Pharmacovigilance and ADRs

PHARMACOVIGILENCE
PRESENTED BY:
Dr. S P SRINIVAS NAYAK, Assistant
Professor, SUCP, Hyderabad.

Lets start with a case.
• A 25 year old woman was admitted to a medicine ward
with the complaints of 4-5 episodes of vomiting and
epigastric discomfort. she had been diagnosed with type 2
diabetes and was receiving glimepride 1 mg with
metformin 500 mg once daily. her blood glucose level was
under control. on admission she was prescribed with oral
pantoprazole 40 mg once daily and IV ondansetron 4mg
thrice daily.
• She continued OHD, WITHIN A FEW MINUTES OF
RECEIVING ONDONSETRON, the pt developed
utricaria and redness all over the body. She didn’t
complain of pruritis. She was treated with inj.
Dexamethasone 4mg and oral cetrezene 10mg. The
reaction abated within few minutes.
sultan-ul-uloom college of pharmacy

Concepts and learning objectives.
1. What is ADR/ADE their classifications.
2. Mechanisms of ADRs
3. Identification of predisposing factors of
ADRs
4. Establish causality relationship
5. How to report ADRs
6. Prevention of ADRs
7. Role of pharmacist in decting, Assessing and
managing ADRs

Definitions
• Adverse Event (AE): 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.
• Adverse Drug Reaction (ADR): Any response to a drug
which is noxious and unintended occurs at doses
normally used in man for prophylaxix, trreatment,
diagnosis or modyfying physiologic function it requires
treatment or decrease in dose or indicates caution in
future use of the same drug.
• Therefore, an adverse drug reaction is an adverse event
with a causal link to a drug

What is Pharmacovigilance?
Pharmacovigilance is the science of collecting, monitoring,
researching, assessing and evaluating information from
healthcare providers and patients on the adverse effects of
medications, biological products, herbalism and traditional
medicines.

What is the minimum criterion required
for a valid case according to WHO?
• a. An identifiable reporter
• b. An identifiable patient
• c. A suspect product
• d. An adverse drug event

Classification of ADRs
Depending on Onset of event:
Acute (<60 minutes),
Sub-acute (1-24 hrs) and
Latent (>2 days)
Type of reaction:
Type A (Augmented),
B (Bizarre),
C (Chemical),
D (Delayed),
E (Exit),
F (Familial),
G (Genotoxicity),
H (Hypersensitivity),
U (Un classified) Severity: Minor, Moderate, Severe, Lethal ADRs
Others: Side effects, Secondary effects, Toxic effects, Intolerance, Idiosyncrasy,
Drug allergy, Photosensitivity, Drug Dependence, Drug Withdrawal Reactions,
Teratogenicity, Mutagenicity, Carcinogenicity, Drug induced disease (Iatrogenic)

Type A (Augmented) reactions
• Type A (Augmented) reactions are those which can be
predicted from the known pharmacology of the drug
• Dose dependent,
• Can be alleviated by a dose reduction
• Examples:
• Anticoagulants - Bleeding,
• Beta blockers - Bradycardia,
• Nitrates - Headache,
• Prazosin - Postural hypotension.
• Benzodiazepines - Sedation
• Furosemide - Water and electrolyte imbalance
• Heparin, warfarin - Spontaneous bleeding
• Insulin - Hypoglycemia

More examples of type A ADRs
• INH, Rifampicin, PZA – Hepatotoxicity
• Streptomycin -Ototoxicity, nephrotoxicity
• Captopril – Cough
• Simvastatin – Rhabdomyolysis
• Nitrates – Headache
• Propranolol – Bronchial asthma
• Tetracycline – Hypoplasia of the teeth

Type B (Bizarre) reactions
• Type B (Bizarre) reactions are those
• Cannot be predicted from the pharmacology of the drug
• They are Not dose dependent,
• Host dependent factors important in predisposition
• E.g.
• Penicillin causes Anaphylaxis,
• Anticonvulsant induced Hypersensitivity
• Stevens-Johnson’s Syndrome by mostly antibiotics
• Hemolytic anemia induced by Cephalosporins, Dapsone,
Levodopa, Levofloxacin, Methyldopa, Nitrofurantoin

TYPE C REACTIONS/CONTINUOUS/
CHEMICAL REACTIONS
• The Biological characteristics can be predicted from the
chemical structure of the drug/metabolite
E.g. Paracetamol - Hepatotoxicity
• long term effects are usually related to the dose and
duration of treatment.
Examples:
• Ethambutol – Retinopathy.
• NSAIDs - Nephrotoxicity

Type D (Delayed) reactions
• Occur after many years of treatment. Can be due to
accumulation.
• E.g.
Chemotherapy - Secondary tumours
Phenytoin during pregnancy - Teratogenic effects
Antipsychotics - Tardive dyskinesia
Thalidomide - Phocomelia

TYPE E REACTIONS OR ENDING OF USE
• These are usually the Withdrawal Syndromes
• Examples:
• Benzodiazepines – Rebound insomnia, agitation
• Clonidine – Rebound hypertension
• Corticosteroids – Acute adrenal insufficiency.

TYPE F REACTIONS OR FAILURE OF
EFFICACY
Main causes for type f reactions are medication errors:
Counterfeit medicines
Underdosing of medications
Drug interactions
Examples:
1. Warfarin which is highly protein bound is displaced by
valproic acid leading to bleeding.
2. Aspirin inhibit platelet aggregation together with heparin
an anticoagulant leads increased risk of bleeding.
3. SU with Sulfonamides.

OTHER EXAMPLES
• Secondary Effects-
a)Corticosteroids → ↓Immunity → Latent T.B. activated
b)Tetracyclines → ↓Bacterial flora → Super-infection.
3. Toxic Effects-Exaggerated form of side effects due to
overdosage/prolonged use like
a)High dose heparin → Bleeding
b)Prolonged use of streptomycin →Ototoxicity,
nephrotoxicity

Factors causing ADRs
• Many factors can increase the likelihood of
an adverse drug reaction (any unwanted effects of a
drug).
They include:
• Hereditary factors
• Certain diseases
• Simultaneous use of several drugs
• Very young or old age
• Pregnancy
• Breastfeeding

POST MARKETING SURVEILLANCE:
• Postmarketing surveillance (PMS), also known as post
market surveillance, is the practice of monitoring the
safety of a pharmaceutical drug or medical device after it
has been released on the market and is an important part
of the science of pharmacovigilance

ADR REPORTING
• It is reporting of undocumented ADRs.
• Benefits of ADR Reporting:
• Assess the safety of drug therapies, especially recently
approved drugs.
• Provides updated drug safety information to health care
professionals and other stakeholders
• Measuring the economic impact of ADR prevention as
manifested through reduced hospitalization, optimal and
economical drug use, and minimized organizational
liability Indian Pharmacopoeia Commission,
Pharmacovigilance Programme of India

Types of ADR reporting
• EXPEDITED REPORTING
• This refers to ICSRs (individual case safety reports) that
involve a serious and unlisted event (an event not
described in the drug's labeling) that is considered related
to the use of the drug (US FDA).

CLINICAL TRIAL REPORTING
Also known as AE (adverse event) or SAE (serious AE)
reporting from clinical trials, safety information from clinical
studies is used to establish a drug's safety profile in
humans and is a key component that drug regulatory
authorities consider in the decision-making as to whether to
grant or deny market authorization (market approval) for a
drug.

SPONTANEOUS REPORTING
Spontaneous reports are termed spontaneous as they
take place during the clinician's normal diagnostic
appraisal of a patient, when the clinician is drawing the
conclusion that the drug may be implicated in the
causality of the event.
Spontaneous reporting system relies on vigilant
physicians and other healthcare professionals who not
only generate a suspicion of an ADR, but also report it.
It is an important source of regulatory actions such as
taking a drug off the market or a label change due to
safety problems.

AGGREGATE REPORTING
• Aggregate reporting, also known as periodic reporting,
plays a key role in the safety assessment of drugs.
• Aggregate reporting involves the compilation of safety
data for a drug over a prolonged period of time (months or
years), as opposed to single-case reporting which, by
definition, involves only individual AE reports.
• This is a document that is submitted to drug regulatory
agencies in Europe, the US and Japan (ICH countries), as
well as other countries around the world.

SPONTANIOUS ADR REPORTING FORM

Causality Assessment
• Causality refers to the relationship of a given adverse
event to a specific drug. Causality determination (or
assessment) is often difficult because of the lack of clear-
cut or reliable data.
• While one may assume that a positive temporal
relationship might "prove" a positive causal relationship,
this is not always the case.
METHODS:
• Opinions of experts, clinical judgements
• Algorithms or assessment methods
• Probabilistic and bayesian approaches

WHO–UMC CAUSALITY scale
CAUSALITY TERM ASSESSMENT CRITERIA (ALL POINTS
SHOULD BE REASONABLY COMPLIED)
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 (ie, an objective and
specific medical disorder or a recognized
pharmacologic phenomenon)
•Rechallenge satisfactory, if necessary
Probable/likely •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
•Rechallenge not required

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 may be lacking or
unclear
Unlikely •Event or laboratory test abnormality, with a time to drug
intake that makes a relationship improbable (but not
impossible)
•Disease or other drugs provide plausible explanation
Conditional/unclassified •Event or laboratory test abnormality
•More data for proper assessment needed, or
•Additional data under examination
Unassessable/unclassifiable •Report suggesting an adverse reaction
•Cannot be judged because information is insufficient or
contradictory
•Data cannot be supplemented or verified

ROLE OF PHARMACIST IN ADR monitoring
• Clinical pharmacists have a crucial role in reporting a
larger number of ADRs which leads to fast management
and in turn resulted in reduced number of morbidity and
mortality cases.
• Moreover, clinical pharmacists could discuss the
prescribed medication with the physician to change it if it
isn’t suitable for the patient, thereby improving the
patients’ outcome.

• A pharmacist plays a pivotal role in the identification,
detection, prevention, and management of drug-drug
interactions, drug-food interactions and adrs.
• Pharmacist can carry out such activities in inpatient
setting, while taking part in viewing charts during ward
rounds, and during medication management while dealing
with prescriptions.
• Since pharmacists have a vast knowledge on drugs and
therapeutics, their ability to discover and deal with adrs is
quite important.
• Keeping in view the reporting of adrs, a pharmacist’s
participation enhances reporting rate with higher calibre.

• The intervention of pharmacists by organising lectures and group discussions
thus providing information about the importance, seriousness, preventability
and necessity of reporting shows heightened improvement of knowledge,
attitude and perception about adrs.
• All health professionals play their respective roles in balancing between
benefits and risks of medication when it is introduced in the market.
• However, the expertise of a pharmacist about a drug, especially if newly
marketed, play a more important role in adrs reporting to the authorities which
helps in either withdrawing the product from the market or cause labelling
changes.
• Pharmacists working in community pharmacy have an added advantage of
detecting and reporting adrs while dealing with on the counter prescriptions
and herbal products.
• In a community pharmacy, a pharmacist may not have direct and definite
patient list but the patients coming to the same pharmacy to refill their
prescription gives the pharmacist an opportunity to detect a possible adr that
the patient might be experiencing and can help in the management and the
reporting of the said adr.

THANK YOU
--- Dr. S P Srinivas Nayak,
Sultan-ul-Uloom college of Pharmacy,
Hyderabad, Telangana, India.
Email: spnayak@sucp.ac.in

Pharmacovigilance and ADRs

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