Professional Documents
Culture Documents
CONTENTS
n Interim update on risk of serious
ketoacidosis associated with sodium-glucose
cotransporter-2 (SGLT2) inhibitors......Page 1&2
n Risk of pancreatitis associated with
vemurafenib.........................................Page 2
n Testosterone and risk of cardiovascular
events....................................................Page 3
n Partnership in vigilance: Reporting
adverse events related to health
products................................................Page 4&5
n Azithromycin and drug reaction with
eosinophilia and systemic symptoms
(DRESS)..................................................Page 5
n Recent detection of adulterated
products................................................Page 6
n List of Dear Healthcare Professional
Letters...................................................Page 7
n Risk of intussusception following rotavirus
immunisation in Singapore.................Page 8
Review by
agencies
overseas
regulatory
Local situation
To date, HSA has not received any adverse
reaction report of pancreatitis associated with
vemurafenib. The local package insert (PI) for
Zelboraf currently lists pancreatitis as an
uncommon adverse drug reaction. In view of overseas safety signals,
the local PI has been strengthened to include information on patient
monitoring and detection of pancreatitis.
HSAs advisory
Healthcare professionals are advised to remain vigilant to the possible
signs and symptoms of pancreatitis in patients who are prescribed
vemurafenib, and to consider the possibility of pancreatitis in the
event of unexplained abdominal pain.
References
1 http://www.ema.europa.eu/docs/en_GB/document_library/
Minutes/2012/10/WC500133303.pdf
2 http://www.ema.europa.eu/ema/index.jsp?curl=pages/
medicines/human/medicines/002409/human_med_001544.
jsp&mid=WC0b01ac058001d124
3 http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/
vemurafenib-eng.php
Rationale
Patients details
Initials, gender, age/date of birth
Reporters details
Name, profession, place of practice, contact number, email address
Details of AE
Date of onset/latency, concise description of AE (e.g., type of rash),
severity
Suspected health product(s)
Brand name or active ingredient(s), dose, indication, therapy dates,
batch number*
Concomitant health product(s)
including vaccines, complementary health products consumed at
the same time and/or three months before the AE
Other relevant information
Pre-existing conditions, known allergies, pregnancies, laboratory
tests done and results
Seriousness of event and outcome
Was the patient hospitalised due to the event? Recovery status,
sequelae
Treatment of AE
Yes/No. If Yes, specify the treatment
To identify confounders
* Only for vaccine reports and/or where there are suspected quality defects
continued on Page 5
Azithromycin and drug reaction with eosinophilia and systemic symptoms (DRESS)
HSA would like to highlight to healthcare
professionals overseas cases of drug
reaction with eosinophilia and systemic
symptoms (DRESS) associated with the use of
azithromycin.
By email to HSA_productsafety@hsa.gov.sg
HSAs advisory
Rationale
Source of purchase
(POM)
Type I endoleak,Antineoplastic
migration andagent
aneurysm
growth
For details
of the DHCPL, pleasegrouP
log on to Aflibercept
MOHAlert 25
via mg/ml
your
y
PharmacotheraPeutic
ZALTRAP concentrate for solution for during
infusion
professional
boards
website.
on-going
longer-term
follow-up
of
patients.
Antihypertensive agent (POM)
Aprotinin 2250 3750 KIU/ml,
Tissue
adhesive
local
The findings were
found
to be &
associated
with
Therapeutic products
Calcium chloride 36 44 mol/ml,
haemostatic agent (POM)
thoracic
treated with a single proximal
Systemic
antihistamine
(POM)
Fibrinogen
72 110 mg/ml, Thrombin 400
625 aneurysms
IU/ml
9 Jun 2015
Dobuject
(dobutamine)
Injection
50mg/ml
component
that
resulted
in a short distal seal length
TISSEEL
fibrin
sealant
VH
S/D
(frozen)
(Batch MA00X7F):
and likely inadequate
distal
oversizing
Antineoplastic
agent
(POM)
Ciprofloxacin
2 mg/ml
Otological
agent
(POM)for the device
Important
advisory
to visually inspect
all ampoules
Cetraxal
ear
drops
solution
prior to administration due to presence of
23 Apr 2015 Medtronic DBS System Extensions Models 37085
Ciprofloxacin 3 mg/ml,
precipitation found in Batch MA00X7F
and 37086: Otological agent (POM)
Fluocinolone acetonide 0.25 mg/ml
Oral antidiabetic agent (POM)
Important update on the results from returned
30 Jun 2015 Pomalyst (pomalidomide): Cetraxal Plus ear drops solution
product
analysisPeripherally
of Medtronic
DBSmuscle
system extensions
Updated
product
information
on
risk
of
serious
Clostridium
botulinum
neurotoxin
type
A (150 kD),
acting
Oral antidiabetic agent (POM)
with reports of relaxant
high impedances.
The letter reinforces
free from
complexing
(POM)
hepatotoxicity (acute hepatitis), interstitial
lung
disease proteins 50 LD50 units/vial,
100 LD50 units/vial
device labelling specific to the handling of extensions
andpeptic
cardiac
failure
Agent for
ulcer
&
XEOMIN powder for solution for injection
gastrooesophageal reflux
and performing system integrity checks during implant
9 Jul 2015
Jardiance (empagliflozin):
Donepezil hydrochloride 23 mg
Antidementia agent (POM)
disease (POM)
procedures
Risk of diabetic ketoacidosis (DKA)Aricept
during treatment
film-coated tablet
Systemic antiviral agent (POM)
25mg
May 2015 Pulsar-18, Peripheral
with sodium glucose co-transporter
2 (SGLT2) 600 mg, 1200
Guaifenesin
Cough &Self-expanding
cold preparationNitinol
(GSL) Stent
Mucinex extended-release tablets
System:
inhibitors
Oral antidiabetic agent (POM)
Voluntary
recallImmunoglobulin
of selected lots of
stent length
Human hepatitis B immunoglobulin
in 150
g/l
(POM)
15 Jul 2015 Invokana (canagliflozin):
human plasma protein (IgG 96%) 500 200mm
iu/ml;
Risk of diabetic
ketoacidosis (DKA)Human
during hepatitis
treatmentB immunoglobulin in 50 mg/mldue to a higher than expected number of
Antineoplastic
agent (POM)
complaints regarding incomplete stent deployments
g/ml
with sodium glucose co-transporter
2 (SGLT2)
human
plasma protein (IgG 96%) 50 iu/ml
with specific sizes and lots
200 mg;
Antiepileptic
agent
(POM)
Zutectra solution for injection;
inhibitors
Hepatect CP solution for
infusion
3
Jun
2015
Palindrome Precision SI Chronic Catheter,
solution20 Jul 2015 Forxiga (dapagliflozin):
Hydroxocobalamin 1 mg/1ml
Antianaemic preparation (P)
Risk of diabetic ketoacidosis (DKA)HYDROXO-B12
during treatmentsolution for injection Palindrome SI Chronic Catheter, Palindrome
Precision HSI Chronic Catheter, and Palindrome
with sodium
glucose co-transporter
2 (SGLT2)
Antidiabetic
agent (POM)
Interferon beta-1a 22 mcg/0.5 ml, 44 mcg/0.5 ml
Immunostimulant (POM)
HSI
Chronic Catheter:
inhibitors
Rebif solution for injection in pre-filled
pen
e-filled
(live, attenuated,
Voluntary recallViral
of selected
of Palindrome
Japanese encephalitis virus
vaccinelots
(POM)
23 Jul 2015 Metoclopramide-containing products:
on for
Chronic
Catheter
due
to
failure
to meet the minimum
recombinant)
4.0
5.8
log
PFU/dose
Restrictions on the indications, dose and duration of
0 mcg
IMOJEV powder & diluent for suspension
silver release specification for the entire 30-day
use
of
metoclopramide-containing
products
in
order
Agent for urinary frequency &
for injection
period
to reduce
the risk of neurological and other doseincontinence
(POM)
Leuprorelin acetate 7.5 mg, 22.5 mg, 45 mg
Antineoplastic &
20
Jul
2015
HeartWare Ventricular
Assist System
related
adverse
reactions
Ophthalmological agent (POM)
ELIGARD powder & solvent for solution
immunomodulating
agent (HVAS):
r injectionMedical
vial
Important
information
about
potential
issues which
for
injection
(POM)
devices
Antineoplastic
agent
(POM)
arose
from
HeartWares
review
of
complaints
related
Neiserria
meningitidis
serogroups
polysaccharide
Meningococcal
vaccine
(POM)
15 Apr 2015 Nellix EndoVascular Aneurysm Sealing System:
for
A, C, W-135 & Y 5 mcg/0.5 ml,
to the HVAS and ongoing product performance
Important update to the instruction
for
use
(IFU)
Tetanus toxoid carrier protein ~ 44 mcg
monitoring
on key safety-related changes thatNimenrix
are intended
to
powder
& solvent for solution for injection
Agent for obstructive airway
mitigate
the
potential
for
EndoBag
filling-related
28
Jul
2015
Birmingham Hip
Resurfacing
(BHR)
system:
inhalation
diseases (POM)
Paclitaxel 100 mg/vial
Antineoplastic
agent
(POM)
incidents
Abraxane
for
injectable
suspension
Voluntary
market
removal
of
smaller
size
components
mg
Lipid modifying agent (POM)
of BHR system Analgesic
and contraindication
of agent
BHR system
Paracetamol
500 mg
& antipyretic
PA) 460 mg
22&Apr 2015 BIRMINGHAM HIP Modular Head
(BHMH):
Panadol with OPTIZORB caplet
ethyl esters,
in females, due(GSL)
to observed revision rates which are
Important update concerning patients
implanted
Raltegravir
mg, 100 mg
Systemic benchmarks
antiviral agent (POM)
higher than established
with BHMH, who may be at a greater
risk for 25
revision
ISENTRESS chewable tablet
surgery
due
to
a
decline
in
the
performance
of
the
29
Jul
2015
Aesculap
Cementless
Columbus Knee System:
Antineoplastic agent (POM)
Rivastigmine 13.3 mg/24 hr
Antidementia agent (POM)
product
Important
information
on
a higher than anticipated
or infusion
Exelon patch 15
revision rate observed
the Australian
market and
4 mg, 6 mg,
Antiepileptic
(POM)
22 Apr 2015
Zenithagent
Alpha
Thoracic Endovascular
Graft:250 mcg/vial
Romiplostim
Systemicinhaemostatic
agent
Romiplate
powder for solution for injection
the withdrawal(POM)
of the device from the Australian
Important update to the instruction
for use
Triptorelin
Antineoplastic &
(IFU) following recent clinical findings
of distal3.75 mg/vial, 11.25 mg/vial market
Antineoplastic agent (POM)
Immunosuppressant (POM)
Antineoplastic agent (POM)
300 mg
tablet
160 mg/vial
r
The Therapeutic
poster on radiopharmaceutical
Drugs approved in
agent
(POM)
2014
that
was distributed with the
MayAntiepileptic
2015 issue agent
of the(POM)
HSA Adverse
Drug Reaction News has been updated
Antihypertensive agent (POM)
to add in drugs with new dosage
forms. The updated poster can be
downloaded
the hyperlink
Poster
Systemic via
opioid
analgesic to
(POM)
of new products available in PDF at
www.hsa.gov.sg/adrbulletin.
Immunosuppressant (POM)
2014
immunomodulating agent
(POM)
Sex hormone & modulator of
the genital system (POM)
Cholelitholytic agent (POM)
PharmacotheraPeutic grouP
Amlodipine 5 mg, 10 mg
NORVASC ODT (orodispersible tablet)
Amoxicillin (as amoxicillin trihydrate) 562.5 mg
(IR layer), Amoxicillin (as amoxicillin sodium)
437.5 mg (SR layer), Potassium clavulanate :
Microcrystalline cellulose 1 : 1 blend 62.5 mg (IR layer)
AUGMENTIN SR tablet 1000/62.5 mg
Ibuprofen 200 mg, 400 mg
NUROFEN EXPRESS liquid capsule
Paracetamol 10 mg/ml
PARACETAMOL-AFT solution for infusion
Prednisone 1 mg, 2 mg, 5 mg
Lodotra modified-release tablet
Sildenafil 50 mg
VIAGRA ODT (orodispersible) tablet
Sitagliptin, Metformin hydrochloride
JANUMET XR tablet 50 mg/500 mg,
50 mg/1000 mg, 100 mg/1000 mg
POM: Prescription only medicine P: Pharmacyonly medicine GSL: General Sales List
or infusion
mg
Background
The safety concern of intussusception with rotavirus immunisation was
first identified in 1999 with RotaShield, which led to its withdrawal
from the market.2 The risk of intussusception was estimated at 10-20
cases per 100,000 Rotashield recipients.3 Consequently, two newer
oral rotavirus vaccines, RV1 and RV5, underwent large-scale clinical
trials to ensure that there was no elevated risk with intussusception
prior to their market approval in many countries (including US, Europe
and Singapore) in the mid to late 2000s. However, recent postlicensure studies in some settings, namely Latin America (Mexico and
Brazil), Australia and the US, have estimated the attributable risk of
intussusception after rotavirus vaccination to be approximately 1.5 to
6 per 100,000 infants vaccinated.4-6
Local situation
Since the approval of RV1 in October 2005, more than 300,000
doses have been sold locally. To date, HSA has received 16 reports*
of intussusception suspected to be associated with this vaccine,
including the cases mentioned in the KKH study. Ten cases occurred
within seven days of vaccination and one occurred on day eight of
vaccination. Of these 11 cases, eight cases were reported with dose
1 and three cases with dose 2. The remaining five cases occurred
beyond the 21-day risk period identified with rotavirus vaccination.6
There were also three reports of intussusception associated with RV5,
which is less commonly used in Singapore. All the patients had either
recovered or were recovering at the time of reporting.
* The data provided should not be used to draw comparisons on the safety of the
different brands of rotavirus vaccines as this is confounded by factors such as extent
of use and patient factors. The temporal association of these cases with rotavirus
immunisation does not mean they were caused by the vaccine.
HSAs advisory
Healthcare professionals are advised to be vigilant to any symptoms
indicative of intussusception (e.g., vomiting, palpable abdominal
mass, abdominal pain or diarrhoea) following rotavirus vaccination.
They are also advised to inform parents or caregivers to seek
treatment early if the child experiences abdominal pain or bloating,
often accompanied with persistent or bouts of crying, vomiting, blood
in the stool or change in bowel movements at any time after each
dose of the vaccine.
Healthcare professionals are encouraged to report any adverse events
suspected to be associated with rotavirus vaccines to HSA as we
continue to monitor these reports closely.
The editorial team would like to thank Dr Yung Chee Fu (Epidemiologist, Infectious
Disease Service, Departmentof Paediatric Medicine, KKH) for his contribution to the
above article.
References
1 J Pediatr 2015; 167: 163-8
2 World Health Organisation position paper on rotavirus vaccines,
Jan 2013
3 J Infect Dis 2003; 187: 1309-13
4 N Eng J Med 2011; 364: 2283-92
5 Clin Infect Dis 2013; 57: 1427-34
6 N Eng J Med 2014; 370: 503-12
7 Pediatr Infect Dis J 2013; 32: e426-31
No. of cases
p value
8.36 (2.42-28.96)
0.001
3.09 (0.41-23.37)
0.28
1.54 (0.20-11.69)
0.67
Editor-in-Chief
A/Prof. Chan Cheng Leng,
BSc (Pharm) Hons
Executive Editor
Dr Han Phey Yen, MClinPharm, PhD
Editorial Board
Clinical Prof. Goh Chee Leok
Prof. Edmund Lee Joo Deoon
Clinical Prof. Chng Hiok Hee
Clinical A/Prof. Gilbert Lau Kwang Fatt
Asst Prof. Tan Tze Lee
Contributing Authors
Adena Lim, BSc (Pharm) Hons, MPharm
Dr M Limenta, BSc (Pharm) Hons, PhD
Patricia Ng, BSc (Pharm)
Sally Soh, BSc (Pharm) Hons
Liesbet Tan, BSc (Pharm) Hons
Dr Dorothy Toh,
BSc (Pharm) Hons, MPH, PhD
Photography
Saw Huiping