pharmacovigilance

2. WHO DEFINITION:
 The science and activities relating to the detection,
assessment, understanding and prevention of adverse
effects or any other drug-related problem.
 pharmakon (Greek), “drug;” and vigilare (Latin), “to
keep awake or alert, to keep watch.”
 This applies throughout the life cycle of a medicine
equally to the pre-approval stage as to the post-
approval.

3. AIMS OF PHARMACOVIGILANCE
 Early detection of hitherto unknown adverse reactions
and interactions
 Detection of increases in frequency of (known) adverse
reactions
 Identification of risk factors and possible mechanisms
underlying adverse reactions
 Estimation of quantitative aspects of benefit/risk
analysis and dissemination of information needed to
improve drug prescribing and regulation.

4.  Improve patient care and safety in relation to the use of medicines, and
all medical and paramedical interventions
 Improve public health and safety in relation to the use of medicines
 Contribute to the assessment of benefit, harm, effectiveness and risk of
medicines, encouraging their safe, rational and more effective (including
cost-effective) use
 Promote understanding, education and clinical training in
pharmacovigilance and its effective communication to the public.

5.  The Central Drugs Standard Control Organization (CDSCO),
Directorate General of Health Services under the aid of Ministry of
Health & Family Welfare, Government of India in collaboration with
Indian Pharmacopoeia commission, Ghaziabad has
started Pharmacovigilance programme for protecting the health of
the patients by assuring drug safety in India.
 The programme is coordinated by the Indian Pharmacopeia
commission, Ghaziabad as a National Coordinating Centre (NCC).
The centre operates under the supervision of a Steering Committee
headed by the Drug Controller of India.

8. CDSCO Headquarter is responsible for:
 Taking appropriate regulatory decision and action regarding drug
safety
 Propagating medicine safety related decisions to stakeholders
 Provide administrative and Technical support to run PvPI
Regional Centres under PvPI
 Eastern Region: IPGMER, Kolkata
 Western Region: KEM Hospital, Mumbai
 Northern Region: PGIMER, Chandigarh
 Southern Region: JSS Hospital, Mysore

11.  Adverse Drug Reaction: A response to a drug which is noxious
and unintended, and which occurs at doses normally used in man
for the prophylaxis, diagnosis, or therapy of disease, or for the
modification of physiological function.
 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 this
treatment.
 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.

13.  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
MODERATE
SEVERE
LETHAL
LETHAL

14.  Abnormal pharmacokinetics due to
genetic factors
Co-morbid disease states
 Synergistic effects between either
a drug and a disease
two drugs

15. PREDISPOSING FACTORS FOR
ADRs
 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
 Specific diseases - e.g. asthma and beta-blockers
 Poly-pharmacy - drug interactions
 Any previous history of an adverse drug reaction.
 Lack of formal system for monitoring ADRs
 Reporting is not mandatory to clinicians

16. Various Algorithms/methods can be
adopted for causality assessment:
Naranjo’s algorithm
Kartch Lasagna’s algorithm
WHO probability scale
Spanish quantitative imputation scale
Kramer's scale
Jones scale
European ABO system
Bayesian system

19. INTERPRETATION:
 Total scores of 9 or more mean that ADR is highly
probable.
 Scores from 5 to 8 mean that ADR is probable.
 Scores from 1 to 4 that ADR is possible.
 Scores of zero or less mean that ADR is doubtful

20. WHO probability scale
Certain
 Event or laboratory test abnormality with plausible time
relationship to drug intake
 Cannot be explained by disease or other drugs
 Response to withdrawal plausible (pharmacologically,
pathologically)
 Event definitive pharmacologically or phenomenologically
(An objective and specific medical disorder or recognised
pharmacological phenomenon)
 Rechallenge (if necessary)

21. Probable
 Event or laboratory test abnormality with reasonable time
relationship to drug intake
 Unlikely to be attributed to disease or other drugs
 Response to withdrawal clinically reasonable
 Re-challenge not necessary
Possible
 Event or laboratory test abnormality with reasonable time
relationship to drug intake
 Could also be explained by disease or other drugs
 Information on drug withdrawal lacking or unclear

22. Unlikely
 Event or laboratory test abnormality with a time
relationship to drug intake that makes a connection
improbable (but not impossible)
 Diseases or other drugs provide plausible
explanations
Conditional / Unclassified
 Event or laboratory test abnormality
 More data for proper assessment needed
 Or additional data under examination

23. Pharmacist
Doctor
Dentist
Nurse
Drug manufacturer
Other health
care professionals

24. Whom to Report?
 Use the ‘Suspected Adverse Drug Reaction Reporting
Form’ to report any ADR
 Form available in all AMCs or download from
www.ipc.gov.in or www.cdsco.nic.in
 The filled reporting form can be submitted to the AMC
or directly to the NCC
 A reporter can also mail the form at
pvpi.ipcindia@gmail.com
 Toll free number 1800-180-3024 for reporting ADR

25. FACTORS TO BE REPORTED
 New drugs: Report all suspected reactions including minor ones
 For established or well known drugs : All serious,
unexpected, unusual ADRs
 Change in frequency of a given reaction
 ADRs to generics not seen with innovator products
 ADRs to traditional medicines
 All suspected drug-drug, drug-food, drug-food
supplement interactions
 ADRs associated with drug withdrawals
 ADRs due to medication errors
 ADRs due to lack of efficacy or suspected
pharmaceutical defects

26. PHARMACOVIGILANCE METHODS:
1. Passive surveillance:
 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.
 Case series: Series of case reports can provide evidence of an association of a drug
and AE.
 Stimulated Reporting: A method used to encourage and facilitate reporting by health
professionals for new products, or for limited time period.
2. Active surveillance
 Sentinel sites: Active surveillance carried out at Institutions, Nursing homes,
hospitals etc. Provide information such as data from specific patient subgroups, drug
abuse etc.
 Drug event monitoring: Patients are identified by electronic prescription data or
automated health insurance claims (questionnaire).
 Registries: A registry is a list of patients presenting with same characteristics.eg:
Disease registry, drug registry or pregnancy registry. Information can be obtained by
using standard questionnaire.

27. 3. Comparative observational studies
 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.
 Case-control study : cases of disease (or events) &
Controls, or patients without the disease or event of interest,
are selected from the source population. Exposure status of
the two groups is then compared using the odds ratio.
 Cohort study : a population-at-risk for the disease (or
event) is followed over time for the occurrence of the disease
(or event). Multiple adverse events can also be investigated
using the same data source in a cohort study.

28. 4. Targeted Clinical Investigations: When significant risks are
identified from pre- approval clinical trials, further clinical studies
might be called to evaluate the mechanism of action for ADRs.
5. 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
 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.

29.  Avoid inappropriate drugs in the context of clinical condition
 Use right dose, route, frequency based on patient variables
 Elicit medication history; consider untoward incidents
 Elicit history of allergies [↑in patients with allergic diseases]
 Rule out drug interactions
 Adopt right technique: slow iv injection of aminophylline


30. Management of the adverse reaction
 Confirmation of the ADRs: indicate what assisted in confirming the
suspected adverse reactions. For example:
i. Drug reactions confirmed by disappearance of the reaction after
stopping administration of the drug or reducing the doses.
ii. Recovery on withdrawal of suspected drug(s) if no other drug is
withdrawn and no therapy given.
iii. Recovery follows treatment of the reaction in addition to withdrawal of
drug.
 Mention the criteria for regarding the reaction as serious
 Mention any treatment given to the patient after experiencing the ADRs.
 Outcome: indicate the outcome of the adverse reaction by marking X in
the appropriate box with dates in case of fatal outcome.

31. THE PHARMACIST SHOULD FACILITATE
 Analysis of each reported ADR
 Identification of drugs and patients at high risk for being involved in ADRs
 The development of policies and procedures for the ADR-monitoring and reporting program
 A description of the responsibilities and interactions of pharmacists, physicians, nurses, risk
managers, and other health professionals in the ADR program
 Use of the ADR program for educational purposes
 Development, maintenance, and evaluation of ADR records within the organization
 The organizational dissemination and use of information obtained through the ADR program
 Reporting of serious ADRs to the FDA or the manufacturer (or both), and
 Publication and presentation of important ADRs to the medical community.
 Direct patient care roles for pharmacists should include patient counseling on ADRs,
identification and documentation in the patient’s medical record of high-risk patients,
monitoring to ensure that serum drug concentrations remain within acceptable therapeutic

32. In general reporting forms should be simple and user friendly, contain
the following elements:
1. Patient information (Medical record number, age, sex, weight, height)
2. Adverse Drug Reaction
 Patient outcome.
 Description of the reaction.
 Relevant laboratory tests or diagnostics.
 Medical history.
3. Drug/Product
 Name/Dose/frequency/Route/duration.
 Indication for use.
 Lot number/expiration date.
4. Treatment given.
5. Reporter information.

34. WHO & UMC
 Uppsala Monitoring Centre (UMC) is a field name of the WHO collaborating Centre for
International Drug Monitoring.
 It is responsible for the management of the WHO program for International Drug
Monitoring.
Functions of WHO Program for international drug monitoring
include:
 Identification and analysis of new adverse reaction signal from the case report
information submitted to the National Centers and from them to the database
 Information exchange between WHO and National Centers, mainly through ‘Vigimed’ an
e-mail information exchange system
 Publication of periodical newsletters, guidelines and books in the pharmacovigilance
and risk management area
 Supply of tools for management of clinical information including adverse drug reaction
case reports – WHO Drug Dictionary – WHO Adverse Reaction Terminology

35.  Computer software for case report management designed to suit the needs
of National Centers (Vigiflow)
 Annual meetings for representatives of National Centers at which Scientific
and Organizational matters are discussed
 Methodological research for the development of pharmacovigilance as a
science
Functions of UMC :
 To co-ordinate the WHO program for international drug monitoring and its
more than eighty member countries
 To collect, assess and communicate information from member countries
about the benefits, harms and risks of drugs and other substances used in
medicine to improve patient therapy and public health worldwide
 To collaborate with member countries in the development and practice of
the science of pharmacovigilance