Pharmacovigilance Basics Methods Practices

Pharmacovigilance:
Basics, Methods &
Practices
Indian Pharmacopoeia Commission, Pharmacovigilance Programme of India

Title
• To identify , assess and report an adverse drug
reaction.

Objective:
• How to Identify an ADR.
• Understand the process and importance of ADR
Monitoring.
• Understand the concept and organization of
National Pharmacovigilance Programme of India(PvPI)
• How to fill the Adverse drug reaction form and submit
the ADR to ADR monitoring centre.

History of ADRs
• Elixir of Sulfanilamide Tragedy, 1937
• Chloramphenicol Grey Baby Syndrome,
1950’s
• Thallidomide Teratogenicity, 1960’s

Elixir of Sulfanilamide Tragedy
• In 1937 in USA, Approx. 170 people died from
taking an Elixir of Sulphanamide that contained
solvent Diethylene glycol to improve palatability
• Ethylene glycol - a potent nephrotoxin
• No pre-marketing toxicity studies done
• Deaths from renal failure, mostly among children
• Responsible chemist committed suicide
• This Led to the current drug regulatory system,
FDA which was given task to regulate the safety of
new drugs before allowing them to be marketed

• The major catastrophe that changed professional and
public opinion towards medicine was the Thalidomide
Tragedy
• In 1961, in West germany, there was an outbreak of
phocomelia (Hypoplastic and aplastic limb
deformities) in the new born babies
• Later it was found that Thalidomide, a non-
barbiturate hypnotic was to blame
• The crucial period of pregnancy during which
thalidomide is teratogenic is the first three months
• Thalidomide Tragedy

Result of Thalidomide Disaster
• USA : 1962 - Amendment to Federal Food, Drug &
Cosmetic Act -required both safety and Efficacy Data.
• UK : 1964 - Yellow Card System.
• WHO : 1968 - International Drug Monitoring System.
• 1997 : India joined WHO-ADR monitoring programme

• The Central Drugs Standard Control Organization (CDSCO),
Directorate General of Health Services under the aegis of
Ministry of Health & Family Welfare, Government of India in
collaboration with Indian Pharmacopoeia commission,
Ghaziabad is initiating a nation-wide Pharmacovigilance
programme for protecting the health of the patients by assuring
drug safety.
Pharmacovigilance Programme of India (PvPI)

JULY
2010
• Pharmacovigilance programme of
India (PvPI), initiated with AIIMS, New
Delhi as national coordination center
for monitoring ADRs in the country.
15 APR
2011
• The NCC shifted from AIIMS New Delhi
to Indian Pharmacopoeia Commission
(IPC) , Ghaziabad

Launch of IPC, NCC-PvPI as WHO Collaborating Centre for Pharmacovigilance in
public health programmes and regulatory health services
on October 30, 2017 at IPC Ghaziabad
NCC-PvPI -WHO Collaborating
Centre for Pharmacovigilance

Greek word ‘Pharmacon’ - drug.
Latin word ‘Vigilare’ - to keep watch,
awake or alert
– Process of paying close & continuous attention
• World Health Organization (WHO) defines Pharmacovigilance (PV)
as ‘‘the science and activities relating to detection, assessment,
understanding and prevention of adverse effects or any other
drug related problem.’’
Introduction

Aims of Pharmacovigilance
• Identify previously unrecognized adverse effects or
changes in the patterns of adverse effects.
• Assess the risks and benefits of medicines to improve their
safe use.
• Preventing patients from being affected unnecessarily.
• Provide information to healthcare professionals and patients
to optimize safe and effective use of medicines.
• Thus, the ultimate purpose of ADR reporting and monitoring is
to reduce risks associated with drug prescribing and
administration.

“Keep Me Safe”
“Get Me Well”
“Treat Me Nice”
Voice of the Patients

Why Pharmacovigilance?
A lesson from history
1959 – 1961 thalidomide 4,000 – 10,000 cases of
phocomelia (congenital limb defects)
This lead to withdrawal of the drug from the market

Cases reported from India
Omeprazole
induced FDE
Carbamazepine
induced SJS
*Source : National Cordination Center (NCC), Pharmacovigilance Programme of India, IPC, Ghaziabad
Lip edema from
Urografin
Acne aggravation
from topical
steroids

Recent Drugs Banned Drugs
 Sibutramine – Adverse Cardiac Event
 Rimonabant- Suicidal Ideation
 Nimsulide below 12 year age- Hepatitis
 Rofecoxib- CVS
 Valdecoxib- CVS
 Rosiglitazone – Heart Attack
 Gatifloxacin – Severe hypo/Hyperglycemia
 Astemizole - Adverse Cardiac Event
 Terfinadine- Adverse Cardiac Event
 Cisapride- Adverse Cardiac Event
 Phenylpropanolamine - Hemorrhagic Stroke
Why Pharmacovigilance?

Need for Pharmacovigilance
• Animal toxicology is often not a good predictor for
human effects
• Evidence of safety from clinical trials is insufficient due
to some limitations
• phase 1-3: limited size
• narrow population (age & sex specific)
• narrow indications (only specific disease)
• short duration

Need of Pharmacovigilance?
Medicines are supposed to save lives (Dying from a
disease is sometimes unavoidable; dying from a
medicine is unacceptable).
To protect patients from unnecessary harm (Many
ADRs are preventable and these are a huge
economic burden).

Ethics
To know of something that is harmful to another person
who does not know, and not telling, is unethical.
Not reporting a serious unknown reaction is unethical
• Patients
• Healthcare Professionals
• Manufacturers
• Authorities
Need of Pharmacovigilance?

ADR Monitoring Centre in India
Currently, we have
311 AMC throughout
India and we are
continuously in the
process of expansion

Adverse Drug Reaction (ADR)
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 modifications of physiological
function. (WHO, 1972)
Unexpected Adverse Drug Reaction
An adverse reaction, the nature or severity of which is not consistent with the
applicable product information (P.I.)
Pharmacovigilance (Pv) Terminologies

Adverse Event (AE)
An adverse event (AE) can be any unfavourable and unintended sign
(including an abnormal laboratory finding), symptom, or disease temporally
associated with the use of a medicinal product, whether or not related to
the medicinal product.
[Source:- Guideline for good clinical practice E6 (R1)]

Serious Adverse Event (SAE) or
Serious Adverse Drug Reaction
Any untoward medical occurrence at any dose that: -
 Results in death,
 Is life-threatening,
 Requires inpatient hospitalization or prolongation of existing hospitalization,
 Results in persistent or significant disability/incapacity,
 Is a congenital anomaly/birth defect
[Source:- Guideline for Good Clinical Practice E6 (R1)]

Severity Assessment of ADRs
Karch and Lasagna classified severity as following :
 Minor: no antidote, therapy or prolongation of hospitalization required.
 Moderate: requires a change in drug therapy, specific treatment or an increase
in hospitalization by at least 1 day.
 Severe: potentially life threatening, causing permanent damage or requiring
intensive medical care.
 Lethal: directly or indirectly contributes to the death of the patient.

Cont…
Suspected Unexpected Serious Adverse Reactions (SUSAR)
An adverse reaction that is both unexpected (not consistent with the applicable
product information) and also meets the definition of a Serious Adverse
Event/Reaction.
Indian Pharmacopoeia Commission, Phrmacovigilance Programme of India

Who can report an ADR?
Patient or his
relatives
Healthcare
professionals
Manufacturers Authorities
Who can
report an
ADR ?

Sources of Reporting in PV
Spontaneous
reports
Literature
Internet Clinical trial studies
Reporting
In PV

All suspected ADRs with pharmaceutical medicines &
vaccines
• known or unknown
• serious or non-serious
• frequent or rare
Adverse reactions associated with
• drugs used in traditional medicine (e.g. herbal remedies)
• Drug withdrawal
• Medication errors
• Lack of efficacy
• medical devices
• contrast media
• other pharmaceuticals
What to report?

• ADR Reporting Form
• -Suspected Adverse Drug Reaction Reporting Form (SUSAR) for
healthcare professionals (Available in red colour)
• - Medicine Side Effect Reporting Form for Consumers (Available in Blue
colour)
• - AEFI (Adverse events following Immunization) Reporting form (Case
reporting form (CRF) & CIF- Case Investigating Form).
• - Transfusion Reaction Reporting Form (TRRF) for Blood & Blood
Components & Plasma Products.
• Medical Devices Adverse Events Reporting Form (MDAER)
• Website Email- pvpi@ipcindia.net or pvpi.ipcindia@gmail.com
• Telephone- 1800 180 3024 (Monday to Friday 9:0AM tom 5:30 PM
• App- Android, free
Where to report?

Validation of case report
Identifiable
Patient
Identifiable Event
Identifiable
Reporter
Identifiable Drug
Valid ICSR

Worldwide Reporting Forms
CIOMS MED-WATCH

ICSRs uploaded in Vigiflow
Received at NCC
for Quality
assessment
CDSCO-HQ
WHO-UMC
Sweden
Valid or
complete ICSRs
Invalid or
incomplete
ICSRs
Revert to AMC
Safety updates
Submit to
Transmission of an ICSR

Data collected in PV can be used in variety of ways:
1. Signal generation and strengthening
2. Risk management
3. Drug regulation
4. Education
Utilisation of data

Evaluation of the likelihood that a medicine was the causative
agent of an observed adverse event.
Causality is assessed on the basis of:
• Temporal relationship: timely relation
of event with drug administration.
• Previous knowledge: whether the drug is known to
produce the event in earlier recipients.
• Dechallenge: whether the event is subsided on
stopping the drug.
• Rechallenge: whether the event reappeared when the
drug was administered.
Causality Assessment

The WHO–UMC causality
assessment criteria
• Certain
• Probable/likely
• Possible
• Unlikely
• Conditional/Unclassifiable
• Unassessible /Unclassifiable

Materiovigilance : Medical Device Adverse Event
(MDAE)
• An adverse event (AE) is any untoward medical occurrence in patient or clinical
investigation subject administered a pharmaceutical product/medical device and
which does not necessarily have a causal relationship with treatment.
A.Medical Device Adverse Event Reporting Form : Six parts
• Patient Details
• Event Details
• Medical Device Detail
• Regulatory Detail
• Reporter Details
• Causality Assessment
Indian Pharmacopoeia Commission, Materiovigilance Programme of India

Adverse event following immunization (AEFI) - Any untoward
medical occurrence following immunization and which does
not necessarily have a causal relationship with the usage of the
vaccine.
The adverse event may be any unfavorable or unintended
sign, abnormal laboratory finding, symptom
or disease.
What is an AEFI?
Types of AEFIs
• Minor
• Severe
• Serious

Haemovigilance is a set of surveillance procedures covering the whole transfusion
chain from the collection of blood and its components to the follow-up of its
recipients intended to collect and assess information on unexpected or undesirable
effects resulting from the therapeutic use of labile blood products and to prevent
their occurrence and recurrence. It is an important tool for improving safe blood
transfusion practices in a country.
The Haemovigilance Programme of India (HvPI) was launched on 10th December,
2012 in the country.
Reporting Form : Transfusion Reaction Reporting Form (TRRF) For Blood & Blood
Components & Plasma Products
Haemovigilance Programme of
India(HvPI)

Ravi Kumar, a 50 yr old male (Wt-78kg) and known case of Type 2 Diabetes Mellitus
having a Fasting Blood Glucose-110mg/dl, HbA1c 7.5% was maintained on Tab
Glibenclamide 5mg twice daily for the last 6 months.
Two days ago he had a binge of alcohol at a late night party. An hour later he was
brought to emergency with symptoms of throbbing headache, palpitations, tightness
in chest, sweating, vomiting and mental confusion.
On examination he showed disorientation, flushing, Pulse rate- 104 per min, BP-
120/80 mmHg, RR- 22 per min, Blood sugar- 112 mg/dl
Case Report 1

1. What is the probable ADR?
2. How can you prevent it?
3. Fill up the ADR form based on the information provided.

Name of the patient –Adarsh ,Age - 19 years, Sex –M, Wt: 58kg
Presenting Complaint- presented in emergency with breathlessness and wheezing.
History of present Illness-He had a throbbing headache while he was writing exam in his
college. The invigilator gave him 2 dispersible tablets of Disprin (Aspirin-350 mg each) to
get quick relief .
Past History - In the past he had been allergic to dust and smoke but he never took any
treatment. He always experienced throbbing headache when his exams were near, for
which he used to take a tablet of Crocin. (Paracetamol-500mg) and got relieved.
-On examination his BP 120/80mmHg and Pulse was 74/min.
CASE NO- 2

Bharat Bhushan, a 50 year old mild hypertensive male (Wt-62kg) was
stabilized (BP-120/80 mmHg) on Tab Lisinopril 5mg once daily for 6 months.
For the last one month, he had intractable, brassy and dry cough. He was
prescribed Syrup Benadryl (Diphenhydramine) 2 tsf thrice daily, and Tab
Augmentin 625 mg (Amoxycillin 500mg + Clavulanic Acid 125mg) three times
daily for five days, but he was not relieved of his cough. Chest X-Ray showed
normal lung shadows, and sputum examination revealed no abnormality.
CASE NO- 3

Vibha, a 22 year old woman (Wt-52kg) and known case of paranoid schizophrenia
was stabilized on Tab Haloperidol 20 mg once daily for last 2 months. About 2
weeks ago, she presented in neurology OPD with complaints of tremors, rigidity
and akinesia
CASE-04

Sita Ram, a 45 year old man (Wt- 60kg) and known case of Pulmonary Tuberculosis
was stabilized on intensive regimen of DOTS-ATT (Isoniazid-10mg/kg/day,
Rifampicin-10mg/kg/day, Pyrazinamide-25mg/kg/day and Ethambutol-20mg/kg/day)
since last one month. Since last 2 weeks he developed persistent vomiting, loss of
appetite and yellow discoloration of urine.
On examination, he showed signs of jaundice like yellowish discoloration of skin and
sclera.
Investigations revealed Total Serum Bilirubin- 10mg/dl, AST-500U/ml, ALT- 550U/ml.
CASE -05

1. What is the probable ADR?
2. How can you manage it?
3. Fill up the ADR form based on the information provided.

Let’s join hands
“to Ensure Safe
and effective
Use of
Medicines”

THANK YOU

Pharmacovigilance Basics Methods Practices

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