ADR Reporting, Medication

Error Reporting System

(MERS) & Cold Chain
Management
Updates from ‘Bengkel Laporan Kesan
Advers Ubat-Ubatan dan Vaksin’
18-20 March 2009
Organized By: Bahagian Perkhidmatan
Farmasi, KKM
 Pharmacovigilance:
Ensuring the Safe use of
Medicine and Role of
Pharmacists
Registration Criteria
 Efficacy
– Evaluated from data obtained from clinical trials
 Quality
– Compliance to established standards,
manufacture by GMP licensed premise
 Safety**
– Toxicology, clinical trials

** (Very limited information)

(Further established through post registration studies)
(Discovering new dangers of drugs after marketing is common)
What is Pharmacovigilance
(PV)?
 The science and activities
relating to the detection,
assessment, understanding
and prevention of adverse
effects or any other medicine-
related problem - WHO
Why is PV needed?
HISTORY
 Registration of New Chemical Entities was
very much dependent on the status of
products in the reference countries
 Changes to product information was mainly
industry driven
 Few pre-clinical studies conducted in the
region and hardly any Phase IV studies
 Adverse drug reaction reporting was very
minimal involved reports submitted by
health care professionals
CONT…..
 Most reports were for known reactions
involving older drugs which were used in
government-run hospitals
 Signal detection not possible as there were too
few reports
 Only able to detect some quality defects of
generics which manifested as ADRs
 Pharmacovigilance was mainly about getting
ADR reports and submitting them to WHO
 No significant regulatory changes made based
on these reports
CURRENT SCENARIO
 Increased awareness and interest
amongst doctors and pharmacists to
report ADRS as they have seen some
benefit in reporting
 Increasing number of clinical trials being
conducted especially in Singapore,
Thailand and Malaysia
 GCP training for investigators served to
increase awareness of SAE and ADR
reporting amongst health care
professionals and the industry
CONT….
 More hospitals and companies using
on-line reporting system – less hassle
than submitting hard copy reports
 Increasing involvement by hospital
pharmacists in pharmacovigilance –
during clinical ward rounds and when
counseling patients
The aims of
Phamacovigilance
 To improve patient care and safety
 To improve public health and safety
 To contribute to the assessment of
benefit, harm, effectiveness and
risk of medicines
 To promote understanding,
education and clinical training
Who are the partners?
 Government
 Industry
 Hospitals and academia
 Medical and pharmaceutical associations
 Poisons information centres
 Health professionals
 Patients
 Consumers
 Media
 WHO
 DEFINITION
 Adverse Drug Reaction
 "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 modification of
physiological function."
 Adverse Event
 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
 Side Effect
 Any unintended effect of a pharmaceutical product
occurring at doses normally used in man which is
related to the pharmacological properties of the
drug
 WHAT TO REPORT?
SERIOUS ADRS
 A serious adverse event (experience) or reaction is
any untoward medical occurrence that at any dose:
– results in death,
– is life-threatening,
– requires inpatient hospitalization of prolongation of
existing hospitalization,
– is a congenital anomaly/birth defect.
NOTE: The term “life-threatening” in the definition of
“serious” refers to an event in which the patient
was at risk of death at the time of the event; it
does not refer to an event which hypothetically
might have caused death if it was more severe.
Adverse Reactions: Possible
Causes
 Intrinsic factors of the drug
 Pharmacological
 Idiosyncratic
 Carcinogenicity, Mutagenicity
 Teratogenicity
 Extrinsic factors
 Adulterants
 Contamination
 Underlying medical conditions
 Interactions
 Wrong usage
 WHAT SHOULD BE
REPORTED
 New drugs
– Report all suspected reactions including
minor ones
 For established or well known drugs
– All serious, unexpected, unusual ADRs
 Change in frequency of a given
reaction
 ADRs to generics not seen with
innovator products
 ADRs to traditional medicines
 WHAT SHOULD BE
REPORTED
 All suspected drug-drug, drug-food,
drug-food supplement interactions
– Statement highlighting marine source of
supplements such as glucosamine so that
can be avoided by those with allergy to
sea food
 ADRs associated with drug withdrawals
 ADRs due to medication errors
 eg vincristine given IT
 ADRs due to lack of efficacy or
suspected pharmaceutical defects
 INNOVATOR PRODUCTS
 Limited information available at time
when drug is first marketed
 Minimal information on use in Asian
population, interactions with
indigenous medicines
 Conduct intensive monitoring to
identify new, unlabeled adverse
reactions, monitor for ‘rare reactions’
 Provide updates to prescribers on
new findings, labeling changes,
safety issues
GENERIC PRODUCTS
 Monitor efficacy  Does the problem
 Monitor adverse arise due to ADR
effect profile to or quality defects?
study differences  Problems
in ADR pattern appearing in
sequence
compared with  Abrupt increase in
innovator products frequency
 Help in improving  Problem only
quality of generics arises with certain
used brands
 NON-PRESCRIPTION
MEDICATIONS
 Quality defects can also lead to ADRs
e.g. Pan Pharmaceuticals (Australia)
case
 Patients can develop ADRs to food
supplements, “health products”
 Overuse of supplements
 Current issue of dioxin contamination in
Cod Liver Oil preparations resulting in
product withdrawals in UK
 TRADITIONAL & COMPLEMENTARY
MEDICINES
 Minimal information available on traditional
medicines
– ADRs
– Drug interactions
– At risk groups e.g. alfalfa and exacerbation of
SLE
 Misnomer of “because it is natural, it is safe
– Association of Black Cohosh with liver problems
 Health professionals should try to get as much
information as possible
– Name of product
– Indication
– Place of purchase (esp for unregistered
products)
 PREGNANCY
 Very little information on outcome
data for drugs used in pregnancy
– Current issue of association between
lamotrigine use and cleft palate
syndrome
 Should follow-up cases where drugs
are prescribed intentionally or have
been used inadvertently to monitor
outcome of pregnancy, effect to the
foetus/baby
 COMMUNICATING THE
OUTCOME OF PV
 DHCP Letter – product holders
 Product Alerts – National Health
Authorities
 Media statements - National Health
Authorities/Pharmacovigilance Centres
 Newsletters – National Pharmacovigilance
Centres and WHO
 Feedback to reporters – National
Pharmacovigilance Centres
 INTERNATIONAL
COOPERATION

MALAYSI
A
WHO

OTHER REGULATORY AGENCIES eg

USFDA, EMEA, TGA, HSA
 WHO PROGRAMME FOR
INTERNATIONAL DRUG
MONITORING
 Started 1968
 Located in Uppsala, Sweden
 Collaborating centre for maintaining
global ADR database – Vigibase
 The National Drug Safety Monitoring
Centre, was accepted as the 30th
member of the WHO Safety Monitoring
Program in 1990.
Roles of WHO Collaborating
Centre
 Identify early warning signals of
serious adverse reactions to
medicines
 Evaluate the hazard
 Undertake research into the
mechanisms of action to aid the
development of safer and more
effective medicines
SO….WHAT IS OUR ROLE?
 SEND NOT
ONLY
QUANTITY
BUT….

QUALITY
REPORTS
 HOW?

 Monitor clinical status of patients

 Identify the correct ADRs not side
effects
 Get more information
 Investigate at hospital level
 Help doctors to fill-up the forms
 Keep patient’s record if more
information needed
Recognizing, Reporting
and Reducing Adverse
Drug Reactions
 Limitations of Clinical
Trials
 too few - normally < than 1500
patients
 too simple - use patients without
complications, other medical
conditions
 too narrow - limited indications
 too brief - limited time
 too median - very old/very young
patients, pregnant women not included
 Classification of ADRs
 Type A (Augmented ) reactions
 Reactions which can be predicted from
the known pharmacology of the drug
 Dose dependent, can be alleviated by a
dose reduction
 E.g. Bleeding with anticoagulants,
bradycardia with beta blockers,
headache with nitrates, postural
hypotension with prazosin
 Classification of ADRs
 Type B (Bizarre) reactions
Cannot be predicted from the
pharmacology of the drug
Not dose dependent, host
dependent factors important
in pre-disposition
E.g. anaphylaxis with
penicillin, anticonvulsant
hypersensitivity
 Classification of ADRs
 Type C (Chemical) reactions
 Biological characteristics can be predicted
from the chemical structure of the
drug/metabolite
 E.g. paracetamol hepatotoxicity
 Type D (Delayed) reactions
 Occur after many years of treatment. Can be
due to accumulation
 E.g. Secondary tumours after treatment with
chemotherapy, teratogenic effects of
phenytoin taken during pregnancy, analgesic
nephropathy, tardive dyskinesia with
antipsychotic agents
 Classification of ADRs
 Type E ( End of treatment) reactions
Occur on withdrawal especially
when drug is stopped abruptly
E.g. withdrawal seizures on stopping
phenytoin, adrenocortical
insufficiency on withdrawal of
steroids
 How to recognize ADRs?

 Since ADRs may act through

the same physiological and
pathological pathways as
different disease, they are
difficult and sometimes
impossible to distinguish
 Drug administered

Pt develops a new condition/symptoms

Drug suspected?

Check literature

Documented ?– (for the product

or similar class of products)

Highly suggestive of
ADR
 Not documented in literature

Drug continued Drug discontinued

Symptoms improve
Worsening of (+ve dechallenge)
symptoms

Drug restarted

Any other possible causes?

• Concomitant therapy
Symptoms recur
• Underlying conditions (+ve rechallenge)
Definitions
 Dechallenge – withdrawing the
drug(s) and recording the
outcome – improved or not
improved
 Rechallenge – giving one drug
again under the same conditions
as before and recording the
outcome – recurrence or no
recurrence.
Preventing, Reducing and
Reporting ADRs
 Completely avoiding ADRs may
be impossible
 Some simple approaches to
prevent the occurrence can be
applied
HOW?
 Charting all medications when ordered and
refilled – drug allergies, types of allergy
 Close attention to the written prescription –
correct dosing, proper dosage form, avoid
abbreviations, cautious of drugs with
similar names
 Being familiar with all potential side effects,
interactions
 Choosing the oral route when possible
 Taking careful history of patients esp.
elderly pts
CONT….
 Initiate a committee of Post-Marketing
Drug Risk Management at hospital
level
 Initiate active surveillance (rather than
relying on spontaneous reporting)
 Assess whether physicians are
following recommended DCA
warnings
 Having a high index of suspicion for
ADRs
 ADR Reporting

 Intensive safety surveillance

New Zealand
 Prescription event
monitoring
US, UK
 Spontaneous adverse drug
reaction monitoring
Australia, Malaysia
 SPONTANEOUS
REPORTING SYSTEM
 Passive surveillance system
 Spontaneous ADR reporting
system has 3 phases:
 Data collection most
problematic
 Data processing

 Data analysis and interpretation

 HOW TO REPORT?
 ONLINE REPORTING
 www.bpfk.gov.my
 ADR forms

REPORTING MECHANISM
 Directly by the prescribers
 Through the pharmacists
 Through the drug companies
 CAUSALITY
ASSESSMENT OF
SUSPECTED ADVERSE
DRUG REACTION
 INTRODUCTION

 Spontaneous reporting system –

data acquisition, assessment,
presentation and interpretation.
 Causality assessment – part of
the 1st step in case assessment
and is based on a general system
that is intended for all reactions
and all drug.
 Standardized case causality
assessment has become a routine at
pharmacovigilance centre around the
world.
 Decrease the ambiguity of the data
and prevention of erroneous
conclusion
 It neither eliminates nor quantifies
uncertainty but, at best, categorizes it
in a semi quantitative way
 METHODS OF CAUSALITY
ASSESSMENT
There were several method that can be use to
make a causality assessment of ADRs reports.
 The literature (9 points of consideration –
Morges, Switzerland , 1981)
 Probability calculation (Bayes’ Theorem)
 Aetiological – Diagnostic Systems (Bénchiou’s
group method)
 French imputation systems
 The European ABO Systems
 The US Reasonable Possibility Systems
 The Naranjo ADR Probability Scale
 WHO Causality Categories
The Naranjo ADR Probability Scale
Questions Yes No Don’t
Know
1) Are there previous conclusive reports on this +1 0 0
reaction?
2) Did the ADR appear after the suspected drug +2 -1 0
was administered?
3) Did the ADR improve when the drug was +1 0 0
discontinued?
4) Did the ADR appear with re-challenge? +2 -1 0
5) Are there alternative causes for the ADR? -1 +2 0
6) Did the reaction appear when placebo was -1 +1 0
given?
7) Was the drug detected in blood at toxic levels? +1 0 0

8) Was the reaction more severe when the dose +1 0 0

was increased, or less severe when the dose was
decreased?
9) Did the patient have a similar reaction to the +1 0 0
same or similar drug in any previous exposure?
10) Was the ADR confirmed by any objective +1 0 0
evidence?
 The Naranjo Probability
Scale
The score :-

> 8 = Highly probable

5-8 = probable
1-4 = possible
0 = doubtful
WHO Causality Categories

 C1 – Certain
 C2 – Probable

 C3 – Possible

 C4 – Unlikely

 C5 – Unclassifiable
WHO Causality Categories
 C1: Plausible time, not related to
underlying condition, concurrent
disease, other drugs or chemicals,
related pharmacologically, +ve
dechallenge, +ve rechallenge
 C2: Reasonable time, unlikely to be
related to concurrent disease, other
drugs,+ve dechallenge, no rechallenge
CAUSALITY ASSESSMENT
 C3: Reasonable time, may be due to
concurrent disease, other drugs, no
information on dechallenge
 C4: Improbable temporal relationship,
other confounding factors such as
drugs, chemicals, underlying disease
 C5: Insufficient information to analyse
the report
 Case causality
assessment
 How close is the relationship
between drug and event?
 Did the drug cause the
event?
 CONSUMERS
MEDICINES
SURVEILLANCE
The protocol for the medicines
surveillance integrating
consumer reporting
 The surveillance of medicines
integrating consumer reporting will be
an extension and expansion of the
existing surveillance activities carried
out by NPCB
 NPCB will be the focal point which will
receive, analyze and investigate the
reports submitted by the consumers.
The importance of involving
consumer in medicines surveillance
 The ultimate goal is to improve the
quality, efficacy and safety of the
marketed product
 Empower consumers to be aware of
 Quality
 Safety
 Correct usage of medication
 Alleviate the problem of consumers
wasting their valuable resources on
medicines which may expose their
health to risks.
 Reporting by consumers can be done
through
 Reporting forms
 On-line reporting
 Other channels eg: letters, phone calls,
emails and complaints done personally to
Drug Regulatory Agencies (DRA)
 Information channeled through health
professionals, the product owner, consumer
associations or other trade and industry
organizations which will then be directed to
NPCB
What to report?
 Quality defects
 Lack of efficacy
 Adverse drug reactions
 Suspected counterfeit product
 Unregistered product
 Suspected adulterated products
 Medication error / near misses
 Fraudulent / misleading claims
 WORK PROCESS
Receive product complaint

Verify registration status

Inform reg. holder without BPFK conduct own

identifying complainant investigations based on
- Must respond with findings within 2 wks nature of complaint

Decide on action to be taken based on outcome of the findings

-Product recall
- Intensified surveillance
-GMP inspection of premises, of manufacturer/other products
-No generalised action because problem is not due to product per se

Inform complainant on action

taken
QAP indicator: 85% of all complaints received must be resolved within 6 weeks
 Quality Defects

Can arise due to

 Manufacturing problems

 Improper storage and handling

by
 Manufacturer / distributor
 End user
 Inappropriate handling during
repacking
Decision Making Process
 Problem identified confined to a
particular batch
 Batch recall
 Warning letter

 Problem involves product in general

 Total product recall
 Suspension / cancellation of registration

 GMP inspection of premise

– Cancellation of manufacturing license
 Legal action if necessary
 Regulatory actions taken
 Active ingredients withdrawn
 Revocation of product,
manufacturing license
 Product withdrawn from the market
 Restriction of usage
 Carries a warning
 Precautionary statement included
 Review of labeling requirements
 Make changes to product information
based on new findings
Report acknowledgement

 All complainants will receive an

acknowledgement from NPCB
 Information on actions which are
taken based on the report will
be made known to the
complainant after the necessary
actions have been taken
 Confidentiality

 The confidentiality of complaints

will be maintained as far as
possible
 Only the outcome of actions
may need to be publicized in the
interest of public safety
 REPORTING

The information that you p

be used for the sole purpos
The r eporter is require
information is required
any person outside the drug
Links

 Form BPFK 418.3 – Product Comp

ADVERSE EVENTS
FOLLOWING
IMMUNIZATION
Definition of Adverse Events
Following Immunization
“Any adverse event that follows
immunization that is believed to
be caused by the immunization”
 Classification of AEFIs
Vaccine reaction
 Event caused or precipitated by the vaccine when
given correctly, caused by the inherent properties of
the vaccine
Programme error
 Event caused by an error in vaccine preparation,
handling or administration
Coincidental
 Event that happens after immunization but not
caused by the vaccine – a chance association
Injection reaction
 Event from anxiety about, or pain from, the injection
itself rather than the vaccine
Unknown
 Event’s cause cannot be determined
 A. Vaccine Reactions

 Classified as common, minor reactions

and rare, serious reactions
 Most reactions are minor and settle on
their own
 Serious reactions – very rare and
generally do not result in long-term
problems
 Common, Minor Reactions
 Immune responses such as local
reactions (pain, swelling, redness of
inj. site), systemic reactions (fever,
irritability, malaise, loss of appetite)
 Some vaccine’s components such as
adjuvant, stabilizers or preservatives
can lead to reactions
 Only last for one/two days except
measles/MMR (6-12 days)
 Rare, Serious Reactions

 Eg : seizures,
thrombocytopenia, hypotonic
hyporesponsive episodes,
persistent inconsolable
screaming, anaphylaxis,
paralytic poliomyelitis,
disseminated BCG infection
 Prevention and Treatment

 Rarely contraindicated – check

allergy status (vaccines and its
components)
 Advice parents on managing
common reactions/serious
reactions
 B. Programme Errors

 Result from errors and incidents

in vaccine preparation, handling
or administration
 Eg : reuse of syringes/needles,
incorrect diluents, wrong injection
sites, improper storage/transport,
contraindications ignored
 May lead to a cluster of events
 How to avoid programme
errors?
 Reconstituted with correct diluents
(supplied by manufacturers)
 Discard any leftover at the end of
immunization session
 Provide refrigerator specially for
vaccines
 Trained workers, closely supervised
and procedures followed
 Investigation team for AEFI
 C. Coincidental Events

 Falsely considered to be caused

by immunization (event happens
after immunization)
 Eg : sudden death after the
mass campaign
 D. Injection Reactions

 Unrelated to the content of the

vaccine
 Eg : fainting (older children – due
to stress), hyperventilation,
vomiting, convulsion (due to
anxiety), hysteria (needle-phobic)
 AEFIs vs ADRs
 Vaccines administered to large
numbers of healthy people
 Vaccines not only benefited to
individuals but community as well
 Vaccines given to an entire cohort of
population
 Events normally serious, clusters and
cause public concern
– AEFI is part of the monitoring system of adverse
drug reactions (not similar to individual drugs)
– The priority for immunization safety surveillance
is to identify and correct programme errors
Estimated AEFI Rates Following
Vaccination (WHO figures)
Vaccine Estimated rate
(severe reactions
only)
BCG 1 in 1 000 – 1 in 50 000
doses
Oral Polio Vaccine 1 in 2-3 million doses
(or 1 in 750 000 doses
for the first dose)

Measles 1 in 1 million doses

DTP 1 in 750 000 doses

 Errors Which Can Lead to
AEFIs
 Too much vaccine given/dose
 Improper immunization site or route
 Syringes/needless improperly sterilized
 Incorrect diluents, wrong amount used
 Drug given instead of vaccine
 Vaccine prepared incorrectly (not to be shaken)
 Vaccine/diluent contaminated
 Vaccine stored incorrectly
 Contraindications ignored
 Expired vaccines have been used
 List of reportable AEFIs
Occurring within 24
hours of immunization
Occurring within 5 days
of immunization
Occurring within 15
days of immunization
Occurring within 3
months of immunization
Occurring between 1
and 12 months after
BCG immunization
No time limit
# limit reporting to these events, if only limited reporting capacity
Anaphylactoid reaction (acute hypersensitivity reaction)
· Anaphylaxis
· Persistent (more than 3 hours) inconsolable screaming
· Hypotonic hyporesponsive episode (HHE)
· Toxic shock syndrome (TSS) #
· Severe local reaction #
· Sepsis #
· Injection site abscess (bacterial/sterile) #
· Seizures, including febrile seizures (6-12 days for measles/MMR; 0-2 days for DTP)
· Encephalopathy (6-12 days for measles/MMR; 0-2 days for DTP)
· Acute flaccid paralysis (4-30 days for OPV recipient; 4-75 days for contact)
· Brachial neuritis (2-28 days after tetanus containing vaccine)
· Thrombocytopenia (15-35 days after measles/MMR)
· Lymphadenitis #
· Disseminated BCG infection
· Osteitis/Osteomyelitis
Any death, hospitalization, or other severe and unusual events that are
thought by health workers or the public to be related to immunization #
 Reporting AEFIs
• Who should report?
Peripheral health workers
Detect and report event

Doctors/Pharmacists/Industries
Stimulates report, investigates, filters,
provides feedback, proposes classification

National Drug Safety Monitoring Centre Product holders

Receives, transmits, share database,
evaluates, take action, notifies
WHO
 Reporting AEFIs

 When to report?
 Immediately
 Reporting AEFIs

 How to report?
 ON-LINE REPORTING
 www.bpfk.gov.my

 MANUAL

 ADR Forms (Fax & Mail)

 Reporting AEFIs
 Barriers to reporting?
 Not considering the event as related to
immunization
 Not knowing about the reporting system
and process
 Lethargy – lack of interest/time, inability
to find report form
 Fear that the report will lead to personal
consequences
 Guilt about having caused harm and
being responsible for the event
 Diffidence about reporting an event when
not confident
 Reporting AEFIs
 How to overcome?
 Increase awareness
– Importance of reporting, system of reporting,
user friendly, posters, training, talks
 Emphasizing that investigations are
finding problems, not blaming individuals
 Giving positive feedback for reporting
 Investigating AEFIs
 Which reports should be investigated?
 May have been caused by programme error
 Not listed events defined for AEFI surveillance
 Serious event of unexplained cause
 Causing significant parental or community concern
[accurate denominator of vaccine use (to get the
rate) is important compared to the number of
reports]

 Who should investigate?

 National Drug Safety Monitoring Centre together with
the state/districts committee

 When to investigate?
 As soon as practicable
Why local reports are
important?
 Differ among countries in the occurrence
of AEFIs and other related problems
 Due to differences
 diseases and prescribing practices
 genetics, diet, traditions

 drug manufacturing process

 drug distribution and use

 use of traditional and complementary drugs

Actions taken upon completion of
the investigation/assessment by
DCA
 Recall
 Suspension
 Withdrawal
 Advice – logistics, procedure,
storage, training
 Labeling changes – boxed warning,
CI
 DHCP Letter
 Circulars
 Media
 RATIONAL DRUG USE
 Knowledge of AEFIs should be used
to
 Minimise adverse events in susceptible
patients, at risk groups
 Advice prescribers/consumers on the
proper use of vaccines
 Monitor patients in order to further
enhance knowledge on safety issues
 Provide information to regulators,
decision makers on vaccines being used
so that appropriate action may be taken
if warranted
CASE REPORT - PEDIACEL

A 3-month old female child was vaccinated with a second dose of Pediacel which
contains DPT/Polio/HIB on 29th December 2006 at 9.50am. The child developed
lethargy, poor feeding and intermittent cry with no fever in the afternoon of the
vaccination day.

The child was only brought back to the clinic on 30th December 2006 at about
4.20pm in near collapse condition. The child was pallor with perfusion > 3 second,
heart rate 100/min, poor pulse volume and poor lung function. She was
resuscitated at the clinic but collapsed at 5.45pm. CPR was given for about one
hour but unfortunately the child passed away at 6.45pm. Her body was sent to
Hospital Kajang.

The post mortem was done in Hospital Kajang and the result shown she died due to
Acute Lymphocytic Infiltration to Heart and Mild Endocarditis (viral).

This report was sent to MADRAC on 3rd January 2007. The reporter also reported
that the child was well prior to the 1st dose of Pediacel.
CASE REPORT ON TRITANRIX HB – HiB VACCINE

A 3 month old infant received the 2nd dose Tritanrix HB – HiB and OPV Vaccine given at
Klinik Desa Mata Air. The vaccine was administered intramuscularly into left thigh at around
9am on the 18/06/2008.

Within 2 hours after administration, the baby started crying excessively and soon collapsed.
She was immediately brought to Hospital Tuanku Fauziah, where she was confirmed dead
upon arrival at the hospital.
Previous exposure, 1st dose vaccination with the same vaccine did not result in any adverse
event. The baby was otherwise well with no significant background medical history or known
allergies.

From the post mortem and toxicology findings, the cause of death was interstitial pneumonia.
There is no objective evidence showed the possibility of fatal anaphylaxis reaction
towards the vaccine.

Information from the WHO Immunization Safety Programme, showed the expected rate for
“crying abnormal” and “collapsed” after vaccinated with the DTP was 1/100 dose and
1/1750 doses respectively.

After the discussion, MADRAC agreed that the adverse event “crying abnormal” and
“collapsed” cause by the vaccine. Causality C1 (certain) had been given for the reaction
because, there was no other concomitant drug given together with the vaccine, with a
plausible temporal relation time and there was no other underlying disease which can be
link to the ADR.
CASE REPORT - Pentaxim and Euvax

2 month old male infant received the 1st dose of DTAP-IPV given at Klinik
Kesihatan WP Labuan. The vaccine was administered on 12/1/2009 (time was
unknown). The baby then developed low grade fever at 12.00 noon on the same
day and 1.5mls Syrup Paracetamol given. The baby fed as usual after that. The
mother then noticed that the baby had an injection site swelling and the mother
put a warm compress at the injection site.
The baby was again given Paracetamol Syrup at 8 pm and a last dose at 4 am.
The mother noticed that the infant choked a little after the administration of the
last dose of paracetamol and had fed the child immediately after giving the
medicine. Mother and child went to sleep. At around 6 am the mother found that
the baby was not moving, looked pale and had bleeding from the ears and nose.
The parents brought the baby to the Hospital WP Labuan at 7.50 am. At the
A&E Department the baby was found to have already stopped breathing. The
parents refused to do a postmortem.

Cause of death - UNKNOWN.

Suspected drug - Pentaxim and Euvax
ADR- low grade fever
Concomitant drug – Paracetamol
MADRAC’s Causality – C2
February 13, 2007
The Food and Drug Administration (FDA) is notifying health care providers
and consumers about 28 post-marketing reports of intussusception
following administration of Rotavirus, Live, Oral, Pentavalent vaccine (trade
name RotaTeq), manufactured by Merck and Co., Inc. Intussusception is a
serious and potentially life-threatening condition that occurs when the
intestine gets blocked or twisted. One portion of the intestine telescopes
into a nearby portion, causing the intestinal obstruction. The most common
site is where the small intestine joins the large intestine.
In Malaysia, Rota Teq, marketed by MSD and the company has been
informed to disseminate this information to relevant healthcare
professionals.
 T R E N D L A P O R A N V A K S IN

140 132
120
100
75
80 68
BIL. LAPORAN VAKSIN

60 52
39
40 26
14 10 13
20
0
2000 2001 2002 2003 2004 2005 2006 2007 2008
TAHUN
 T R E N D L A P O R A N A D R D A N V A K S IN

6000
5000 4826
4000
BIL. LAPORAN

B IL . L A P O R A N A D R
3000 3068
2 3 6 32 5 4 3 B IL . L A P O R A N V A K S IN
2000
1665
1000 792 787 1 0 0 01 0 6 3
0 14 10 26 13 52 68 39 75 132
2 0 0 02 0 0 12 0 0 22 0 0 32 0 0 42 0 0 52 0 0 62 0 0 72 0 0 8
T AH U N
THANK YOU