EPVC newsletter sixty january 2015

1. Part I of II
EPVC Newsletter
Egyptian
Pharmaceutical
Vigilance Center
(EPVC)
Pharmacovigilance
Department
Inside this issue:
EPVC regional
center in Cairo -
Hospitals QPPVs
Pharmacovigilance
training workshop
in Mansoura
1
Noradrenaline -
Case of Peripheral
Limb Ischemia/
Cyanosis in Female
Patient in Cairo.
1
Heparin Sodium -
High Sodium level
in withdrawn blood
sample - Case of
High Sodium level
in withdrawn blood
sample due to Hepa-
rin sodium flushing
solution - Cairo"
4
Volume 6, Issue 1January 2015
EPVC regional center in Cairo - Hospitals QPPVs
Pharmacovigilance training workshop in Mansoura
During the period from 2nd to
3rd December 2014, The regional
center in Cairo had organized
“hospital QPPVs training workshop”
which was held in Mansoura gover-
norate.
156 pharmacists from all Man-
sora hospitals and health institutions,
were highly selected by their manag-
ers to act as QPPV representatives
and contact points at their work plac-
es.
The regional center in Cairo is
willing to organize another wave in
El-Menoufya at the end of February
2015, in order to introduce and apply
the Pharmacovigilance system to all
Cairo hospitals and health care insti-
tutions.
Noradrenaline - Case of Peripheral Limb Ischemia/
Cyanosis in Female Patient in Cairo
The regional center in Cairo re-
ceived a yellow card concerning a Nine-
ty Two Years old female who was ad-
mitted to ICU by abdominal distension,
anorexia, and was diagnosed by acute
renal failure, anemia, septic shock, in-
testinal obstruction with history of DM.
The patient received Noradrenaline IV
for hypotension (dose ranging from 0.01
to 0.4 mcg/kg/min according to her
blood pressure) to control her blood
pressure. She developed Peripheral
Limb Ischemia and Cyanosis (blue dig-
its)
Background:
Noradrenaline is indicated for the emer-
gency restoration of blood pressure in
cases of acute hypotension.(1, 2)
Each
8ml ampoule contains 16mg Nora-
drenaline tartrate equivalent to 8mg
Noradrenaline base. (1)
Blue digits: ischemic injury and cya-
nosis due to potent vasoconstrictor
action, resulting from norepineph-

2. Volume 6, Issue 1Page 2 Part I EPVC
rine treatment. (1)
Extravasation risk: The infusion site should be
checked frequently for free flow. Care should be
taken to avoid extravasation that would cause a
necrosis of the tissues surrounding the vein used
for the injection. (1)
Labeled Information:
According to Noradrenaline Summary of product
Characteristics (SmPC) (1)
it was stated under sec-
tion (4.2 Posology and method of administration),
the following:
Titration of Dose:
The dose should be titrated according to the pressor
effect observed. There is great individual variation
in the dose required to attain and maintain nor-
motension. (1, 2)
The aim should be to establish a low normal sys-
tolic blood pressure (100-120 mm Hg) or to
achieve an adequate mean arterial blood pressure
(greater than 65 to 80 mm Hg - depending on the
patient's condition). (1, 2)
Duration of Treatment and Monitoring:
Noradrenaline should be continued for as long as
vasoactive drug support is indicated. The patient
should be monitored carefully for the duration of
noradrenaline therapy. (1, 2)
Dilution Instructions:
Either add 2 ml of Noradrenaline 1 MG/ML to 48
ml 5% dextrose (or isotonic dextrose saline) for
administration by syringe pump, or add 20 ml of
Noradrenaline 1 MG/ML to 480 ml 5% dextrose
(or isotonic dextrose saline) for administration by
drip counter. (1, 2)
In the both cases the final concentration of the
infusion solution is 80 mg/litre noradrenaline
tartrate, which is equivalent to 40 mg/litre nora-
drenaline base. If other dilutions are used check
the calculation carefully before starting treat-
ment. (1, 2)
Blood Pressure Control:
Measure blood pressure every two minutes at the
beginning of the infusion until the desired blood
pressure is obtained. Then every five minutes
when desired the blood pressure is obtained, if
the administration has to be continued. The infu-
sion should be at a control rate and the patient
should be monitored carefully for the duration of
noradrenaline (norepinephrine) therapy. (1, 2)
Treatment of the Ischemia Due To
Extravasation:
During an extravascular leak of the product or an
injection besides the vein, tissue destruction can
appear resulting from the vasoconstrictive action
of the drug on the blood vessels. The injection
zone must be then irrigated as quickly as possible
with 10 to 15ml of physiological salt solution con-
taining 5 to 10 mg of phentolamine mesilate. For
this purpose, it is necessary to use a syringe pro-
vided with a fine needle and to inject locally. (1)
Use in the Elderly:
Clinical studies did not include sufficient numbers
of subjects aged 65 and over to determine whether
they respond differently from younger subjects. In
general, dose selection for an elderly patient
should be cautious, usually starting at the low end
of the dosing range, reflecting the greater frequen-
cy of decreased hepatic, renal, or cardiac function,
and of concomitant disease or other drug therapy.
Noradrenaline should not be administered into
the veins in the leg in elderly patients. (3)
Overdosage:
May result in severe hypertension, reflex brady-

3. Volume 6, Issue 1Page 3 Part I EPVC
cardia, marked increase in peripheral resistance and decreased cardiac output. Headache may indicate
severe hypertension. (3)
Recommendations for Healthcare Professionals:
1. Noradrenaline is for intravenous use only.(1,2)
2. Dilute before use. (1,2)
3. Administer as a diluted solution via a central venous catheter. (1,2)
4. The infusion should be at a controlled rate using either a syringe pump or an infusion pump or a
drip counter. (1,2)
5. Noradrenaline should be administered through central venous devices to minimize the risk of ex-
travasation and subsequent tissue necrosis. (1,2)
6. Avoid administration of vasopressor (to maintain blood pressure) in absence of blood volume re-
placement to avoid severe peripheral and visceral vasoconstriction, hypoxia and decrease in renal
blood flow. (2)
7. The infusion must not be stopped suddenly but should be gradually withdrawn to avoid disastrous
falls in blood pressure. (2)
8. Caution and respect of the strict indication must be retained in the following conditions:
 Elderly ( may be especially sensitive to the effects of noradrenaline) (2)
 Diabetic Patient. (2)
 Hypotension following a heart attack. (2)
 Clots or obstructions in the blood vessels supplying the heart, intestines, or other parts of the
body.(2)
Treatment:
The limb should be placed in loosened bandage, and apply an extremely warming device, such as Bair
Hugger, then:
 consider pharmacologic therapy: Nifedipine 10 to 60 mg with aspirin 81 mg daily,
 if no response occurred, chemical sympathectomy(5)
, by local infiltration of plain lidocaine,
 if no improvement combine the use of transdermal nitroglycerin,
 finally, short term heparin drip for 24 to 72 hours could be applied. (4)
References
1. Medicines.org.uk. (Click here)
2. Drugs.com. (Click here)
3. TGA eBS - Product and Consumer Medicine Infor-
mation Licence. (Click here)
4. Ravenell R, Powell D, Ryan J. Vasospastic Disor-
ders, Ischemic Digits, and The Use of Epinephrine in
Digital surgery [Internet]. The Podiatry Institute.
(Click here)
5. TheFreeDictionary.com. (Click here)
Real Photo of the Patient by the Report-

4. Volume 6, Issue 1Page 4 Part I EPVC
"Heparin Sodium - High Sodium level in withdrawn blood sample - Case of
High Sodium level in withdrawn blood sample due to Heparin sodium
flushing solution - Cairo"
The regional center in Cairo received a complaint
concerning intravenous devices that are flushed by
"Heparin sodium flushing solution" leading to
interference with results of the desired blood tests
"High Sodium level in withdrawn blood sample".
:Background
Heparin is a naturally occurring
mucopolysaccharide with in vitro and in vivo
anticoagulant activity. Heparin acts at multiple
sites in the normal coagulation systems. Small
amounts of heparin in combination with
antithrombin III (heparin cofactor) can inhibit
thrombosis by inactivating activated factor X and
inhibiting the conversion of prothrombin to
thrombin. (1)
Once active thrombosis has developed, larger
amounts of heparin can inhibit further
coagulation by inactivating thrombin, which in
turn prevents the conversion of fibrinogen to
fibrin. Under normal conditions, equilibrium
between fibrinogen deposition and lysis keeps the
vascular system free of thrombi. Under abnormal
conditions of trauma, surgery or circulatory
collapse, the equilibrium shifts towards clot
formation. The action of heparin is to shift the
equilibrium back towards normal thereby
reducing clot formation. (1)
Heparin catheter lock-flush solution Products
are intended to enhance the performance of intra-
vascular catheters. An intravascular catheter is a
device that consists of a slender tube and any
necessary connecting fittings that are inserted into
a patient's vascular system for short-term use (less
than 30 days )to sample blood, monitor blood
pressure, or administer fluids intravenously).
Heparin catheter lock-flush solutions are periodi-
cally inserted into and stored within the catheter
to keep the catheter patent and to prevent blood
from clotting within the catheter between uses. (2)
Labeled information:
According to Heparin Sodium 100 I.U./ml
flushing solution for maintenance of patency of
intravenous devices Summary of product Charac-
teristics (SmPC) (1)
it was stated under section
(4.5) Interaction with other medicinal products
and other forms of interaction) that:
When an indwelling device is used for repeated
withdrawal of blood samples for laboratory anal-
yses and the presence of heparin or saline is likely
to interfere with or alter results of the desired
blood tests, the in situ heparin flush solution
should be cleared from the device by aspirating
and discarding a volume of solution equivalent to
that of the indwelling venipuncture device before
the desired blood sample is taken. (3)
Recommendations for Healthcare
:Professionals
1. Heparin is not recommended for systemic use(3)
2. Caution should be exercised in patients with
known hypersensitivity to low molecular
weight heparins(3)
.
3. Rigorous aseptic technique should be observed
at all times in its use. (3)
4. Material to be used as an intravascular cannula
or catheter flush in doses of 200 units every 4

5. Volume 6, Issue 1Page 5 Part I EPVC
hours or as required. (3)
5. To maintain the patency of intravenous injection devices and prevent clot formation, flush the cathe-
ter/cannula with 10 - 50 IU every four hours. The solution may be used following initial placement
of the device in the vein, after each injection of a medication, or after withdrawal of blood for labora-
tory tests. (1)
6. Carefully examine all presentations of heparin sodium to confirm the correct formulation prior to ad-
ministration of the drug. (4)
7. When an indwelling device is used for repeated withdrawal of blood samples for laboratory analyses
and the presence of heparin or saline is likely to interfere with or alter results of the desired blood
tests, the in situ heparin flush solution should be cleared from the device by aspirating and discarding
a volume of solution equivalent to that of the indwelling venipuncture device before the desired blood
sample is taken. (3)
8. If the drug to be administered is incompatible with Heparin, the device must be flushed through with
normal 0.9% Sodium chloride solution before and after the drug is administered. (1)
9. Repeated flushing of a catheter device with heparin may result in a systemic anticoagulant effect. (3)
10. Platelet counts should be measured in patients receiving heparin flushes for longer than five days (or
earlier in patients with previous exposure to heparin). In those who develop thrombocytopenia or
paradoxical thrombosis, heparin should immediately be eliminated from all flushes and ports. [3]
11. Since repeated injections of small doses of heparin can alter tests for activated partial thromboplastin
time (APTT), a baseline value for APTT should be obtained prior to insertion of an intravenous de-
vice. (1)
References
1. Ebs.tga.gov.au. TGA eBS - Product and Consumer Medicine Information Licence [(Click Here)
2. Fda.gov. (Click Here)
3. Medicines.org.uk. (Click Here)
4. Health Canada. (Click Here)

6. Egypt reports 13th human H5N1 avian flu case in a month.National Organization
for Research &
Control of Biologicals
Post Marketing
Surveillance and
Adverse Event
Following
immunization
Department
Inside this issue:
Egypt reports 13th
human H5N1 avian flu
1
Powdered measles
vaccine, safe in phase I,
could aid vaccination in
1
Middle East respiratory
syndrome coronavirus
2
Breast cancer vaccine
looks promising in early
2
Universal dengue vac-
cine may be possible
thanks to antibody
3
FDA approves latest
HPV vaccine
3
NORCB Newsletter
Volume 5, Issue 12December 2014
The number of human H5N1 avian in-
fluenza (AI) cases continue their spike
in Egypt as health ministry officials ad-
vise of the 17th case of the year in three
year old child from Sohag Governorate.
This is the 13th H5N1 infection reported
out of Egypt in less than a month. Eight
fatalities have been reported.
This is the most cases and deaths due to
H5N1 AI in Egypt since 2011 when the
north African country reported 39 cases
and 15 deaths.
Since 2003, there has been nearly 700
human H5N1 AI cases reported with
only Indonesia reporting more cases
than Egypt.
H5N1 infection in humans can cause
severe disease and has a high mortality
rate. Almost all cases of H5N1 infection
in people have been associated with
close contact with infected live or dead
birds, or H5N1-contaminated environ-
ments.
The symptoms of H5N1 infection may
include fever (often high fever, > 38°C)
and malaise, cough, sore throat, and
muscle aches. Other early symptoms
may include abdominal pain, chest
pain and diarrhoea. The infection may
progress quickly to severe respiratory
illness (for example, difficulty breath-
ing or shortness of breath, pneumonia,
Acute Respiratory Distress Syndrome)
and neurologic changes (altered mental
status or seizures).
Reference
Outbreak News Today: (Click Here)
Powdered measles vaccine, safe in phase I, could aid
vaccination in developing world.
A powdered measles vaccine could
mean a cheaper option for the develop-
ing world that eliminates storage, con-
tamination and waste challenges. And
researchers now have one that looks
safe in Phase I.
In a Gates Foundation-backed study of
60 healthy, measles-immune men, re-
searchers from the Centers for Disease
Control and Prevention (CDC),
the Serum Institute of Indiaand else-
where found no clinically relevant side
effects and some evidence of a positive
immune response to the vaccine, ac-
cording to a paper published last week
in the journal Vaccine. The vaccine,
made of fine dry powder and delivered
with a puff of air, could cut out some
key hurdles to vaccination in resource-
poor parts of the world.
Reference
Fierce Vaccines: (Click Here)

7. Volume 5, Issue 12Page 2 Part II NORCB
Middle East respiratory syndrome coronavirus (MERS-CoV)
the National IHR Focal Point for the King-
dom of Saudi Arabia (KSA) notified WHO
of 11 additional cases of Middle East respir-
atory syndrome coronavirus (MERS-CoV)
infection, including 4 deaths.
WHO advice:Infection prevention and con-
trol measures are critical to prevent the pos-
sible spread of MERS-CoV in health care
facilities. It is not always possible to identify
patients with MERS-CoV early because like
other respiratory infections, the early symp-
toms of MERS-CoV are non-specific.
Therefore, health-care workers should al-
ways apply standard precautions consistent-
ly with all patients, regardless of their diag-
nosis. Droplet precautions should be added
to the standard precautions when providing
care to patients with symptoms of acute res-
piratory infection; contact precautions and
eye protection should be added when caring
for probable or confirmed cases of MERS-
CoV infection; airborne precautions should be applied
when performing aerosol generating procedures. Until
more is understood about MERS-CoV, people with dia-
betes, renal failure, chronic lung disease, and immuno-
compromised persons are considered to be at high risk
of severe disease from MERS‐CoV infection. Therefore,
these people should avoid close contact with animals,
particularly camels, when visiting farms, markets, or
barn areas where the virus is known to be potentially
circulating. General hygiene measures, such as regular
hand washing before and after touching animals and
avoiding contact with sick animals, should be adhered
to.
Reference
World Health Organization: (Click Here)
Breast cancer vaccine looks promising in early trial
the trial was undertaken to test the safety of
the vaccine, it showed that the vaccine slowed
cancer progression, even in patients with
weakened immune systems from advanced
cancer and exposure to chemotherapy. Based
on these preliminary results, the team at
Washington University is planning a larger
trial to test the vaccine in newly diag-
nosed breast cancer patients, who should have
stronger immune systems .
The vaccine causes the immune system to tar-
get a protein called mammoglobin-A, which is
found almost exclusively in breast tissue. In
response to the vaccine, a type of white blood
cell seeks and destroys cells that have the
mammoglobin-A protein. While the protein's func-
tion in healthy tissue is unclear, it is expressed in
abnormally high levels in up to 80% of breast tu-
mors. This means that the vaccine could potential-
ly be used to treat a large number of breast cancer
patients with fewer side effects.
Reference
Fierce Vaccines: (Click Here)

8. Volume 5, Issue 12 Part II NORCB Page 3
Universal dengue vaccine may be possible thanks to antibody discovery
Several recent clinical trials indicate that Gar-
dasil 9 is 97 percent effective in preventing peo-
ple from contracting vaginal, vulvar and cervical
cancers.
Previous Gardasil vaccines only protected
against five HPV strains and were limited to only
female recipients which protects against nine
strains, amounting to 90 percent of anal, vulvar,
vaginal and cervical cancers.
Despite these findings, the Center for the Biology
of Chronic Disease (CBCD) continues to recom-
mend natural HPV remedies, such as Gene-Eden
-VIR or Novirin, over the vaccine.
Gene-Eden-VIR and Novirin contain natural die-
tary supplements that are antiviral, such as Ca-
mellia Sinesis extract (a trace element), selenium,
Cinnamomum extract, quercetin and licorice ex-
tract.
PolyDNA, the company responsible for develop-
ing and patenting the natural treatments, exten-
sively researched thousands of medical and scien-
tific papers, journals and studies to find natural in-
gredients that safely and effectively protect against
latent viruses.
As of today, Gene-Eden-VIR and Novirin are the
only two natural products on the market with pub-
lished clinical studies that support their efficacy.
Reference
Vaccine news daily: (Click Here)
In findings published on Monday in Nature Immu-
nology, scientists studied 145 human antibodies
and found new ones that neutralize all four types
of dengue virus--including serotype 2 In 2012, a
company conducted a Phase IIb trial in Thailand
of its tetravalent dengue candidate, which success-
fully defended against serotypes 1, 3 and 4, but fal-
tered against serotype 2.
It didn't do much better in Phase III trials held this
year in Asia, posting a 35% efficacy in serotype 2,
just a little higher than the approximately 30% effi-
cacy it registered in the 2012 trial.
While results from a Phase III trial conducted in
Latin America showed improvement against sero-
type 2--42% efficacy--they still didn't come close to
the company’s initial estimate, which was more
than 70% efficacy.
Despite its lackluster performance against serotype
2, the vaccine, by blocking three out of the four
dengue viruses, lowered the overall risk of con-
tracting dengue as well as reduced hospitalization.
Following the announcement of the Latin Ameri-
can trial results, the company said it could have
the vaccine to market by the second half of 2015.
It could be the world's first dengue vaccine.
Reference
Fierce Vaccines: (Click Here)
FDA approves latest HPV vaccine

9. A call for reporting
Please remember that you can report suspected adverse
reaction of medicines to EPVC, and adverse reaction
following immunization to NORCB using the follow-
ing communication information
51 Wezaret El Zeraa Street, Agouza, Giza P.O. Box: 354 Dokki
Phone: +202 – 37 480 478 ext. 118
Fax: +202 – 37480472
Email: pmsdep@yahoo.com
National Organization for Research & Control of Biologicals
Post Marketing Surveillance and Adverse Event Following
immunization Department
21 Abd El Aziz Al Soud Street. El-Manial, Cairo, Egypt, PO Box: 11451
Phone: +202 – 23684288,
Fax: +202 – 23610497
Email: pv.center@eda.mohealth.gov.eg
Central Administration of Pharmaceutical Affairs
Egyptian Pharmaceutical Vigilance Center
Pharmacovigilance Department
www.epvc.gov.eg
Communications information
What is Pharmacovigilance
According to the WHO, Pharmacovigilance is
the science and activities relating to the de-
tection, assessment, understanding and pre-
vention of adverse effects or any other medi-
cine-related problem.
What is the Egyptian Pharmaceuti-
cal Vigilance Center
With the increasing demand for patient's
safety which is becoming more stringent, the
regulatory authorities are facing an in-
creased demand for patient welfare and
safety. Thus, The Egyptian Pharmaceutical
Vigilance Center (EPVC) is constructed within
The Central Administration of Pharmaceuti-
cal Affairs (CAPA) Ministry of Health to be
responsible for the collection and evaluation
of information on pharmaceutical products
marketed in Egypt with particular reference
to adverse reactions. Furthermore, EPVC is
taking all appropriate measures to:
1.Encourage physicians and other healthcare
professionals to report the suspected ad-
verse reactions to EPVC.
2.Necessitate the pharmaceutical compa-
nies to systematically collect information
on risks related to their medical products
and to transmit them to EPVC.
3.Provide information to end-users through
adverse drug reaction news bulletins, drug
alerts and seminars.