 Definition

 Types of ADRs
 Detection of ADRs
 Severity Assessment
 Seriousness and Predictability Assessment
 Reporting of ADRs
 Reference
 According to WHO Adverse drug reaction is defined as ”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.” Excludes overdose(either
accidental or intentional), drug abuse, treatment failure and drug
administration errors.

 Adverse event is defined as ” Any medical occurrence temporally associated

with the use of a medicinal product, but not necessarily causally related ”
1. Pre- marketing studies
2. Post- marketing surveillance
3. Assessing Causality
4. Communicating ADRs
5. Postal Survey Method
 During the development of new medicines, their safety is tested in animal
models.
 Specific animal studies for carcinogenicity, teratogenicity and mutagenicity are
also available.
 Clinical trials are carried out in 3 different phases prior to the submission of a
marketing authorization application.
 Clinical trials normally identifies ADRs of frequency greater that 0.5-1.0%.
 Pharmavigilance methodologies are used for detection of risk and for the
collection of risk information.
 Powerful and cost effective system for the identification of unknown
drug-related risk is spontaneous adverse drug reactions reporting.
 Health care practitioner should see it as a part of professional duty report
ADR result in a patient under his care.
 Concerned identifying product defect, intoxicants and abuse and unexpected
lack of therapeutic effect.
Cont..
 Two epidemiological methods are most commonly used are :
1. Cohort studies
2. Case-Control studies

1. Cohort studies: Patient exposed to a particular drug are followed up

actively and systematically and ADR frequencies are compared to an
unexposed control population.
2. Case-Control studies
 Individuals affected by the adverse event being studied are identified . Each

case is matched with several disease – free control patients randomly

recruited from the study base.
 Both cases and controls are investigated their exposure to possible
causative agents prior to occurrence of the event.
 The odd ratio calculated on the basis of exposure data.
 Causality assessment is a method by which the extent of relationship
between a drug and a suspected reaction is established.
 If an ADR is suspected, the assessment starts with the collection of all the
relevant data pertaining to patients demographics; medications including
OTCs; time of onset and duration of reaction; treatment of reaction and it's
outcome and reports.

 In assessing causality, any of the following approaches may be appropriate:

- opinion of individual experts
- opinion of penal of experts
- formal algorithms
Cont..

Formal Algorithms

Using formal algorithms, collected data are subjected and assessed by

using one or more standard algorithms.
 Naranjo’s algorithm
 Kartch Lasagna’s algorithm
 WHO probability Scale
 Spanish quantitative imputation scale
 Kramer’s scale
 Jones scale
 European ABO system
 Bayesian System
WHO Probability Scale
 Knowledge about rational and safe use of medicines needs to be
provided,
1. During basic training of health professionals
2. Through continuous education programmes to health professionals.
3. By specially designated drug information centers.
4. Through packaged inserts and patient counseling
 This consists of a specific drug related questionnaire.

 This method is primarily used for ADR monitoring of new drugs.

1-2 years after the drug is launched.

 The questionnaire asks for details of drug, usage, dose, brand

used, number of patients treated in a given period.

 Common ADRs seen with the drug as mentioned in the literature

are listed at the end of questionnaire.

 The questionnaire along with a prepaid envelope is then

mailed to practitioners all over the city/state who are likely to
use the drug.
 Severity describes the extent to which the ADRs influence the
everyday life of a patients.

 Karch and Lasagna classify severity into minor, moderate, severe

and lethal.
1. Mild(Minor)
2. Moderate
3. Severe
4. lethal
Severity Description Example
Mild No antidote or treatment is required; Some Antihistamines(some)
hospitalization is not prolonged Drowsiness
Opioids; constipation

Moderate A change in the treatment (e.g. modified Hormonal contraceptives: Venous

dosage, addition of a drug), but no thrombosis
necessarily discontinuation if drug is NSAIDs: Hypertension and edema
required; hospitalization may be
prolonged, or specific treatment may be
required

Severe ADR may be life threatening and requires ACE inhibitors: Angioedema
immediate discontinuation of drug and Phenothiazines: Abnormal heart
specific treatment for ADR rhythm

Lethal Contributes to patient’s death Acetaminophen over dosage: Liver

failure
Anticoagulants: hemorrhage
 Hartwig et al categorized ADRs into seven levels as per their
severity.

 Level 1 & 2 fall under mild category, level 3 & 4 under moderate
and level 5, 6 & 7 fall under severe category.
Level 1 An ADR occurred but required no change in treatment with the suspected drug

Level 2 The ADR required that treatment with the suspected drug be held, discontinued, or otherwise
changed. No antidote or other treatment requirement was required. No increase in length of stay
(LOS)
Level 3 The ADR required that treatment with the suspected drug be held, discontinued, or otherwise
changed. AND/OR An Antidote or other treatment was required. No increase in LOS

Level 4 Any Level 3 ADR which increases length of stay by at least 1 day. OR The ADR was the reason for
the admission

Level 5 Any Level 4 ADR which requires intensive medical care

Level 6 The adverse reaction caused permanent harm to the patient

Level 7 The adverse reaction either directly or indirectly led to the death of the patient

Mild = Levels 1 and 2; moderate = Levels 3 and 4; severe = Levels 5, 6 and 7.

 Seriousness of an ADR is related to its life threatening nature and is
defined as any untoward reaction to the medicinal product that may
result in death and requires patient hospitalization.

 Seriousness of reaction is categorized according to FDA criteria on the

basis of their life threatening nature.
 Death
 Life-threatening
 Hospitalization (initial or prolonged)
 Disability or Permanent Damage
 Congenital Anomaly/Birth Defect
 Required Intervention to Prevent Permanent Impairment or Damage (Devices)
 According to WHO factsheet, it is estimated that at least 60% of
ADRs are preventable. In some countries ADR-related costs, such
as hospitalization, surgery and lost productivity, exceed the cost of
the medications.

 Historically, studies have shown that between 20% and 80% of

ADEs and ADRs are preventable with the majority of latter studies
showing around 60- 70% preventability.

 Preventability of ADRs is assessed by using Schumock and

Thornton scale.
 Definitely Preventable
1. Was there a history of allergy or previous reactions to the drug?
2. Was the drug involved inappropriate for the patient’s clinical condition?
3. Was the dose, route or frequency of administration inappropriate for the patient’s age, weight or disease state?
4. Was a toxic serum drug concentration (or laboratory monitoring test) documented?
5. Was there a known treatment for the Adverse Drug Reaction?
Probably Preventable
6. Was required Therapeutic drug monitoring or other necessary laboratory tests not performed?
7. Was a drug interaction involved in the ADR?
8. Was poor compliance involved in the ADR?
9. Were preventative measures not prescribed or administered to the patient?
Not preventable
If all above criteria not fulfilled
 Type A(Predictable)
 Extension of pharmacologic effect
 Often predictable and dose dependent
 Responsible foe at least 30% od ADRS
 E.g. anticholinergics and dry mouth

 Type B(unpredictable)
 Idiosyncratic or immunologic reactions
 Rare and unpredictable
 E.g. chloramphenicol and aplastic anemia, penicillin induced
anaphylactic shock
 WHAT TO REPORT
All types of suspected ADRs- irrespective of whether they are known or unknown,
serious or non-serious, frequent or rare and regardless of a established causal
relationship.

 WHO SHOULD REPORT

All health care and non-health care professionals, hospitals, health centres,
consumers, Pharmaceutical companies.
 HOW AND WHOM TO REPORT

Use the “Adverse drug reaction reporting form” which is available on official site of IPC
as well as CDSCO.

Helpline Number : 1800-180-3024

E-mail : [Link]@[Link]
1. Parthasarathy G, Hansen k Nyfort, Nahata CM; A textbook of
Clinical Pharmacy Practice; pp 89-97
2. Schumock GT and Thornton JP. Focusing on the Preventability of
Adverse Drug Reactions. Hosp. Pharm. 1992;27:538.
3. Uppsala Monitoring Centre. Hospital based pharmacovigilance: a
clinical pharmacist’s perspective. Uppsala reports. 2002;20:10–11.
4. G Petrova, A Stoimenova, M Dimitrova. Assessment of the
expectancy, seriousness and severity of adverse drug reactions
reported for chronic obstructive pulmonary disease therapy. SAGE
Open Medicine; Volume 5: 1–8
5. Gogtay NJ, Mangalvedhekar SS, Kshirsagar NA; Adverse Drug
Reaction (ADR) Monitoring in India and the Postal Survey as a
Useful Tool for ADR Detection; Pharmacoepidemiology and drug
safety 2000; 8:235-236