Drug Safety and Pharmacovigilance with Examples

PPt related to drug safety and pharmacovigilance

1. Drug Safety

2. “Medicines are nothing in
themselves, but are the very
hands of gods if employed with
reason and prudence.”
-Herophilus

3. Allsubstancesarepoisons,
thereisnonethatisnota
poison:therightdose
differentiatesapoisonanda
remedy.
-Paracelsus,16
th
Cent.

4. Historical background
-2000 B.C. Babylonian code of conduct.
-1787 “ digitalis toxicity” by William Withering.
-1961 Thalidomide disaster.
-1968 International drug monitoring centre at Uppsala Sweden
-Nov. 04 National pharmacovigiolance programme .

6. Definitions
Adverse drug event
Adverse drug reaction
Side effect
Pharmacovigilance
Signal

7. Adverse drug event
“Any untoward medical occurrence that may present
during treatment with medicine but does not
necessary have causal relationship with the
treatment. “

8. Adverse drug reaction
“Any response to drug which noxious & unintended
which occurs at doses normally used for prophylaxis,
treatment, diagnosis, or modification of physiological
function.”

9. Side effect
“Any undesirable or unintended consequence
of drug administration.”

10. Pharmacovigilance
“Science & activities relating to the detection,
assessment, understanding & prevention of adverse
effects or any other drug related problem.”
Signal
-reported information on possible causal relation ship
between adverse event & drug.

11. Factors predisposing to ADR
1] RACE -white more susceptible than black.
-rapid & slow acetylators .
-G6PD Deficiency e.g. Africans /Jews.
2] Genetic influence
–plasma pseudocholine esterase
-malignant hyperthermia

12. 3] Gender –
women susceptible to digoxin.
Drug induced lupus is common in female.
4] AGE –
Elderly & anticoagulation.
diuretics & Elderly.
Chloramphenicol –gray baby syndrome.

13. OTHER FACTORS
-allergic disorder.
-previous H/O ADR
-Renal & hepatic disorders
-Plasma protein binding
-Formulation

14. Classifications of ADR
Rowling & Thomson Classification

15. Wills & brown classification

16. Incidence

17. Time dependent classification

18. Classification based on severity

19. Causality assessment scales
WHO Probability scale
Naranjo scale
ABO European scale
Karch & lasagna scale
Kramer's scale
Jones scale
Bayesian scale

20. WHO scale
Certain
Probable
Possible
Unlikely

21. Unclassified
Unclassifiable

22. PHARMACOVIGILANCE
Pharmacovigilance(PV) is defined as the science and activities relating
to the detection, assessment, understanding and prevention ofadverse
effects or any otherdrug relatedproblem.
Pharmacovigilance(PV)DrugSafety
Pharmakon-drug +Vigilare-to keep watch =PHARMACOVIGILANCE
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

23. Need of Pharmacovigilance
1959-61 Thalidomide disaster
In 1959 -1961, it was reported in that there
was an outbreak of PHOCOMELIA
(hypoplastic and aplastic limb deformities)
in the new born babies
This led to awareness of adverse
effect of drugs and methods of detecting
them…
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

24. Pharmacovigilance Programme of India
InitiatedwithAIIMS,NewDelhiasNationalCoordination
CenterformonitoringADRsintheCountryJuly2010,
thenshiftedtoIndianPharmacopoeiaCommission(IPC),
Ghaziabadon15thApril2011
Vision:
ToimprovepatientsafetyandwelfareofIndian
population monitoringthedrugsafetyandthereby
reducingtheriskassociatedwiththeuseofmedicines.
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

25. Rationale For ADRReporting
Theinformationcollectedduringclinicaltrialsofdrug
developmentisinevitablyincompletewithregardtopossible
ADRs.Thisismainlybecause:
•Insufficient evidence of safety in Clinical trials
•Limited size of patients
•Narrow & selective population (Age / Sex specific)
•Narrow indications (Only specific disease)
•Limited duration of trials (Phase I to III)
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

26. BENEFITSOFADRREPORTING
•Contributetotheassessmentofbenefits,uses,side effects,
harm, effectiveness and risk of medicines.
•Assess the safety of drug therapies, especially recently
approved drugs.
•MeasuretheeconomicimpactofADRpreventionas
manifestedthroughreducedhospitalization,optimaland
economicaldruguse,andminimizedorganizationalliability.
•Providesupdateddrugsafetyinformationtohealthcare
professionalsandotherstakeholders
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

27. Upgrading packageinsert
Marketing Authorizationrecall.
Batch recall based on clustering ofADR.
Changes in classification-
•from over the counter to prescription onlymedicines.
•Specialprescription
•Restrictedprescription
REGULATORY ACTIONONTHE
BASISOFADRREPORTS
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

28. A lady lodged complaint to Police Officer
about chainsnatchingin herarea.
The police put FIR and arrested the culprits
and no more
snatching in thatarea.
ADRREPORTING
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

29. Lady
Culprits
Chainsnatching
PoliceOfficer
Consumer/Patient(Reporter)
Drug
AdverseEvent
Healthcareprofessional
FIR-Source - Caseforms
Arresting theculprits
No moresnatching
Actiontaken
Outcome
Proving that these culprits involved in Crime or not-Causality
ADRREPORTING
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

30. ADRREPORTINGPROCEDU RE
Who can report ?
What to report ?
Where to report ?
Whom to report ?
How to report ?
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

31. HealthCare
Professionals
Consumer
WHOCANREPORT?
NCC-PvPI
Ghaziabad
AMCs
Indian Pharmacopoeia Commission -Pharmacovigilance Programme ofIndia
Industry

32. All types of adversereactions
•Known orunknown,
•Serious or non-seriousand
•Frequent orrare
Reactions from all types of pharmaceuticalproducts
•Allopathy
•Ayurvedic
•Vaccines
•Medical devicesetc.
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia
WHAT CANREPORT?

33. Indian Pharmacopoeia Commission -Pharmacovigilance Programme ofIndia
HOW&WHOMTOREPORT?
•Use the ‘Suspected Adverse Drug Reaction Reporting
Form/ Medicine side effect Reporting form which are
available on the official website of IPC (www.ipc.gov.in)
to report any ADR.
•Filled ADR form submitted to nearest AMCs
(Department of Pharmacology, AFMC, Pune).
•A reporter can also e-mail the Suspected ADR form at
[email protected].
•Serious ADR should be reported to AMC within 14days.

34. REPORTING
FORM

37. An identifiable patient
A suspected medicinal
product
An identifiable reporting
source
An event or outcome
MINIMUM REQUIREMENTS
FOR REPORTING ADR
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

38. This form is divided into foursections:
A.PatientInformation
B.Suspected AdverseReaction
C.SuspectedMedication(s)
D.ReporterDetails
SUSPECTEDADVERSE DRUG
REACTION REPORTING FORM
FORHCPS
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

39. HOW TO FILL SUSPECTED ADR
REPORTING FORM
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

40. A.PATIENTINFORMATION
A. Patient Information
1. Patient
Initials
2. Age at time of event or date
of birth
3.M □F □ Other □
4.Weight Kgs
Indian Pharmacopoeia Commission,Pharmacovigilance Programme ofIndia

41. B.SUSPECTED ADVERSE REACTION
Indian Pharmacopoeia Commission,Pharmacovigilance Programme ofIndia

42. C.SUSPECTED MEDICATIONS
C. Suspected medication(s)
S.
No
8. Name
(Brand
/Generic)
Manufa
cturer (If
known)
Batc
h No./
Lot
no.
Exp. Date
(if known)
Dose
used
Route
used
Frequen
cy
(OD,BD,
etc.)
Therapy dates Indic
ation
Causal
ity
assess
ment
Date
start
ed
Date
stopped
i
ii.
Indian Pharmacopoeia Commission,Pharmacovigilance Programme ofIndia

43. C.SUSPECTED MEDICATIONS CONT...
Action taken-Mark the appropriate option for the action takenwith
respect to Suspecteddrug.
S.No.
as per
C
9.Action Taken ( Please Tick)
Drug
withdrawn
Dose
increased
Dose
reduced
Dose not
changed
Not
applicable
Unknown
i
ii
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

44. C.SUSPECTED MEDICATIONS
CONT..
•Rechallenge/ Reintroduction -The point at which a drug is again
given to a patient after its previous withdrawal.
•Mark the appropriate option whether the suspected drug reintroduced & reaction
occurred or not or effect unknown.
10.Reaction reappeared after reintroduction ( Please Tick)
S.No. Yes No Effect Unknown Dose
(If reintroduced)
i
ii
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

45. C.CONCOMITANT MEDICATIONS
CONT..
Concomitant medical product (s) information given in the followingtabs.
11.Concomitant medical product including self medication and herbal
remedies with therapy dates (exclude those used to treat reaction)
S.No. Name
(Brand
/Generic)
Dose
used
Route
used
Frequency
(OD, BD,
etc.)
Therapy dates Indication
Date
started
Date
stopped
i
ii
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia

46. D.REPORTER DETAILS
Indian Pharmacopoeia Commission,Pharmacovigilance Programmeof India

47. OTHERIMPORTANTSECTIONSOF ADR
REPORTINGFORM
Indian Pharmacopoeia Commission, Pharmacovigilance Programme ofIndia
15.Outcome (please tickanyone)
□Recovered □Recovering
□NotRecovered □ Fatal
□RecoveredwithSequelae □Unknown
Additional Information:
More information on the ADR report that are not fit in the respective column given
in ADR form can be entered in the filed of additional information (i.e. More
information about suspected drug, indication etc.)

48. COLLECTION,ANALYSISAND
EVALUATIONOFADRs
Indian Pharmacopoeia Commission -Pharmacovigilance Programme ofIndia

49. ADR CASE
Indian Pharmacopoeia Commission -Pharmacovigilance Programme ofIndia

50. •MrSushant A Gupta, a 30-years old male with 68 kg weight was diagnosed as a case of
bacterial meningitis.
•He was started empirically with:
-Inj Ceftriaxone 1g IV BD and
-Inj Vancomycin 500 mg IV QID on 12.01.2016.
•First dose of Inj. Ceftriaxone was given at 8 am and Inj. Vancomycin was given at 9 am on
12.01.2016
•After 10 minutes of second drug administration, he started developing chills, rigors, fever,
urticaria and intense flushing.
•He was treated with Inj. Pheniramine 25 mg IM, following which the reaction completely
subsided. Inj.Ceftriaxonewas continued.
•However, next doses of Inj. Vancomycin scheduled on
day 1were not given.
•Inj Vancomycin • Inj Ceftriaxone
Brand Name: Taximax Brand Name: Vanzid
Manufacturer: WedleyLabs Manufacturer: SWACH Healthcare
Batch number: OPO659 Batch number: KKIL098
Expiry date: Dec 2016 Expiry date: Mar 2016
Indian Pharmacopoeia Commission -Pharmacovigilance Programme ofIndia

51. Lets join hands to promote patientsafety