The document provides a comprehensive overview of pharmacovigilance, which involves the monitoring and prevention of adverse drug reactions (ADRs) in pharmaceutical products. It highlights the importance of pharmacovigilance in improving patient care, ensuring public health safety, and the ethical necessity of reporting serious drug reactions. Additionally, it discusses historical drug disasters that led to the establishment of regulatory mechanisms and outlines the types of ADRs, steps for monitoring them, and gives examples of drugs that have been withdrawn due to safety concerns.

1. AVILEEN KAUR
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
ISF COLLEGE OF PHARMACY
WEBSITE: - WWW.ISFCP.ORG
EMAIL: avileenkaurbrar@gmail.com
ISF College of Pharmacy, Moga
Ghal Kalan, nGT Road, Moga- 142001, Punjab, INDIA

2. 2Contents
Introduction
Aim And Scope
Need of pharmacovigilance
Governing bodies
Other historic violations
Adverse drug reaction
Type of drug reaction
Steps of ADR monitoring
Withdrawal of drug from market
Recently banned drug in India

3. 3Introduction
 It is the pharmacological science relating to the collection, detection,
assessment, monitoring, and prevention of adverse reaction with pharmaceutical
products.
"Pharmacovigilance”
( Pharmakon - drug + vigilare - to keep watch)
What is Pharmacovigilance ?

4. 4Aim and Scope
 Patient care • to improve patient care & safety in relation to medicines & all
medical & para-medical interventions
 Public health • to improve public health & safety in relation to the use of
medicines in public health
 Risk benefit assessment • to contribute to the assessment of benefit, harm,
effectiveness and risk of medicines risk benefit assessment
 Communication • to promote understanding, clinical training & effective
communication to health professionals & the public

5. 5Need of Pharmacovigilance
1.Humanitarian concern
-Animal toxicology is often not a good predictor for human effects .
-Evidence of safety from clinical trials is insufficient due to some limitations
Limitations (phase 1-3):
-Limited size
-Narrow population (age &sex specific),
-Narrow indications (only specific disease),
-Short duration

6. 6Contd.....
2. Safe use of medicines- It Has Been Suggested That ADRs May
Cause 5700 Deaths Per Year In UK
3.Promoting Rational Use of Medicines
4.Ensuring Public Confidence
5.Ethical Concern
Not reporting a serious reaction is unethical

7. 7Governing Bodies
 The pharmaceutical industry
 Regulatory authorities
 WHO Collaborating Centre for International Drug Monitoring
 CIOMS (Council for International Organisation of Medical Sciences)

8. 8Why these Studies Started?
Thalidomide tragedy (1961-62): the greatest of all drug disasters.
Thalidomide had been introduced and welcomed as a safe and effective
hypnotic and antiemetic. It rapidly became popular for the treatment of nausea
and vomiting in early pregnancy.
Tragically the drug proved to be a potent human teratogen that caused major
birth defects in an estimated 10,000 children
Phocomelia was a characteristic feature

9. 9Thalidomide Tragedy

10. 10Other Historic Violations
 Sulfanilamide tragedy: Elixir sulfanilamide was an improperly
prepared sulfanilamide medicine that caused mass poisoning in
the united states in 1937. It caused the deaths of more than 100
people. The public outcry caused by this incident and other
similar disasters led to the passing of the 1938 federal food, drug,
and cosmetic act.
 The thalidomide disaster led, in Europe and else where, to the
establishment of the drug regulatory mechanisms of today.
These mechanisms require that new drugs shall be licensed by
well established regulatory authorities before being introduced
into clinical use.

11. 11
List of a few licenced medicines withdrawn after
marketing for drug safety reasons:
1. Practolol - blindness
2. Benoxaprofen - causes onycholysis, renal,
liver, bone marrow toxicity
3. Encainide - excessive mortality
4. Rofecoxib due to incresed cardiovascular
risks
5. Valdecoxib - due to Stevens-Johnson
syndrome

12. 12Adverse Drug Reaction
Adverse event reporting- comprises 4 elements
1. An identifiable patient
2. An identifiable reporter
3. A suspect drug
4. A suspected adverse event

13. 13Types of ADR
 Non immunological
a) TYPE A (or) predictable
b) TYPE B (or) unpredictable
 Immunological
a) Type -I (IGE mediated)
B) TYPE -II (cytotoxic)
C) TYPE -III (immune complex)
D) TYPE -IV (cell mediated)
 Miscellaneous
a) jarisch - herxheimer reaction
B) infectious mononucleosis

14. 14NON-IMMUNOLOGICAL
TYPE A (or) predictable
1. Side effects
2. Secondary effects
3. Toxic effects
4. Mutagenicity & carcinogenicity
5. Drug interactions
6. Teratogenicity
7. Nonimmunological activation of effector pathways
8. Exacerbation of disease
9. Metabolic alterations
10.Drug induced chromosomal damage
11.Effect on spermatogenesis

15. 15
TYPE B (or) unpredictable:
1. Intolerance
2. Idiosyncrasy
Contd.....

16. 16TYPE A
1.Side effects :
- undesirable and unavoidable effects of drugs due to their pharmacological
property at recommended doses. Ex: dry mouth from atropine therapy
2.Secondary effect:
-Indirect effects of drug due to its principal action.
3.Toxic effect:
-It is a pharmacological action due to over dosage or prolonged usage.
Ex: Coma with Barbiturates

17. 17
4.Mutagenicity & Carcinogenicity:
-Metabolites from drugs can cause structural changes in chromosomes to
produce mutations. Ex: Anti cancer drugs
5.Drug interactions:
-Can occur before its absorption into systemic circulation .
Ex: Phenobarbitone inhibits griseofulvin absorption from intestine
6.Teratogenicity:
-Fetal abnormalities produced due to drug intake by the pregnant woman
Ex: Androgens cause virilization of fetus
Contd.....

18. 18
7.Non immunological activation of effector pathways:
-Some drugs cause release of mediators from mast cells resulting in urticaria.
Ex: Radio contrast media
8.Exacerbation of disease :
-Barbiturates precipitate symptoms of porphyria
9.Drug induced chromosomal damage:
-Also called clastogens
Ex: antibiotics, anticonvulsants
10.Effect on spermatogenesis:
-Cytotoxic drugs causes oligospermia.
Contd.....

19. 19TYPE B
1. Intolerance:
-Appearance of toxic effects in a recipient to therapeutic doses of drug
Ex: trifluperazine single dose causing muscle dystonia in children
2. Idiosyncrasy:
-Uncertain reaction to a drug in a genetically defect patient
Ex:chloramphenicol causes bone marrow depression

20. 20Miscellaneous
1. Jarisch-herxheimer reaction:
-This is seen when an infective disease is treated with antimicrobials , due
to release of active substances from dead micro organisms and injured tissue
resulting in focal exacerbation of the lesions.
2. Infectious mononucleosis:
-Ampicillin induced morbilliform rash in patients suffering from infectious
mononucleosis.

21. 21Steps of ADR Monitoring
1.Identifying adverse drug reactions
2.Assessing causality
3.Documentation of ADR
4.Reporting serious ADRs to PV centres /ADR regulatory authorities

22. 22Withdrawal of drug from market
Drug name Withdrawn Remarks
Thalidomide 1950s–1960s
Withdrawn because of risk of teratogenicity;
returned to market for use in leprosy and
multiple myeloma under FDA orphan drug
rules.
Lysergic.acid
diethylamide (LSD)
1950s–1960s
Marketed as a psychiatric drug; withdrawn
after it became widely used recreationally.
Diethylstilbestrol 1970s Withdrawn because of risk of teratogenicity.
Phenformin and Buformin 1978 Withdrawn because of risk of lactic acidosis.
Ticrynafen 1982 Withdrawn because of risk of hepatitis.

23. 23
Phenacetin 1983
An ingredient in "A.P.C." tablet; withdrawn
because of risk of cancer and kidney disease.
Methaqualone 1984
Withdrawn because of risk of addiction and
overdose.
Zimelidine 1983
Withdrawn worldwide because of risk of
Guillain-Barré syndrome.
Nomifensine (Merital) 1986 Withdrawn because of risk of haemolytic anaemia.
Triazolam 1991
Withdrawn in the United Kingdom because of risk
of psychiatric adverse drug reactions. This drug
continues to be available in the U.S.
Terodiline (Micturin) 1991 Prolonged QT interval.
Temafloxacin 1992
Withdrawn in the United States because of allergic
reactions and cases of haemolytic anemia, leading
to three patient deaths.

24. 24
Tolrestat (Alredase) 1997 Withdrawn because of risk of severe hepatotoxicity
Terfenadine (Seldane, Triludan) 1998
Withdrawn because of risk of cardiac arrhythmias;
superseded by fexofenadine
Mibefradil (Posicor) 1998
Withdrawn because of dangerous interactions with
other drugs
Etretinate 1990s Risk of birth defects; narrow therapeutic index
Tolcapone (Tasmar) 1998 Hepatotoxicity
Temazepam (Restoril, Euhypnos,
Normison, Remestan, Tenox,
Norkotral)
1999
Withdrawn in Sweden and Norway because of
diversion, abuse, and a relatively high rate of
overdose deaths in comparison to other drugs of its
group. This drug continues to be available in most of
the world including the U.S., but under strict
controls.
Astemizole (Hismanal) 1999 Arrhythmias because of interactions with other drugs

25. 25
 Serodiagnostic test kits for diagnosis of tuberculosis (with effect from
7Jun2013)
 Dextropropoxyphene (with effect from 23May2013)
 Fixed dose combination of Flupentixol+Melitracen (with effect from
18Jun2013)
 Analgin (with effect from 18Jun2013)
 Pioglitazone (with effect from 18Jun2013)
Recently Banned Drugs in India

26. 26Applications of Pharmacovigilance
1. In national drug policy
2.In the regulation of medicines
3.In clinical practice
4.In disease control public health programmes