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in withdrawn blood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in withdrawn blood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 1 January 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-

Volume 6, Issue 1 Page 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-

Volume 6, Issue 1 Page 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-

Volume 6, Issue 1 Page 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

Volume 6, Issue 1 Page 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)

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 12 December 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)

Volume 5, Issue 12 Page 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)

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

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

Pharmacov ig i l ance Depar tmen t

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.