
reactions (ADR).
To ensure implementation of this programme in a more effective way, the National Coordinating
Centre was then shifted from AIIMS , New Delhi to the Indian Pharmacopoeia Commission (IPC),
Ghaziabad (U.P) in April, 2011.
Department of AYUSH, ministry of health and Family Welfare, Government of
India, implemented a National Pharmacovigilance for Ayurveda, Unani, and
Siddha system of medicine, in order to systematically monitor adverse drug
reactions (ADR)

10. PHARMACOVIGILANCE CENTRES IN INDIA
National PV
centre Jamnagar
8 regional PV centres
Varanasi, Thiruvananthapuram,
Jaipur, Bhopal, New Delhi,
Bengaluru, Chennai
30 peripheral
centres

11. INDUSTRIES INVOLVED IN PHARMACOVIGILANCE
COGNIZANT
CLINIGENE
ACCENTURE
CLINTECH
WIPRO
GLENMARK
GSK
AVASTHEGEN
GENPACK
JUBILANT CLINSYS

12. Clinical
Chemistry

14. Safety is a fundamental principle in the provision of herbal medicines and
herbal products for health care, and a critical component of quality
control.
The guidelines were developed with the view that, within current
pharmacovigilance systems, monitoring of the safety of medicines should
be enhanced and broadened in ways that will allow the successful
monitoring of herbal medicines.
These guidelines provide practical, technical guidance for monitoring the
safety of herbal medicines within pharmacovigilance systems.
Introduction

15. PROBLEMS
Among consumers, there is a widespread misconception that "natural"
always means safe, and a common belief that remedies from natural
origin are harmless and carry no risk.
the adulteration of herbal products with other medicines and potent
pharmaceutical substances.
incorrect dosing
errors in the use of herbal medicines both by health-care and
consumers
interaction with other medicines
Adverse events may arise from-

16. ACTIONS REQUIRED
Institution of measure to
prevent adverse events
Clear identification of the
nature of adverse events
For the safety of thoses using herbal medicines, four
complementary actions are needed.
1
2 Management of the risk 4
3
Good communication of the
risks and benefits of herbal
medicines

17. OBJECTIVES
Provide technical guidance on
the principles of good
pharmacovigilance.
The objectives of these guidelines
are to-
Provide standard definations
of terms relating to
pharmacovigilance, and safety
monitoring of herbal
medicines.
Promote the safe and proper
use of herbal medines.

18. #1 Sources of reports
#2 Reporting for suspected adverse
reactions
#3 Assessment of case report
#4 Data management
SAFETY MONITORING OF HERBAL MEDICINES

19. Report from health care professionals
Report from consumers
Report from manufactures
Report from other sources
SOURCES OF REPORTS
The most common sources of information on adverse events
and reactions to medicines are clinical trials and spontaneous
reports

20. WHAT TO REPORT?
Death
Life-threathening
Hospitalisation
Disability(significant, persistent or
permanent)
Report serious adverse drug
reactions. A reaction is serious when
the patient outcome is-
WHAT SHOULD BE REPORTED?
REPORTING OF SUSPECTED ADVERSE DRUG REACTIONS
The Uppsala Monitoring centre (UMC,WHO ), Sweden is maintaining the database of ADR reports
received from several National centres.
ADR due to
overdosing/medication error
All drug interactions
All suspected ADRs of new drugs
and vaccines

21. WHO CAN REPORT?
Doctors-physicians and Dentists
Pharmacists
Nurses
Paramedical professionals
ADR reporting by layman is not
acceptable
Hint: As the volume decreases, the space where molecules can
move also becomes limited.
WHERE TO REPORT?
Duly filled suspected Adverse Drug
Reaction Reporting form can be
send to the nearest Adverse Drug
Reaction Monitoring centre (AMC) or
directly to the National Coordination
Centre (NCC).

22. ADR REPORTING
FORM

23. Age
Sex
And a brief
medical history of
the
consumer/patient
Patient details
species
name
(common
name or
brand
name)
part of the
plant used
manufacture
r
batch no.
expiry date
provider
Details of
suspected
herbal products.
dose
route of
administrati
on
quantity
supplied
dosage
form
Administration
details-
date of onset
description
with
symptoms
and signs
severity and
seriousness
dechallenge/
rechallenge
with the
same
product
Adverse reaction
data-
Details of
the
reporter
All other
medicines
used (
including self
medication)
with
administratio
n detail.
WHAT INFORMATION SHOULD BE REQUESTED?

24. 1
2
3
4
Information provided in this form is handled in
strict confidence.
The causality assessment is carried out at AMCs by using
WHO-UMC scale
The analyzed forms are forwarded to the NCC through
ADR database.
Finally the data is analyzed and forwarded to the global pharmacovigilance
Database managed by WHO Uppsala Monitoring Centr in Sweden.
WHAT HAPPENS TO THE SUBMITTED INFORMATION?

25. Quality assurance and control measures-
national quality specification
standards for herbal materials
GMP for herbal medicines
National regulation and
registration of herbal
medicines vary from
country to country.
Challenges in monitoring the safety of herbal medicines
Regulation Quality assurance and control
Herbal medicines
non-prescription
medicines
prescription
medicines
Weak regulations and quality control may result in a high incidence of adverse reactions
attributable to poor quality of herbal medicines, in particularly resulting from adulteration
with undeclared potent substances or contamination with potentially hazardous
substances and residues

26. Identification of unambiguos
Regulation
Incorrect dosing
Regulation

27. HERBAL DRUG
INTERACTIONS

28. Importance
Definition
The drug whose activity is effected
by such an interaction is called as a
"Object drug."
The agent which precipitates such
an interaction is refered to as the
"Precipitant"
Drug interaction is defined as the
pharmacological activity of one drug is
altered by the concomitant use of
another drug or by the presence of
some other substance.
An interaction is said to occur when the
effects of one drug is changed by the
presence of other drug,herb, food, drink
etc.
This action can be synergistic or
antagonist.
Drug interactions may be the result of
various processes.
These process may include alteration in
the absorption, distribution, metabolism
and excretion of drug.

29. Question 9
TYPES OF DRUG INTERACTIONS
PHARMACOKINETIC PHARMACODYNAMIC
DRUG INTERACTIONS
BIO DRUG-DRUG
INTERACTIONS
BIO DRUG-FOOD
INTERACTIONS

30. Changes in GI pH
Changes GI enzymes
Alteration of gut motility
Absorption interactions are those where the absorption of th object drug is altered.
Most clinically significant interactions occur due to the following factors-
ABSORPTION INTERACTION
object drug precipitant influence on object drug
penicilamine,
Ciprofloxacin
Antacids, food and mineral
supplements containing mg, fe,
zn and ca ions
Formation of poorly soluble and
unabsorbable complex with heavy
metal ions
PHARMACOKINETIC INTERACTIONS
Pharmacokinetic interactions are caused by alterations in the absorption , distribution, metabolism, or
excretion of drugs which results in altered levels of the drug or its metabolites.

31. Anti coagulants
Phenylbutazone, chloral
hydrate
Increased clotting time, increased risk
of haemorrhage
Tolbutamine Sulphonamides Increased hypoglycemic effect
DISTRIBUTION INTERACTION
Are those where the distribution pattern of the object drug is altered.
METABOLISM INTERACTION
Enzyme induction- incresed rate of metabolism
Enzyme inhibition- Decreased rate of metabolism.
Are those where the metabolism of the object drug is altered
Mechanism of metabolism interactions include-

32. ENZYME INDUCTION
Corticosteroids,
oral
contraceptives,
phenytoin
Barbiturates
Decreased plasma levels,
decreased efficasy of object drugs
ENZYME INHIBITION Coumarins Metranidazole Increased anti coagulant activity
Alteration in renal blood flow
Alteration in urine pH
Forced diuresis
Are those where the excretion pattern of the object drug is altered.
Major mechanism of excretion interactions are-
EXCRETION INTERACTIONS

33. Amphetamine
Antacids, Thiazides
cetazolemide
Incresead passive reabsorption of basic
drugs, Increased risk of toxicity
Lithium bicarbonate NSAIDS
Decreased renal clearance of lithium, risk
of toxicity

34. PHARMACODYNAMIC INTERACTIONS
Pharmacodynamic interactions are herb-drug interactions that cause changes in
pharmacological responses.
Herb-drug pharmacodynamic interactions involve
changes in the pharmacological effects of the drug through additive, synergistic
or antagonistic actions
For example, ginger, garlic, ginseng, alfalfa, ginkgo, chamomile (Matricaria
recutita), and danshen may enhance the anticoagulant activity of warfarin
by targeting the same vitamin K epoxide reductase target

35. BIO DRUG DRUG INTERACTIONS
Drug-drug interactions occurs when a drug interacts or interferes with
another drug.
This can alter the way one or both of drugs act in the body or cause
unexpected side effects.
Aspirin + Warfarin= excessive bleeding time ( synergism)
Codeine + Paracetamol + Increased analgesic effect ( additive effect)
Antibiotic + Blood thinner + less effect ( antagonist)
E.g.,

36. BIO DRUG- FOOD INTERACTIONS
Adrug-food interactions happens when the foof you eat affects the ingredients on a
medicine you are taking so the medicine cannot work the way it should.
Aspirin + milk + stomach upset
Acetoaminophen + Alcohol = Liver damage
Tetracycline + Calcium rich food = decrease absorption of drug
Caffein + food = rapid heart rate
E.g.,

37. Thank you for listening!