Escolar Documentos
Profissional Documentos
Cultura Documentos
Pharmacoviglance
Arrangements in New Zealand
New Zealand Pharmacovigilance Centre
Extending NZ initiatives
Future directions
Pharmacovigilance in
New Zealand
Dr Michael Tatley
PRIMUM
NON
NOCERE
First do no harm
Earliest ADRs
The Foxglove, when given in very large and quickly repeated
doses, occasions sickness, vomiting, purging, giddiness,
confused vision, objects appearing green or yellow,
increased secretion of urine with frequent motions to part
with it, and sometimes inability to retain it; slow pulse,
even as low as 35 in a minute, cold sweats, convulsions,
syncope and death.
William Withering 1785
Hippocrates (500BC)
Withering established
The adverse effects of digitalis
ADRs occur with every medicine
A dose-response relationship and, possibly, the
concept of therapeutic index
Harms can be reduced by dose titration
Chloroform
Streptomycin
Chloramphenicol
Phenacetin
Isoniazid
Cardiac Arrest
Deafness, Renal failure
Aplastic anemia
Nephropathy
Hepatitis
1977
1978
1979
1980
1981
1961 Thalidomide
Phocomelia
1962
1963
1964
SLE
Retinopathy
GI Bleeding
Agranulocytosis
Agranulocytosis
Addiction
Thromboembolism
Haemolytic anemia
Nephrotic syndrome
Polyneurophathy/Pneumonitis
Urinary tract carcinoma
Hepatic injury
Vaginal carcinoma (offspring)
Cholestatic hepatitis
Hypo/Hyper thyroid
Stevens Johnson
Sclerosing peritonitis
Agranulocytosis
Anaphylactic shock
1965
1966
1968
1970
1971
1972
1973
1974
1975
1976
Procainamide
Choroquine
Aspirin & NSAIDs
Anti-thyroids
Sulphonamides
Barbiturates
OCs
Methyldopa
Hg Diuretics
Nitrofurantoin
Phenacetin
INH/Rifampicin
Diethylstilbestrol
Erythromycin
Amiodarone
Co-trimoxazole
Practolol
Clozapine
Glafenine
1982
1983
1984
1985
1986
1988
1989
1990
1991
1994
1995
1996
1997
1999
2000
2001
2004
2009
2010
Influenza Vaccine
Perhexiline
Triazolam
Tielenic acid
Ticlodipine
Penicillamine
Fenfluramine
Ketoconazole
Zomepirac
Valproate Sodium
Mianserin
Nomfenasine
Ceftriaxone
Fenoterol
Pirprofen
Deferrioxamine
Fluoroquinolones
Tiaprofenic Acid
Mefloquine
Indinavir
Polyneuropathy, Hepatitis
Psychosis/Behaviour problems
Hepatic/Renal Injury
Agranulocytosis
Auto-immune disease induction
Pulmonary HPT
Hepatitis
Anaphylactic shock
Spina bifida
Agranulocytosis
Fever, Hepatitis, Haemolytic anem
Biliary lithiasis
Asthma mortality increases
Hepatitis
Opportunisitic infection
Achilles Tendinitis & Rupture
Cystitis
CNS effects
Haemolytic Anemia
Thromboembolism (NZ)
Rhabdomyolysis
Cardiovascular Mortality
Cardiac Safety
Cardiac Safety
Rotavirus Vaccine
Intussusception
No Response
Pharmacovigilance
- the early detection of unknown adverse
reactions and interactions.
including
adverse events that follow immunisation that are
believed to be caused by the immunisation
ACC (NZ)
. but
Why Pharmacovigilance ?
Action of drugs not purely selective
Many drug safety related issues have been identified
Considerable impact
efficacy oriented
too small
patient exclusions
Davis P, et al. Adverse events in New Zealand public hospitals Principal findings
from a National Survey. Occasional Paper No3 www.moh.govt.nz
Paul Browne et al Cost of medical injury in NZ: a retrospective cohort study. J. Health Serv Res Policy,7,s1, July 2002
spontaneous reports
selected medicines
selected vaccines
medication error
Reporter
Ministry
VMP
academic
patient
Pharmacovigilance Stakeholders
Ministry of Health
M2
MedSafe
HQSC
Medicines Assessment
Advisory Committee (MAAC)
Immunisation
Programme
GPs & PHOs
NZ Pharmacovigilance Centre
Community
Pharmacists
Pharma
bpac
Spontaneous
Reporting
Programme
Medication
Error
Reporting
Programme
PHARMAC
MARC
Medsafe
NZPhvC
Media
Health Quality &
Safety Commission
District Health
Boards
National Minimum
Dataset (NHI/MWS)
NPC
Universities &
Teaching Institutions
Public
What to Report ?
ANY EVENT OR REACTION
THOUGHT TO BE MEDICINE OR
VACCINE RELATED
adverse reactions of clinical concern
all adverse reactions to new medicines
all serious allergic reactions
drug interactions
Report Sources
www.otago.ac.nz/carm
Other
70%
Drug Co.
60%
Hospital
50%
40%
Pharmacist
30%
Nurses
20%
Doctors
10%
0%
All Reports
Vaccines
NHP's
Report processing
EACH REACTION IS:
opinion of experts
- local / international
Certain
Probable
WHO-method
~ Karch & Lasagne
Possible
Unlikely
Unclassifiable
1. Patterns of reactions
MMR
7
Infanrix-Hexa
Prevenar
Hib
MMR
1.40
Infanrix-IPV
1.20
Rate/1000 vaccines
5
4
3
2
1
Reaction Groups
CV
S
IA
TR
IC
PS
YC
H
1.00
0.80
0.60
0.40
0.20
0.00
K0
90
3
K2
58
5
K5
74
1
K5
74
2
K5
98
3
N0
88
8
N1
76
6
N2
41
2
N2
56
3
N2
56
4
N2
74
6
N2
74
7
N3
10
0
N3
64
7
R0
54
0
R0
54
1
NE
UR
OL
OG
IC
AL
'T
Y
HY
PE
RS
EN
S
SO
MA
TI
C
0
LO
CA
L
Batch #
Oxycodone
Brandswitch patterns
12
10
10
6
4
6
4
0
Aug
Sep
Oct
Nov
Dec
Jan
Feb
Mar
Apr
May
Jun
01
01
01
01
01
02
02
02
02
02
02
Oxycodone
Impetus for
prescriber
reminders
Spontaneous Monitoring
Statins & psychiatric reactions
Leflunomide and pneumonitis
WHO Collaborating
Centre
Dyspnoea = 10
Peripheral oedema = 1
Peripheral oedema & Pulmonary symptoms = 2
Cardiac failure = 3
BNP increased = 2
Spontaneous Reporting
>124 countries
>12million reactions in
database
(SRPs)
The advantages
Uppsala, Sweden
Easy to implement
Inexpensive
Covers all medicines
Rare reactions identifiable
Spontaneous Reporting
Practolol
(SRPs)
The disadvantages
Incomplete (<10%)
No denominator
proportional reporting rates at best
BCPNN
NZPhvC Activities
Adapting Pharmacovigilance
35
30
25
MeNZB+Routine
15
10
5
S
CV
OT
HE
R
SL
HA
EE
P
EM
AT
OL
OG
IC
AL
CA
SI
V
OG
I
NE
UR
OL
tic
ari
a
Ur
NV
UL
CO
AN
XI
ET
Y
HY
PE
RS
EN
S'
TY
SO
MA
TI
C
LO
6/52
Routine
20
CA
L
Reaction Groups
Extending Pharmacovigilance
Medication errors
Missed opportunities lessons
Formulation
Preparation
Route
Dose adjustments
Device
Drug interactions
Drug omission
Under dosing
Monitoring in chronic Rx
Underlying disease
Davis P, et al. Adverse events in New Zealand public hospitals Principal findings
from a National Survey. Occasional Paper No3 www.moh.govt.nz
Paul Browne et al Cost of medical injury in NZ: a retrospective cohort study. J. Health Serv Res Policy,7,s1, July 2002
Pharmacovigilance Synergies
Medication errors
90
80
70
60
50
40
30
20
10
0
2012
2013
2014
90
80
Female
70
60
Male
50
40
30
Unknown
20
10
Pregnan
t female
0
<12 years 12-17
years
18-44
years
45-64
years
65-74
years
> 75
years
Unknown
10
Synthetic Cannabinoids
Adverse Reaction - SOCs
Using NZ Pharmacovigilance
Data
Medication errors
Synthetic Cannabinoids
Psychiatric Events
M2
M2
Highlight potential safety issues from reports of suspected ADRs
Stimulate further reports & information about these potential safety signals.
Using NZ Pharmacovigilance
Data 2
Medication errors
M2
SMARS
SMARS
11
Using NZ Pharmacovigilance
Data
Medication errors
M2
SMARS
New directions.
Broadening the PhV toolbox
New and Enhanced Pharmacovigilance tools Research
Phv Research Network
Conclusion
SUMMARY
12