Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other medicine/vaccine-related problem.  All medicines and vaccines undergo rigorous testing for safety and efficacy through clinical trials before they are authorized for use. The clinical trial process involves studying these products in a relatively small number of selected individuals for a short period of time. Certain side effects may only emerge once these products have been used by a heterogenous population, including people with other concurrent diseases, and over a long period.

1. PHARMACOVIGILANCEOFDRUGS
OFNATURALORIGIN
BY- DURGASHREE.M.D
M.PHARM, PHARMACOGNOSY
KLE COLLEGE OF PHARMACY, BENGALURU
1

2. CONTENT
• Introduction
• WHO and AYUSH Guidelines for Safety Monitoring of Natural Medicine.
• Spontaneous Reporting Scheme for Bio-drugAdverse Reaction
• Drug Interaction
• Bio Drug-DrugInteraction
• Bio Drug-Food Interaction
2

3. Pharmacovigilance
• Pharmacovigilanceis the scienceand activities relatingto the detection,
assessment,understanding, and prevention of adverseeffects or any other
medicine/vaccine-relatedproblem.
• All medicinesandvaccinesundergo rigorous testing for safetyand efficacy
through clinicaltrials before they are authorized for use.
• The clinical trial process involves studying these products in a relativelysmall
number of selectedindividualsfor a short period of time.
• Certain sideeffects may only emerge once these products have been used by a
heterogenous population, includingpeople with other concurrent diseases,and
over a long period. [1]33
3

4. 4

5. 5

6. PharmacovigilanceofNaturalDrugs
• Herbal formulations are widelyacceptedtherapeutic agents as antidiabetics,
antiarthritics, hepatoprotectives, cough remedies, etc….
• The common myth regardingherbal medicinesis that these medicinesare
completely safe, andcan therefore be safelyconsumed by the patient on his/her
own, without a physician'sprescription.
• This belief has led to large-scaleself-medication by people all over the world,
often leading to disappointingresults, side-effects.
6

7. CONT.
Unwanted effects such as:
• Some herbal products were found to contain 0.1 to 0.3 mg of betamethasone per capsule
after some patients developed corticosteroid-like 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, associated with the use of Ginkgo biloba.
7

8. CONT.
• Pharmacovigilanceis extended to herbal, traditional, and
complementary medicines,biologicals, vaccines,blood products,
and medicaldevices.
• In order to provide consistencyin the naming of herbs in adverse
reaction (AR) reports, the WHO Collaborating Centre for International
Drug Monitoring has recommendedthe use of proper scientific
binomial names for herbs used in medicine,including the use of such
names in the coding of AR reports.
• This would ensure comparability between reports from various
international pharmacovigilancedatabases.
• Published case reports would also benefit from analysisof the
suspect product used, for contamination and adulteration, or species
identification, where possible. [2]
8

9. SafetymonitoringofNaturalMedicines
• Drug safety monitoring is a riskmitigationexercisein whichthe ADRs causedby
therapeuticdrugs,biologicals, or devicescan explore, prevented, or minimized.
• It is the process of identifying expected and unexpected adversereactions
resulting from the use of medicinesin the post-marketing phase. [3]
9

10. CHALLENGES INSAFETY MONITORINGOFHERBAL DRUGS
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11. CHALLENGES INSAFETYMONITORINGOFHERBAL DRUGS
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12. 12

13. WHOandAYUSH Guidelines
• WHO has taken the lead in tacklingthe needfor drug safety monitoring since
1970.
• The WHO International Drug Monitoring Programme, together with the WHO
Collaborating Centre in Sweden, the UppsalaMonitoring Centre (UMC).
• This has instituted a coherent programme of action for pharmacovigilance,
which includesthe establishment of a
-programmefor exchangeof safety information,
-maintenanceof the global WHOdatabase of adversedrug
reaction (ADR)reports,
-the provision of numerous guidelines on monitoring drug safety.
• It also seeksto bridge the gap between industry and regulatory authorities.
13

14. UMC- UPPSALA MONITORINGCENTER
• The case reports will be receivedby WHO from
National PharmacovigilanceCenter.
• Thesecase reports and databaseswill be managed
by UMC.
• It uses global WHOdatabase to identify/detect
signals of new ADR.
• They will assessand inform National
PharmacovigilanceCenter about Drug safety. [5]
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15. UMCFUNCTIONS
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16. NATIONALPHARMACOVIGILANE CENTER
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17. 17

18. Objectives:
To strengthen national pharmacovigilancecapacityin order to carry out effective
safety monitoring of herbal medicines
Provide technical guidance on the principlesof good pharmacovigilance,
To facilitate the establishment of an inclusive national drug safety monitoring
system
Provide standarddefinitions of terms relatingto pharmacovigilanceand safety
monitoring of herbal medicines
Promote and strengthen internationally coordinated information exchangeon
pharmacovigilanceand safety monitoring of herbal medicinesamong the Member
States
Promote the safe andproper use of herbal medicines. 18

19. 19

20. a.Sources ofReports
The most common sources of information on adverse events and reactions to
medicinesare clinicaltrials and spontaneous reports.
In many countries, providersof herbal medicinesother than physicians,dentists,
pharmacists,and nurses are excludedfrom reporting systems.
If it is to be achieved,national reporting schemesshould be developed.
This includesall providers of herbal medicines(both prescribersand dispensers),
and providers of traditional, complementary,and alternative medicine,according
to national circumstances
20
SAFETYMONITORINGOFHERBALMEDICINE

21. CONT.
1. Reports from healthcare professionals
• Internationally, adverse drug reaction reporting systemsin the post-marketing
safety surveillance setting dependsprimarilyon healthcare professionals,
(preferablythose directly associatedwith the care of the patient/consumer).
• This is appropriate since the understandingof adversedrug reactions dependson
medicalknowledge and such professionals should be aware of the patient’s
medicalhistory andclinicaldifferential diagnosis.
• Community pharmacistsand nurses can play a particularly useful role in
monitoring the safety of non-prescriptionmedicines.
21

22. CONT.
2. Reports from consumers
• Consumer reports on adversereactions should be
acceptedas a serious source of information.
• This can contribute to the identification of signals for
unknown effects of herbalmedicines.
• For non-prescriptionmedicines,often taken without
health professional involvement.
• Reports receiveddirectlyfrom consumers may provide
the only source of signals.
• With herbal medicinesin the non-prescription
medicines,there is an essentialrole for consumer
reporting.
22

23. CONT.
3. Report from Manufacturer
• Manufacturers of herbal medicinescould be a source of information on adverse
events associatedwith their products.
• Some countries include reporting of adverseevents by manufacturers as part of
their regulatory framework.
• Consumers may report directlyto companies or their representatives.
23

24. CONT.
4. Reports from other Sources
Problems associated with herbal medicinesmay be reported as toxicity to the
following.
• National poisons centre: A poisons centre could play a core role in
pharmacovigilancefor and safety monitoring of herbalmedicines.
• Drug information centre: It may also be the first point of contact and mayprovide a
wealth of clinicalinformation. The National pharmacovigilance centre should have
a good level of communication with such centre.
• Consumer organizations: It receivescomplaints about any type of product in the
marketplaceand may obtain relevant information about herbalmedicines.
• Clinical trials and studies can also be a source of information.
24

25. CONT.
25

26. b.HerbalProductTargetedforSafetyMonitoring
To obtain comprehensivecoverage,it is useful to think of herbal products in the
following categories:
accordingto their regulatory status
– herbal medicinesin the prescription medicinescategory
– herbal medicinesin the non-prescriptionmedicinescategory
accordingto their registration/marketing status
– herbal medicinesundergoing the new drug development process: in clinicaltrials
prior to national drug regulatory approval.
– herbal medicinesundergoing the new drug development process: under post-
marketingsafety surveillance
26

27. c.ReportingsuspectedAdversereactions
Reports should be sent to the appropriate centre by the
particular national reporting scheme.The following should
provide reports.
Health professionals who are providers of herbal medicines,
including physicians,pharmacistsand nurses, should report
to the national pharmacovigilancecentre.
Patients/consumers should normally report to their
physiciansor providers of herbal medicines.They mayalso
report directly to the national pharmacovigilancecentre,
consumer organizations or manufacturers.
Manufacturers should report directly to the national
pharmacovigilancecentre or national regulatory authority.
27

28. d.Assessment ofCase Report
Assessment of reports on adverse reactions to herbal medicines should be undertaken by
national pharmacovigilance centers in the same way as for other medicines.
A change in the procurement sources of herbal materials, misidentification of the
medicinal plant and/or herbal material used, or a change in the mode of preparation may
lead to entirely preventable and sometimes serious adverse reactions. This should be
taken into account when assessing individual cases.
Use of an advisory committee Each national pharmacovigilance center should have an
advisory committee composed of experts to advise on:
♦ Maintaining quality standards in data collection and assessment procedures
♦ Data interpretation
♦ Publication of information
♦ Follow-up action required.
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29. e.DataManagement
Dataquality: Strenuous efforts should be madeto ensure that there arequality
controls on data processingand that the data elements of reports are as complete
and accurateas possible.
Data storage: Computer databasesshould be managed to as high a standardas
possible to facilitate accessto and use of the data. Software should be selected
with expert adviceso that analyticalneedscan be met.
Data analysis:Programs should be developedto provide for regular analysesand
data output appropriate for local needs.
29

30. CONT.
Analysis of the global WHOdatabase:The global WHO databasemanagedby UMC
is being improvedbasedon the proposed “Database management and
classificationfor codingof herbal medicines”.
Support on technical and datamanagement is availablefrom the WHO
Collaborating Centre for International Drug Monitoring, UMC (http://www.who-
umc.org/).
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31. The successful safety monitoring of herbal medicinesdependson
good communication.
There is distrust between some and ignorance of the work and
function of different groups.
Transparentcommunication is essentialto overcome these
problems andensure that all players collaborate to meet the goal
of the safe and effective use of herbal medicines.
Centers should ensure that manufacturers receivetimely
information.
Effective communication of the results of monitoring is also
essentialso that pharmacovigilanceactivitiescan havea positive
impact. [4]
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COMMUNICATION

32. 32

33. SPONTANEOUSREPORTING SCHEME
• Spontaneous reporting is by nature a
passiveapproach to
pharmacovigilance(PV),
• Relyingentirely on the motivation of
individualsto report suspected adverse
drug reactions (ADRs)to a local or national
pharmacovigilancecenter.
33

34. CONT.
General Policy Issues:
• Consumers should be encouraged to report a personal
adversereaction.
• Neither company nor regulator should refer consumer or
patient to a specifichealth care professional.
• ADR should preferably be reported by the Doctor, not by
Thirdparties like a relative of the patient, advocate, etc.
34

35. CONT.
Periodical safety update reports
35

36. MODELREPORTINGFORM
• ADR reporting is an important aspect of an efficient and effective
pharmacovigilanceprogram.
• Although Medwatch,YellowCard,CDSCO form,etc. are the protocol forms of ADR
collection andreports, several countries design and use their respectiveADR
forms. [7]
36

37. CONT.
General considerationof Reporting Form:
• Reporting form for herbalmedicinesshould be the same as other medicines.
• Only basic and important information should be requested.
• Form should be in a simple format. It should have plenty of “white space”.
• It should includethe instruction, on how to complete it.
• This will be used as evidencein the screeningprocess.
• Accurate identification of patient /consumer is important to avoid duplication
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[7]

45. DRUGINTERACTION
• Drug-drug interactions occur when two or more drugs react with each other. This
drug-drug interaction may cause you to experiencean unexpected side effect.
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46. HERB-DRUG INTERACTION
• Herb–drug interaction can occur through the synergisticor additiveactions of
herbal products with conventional medications as a result of affinities for
common receptor sites.
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48. EXAMPLESOF
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49. Sl.
no
HERB ALLOPATHIC DRUG INTERACTIONS
1. Aloe latex Glyburide Lowers blood sugar level
2. Aloe gel Hydrocortisone Enhance the effect of hydrocortisone
to reduce swelling.
3. Aloe latex Digoxin Decrease the level of Potassium.
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ALOE WITHOTHERMEDICATIONS

50. GARLIC WITHOTHERMEDICATION
Sl.
no
Herb Drug Interaction
1. Garlic Indomethacin (Antiplatelet) It exaggerate action of medication and inhibit the
action of platelets
2. Garlic Warfarin Increase risk of bleeding
3. Garlic Indinavir, ritonavir,
etc.(Protease inhibitor)
Reduce blood levels of protease inhibitor
50

51. TURMERIC WITHALLOPATHIC DRUGS
Sl.
no
Herb Drug Interaction
1. Turmeric Cimetidine, Omeprezol Increase production of stomach acid.
2. Turmeric Diabetic medicine Lowers the blood sugar
3. Turmeric Warferin, clopidogrel Risk of bleeding
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52. OTHEREXAMPLES
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53. BIODRUG- FOODINTERACTION
• Food-drug interactions are definedas alterations of pharmacokineticsor
pharmacodynamicsof a drug or nutritional element or a compromise in nutritional
status as a result of the addition of a drug. [8]
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54. CONT.
54

55. CONT.
55

56. CASESTUDIES
1. Effect of gingeron metronidazole:
• Patient X reported, he had tremors in his handand a metallic taste in the mouth
along with sharp pain in the upper abdomen.
• Drug chart- currently he is takingmetronidazole to cure the infestation.
• Diagnosisof the symptoms- due to increasingin C-maxof the drug taken.
• Cause- food habits.
• Assessmentof food habits- patient consumed a large quantity of gingerbread
before taking metronidazole.
• Corrective action- he was advisednot to take ginger and drug at the same time at
least a time gap of 8-48hours.
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57. CASESTUDIES
2. Hydrocortisone ad diosgenin:
• A patient Ywas suffering from a skin allergy,she was reported to take
Hydrocortisone.
• She reported symptoms like irregular mensuration, increasedsweating, bloating
of the stomach.
• Cause- effects are from consuming increasedsteroids.
• Determination of causeof symptoms-due to food habits.
• Food chart determination- patient consumed dietary supplement having high
diosgenin (Diosgeninis a steroid congaingherb)
• Final assessment-high levels of steroids.
• Corrective action- do not consume diosgenin and steroid together. [5]
57

58. REFERENCES
58
1. Pharmacovigilanceby WHO.(https://www.who.int/teams/regulation-prequalification/regulation-
and-safety/pharmacovigilance)
2. Pharmacovigilanceof Herbal Products in India.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159283/)
3. Drug Safety Monitoring. (https://www.jliedu.com/blog/drug-safety-monitoring/)
4. WHO Guidelineson Safetymonitoring HerbalMedicinesin PharmacovigilanceSystems.
(https://apps.who.int/iris/bitstream/handle/10665/43034/9241592214_eng.pdf)
5. Textbook of Advancepharmacognosy I- Dr. DeenanathJhade
6. Comparative evaluationof ADR.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487270/#:~:text=ADR%20reporting%20is%20an%2
0important,use%20their%20respective%20ADR%20forms.)
7. Adversedrug reaction-relatednotification. – CDSCO.
(https://cdsco.gov.in/opencms/opencms/en/Notifications/Adverse-Drug-Reaction-related-
Notifications/)
8. Food and drug interaction: consequences.
(https://pubmed.ncbi.nlm.nih.gov/18382075/#:~:text=Food%2Ddrug%20interactions%20are%20define
d,the%20addition%20of%20a%20drug.)

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