Pharmacovigilance is the science of detecting, assessing, understanding, and preventing adverse effects of drugs. It involves monitoring drugs post-marketing to identify unknown or rare adverse drug reactions. Spontaneous reporting from healthcare professionals is a major method for identifying potential safety issues with drugs after approval. Other methods include active surveillance through sentinel sites, registries, and comparative observational studies which can help validate signals from spontaneous reports. International systems like INNs and ICD codes help standardize drug nomenclature and classification of adverse events globally.

1. PHARMACOVIGILANCE
PRESENTED BY -
SUDIPTA PATTANAIK
DEPT OF PHARMACOLOGY

2. Pharmaco (Greek): drug
Vigilance (Latin): –to keep awake or alert
–to keep watch
–the process of paying close and continuous
. attention
Definition:
PV is the science and activities dealing with the detection,
assessment, understanding and prevention of adverse effects
of drugs. It has been widened to include biological products,
herbals, traditional and complementary medicines.

3. ADVERSE DRUG REACTION
o Adverse Drug Reaction: A response to a drug which is
noxious and unintended at the therapeutic level i.e. occurs at
doses normally used in man for the prophylaxis, diagnosis, or
therapy of disease, or for the modification of physiological
function.
o Adverse Event: Any untoward medical occurrence that may
present during treatment with a pharmaceutical product but
which does not necessarily have a causal relationship with the
treatment.
o Side Effect : Any unintended effect of a pharmaceutical
product occurring at doses normally used in man which is
related to the pharmacological properties of the drug.

4. Severity of ADR:
• Minor: No need of therapy, antidote, or hospitalization
• Moderate: Requires drug change , specific treatment,
hospitalization.
• Severe: Potentially life threatening, permanent damage, and
prolonged hospitalization.
• Lethal: Directly or indirectly leads to death.

5. TRADITIONALLY Classification
• TYPE-A (Augmented)
• TYPE-B (Bizarre)
• TYPE-C (continuous)
• TYPE-D (delayed)
• TYPE-E (End of Dose)
• TYPE-F (Failure of therapy)
• TYPE-G (GENOTOXICITY)
• TYPE-H (HYPERSENSITIVITY)
• TYPE-U (UN CLASSIFIED)

6. TYPE-A (Augmented)-
• Commonest (up to 70%) – Dose dependent, severity
increases with dose.
• Preventable in most part by slow introduction of low
dosages.
• Predictable by the pharmacological mechanisms,
• e.g., hypotension by beta-blockers,
• hypoglycemia caused by insulin or oral hypoglycemic,
• NSAID induced gastric ulcers.
TYPE-B (Bizarre)-
• Rare, idiosyncratic, genetically determined, unpredictable,
mechanisms are unknown, serious, can be fatal; unrelated to
the dose,
• e.g. ,hepatitis caused by halothane,

7. • aplastic anemia caused by chloramphenicol
• neuroleptic malignant syndrome caused by some
anesthetics and antipsychotics.
TYPE-C (continuous)-
• Occurs as a result of continuous drug use.
• May be irreversible, unexpected, unpredictable,
• e.g., Tardive dyskinesia by antipsychotics,
• dementia by ant cholinergic medications.
TYPE-D (delayed)-
• Delayed occurrence of ADRs, even after the cessation of
treatment.
• ophthalmopathy after chloroquine

8. TYPE-E (End of Dose)-
• Withdrawal reactions . Occurs typically with the depressant
drugs.
• seizures on alcohol or benzodiazepines withdrawal;
TYPE-F (Failure of therapy)
• Results from the ineffective treatment .
• e.g., accelerated hypertension because of inefficient
control.

9. PREDISPOSING FACTORS FOR ADRs
The main clinical factors which increase the chance that
patients will experience an adverse reaction are listed below:
 Age - the elderly and neonates are at greatest risk
 Gender - women are generally at greater risk
 Race - ethnic origin may affect drug metabolism
Impaired excretory mechanisms
reduced hepatic and/or renal function
 Polypharmacy
drug interactions
 Any previous history of an adverse drug reaction

10. How to recognize ADRs-:
• Ensure, medicine received & actually taken by the patient
at the dose advised .
• Verify the onset of suspected ADR is after taking the drug.
• Determine the time interval between drug taken – onset of
event.
• Evaluate the suspected ADR after discontinuing the drug /
reduced dose, monitor status.
• Analyse the alternate cause (other than the drug).
• Use relevant literature & experienced physician opinion &
information PV center.
• Report the ADR.

11. • WHAT TO REPORT ?
• WHO SHOULD REPORT
• WHEN TO REPORT
• HOW TO REPORT
• WHERE TO REPORT

12. WHAT TO REPORT ?
• Any undesirable adverse event suspected to be associated
with use of drug.
• Include - All ADRs as a result of prescription and non-
prescription .
• All ADRs – irrespective of the used (acc with PI provided by
company) .
• Unexpected reactions - regardless of their nature or
severity.
• ADRs-in special field – drug abuse, drug use – pregnancy /
lactation.
• ADRs occurring from overdose or medication error.

13. WHO SHOULD REPORT ?
• doctors, dentists, pharmacists, nurses, assistant medical
officers, clinical officers, pharmaceutical technicians,
pharmaceutical assistants, traditional medicine practitioners
and others health care providers.
WHEN TO REPORT ?
• Any suspected ADR should be reported as soon as possible.
• Delay in reporting will make reporting inaccurate and
unreliable.
• If possible, report while the patient is still in the health
facility this gives a chance to reporter to clear any ambiguity
by re-questioning or examining the patient

14. WHERE TO REPORT ?
• Please return the completed form to the nearest
Adverse drug reaction Monitoring Centre (AMC) or to
National Coordinating Centre
• A list of nationwide AMCs is available at:
• http://cdsco.nic.in/pharmacovigilance.htm
HOW TO REPORT ?
• CDSCO suspected ADR Reporting Form.

15. INTERNATIONAL CLASSIFICATION OF DISEASES-:
• International statistical classification of diseases and related
health problems in short “ICD” is the international standard
diagnostic tool for epidemiology, health management and
clinical purposes.
• ICD is designed as health care classification system which
provides the diagnostic codes for classifying diseases
including classification of wide variety of signs, symptoms,
abnormal findings, complaints, social circumstances and
external cause of injury or disease.
Historical synopsis-
• In 1860, Florence nightingale →made first model of
systemic collection of hospital data.

16. • In 1893, French physician, Jacques Bertillon→ introduced
Bertillon classification of cause of death
• In 1898, American public health association→
recommended revision of ICD system every 10 years.
• The revision followed minor changes until 6th version of
ICD→ morbidity and mortality condition and section on
mental disorders
• WHO →responsibility for preparing and publishing the ICD
revisions every 10 years.
• The ICD -10 was formed in 1893, as the Bertillon
classification of international list of causes of death.
• The work on ICD -10 started in 1983 → approved in 1990 at
43rd world health assembly (WHA)

17. Classification (ICD-10)
The ICD -10 is arranged in 21 major chapters
1.Certain Infectious and parasitic diseases.[A00- B99]
2.Neoplasms [C00-D48]
3.Diseases of the blood and blood forming organs and certain
disorders involving the immune mechanism[D50 -D89]
4.Endocrine nutritional and metabolic diseases [E00-E90]
5.Mental and behavioral disorders [F00-F99]
6.Disorders of the nervous system [G00-G99]
7.Diseases of eye and adnexa [H00-H99]
8.Diseases of the ear and mastoid process [H60-H95]
9.Diseases of circulatory system [I00-I99]
10. Diseases of respiratory system [J00-J99]

18. 11. Diseases of digestive system [K00-K99]
12. Diseases of the skin and subcutaneous tissue [L00L9913].
Diseases the musculoskeletal system and connective
tissue[M00-M99].
14. Diseases of genitourinary system [N00-N99].
15. Pregnancy , childbirth and puerperium [O00-O99].
16. Certain conditions originating in perinatal period
[P00P96].
17. Congenital malformations, deformations and
chromosomal abnormalities [Q 00- Q99].
18. Symptoms, signs and abnormal clinical and laboratory
findings, not elsewhere classified [R00-R99].
19. Injury, poisoning [S00-T98].
20. External causes of morbidity and mortality [V01-Y98].
21. Factors influencing health status and contact with health
services . [Z00-Z99].

19. THE CODING SYSTEM-
• The first character of the ICD -10 code is a letter and each
letter is associated with a particular chapter except for letter
D, which is used in chapter 2 and chapter 3, and letter H
which is used in chapter 7 and chapter 8.
• Chapter 1, 2, 19, 20 use more than one letter in the first
position of their codes .
• Each chapter contains sufficient 3 character categories to
cover its contents .
• Most of the 3 character categories are subdivided by means
of a 4th numeric character after a decimal point, allowing up
to 10 subcategories.

20. Z 22 –carriers of infectious diseases
• Z22.0 –carrier of thyroid
• Z22.1 –carrier of intestinal infectious diseases
• Z22.2 –carrier of diphtheria
• Z22.3 –carrier of specific bacterial diseases
• Z22.4 –carrier of infections with predominantly sexual mode
of transmission
• Z22.5 –carrier of viral hepatitis
• Z22.6 –carrier of human T- lymphotropic virus type 1(HTLV-
1) infection
• Z22.8 –carrier of other infectious diseases
• Z22.9 –carrier of infectious disease, unspecified
Example
Chapter 21–factors influencing health status and contact with
health services [Z00 - Z99]

21. Z 72.0 – tobacco use
Z 72.1 – alcohol use
Z 72.2 – drug use
Z 72.3 – lack of physical exercise
Z 72.4 – Inappropriate
Z 72.5 – high risk sexual behavior
Z 72.6 – gambling and betting
Z 72.8 – other problems related to life style
Z 72.9 – problem related to life style, unspecified
Z 72- Problems related to life style

22. INTERNATIONAL NONPROPRIETARY NAMES--:
•Drugs are generally marketed by their brand names though
there is a legal requirement to mention generic names in the
labels. Countries have their own systems of generic
nomenclature for pharmaceutical substances. However owing
to the various languages used by different national
nomenclature systems, there is a need to have a uniform
standardized system of generic names that are accepted
worldwide, which would help in identifying the composition
of a pharmaceutical substance.
• The WHO administers an international generic
nomenclature system called INNs also known as rINN, for
recommended International Nonproprietary Name or pINN
for proposed International Nonproprietary Name.

23. • International Nonproprietary Names (INN) facilitates the
identification of pharmaceutical substances or active
pharmaceutical ingredients. Each INN is a unique name that is
globally recognized and is public property. A nonproprietary
name is also known as a generic name.
THE INN SYSTEM
• Initiated in 1950 by a World Health Assembly resolution
• Began operating in 1953
• Cumulative list of INN now stands at some 7000 names
designated since that time
• 120-150 new INN

24. AIM OF THE INN SYSTEM
• To provide health professionals with a unique and
universally available designated name to identify each
pharmaceutical substance.
• For the clear identification, safe prescription and dispensing
of medicines to patients.
• For communication and exchange of information among
health professionals and scientists worldwide.
• Nonproprietary names are intended for use in Parma,
labeling, product information, advertising and other
promotional material, drug regulation and scientific literature,
and as a basis for product names, e.g. for generics

25. SELECTION OF INN-
• The names which are given the status of an INN are selected
by the World Health Organization on the advice of experts
from the WHO Expert Advisory Panel on the International
Pharmacopoeia and Pharmaceutical Preparations.
• The process of INN selection follows three main steps:
- a request/application is made by the manufacturer or
inventor;
- after a review of the request a proposed INN is selected
and published for comments;
- after a time-period for objections has lapsed, the name
will obtain the status of a recommended INN and will be
published as such if no objection has been raised. Since the
name is available in the public domain it may be used freely.

26. HOW
• INN is designated for the active part of the molecule only, to
avoid the multiplication of entries in cases where several
salts, esters, etc. are actually used. In such cases, the user of
the INN has to create a modified INN (INNM).
• Ex: mepyramine maleate (a salt of mepyramine with maleic
acid)
• The primary principles for selection:
Distinctive in sound and spelling;
Not too long; and
Not liable to confusion with other names in common use.
Ex: anti-inflammatory agents, COX-2 inhibitors, a type of
anti- inflammatory drugs (e.g. celecoxib )

27. • Do not select names for mixtures of substances.
• Do not select for herbal substances (vegetable drugs) or for
homoeopathic products.
• Do not select names for those substances that have a long
history of use for medical purposes under well established
names such as those of alkaloids (e.g. morphine, codeine), or
trivial chemical names (e.g. acetic acid)

28. ADR Detection Methods
• Passive surveillance
Spontaneous reporting system (SRS)
Case series
• Stimulated reporting
• Active surveillance
Sentinel sites
Drug event monitoring
Registries

29. • Targeted clinical investigations
Descriptive studies
Natural history of disease
Drug utilization study
• Comparatives observational studies
Cross sectional study
Case control study
Cohort study

30. SPONTANEOUS REPORTS-
A communication by consumers or health care professionals
to a company or Regulatory Authority that describes one or
more ADR in a patient who was given the drug.
Plays a major role in the identification of safety signals once
the drug is marketed.
 Gives alerts on rare AEs that were not detected in earlier
clinical trials or pre marketing studies.
 Provides important information on at risk groups, risk
factors and clinical features of known serious ADRs.
CASE SERIES-
Series of case reports can provide evidence of an
association of a drug and AE.
 Generally more useful for generating hypothesis than for
verifying an association between drug exposure and outcome.

31. Certain distinct adverse events occur more frequently with
drug therapy, such as anaphylaxis, aplastic anaemia , toxic
epidermal necrosis and Stevens- Johnson Syndrome.
STIMULATED REPORTING-
 A method used to encourage and facilitate reporting by
health professionals for new products.
On line reporting of AE; Systematic stimulation of reporting
of AE.
Limitations
 Data are often incomplete. Not useful to generate accurate
incidence rates.

32. ACTIVE SURVEILLANCE-
 More feasible to get comprehensive data on individual AE
reports.
 To ascertain completely the number of AE via a continuous
preorganised process. E g : Follow up of patients treated with
a particular drugs.
SENTINEL SITES-
Active surveillance carried out at Institutions, Nursing
homes, hospitals etc.
Provide information such as data from specific patient
subgroups, drug abuse etc.
Limitation
Selection biasness, Small number of patients and Increased
costs.

33. DRUG EVENT MONITORING-
Patients are identified by electronic prescription data or
automated health insurance claims.
 A follow up questionnaire can be sent to each physician or
patient at specified intervals.
Information on patient demographics, indication for
treatment, duration of therapy (including start dates), dosage,
clinical events, and reasons for discontinuation can be
included in the questionnaire.
Limitations:
 Poor physician and patient response rates and unfocused
nature of data collection can obscure important signals.

34. REGISTRIES-
 A registry is a list of patients presenting with same
characteristics.eg: Disease registry, drug registry or pregnancy
registry.
 Differ from each other depending on type of patient.
 Information can be obtained by using standard
questionnaire.
COMPARATIVE OBSERVATIONAL STUDIES-
 Traditional epidemiologic methods are a key component in
the evaluation of adverse events.
Observational study designs are useful in validating signals
from spontaneous reports or case series.

35. Types of designs
•Cross sectional study.
•Case control study.
•Cohort study
Cross-sectional study (survey)-
Data collected from a population of patients at a single
point in time (or interval of time) regardless of exposure or
disease status.
 Primarily used to gather data for surveys or for ecological
analyses
Major drawback:
 Relationship between exposure and outcome cannot be
directly addressed.

36. Case-control study
Cases of disease (or events) are identified.
 Controls, or patients without the disease or event of
interest, are then selected from the source population.
The controls should be selected : the prevalence of
exposure among the controls represents the prevalence of
exposure in the source population.
 Exposure status of the two groups is then compared.
Cohort study
A population-at-risk for the disease (or event) is followed
over time for the occurrence of the disease (or event).
 Information on exposure status is known throughout the
follow-up and hence incidence rates can be calculated

37. Comparison cohorts of interest are selected on the basis of
drug use and followed over time.
 Multiple adverse events can also be investigated using the
same data source in a cohort study.
Descriptive studies
Primarily used to obtain the background rate of outcome
events and/or establish the prevalence of the use of drugs in
specified populations.
Natural history of disease:
Focused on the natural history of disease, including the
characteristics of diseased patients and the distribution of
disease in selected populations, as well as estimating the
incidence and prevalence of potential outcomes of interest.

38. Drug utilization study:
These studies provide data on specific populations, such as
the elderly, children, or patients with hepatic or renal
dysfunction, often stratified by age, gender, concomitant
medication, and other characteristics.

39. FORMS FOR REPORTING ADRs IN DIFFERENT COUNTRIES:
Yellow Card Scheme
• UK system for collecting information on suspected ADRs.
• Founded in 1964 after the thalidomide
• Essential information to include on a yellow card
1.Patient details 2.Suspected drug 3.Suspected reaction
4.Reporter details
• Why is the yellow card scheme important?
.Acts as an early warning system for the identification of
previously unrecognized reactions
.Enables to identify risk factors, outcomes of the ADR and
other factors that may affect clinical management

42. ADR REPORTING THROUGH VIGIFLOW
• VigiFlow is a web-based Individual Case Safety Report (ICSR)
management system
•Specially designed for use by national centers in the WHO
Programme for International Drug Monitoring.
•VigiFlow 5.1(Released on 14 June 2013)
• Subscription for VigiFlow is free in India.
• Other tools:
ARISg (mainly used by Drug manufacturer in Europe)
Argus (mainly used by Drug manufacturer in USA