ADVERSE

DRUG
REACTION
By-
Dr.A.Soujanya
PharmD
Assistant professor
Dept of pharmacy practice
DEFINITION
According to World Health Organization
(WHO), an adverse drug reaction (ADR)
may be defined as "Any response to a
drug that is noxious and unintended and
that occurs at doses used in man for the
prophylaxis, diagnosis or therapy of a
disease or for modification of
physiological function". However, the
definition does not take into account the
adverse effects caused by overdose,
poisoning, drug abuse and errors in
administration of drug.
 CLASSIFICATION-
1.Traditional classification:

ADR

TypeA/Predictable/ Type Miscellaneous

Augmented B/Unpredictable/bizarr effects
e
Excessive Genetically
pharmacological effects idiosyncrac determined
y toxicity
secondary
pharmacological effects Allergic drug Carcinogenecit
reactions y/mutagenecity
Sudden drug
withdrawal effects Drug-induced
disease
side effects
teratogenecity
intolerance
2. Novel Classification:
Wills and Brown have classified ADRs into
eight categories according to their
mechanisms.
(a) Type A (Augmented)
(b) Type B (Bugs)
(c) Type C (Chemical)
(d) Type D (Delivery)
(e) Type E (Exit)
(f) Type F (Familial)
(g) Type G (Genotoxicity)
(h) Type H (Hypersensitivity).
Traditional classification-
A. Type-A ADRs:
This type of adverse drug reactions is also known as
predictable/augmented adverse drug reactions.
1.Excessive Pharmacological Effects-
Toxic effects result when the drug has been used
in excessive doses or has been used for
prolonged time periods, due to which the
pharmacological actions of the drug gets
prolonged. Over dosage of a drug may be caused
directly or relatively. It is caused directly when the
drug is ingested by accident or for homicidal or
suicidal intentions, whereas it occurs relatively,
when the normal dose of a drug is given to a
patient with impaired tissue function.
Example: Normal doses of gentamicin in renal
failure may precipitate toxic effects.
The toxic effects can result,
(i) When the functioning of the drug gets
altered. E.g: Atropine in high doses causes
delirium
(ii) When the drug has lead to tissue damage.
Eg: Over dosage of paracetamol leads to
hepatic necrosis.
These toxic effects can be extensions of the
therapeutic effects of the drug or may be
unrelated. Examples of toxic effects.
(i) Barbiturates – Coma
(ii) Digoxin - A.V block
(iii) Heparin – Bleeding
(iv) Morphine - Respiratory failure
(v) Emetine - Damage to myocardium
Poisoning and Its Treatment:
Excessive exposure to or ingestion of drugs,
industrial chemicals, insecticides etc, may cause
harmful effects, on vital organs of the body and
may even result in death. These drugs which have
life- threatening effects on human body are called
as poisons. Toxicology is the branch of science
which deals with the study of poisonous effects of
drugs and other chemicals.
Treatment :The general supportive measures to be
used during poisoning have been outlined below.
1.By employing a selective antagonist, the poison
can be identified.
2. Airway Maintenance: The airways should be
maintained clear by removing any obstructing
substances like vomitus, mucus etc, and the body
parts exposed to poison like skin, eyes etc should
be cleaned properly.
3.Maintenance of Ventilation: Maintenance of
adequate ventilation is necessary as
hypoventilation causes hypoxaemia, while
hyperventilation leads to alkalosis and
hypotension. Hence, the volume of 400 ml
and minute volume of 4 lit/minute are
maintained during poisoning
4. Emesis Induction and Gastric Lavage:
Induction of vomiting and gastric lavage
ensures elimination of the drug and therefore
prevents further absorption. Emesis is usually
induced by apomorphine or ipecac syrup. In
poisoning due to CNS stimulants, corrosive
drugs, kerosene and in comatosed patients,
these methods of drug elimination are not
used as they may cause aspiration into the
lungs.
5. Fluid and Electrolyte Balance: It is
maintained by 0.9% w/v isotonic saline or
5% w/v isotonic glucose, so that proper
blood circulation occurs and cardiac output
is restored. The blood sugar levels are also
maintained by dextrose infusion.
6.Decontamination: The absorption of poisons
into the blood is prevented by the following,
(a)Universal Antidote
It is made up of magnesium oxide (milk of
magnesia), strong tea and burnt toast in the
ratio 1:1:2.
(b) Charcoal: It is administered in the form of
suspension made by dissolving 40g
charcoal in 200 ml water. It binds to
unabsorbed drug and causes its elimination.
 However, charcoal is ineffective in adsorbing
strong acids, alkalies, iodine, cyanide, alcohols,
organic solvents etc.
7. Administration of Antidotes: Antidotes may be
used to treat specific types of poisoning. These
antidotes could be receptor antagonists,
chelating agents or other specific antibodies
which reverses the actions of the poisons.
Examples
(i) Paracetamol poisoning is treated by
acetylcysteine.
(ii) Mercury poisoning is treated by dimercaprol,
which chelates the Hg+ ions.
(iii) Morphine poisoning is treated by naloxone.
(iv) Anticholinesterase poisoning is treated by
atropine.
8. Promotion of Drug Elimination:
(a) By forced diuresis: To prevent the
reabsorption of poison and to rapidly eliminate
it from the body, forced diuresis can be carried
out, using furosemide, mannitol etc. However,
due to its low efficacy, forced diuresis is not
being employed.
(b) By ionization of drugs: Drug elimination can
be promoted by inducing its ionization. Acidic
drugs like phenobarbital, salicylates etc., get
ionized in alkaline pH. Therefore their
reabsorption through kidney tubules is
prevented by increasing urine pH using sodium
bicarbonate. Basic drugs like amphetamine,
pethidine etc., get ionized in acidic pH, hence
reabsorption is prevented by decreasing the
urine pH.
(c) By haemodialysis and peritoneal dialysis: This is
carried out in patients who do not respond to
conventional methods of treatment. Procedure
involves passing the patients blood through a
column containing charcoal or other suitable
adsorbent. Drugs which can be removed by
dialysis are barbiturates, diphenhydramine,
phenytoin etc.
2.Secondary Pharmacological Effects-
Primary therapeutic action of the drug may also
show certain indirect consequences called as
secondary effects.
Examples
(i) Activation of latent tuberculosis occurs upon
administration of corticosteroids as the defense
mechanisms of the host decline.
(ii) Tetracyclines used to inhibit the bacterial flora
causes superinfections as a secondary effect.
3.Sudden Drug Withdrawal Effects-
These effects occur because of drug
dependence or abrupt cessation of drug
therapy. Such drug withdrawal results in
exacerbating and worsening of the disease
condition for which the drug was being
administered.
Examples
(i) Discontinuing the use of clonidine causes
severe hypertension.
(ii) Discontinuing the use of ẞ-blockers leads
to overpowering symptoms of angina
pectoris and myocardial infarction.
(iii) Upon sudden discontinuation of
antiepileptic the occurrence of seizures
intensify.
4. Side Effects-
The undesirable effects of a drug which are observed
along with the intended pharmacological action are called
as side effects. These are generally mild and can be
tolerated. From a drug's pharmacological profile, its
common side effects can be predicted. These side effects
are dose related i.e., as the dose of the drug is
decreased, the side effects decreases.
Sometimes a therapeutic effect may be associated with a
side effect.
Examples
1. The diuretic action of acetazolamide causes acidosis as a
side effect. It is due to the fact that action of
acetazolamide causes elimination of bicarbonate ion
therefore increasing the acid content of the body.
2. The antisecretory action of atropine when administered
as a pre-anaesthetic medication causes dryness of
mouth as a side effect.
3. Promethazine when given as an anti allergic drug
produces sedation as a side effect.
The effect of a drug may be therapeutic in
some context, but referred to as a side
effect in another context.
Example: Codeine as an antitussive causes
constipation which is considered as a side
effect, but as a therapeutic effect it is
given in traveller's diarrhoea.
Other examples of side effects are:

DRUG THERAPEUTIC SIDE EFFECT

ACTION

Estrogens Antiovulatory Nausea

action
Sulfonamides Antibacterial action Hypoglycemia,acid
osis
5. Intolerance-
Sensitivity towards a drug is measured
using Gaussian frequency distribution
curve. The individuals who appear on the
extreme left side of this curve show
intolerance as they experience toxic effects
even in therapeutic doses. Such individuals
are said to be highly sensitive to certain
drugs.
Examples
(i) Vomiting and abdominal pain by only one
tablet of chloroquine, in some individuals.
(ii) Ataxia upon only few doses of
carbamazepine.
(iii) Muscular dystonias in children with single
B.Type-B ADRs-
This type of adverse drug reactions is also known
as unpredictable/bizarre adverse drug
reactions.
1.Idiosyncrasy: The abnormal responses shown
upon administration of a drug because of
genetic defects in the patient are called as
idiosyncrasies. These responses are bizarre
and do not occur in every patient. The
affected individual react in an abnormal way
towards the drug. The study of idiosyncrasies
is called as pharmacogenetics.
Examples
(1) Asthma, vascular collapse, cramps,
diarrhoea, purpurea are observed upon
administration of quinine or quinidine in
certain individuals
(ii) Polyneuritis occurs with isoniazid in slow
acetylators whereas drug resistance and failure
of drug response seen in fast acetylators.
(iii) Resistance to vitamin D in certain individuals.
(iv) Malignant hyperthermia is observed with
halothane as an abnormal response in few
people.
(v) Hereditary methaemoglobinaemia (presence
of methaemoglobin (blood pigments oxidized
from ferrous to ferric form) in blood)
(vi) Idiosyncrasy is also observed in patients who
either completely lack or are deficit in a
particular enzyme. Haemolytic anaemia results
when usual therapeutic dose of primaquine is
administered to a patient with deficiency of
glucose-6 phosphate dehydrogenase enzyme.
2.Allergic Drug Reactions-
An inappropriate immune response by the
body to a drug is called as drug
hypersensitivity or allergy. The allergy is
not dose-related and is not dependent
upon the pharmacological profile of the
drug. It occurs due to the sensitization of
the patient upon first exposure to a drug
acting as allergen. Upon subsequent
administration of the same drug,the
immune system gets activated, thereby
producing antibodies against the drug.
The antigen-antibody reaction results in
rashes, pruritus, oedema, wheezing etc.
Types of Allergic Drug
Reactions/Hypersensitivities
(a) IgE Mediated Hypersensitivity (Type 1)
This is also referred to as immediate or
anaphylactic hypersensitivity. It occurs
immediately within minutes and
disappears after 2-3 hrs. The first
exposure to a foreign antigen (which could
be a drug or chemical substance) causes
the release of IgE antibodies. These IgE
antibodies bind to the Fc receptors
present on cell surface of mast cells and
basophils. Second exposure to the same
foreign antigen causes degranulation of
mast cells and activation of heparin,
histamine and serotonin.
 The activated leucocytes destroy the
foreign antigen which is accompanied
with vasodilation, contraction of smooth
muscles and increased Ca2+ influx. The
allergy if untreated causes anaphylactic
shock. Basophils also release histamine
and heparin. Other inflammatory
mediators released are prostaglandins,
leukotrienes, platelet activating factor
(PAF) etc.
Examples of foreign antigens or allergens
are dust, pollen grains, drugs like
penicillins, anaesthetics, milk, nuts,
eggs, insect products like bees venom,
animal hair, mould spores etc.
Figure: Diagrammatic Representation of Immediate (Anaphylactic)
Hypersensitivity
Symptoms: Anaphylactic shock, rhinitis (runny
nose), facial flushing, itching, nausea, vomiting,
swelling of mouth and tongue, airway
obstruction, low BP, wheezing etc.
Treatment: Administration of epinephrine,
antihistamines, corticosteroids, cromolyn sodium.
Antihistamines can be used in allergic rhinitis and
conjunctivitis, prednisolone in asthma while,
aminophylline in chronic bronchitis and asthma.
(b)Antibody Mediated Hypersensitivity (Type II)-
This type of hypersensitivity is also referred to as
cytotoxic hypersensitivity. It occurs within 72 hrs
of drug administration. Upon first exposure to a
drug, the drug or its metabolite gets converted
into an antigen by getting bound to host proteins
and the antigen so formed is considered as a
foreign substance resulting in activation of IgG
and IgM antibodies.
Upon second exposure to the same drug,
these antibodies (Ab) form a complex with
the antigen (Ag) to form Ag-Ab complex
resulting in the release of chemical
mediators like heparin, histamine from
tissue and mast cells. Thus cytolysis occurs
leading to the destruction of foreign
antigen.
Examples of type-II hypersensitivity reactions
include ABO transfusion reactions, Rh
haemolytic disease, drug induced
haemolytic anaemia etc.
Symptoms: Fever, systemic lupus
erythematosus, haemolysis,
thrombocytopenia, liver, kidney and muscle
damage, aplastic anaemia, agranulocytosis
etc.
(c) Immune Complex Mediated Hypersensitivity
(Type III)-
This type of hypersensitivity is also referred to as
retarded hypersensitivity, because though this
allergy begins after 72 hrs, it generally gets
relieved within 1-2 weeks. In this, the antibodies
(like IgG) binds with foreign antigens & form an
immune complex. These complexes are usually
eliminated by reticuloendothelial system, however
these complexes may get deposited on the vascular
endothelium and act like allergen thus initiating an
inflammatory response.
Examples: Glomerulonephritis, rheumatoid arthritis,
systemic lupus erythematosus, Arthus reaction, and
serum sickness
Symptoms: Rashes, serum sickness, nephritis,
Stevens-Johnson syndrome, polyarteritis nodosa
etc.
(d) Delayed Type Hypersensitivity (Type IV)-
In this type of hypersensitivity, the T-
lymphocytes carry antigen-specific receptors
which get activated when they come in
contact with an antigen, leading to the
formation of lymphokines. These lymphokines
result in inflammatory responses which take
more than 12 hrs to develop by attracting
granulocytes.
Examples: Photosensitivity reactions, contact
dermatitis, skin rashes, fever etc.
Photosensitivity
It is confined to the skin and occurs because
the drug sensitizes the skin to UV radiation. It
is of two types,
(i) Phototoxic Reactions
The drug or its metabolite accumulate in the skin
and absorb UV radiations of the wavelength 290-
320 nm. This results in phototoxic reactions
resulting in erythema, oedema, blistering,
hyperpigmentation and desquamation. Examples
of the drugs causing phototoxic reactions are
tetracyclines, tar products, nalidixic acid etc
(ii) Photoallergic Reactions
These occur due to absorption of longer
wavelengths (320-400 nm) of UV-A radiation by
the drug or its metabolites after it accumulates in
the skin. It is a cell mediated immune response.
Manifestations include eczematous or papular
contact dermatitis. Examples of the drugs causing
photoallergic reactions are sulfonylureas,
chlorpromazine, sulfonamide
Cross Sensitivity
It may be defined as sensitivity to one drug that
makes an individual sensitive to another drug of the
same category.
Examples-
(i)Few people are allergic to non-steroidal
antiinflammatory drugs (NSAIDs). A person sensitive
to ibuprofen also shows sensitivity to naproxen as
they belong to the same class.
(ii)Few people show sensitivity towards drugs used as
antidepressants.
(iii) Cross sensitivity occurs between penicillins and
cephalosporins because they have a common beta-
lactam ring and similar spectrum of allergic reactions.
Symptoms-Anaphylaxis, skin rashes, eosinophilia,
fever, and gastrointestinal defects are common.
Severe urticaria, angioedema, laryngeal oedema, low
BP, wheezing may also occur in few individuals.
 DIFFERENCES BETWEEN TYPE A & TYPE B ADRS
TYPE A ADRS TYPE B ADRS

caused by hyper/hypo response caused by

mechanism genetic/immunological/unknown
mechanism
very common less common

pharmacologically predictable pharmacologically

unpredictable
dose-dependant response not a dose-dependant response

low mortality rate high mortality rate

can be treated by dose requires complete withdrawal of

adjustment the offending drug
Eg: insulin induced Eg: Allergy caused by penicillins
hypoglycemia when given for the first time
C.Miscellaneous Effects-
1.Genetically Determined Toxicity
Genetically determined toxicity also known as
genotoxicity refers to the properties of
chemical agents that damages the genetic
information within a cell causing mutations
leading to cancer. It is important to note that
all mutagens are genotoxic where as all
genotoxic agents are not mutagenic agents.
Basically chemical agents cause
carcinogenesis by inducing mutation in proto-
oncogenes and anti-oncogenes in three
sequential stages which are described below:
(a) initiation-
Chemical carcinogens transform a normal cell
into an initiator cell in the following manner.
(i) Metabolic Activation:
In this step, procarcinogens are rendered
metabolically active by monooxygenases of
CYP450 system in the endoplasmic reticulum of
the liver.
ii) Reactive Electrophiles:
Following metabolic activation, procarcinogens
become electron deficient and hence bind to
electron rich portions of the cell like RNA, DNA
etc.
(iii) Target Molecules:
DNA is the primary target molecule of reactive
electrophiles for binding. Binding induces
mutations in the genes of target molecule
which in turn transforms a normal cell into a
carcinogenesis initiating (mutated) cell.
(iv) Initiated Cell:
When the initiated cell undergoes at least one
proliferation cell cycle, the damage induced in the
DNA of the cell becomes irreversible & permanent
(b) Promotion
In this stage, promoter carcinogens enhance the
effect of direct acting and indirect acting
carcinogens by causing further clonal proliferation
and expansion of mutated cells.
(c) Progression
When the mutated cells undergoes rapid
proliferation, they acquire more and more
mutations as a result of which phenotypic
features of malignancy related to
morphology,molecular features & biochemical
composition become evident in this stage.
2.Carcinogenicity/Mutagenicity-
Carcinogenicity refers to ability of a drug to cause
cancer whereas mutagenicity refers to genetic
defects caused by mutations. Eg of carcinogenicity
is upon prolong usage of estrogens by women
without progesterone develops endometrial cancer.
Example of mutagenicity is hereditary
methaemoglobinemia.
3.Drug Induced Diseases-
The diseases or disturbances in the normal
functioning of the body due to drugs even after
their withdrawal & complete elimination are called
drug-induced diseases or iatrogenic diseases.
Examples
(i) Salicylates and corticosteroids cause peptic ulcer
(ii) Isoniazid causes hepatitis
(iii) Phenothiazines cause parkinsonism
4.Teratogenicity-
A teratogen is an agent that has the potential to cause
malformations and functional abnormalities in the fetus.
Thus the common term that encompasses foetal death,
structural malformations, functional abnormalities and
abnormal foetal development is congenital anomalies. Out
of the numerous drugs scanned for teratogenic potential,
only about 30 drugs have proven teratogenic effects.
These teratogens bring about structural malformations
that may be fatal or demand surgical interventions.
Almost 2% of the children suffering from severe physical
and mental retardation were exposed to teratogens in
uterus.
The extent of damage effected to the foetus is determined
by,
(a) Physico-chemical properties of the teratogen
(b) Dose and route of administration
(c) Foetal stage of exposure to drugs
(d) Genetic composition and biological susceptibility of
mother and foetus
 EXAMPLES OF TERATOGENS:
Teratogenic Time of Fetal adverse effect
drugs exposure
Danazol any trimester virilization of female fetus

spironolactone, any trimester feminization of male fetus

cyproterone

ACE inhibitors 2nd & 3rd impairment of renal function

trimester in fetus & oligohydromnios

sulphonamides end of 3rd neonatal hemolysis

trimester

NSAIDS 3rd trimester closure of fetal ductus

arteriosus,renal
impairment,delayed labour
In order to ease the dilemma encountered by
the physicians in prescribing the drugs in
pregnancy,the food and drug
administration(FDA) has categorised drugs
according to the risk factors associated with
them. Such an approach is based on the
results obtained from both animal and human
studies. Category A drugs are considered
safe, the category B,C and D are associated
with proportionately increasing risks.However
they are commonly recommended to
pregnant women. Category X drugs have high
teratogenic potential and hence are
contraindicated in pregnancy.
categor
risk factors examples of drugs
y
These drugs have failed to
exhibit any risk towards the fetus acetaminophen,meperidine,ep
in 1st trimester.Further possibility hedrine,digoxin,lidocaine,hepa
A
of any fetal effect is also rin,furosemide,amikacin,propr
less,both of which were proven anolol,clonidine etc
by controlled studies in women
either no fetal risk was evident in
animal reproduction studies or
the fetal adverse effect was
diphenhydramine,ibuprofen,ni
B shown in animal reproduction
trofurantoin,indomethacin etc
studies but was not provided in
controlled studies in women in
1st trimester
either animal controlled studies
exhibited fetal adverse effects
but there were no controlled bismuth
studies in women or no subsalicylate,chloramphenicol
C controlled studies have been ,codeine,epinephrine,fluconaz
performed in both animals and ole,phenylephrine,quinolones,
women. These drugs should be rifampin,oral sulphonyl ureas
prescribed only when the
benefits outweigh risk to fetus
category risk factors examples of drugs

D The risk associated with the drug is Amiodarone,amitryptilli

high ,however its use is justified in ne,carbamazepine,hydr
certain life-threatening situations or oxyurea,imipramine,pe
in severe diseases in which the other nicillamine,phenytoin,pr
safer drugs either prove to be opylthiouracil
ineffective or cannot be used.

X either the fetal abnormality was Danazol,diethylstibester

evident in both human and animal ol,ethanol,sodiumiodide
studies or the fetal risk was and iodine,methyl
evaluated based on human mercury,leflunomide,iso
experience. These drugs are tretinoin
contraindicated in women who are or
likely to be pregnant
ADRS REPORTING AND
MANAGEMENT PHARMACOVIGILANCE
 WHO defines pharmacovigilance as "science
and activities relating to the detection,
assessment, understanding and prevention of
adverse effects or any other medicine related
problems". The main aim of
pharmacovigilance is to recognize drug-
related adverse effects by gathering,
researching and evaluating data obtained
from the patients and other healthcare bodies.
 Post-marketing pharmacovigilance is an
important tool to identify long-term adverse
effects which often go unnoticed în clinical
trials.
• This is because clinical trails are carried out
for shorter periods as they are very
expensive, and are done on healthy human
volunteers excluding children, elderly and
patients with complicated diseases who are
more susceptible to ADRs
• Strict pharmacovigilance should be carried
out by healthcare professionals. Potential
ADRs can be detected during ward rounds in
the hospital or during review of patient's
medical profile. The following patients are at
high risk of ADRs and should be closely
monitored.
 Patients with renal or hepatic impairment.
 Patients on drugs known to cause ADRs
 Patients on multiple drug therapy.
 Patients with any previous medical history of
allergenic reactions.
 The information required for detecting ADRs is as
follows,
 Demographic data of the patients.
 Details of suspected ADR such as onset and
duration, severity, dose, frequency, route of
administration of the offending drug and its plasma
levels.
 Previous medical history of the patients.
 Details of drug therapy (OTC drugs, present
medication).
 Clinical laboratory data of the patients
 The above mentioned information can be sourced
from case details and treatment chart of patients,
laboratory data interaction with the patient himself
and by interaction with other healthcare
professionals.
 The suspected ADR should be documented
in the patient's medical record, which helps
to alert the physicians that the particular
drug is capable of causing an ADR.
Moreover, the ADR should be reported to
the pharmacovigilance centres.
 Earlier, very few novel drugs were
discovered in India and hence the need for
a pharmacovigilance system was less.
India is now rapidly progressing in the field
of drug discovery. There is also a rapid
increase in the marketing of foreign
branded drugs. These developments have
led to the emergence of a strong
pharmacovigilance system in our country
 Pharmacovigilance system in India is regulated by
Schedule Y of the Drugs and Cosmetics Act, 1945.
This Schedule contains all specifications for
conducting trails on animals and humans for the
development of a new drug and requirements of
clinical trails for the import, manufacture and
approval of marketing of a new drug in India. The
Schedule contains a section on post-marketing
surveillance which outlines the details about the
format to be followed for drafting (periodic safety
update reports (PSURs) their submission and PSUR
cycle. It also contains time frames in which these
reports should be submitted to the concerned
authorities. Unexpected and serious adverse effects
in clinical trials are to be reported by the investigator
to the sponsor and to the ethics committee within 24
hours and 7 days respectively. These should be
reported by the sponsor to the licensing authority
within 14 days of occurrence.
Pharmacovigilance for Generic Industry
in India
The generic drug already has a prototype in
the form of innovator (branded) drug with
which it is compared for its pharmacokinetic
properties. The safety data should be similar
for both innovator and generic drugs, but it
is always better to monitor ADRs, if any,
produced in the population upon usage.
Post-marketing surveillance should be strong
enough in such cases.
As India is more involved in the production of
generic drugs, the industries follow the
procedures of monitoring of ADRs, collection
of such data,reporting of spontaneous and
serious unexpected ADRs & preparation of
safety update reports (PSURs) for their products.
Preparation of PSURs by the industries include vast
literature review, management of safety profiles of
drugs, detection of ADRs and analyzing the benefit
to risk ratio of the products
Current System of Reporting ADRs in India
All the reports including safety reports, reports
obtained through post-marketing surveillance,
serious adverse events (SAEs) from clinical trials and
reports from the zonal pharmacovigilance centres
and individual reports, from hospitals, physicians,
patients etc., are submitted to the office of the Drug
Controller General of India where they are saved in
the form of databases. These are made available to
research institutions and pharmaceutical companies.
The reports from the office of DCGI are submitted to
the National Pharmacovigilance Advisory Committee
taking decisions regarding safe drug use.
Requirements for Reporting ADRS
1.Patient Information
Name or record number, date of birth, sex and
weight of the patient are required to be
reported.
2.Details of the Adverse Reaction
Date of onset of the reaction, time required for
reaction to occur from the date of
administration of the drug and a brief
description of the ADR including the affected
body part, severity of reaction etc, are required.
Other relevant information like medical history
of patient, laboratory tests done and the results
obtained should be clearly specified.
3.Information Related to Suspected Drugs
Following details about the drug suspected to
cause adverse reaction is needed,
(a) Brand or generic name whichever is available,
strength of the drug, batch number, expiry date,
reason for use of drug, dosage form used,route of
administration, dosing frequency, duration of drug
therapy and details of other drugs used
simultaneously with the suspected drug.
(b) Details of medical devices used, if any.
4. Information about Management of ADR
Reasons linking the ADR to the suspected drug
should be specified. Reasons for regarding the ADR
as serious should also be mentioned along with the
treatment given to reduce the reaction and the
results of treatment.
5.Reporter Information
Reporter's details like name, contact number,
signature are required. Date of reporting of reaction
and address of the hospital, institution etc., where
therapy was given are also required.
 SPONTANEOUS CASE REPORTS
 Spontaneous case reports are the unsolicited cases
of drugs in market that are reported to the
company either by consumer, lawyer, nurse,
pharmacist, prescriber or sales representative of a
different company. In isolation these reports exhibit
information of limited importance. However they
prove to be important when these are clinically
confirmed by the prescribing physician,
 The adverse effects that are spontaneously
reported can be considered as drug-related even
though the report is only used to enquire about the
drug whether it causes any adverse effect in
patient or not. In certain situations, a case report
from patient describes the adverse effects
(including positive rechallenge) which is very
important information that plays vital role in safety
profile of drug.
 Generally, the spontaneous case reports
describe Type B reactions instead of
pharmacological side effects
 As the database of these reports are
unsolicited, these databases cannot be used
in providing an accurate incidence of adverse
effects (even Type B) because all cases
reported are by someone who acts as
reporter and are unqualified and cannot
recognize the case as an adverse reaction in
patients.
 Sometimes some cases are reported not
because of drugs but due to change in
reporting pattern from time to time since
their launch also because the rate of
reporting of a particular adverse effect
 The spontaneous reports can be advantageous
when they are reviewed properly and thus provide
important signals. Not only they have occasional
individual importance but they also exhibit
consistency of time of onset & pattern of
presentation that are important as well. The
database of this overview is facilitated by
pharmaceutical Health Organization (WHO).
 The database now-a-days is stored electronically
(e.g: imaging) and eliminate the paper transmission
of case reports. During the analysis, the standard
coding dictionary of adverse effect terms and the
method which is accepted as the ‘gold standard'
i.e., Med-DRA (Medical Dictionary for Regulatory
Activities) is used. However, it is important that the
routine review of cases should be done by
experienced and responsible reviewers for
identifying new signals and to ensure patient's
safety.