Adverse drug reaction , types ,Detection and Reporting,severity and seriousness(Hartwig'severity assessment), preventibility(Schumock and thornston) and predictability, causality assessment Naranjo"s algotithm, WHO UMC causality scale

1. ADVERSE DRUG REACTION
SUBMITTED To:-
DR. NIRMAL SINGH
(HEAD OF DEPARTMENT OF PHARMACEUTICAL SCIENCES)
SUBMITTED BY:-
SHUBHAM CHAUDHARY
M.PHARMACY (PHARMACOLOGY)
PUNJABI UNIVERSITY PATIALA,
PUNJAB

2. Definitions
ADVERSE DRUG REACTION
“A response to a drug which is noxious and unintended and which occurs at doses normally used
in man for prophylaxis, diagnosis, or therapy of disease.
ADVERSE DRUG EVENT
The World Health Organization (WHO) defines an ADE as “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”
SERIOUS ADVERSE EVENT OR SERIOUS ADR
Any untoward medical occurance that at any dose cause :
• result in death
• is life threatening
• Requires inpatient hospitalization or prolongation of existing hospitalization
• Results in persistent or significant disability/incapacity
• Or is congenital anomly/birth defect

4. Detection and reporting methods
Post– Marketing SurveillancePre- Marketing Studies
PHASE 3
PHASE 2
PHASE 1
Epidemiological
methods
Spontaneous
adverse reaction
reporting
Cohort
Studies
Case Control
Studies
DETECTION OF ADR
Yellow caRd system UK
FDA Medwatch
VAERS(vaccine adverse event
reporting system)
International reporting
system

5. PRE-MARKETING STUDIES
• Although valuable information about ADRs can be obtained from
reviews of premarketing clinical trials
• These trials are often of short duration and the trials may have a
narrow patient population
• A great deal of risk information may be obtained from such tests, such
as the level of acute toxicity and which organs will be affected in
case of toxicity
LIMITATIONS:-
• Animal can only serve as approximate model for humans
• Premarketing studies may not reveal ADRs because of small sample
sizes that lack the power to detect rare ADRs

6. REPORTING of ADR
 Who can Report ?
• All healthcare professionals (clinicians, dentists, pharmacists, nurses etc)
• Non-healthcare professionals including consumers can report suspected adverse
drug reaction
 Where to Report ?
• All healthcare professionals (clinicians, dentists, pharmacists, nurses) and
patient/consumers can report ADRs to NCC ( National Coordination Centre) or
AMCs( ADR monitoring centres)
• The pharmaceutical companies can also send individual case safety reports for
their product to NCC.

7. What to Report ?
 All types of suspected ADRs reporting whether they are known, unknown,
serious, or nonserious, frequent, or rare regardless of an established causal
relationship between a drug and the reaction.
 Report serious adverse drug reactions. A reaction is serious when the patient
outcome is:
• Life-threatening
• Hospitalization (initial or prolonged)
• Disability (significant, persistent or permanent)
• Congenital anomaly
• Required intervention to prevent permanent impairment or damage
 Mandatory field for suspected ADR reporting form:-
• Patient initial
• Age at onset of reaction Reaction term(s)
• Date of onset of reaction
• Suspected medication(s) and reporter information

8. How to Report ?
 Suspected ADR reporting forms for healthcare professionals and consumers are
available on the website of IPC to report ADR. To remove language barrier in ADR
reporting, the consumer reporting form are made available in 10 vernacular
languages (Hindi, Tamil, Telugu, Kannada, Bengali, Gujarati, Assamese, Marathi,
Oriya, and Malayalam)
What happen to the submitted information ?
ADR reported by HCP, Patient or Other
Causality assessment at AMCs
Forward to NCC-PvPI through ADR database
Data is Analysed & forwarded
Global Pharmacovigilance Database (Managed by WHOUMC)
Reports are periodically reviewed by the NCC-PvPI
Information is submitted to the Steering committee of PvPI
Suggests required interventions

10. Causality assessment of ADR
The causality of ADRs describes the connection between the ADRs appearance and
medicinal product utilization. It requires solid medical judgment based on
observations of its onset and patient’s status.
There are different algorithms for evaluation of causality of ADRs.
• Jones’ algorithm
• Naranjo algorithm
• The Yale algorithm
• Adverse drug reaction advisory committee (ADRAC)
• The WHO Uppsala Monitoring Center (WHO-UMC)
• Kramer’ algorithm

11. Naranjo’s algorithm
This questionnaire was designed by Naranjo et al.for determining the likelihood
of whether an ADR is actually due to the drug rather than a result of other
factors. Probability is assigned via score termed as definite, probable, possible or
doubtful.

12. Scoring
 ≥ 9 = definite ADR
 5-8 = probable ADR
 1-4 = possible ADR
 0 = doubtful ADR

13. WHO-UMC CAUSALITY ASSESSMENT SCALE
Causality term Assessment criteria
Certain • Event or laboratory test abnormality with plausible
time relationship to drug intake.
• Cannot be explained by disease or other drugs
• Response to withdrawal possible(pharmacologically,
pathologically)
• 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 drug
• Response to withdrawal clinically reasonable
• Re-challenge not required
Possible • Event or laboratory test abnormality, with reasonable
time relationship to drug intake
• Could also be explained by disease or other drug
• Information on drug withdrawal may be lacking or
unclear

14. Causality Assessment criteria
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
• Event or laboratory test abnormality
• More data for proper assessment needed or
• Additional data under examination
Conditional/ unclassified
• Report suggesting an adverse reaction
• Cannot be judged because information is
insufficient or contradictory
• Data cannot be supplemented or verified
Unassessable/
unclassifiable

15. Severity and seriousness assessment
 Severity describes the extent to which the ADRs influence the everyday life of the
patient
 Karch and Lasagna classify severity into Mild,Moderate,Severe and lethal.
Severity Description Example
Mild No antidote or treatment is required;
hospitalization is not prolonged
Some Antihistamines(some)
Drowsiness Opioids; constipation
Moderate A change in the treatment (e.g.
modified dosage, addition of a drug),
but no necessarily discontinuation if
drug is required; hospitalization may
be prolonged, or specific treatment
may be required
NSAIDs: Hypertension
Severe ADR may be life threatening and
requires immediate discontinuation of
drug and specific treatment for ADR
ACE inhibitors: Angioedema
Phenothiazines: Abnormal heart
rhythm
Lethal Acetaminophen over
dosage
Contributes to patient’s death

16. Seriousness assessment
 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
• Death
• Life-threatening
• Hospitalization (initial or prolonged)
• Disability or Permanent Damage
• Congenital Anomaly/Birth Defect

17. Hartwig’s Severity Assessment Scale.
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.
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 length of stay.
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:
Moderate:
Severe:
LEVEL 1 and 2
LEVEL 3 and 4
LEVEL 5,6 AND 7

18. Preventability criteria Schumock and Thornston
scale
Preventability was assessed using modified Schumock and Thornton scale . Any answer of
“yes” to any question in this scale suggests that the ADR might have been
preventable.ADRs are categorized as definitely preventable, probably preventable or not
preventable.
Definitely Preventable
o Was there a history of allergy or previous reactions to the drug?
o Was the drug involved inappropriate for the patient’s clinical condition?
o Was the dose, route or frequency of administration inappropriate for the patient’s age, weight or
disease state?
o Was a toxic serum drug concentration (or laboratory monitoring test) documented?
o Was there a known treatment for the Adverse Drug Reaction?
Probably Preventable
o Was required Therapeutic drug monitoring or other necessary laboratory tests not performed?
o Was a drug interaction involved in the ADR?
o Was poor compliance involved in the ADR? Were preventative measures not prescribed or
administered to the patient?
Not Preventable
o If all above criteria not fulfilled

19. Management of ADRs
1. If the reaction is mild
• Continue treatment if necessary
• Stop unnecessary drugs
• Consider dose reduction
• Symptomatic treatment if warranted.
2. If the reaction is serious
• Withdraw suspected (all?) drugs
• Treat urgent
3. If the disease is serious
• Consider the effect of not having treatment
• Continue treatment and treat symptoms of reaction if necessary
• Consider an alternative drug
• Stop unnecessary drugs
Rapid action is sometimes important:-
• First and foremost step is to withdrawal the suspected drug(s)
• If the reaction is likely to be dose related, dose reduction should be consider.

20. Role of Healthcare Professionals in Detecting
ADRs
 Possibility of an ADR should always be considered during differential
diagnosis.
 ADR may be detected during ward round with the medical team.
 Patient counselling , medication history interview and communicating with
other healthcare professional may provide additional clues.
 Patients who are at higher risk should be monitored closely
• Patients with renal or hepatic impairment.
• Patients who had histrory of allergic reactions.
• Patients taking multiple drugs.
• Pregnant and breastfeeding women.

21. THANKYOU