ADVERSE DRUG REACTIONS

AND
SERIOUS ADVERSE EVENTS

Dr. Manjunath.G.N
SSMC
Tumkur
Definition

 Any occurrence or worsening of an

undesirable or unintended sign, symptom
(including an abnormal laboratory finding), or
disease temporally associated with the use of
a medicinal product/procedure, whether or
not related to the medicinal
product/procedure.
Types

 Dose related (Predictable – type A)

 Non dose related (Unpredictable – type B)
 Long term effects
 Delayed effects
Severity
 Grade 1, Mild: Transient or mild discomfort; no limitation in
activity; no medical intervention/therapy required
 Grade 2, Moderate: Mild to moderate limitation in activity –
some assistance may be needed; no or minimal medical
intervention/therapy required
 Grade 3, Severe: Marked limitation in activity, some
assistance usually required; medical intervention/therapy
required and hospitalization possible
 Grade 4, Life-Threatening: Extreme limitation in activity,
significant assistance required; significant medical
intervention/therapy required; hospitalization or hospice
care probable
Incidence

 Hospital in-patients – 10-20%

 Deaths in hospital in-patients - 0.24-2.9%
 Hospital admissions – 0.3-5%
Classification of ADR
 Dose related
1.Pharmaceutical variation
2.Pharmacokinetic variation
a) Pharmacogenetic variation
b) Hepatic disease
c) Renal disease
d) Cardiac disease
3.Pharmacodynamic variation
a) Hepatic disease
b) Altered fluid and electrolyte imbalance
Contd.

 Non dose related

a) Immunological reaction
b) Pharmacogenetic variation
 Long term effects
a) Adaptive changes
b) Rebound phenomena
c) Other long term effects
Contd.

 Delayed effects
a) Carcinogenesis
b) Effects connected with reproduction
a) Impaired infertility
b) Teratogenesis
c) Drugs in breast milk
Various ADR

 Side effects
 Secondary effects
 Toxic effects
 Intolerance
– quantitative
- qualitative 1. Idiosyncracy
2. Hypersensitivity
 Photosensitization
Contd.

 Drug withdrawal reaction

 Drug dependence
 Teratogenecity
 Carcinogenecity/mutagenecity
 Iatrogenecity
Manifestations of ADR

 Haemopoietic toxicity
 Hepatotoxicty- direct

immunological
 Nephrotoxicity
 Ocular toxicity
 Ototoxicity
Contd.
 Behavioural toxicity
 Electrolyte imbalance
 Endocrine disturbance
 Skin toxicity
 Unmasking and exacerbation of disease
 Acute withdrawal reaction
Contd.

 Carcinogenesis
 Teratogenesis
 Alteration
of taste
 Drug dependance
 Types of ADR

Type Type of effect Features examples

A Augmented Common, predictable, low mortality Bradycardia–β-blockers

B Bizarre Uncommon, unpredictable, high morbidity & Anaphylaxis - Penicillin

high mortality

C Chronic Dose related & time related Dyskinesia - Levodopa

D Delayed Time Related Teratogenesis

E End of use Withdrawal of chronic therapy abruptly Corticosteroids

F Failure Unexpected failure of therapy Oral contraceptive failure -

Rifampin
What is a Serious Adverse Event?

A serious adverse event or reaction is

defined as any adverse event that suggests a
significant contraindication to ongoing
therapy
 Criteria

1.Death
Report if the patient's death is suspected as being a direct
outcome of the adverse event.
2.Life-Threatening
Report if the patient was at substantial risk of dying at the time
of the adverse event or it is suspected that the use or continued
use of the product would result in the patient's death.
Examples: Pacemaker failure; gastrointestinal hemorrhage;
bone marrow suppression; infusion pump failure which permits
uncontrolled free flow resulting in excessive drug dosing.
3.Hospitalization (initial or prolonged)
Report if admission to the hospital or prolongation of a hospital
stay results because of the adverse event.
Examples: Anaphylaxis;or bleeding causing or prolonging
hospitalization.
4.Disability
Report if the adverse event resulted in a significant, persistent,
or permanent change, impairment, damage or disruption in the
patient's body function/structure, physical activities or quality of
life.
Examples: Cerebrovascular accident due to drug-induced
hypercoagulability; toxicity; peripheral neuropathy.
6. Requires Congenital Anomaly
Report if there are suspicions that exposure to a medical product prior
to conception or during pregnancy resulted in an adverse outcome in
the child.
Examples: Vaginal cancer in female offspring from diethylstilbestrol
during pregnancy; malformation in the offspring caused by thalidomide.
7. Intervention to Prevent Permanent Impairment or Damage
Report if you suspect that the use of a medical product may result in a
condition which required medical or surgical intervention to preclude
permanent impairment or damage to a patient.
Examples: Acetaminophen overdose-induced hepatotoxicity requiring
treatment with acetylcysteine to prevent permanent damage;
breakage of a screw requiring replacement of hardware to prevent
malunion of a fractured long bone.
Schedule Y requirement

 Unsuspected adverse event is

communicated from
1.Sponsor to regulatory authorities within 14
days
2. Investigator to sponsor within 24 hours
3. Investigator to ethics committee
within 7 days
Serious Adverse Event Reporting

 Within 24 hours of the event, complete a serious

adverse event form
 Fax supporting documentation
– Narrative summary
– Discharge summary (if applicable)
– Laboratory tests, consultation and biopsy reports, and/or
any other reports
– Any additional information related to the event
– All information contained in the form should be supported
by source documentation
External SAEs - outside the site

Is the event serious?

Internal SAEs

Is the event serious?

Thank you

Dr.Manjunath