EPVC Newsletter

Part I of II
EPVC Newsletter
June 2015
Egyptian
Pharmaceutical
Volume 6, Issue 6
Eosinophilia induced by Tegretol –Case Reports
Vigilance Center
(EPVC)
Pharmacovigilance
Department
Inside this issue:
Eosinophilia
in- 1
duced by Tegretol –
Case Reports
Vaginal itching and 2
inflammation
induced by off label
use of Sildenafil
tablets-Case
Reports
WHO Calls for 3
Worldwide Use of
“Smart” Syringes
“Batches” Recall of 4
some pharmaceutical products from
the Egyptian market
Recall from the 4
Egyptian
market
due to counterfeit
EPVC – “ICSRs 6
Processing” workshop in Cairo
EPVC
regional 7
center in Cairo Hospitals QPPVs
Pharmacovigilance
training workshop
Memorandum
7
among the (EPVCSohag) and DIC of
Faculty of Pharmacy, Assiut University
The Egyptian pharmaceutical Vigilance regional center in Sohag has
received three reports from ELMinya QPPVs about different
medical conditions for patients
with varying ages and genders who
had administered Tegretol with
another antipsychotic drug for a
long time then the automatic analysis detected eosinophilia.
Carbamazepine: is an anticonvulsant. It works by decreasing nerve
impulses that cause seizures and
pain. Carbamazepine is used to
treat seizures and nerve pain such
as trigeminal neuralgia and diabetic neuropathy. It is also used to
treat bipolar disorder.
By search found that:
Drug Reaction with Eosinophilia and
Systemic Symptoms (DRESS)/
Multiorgan Hypersensitivity
Drug Reaction with Eosinophilia
and Systemic Symptoms (DRESS),
also known as Multiorgan hypersensitivity, has occurred with Tegretol.
Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with
other organ system involvement,
such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or
myositis sometimes resembling an
acute viral infection. Eosinophilia is
often present. This disorder is variable in its expression, and other organ systems not noted here may be
involved. It is important to note that
early manifestations of hypersensitivity (e.g. fever, lymphadenopathy)
may be present even though rash is
not evident. If such signs or symptoms are present, the patient should
be evaluated immediately.
Hemopoietic System: Aplastic anemia, agranulocytosis, pancytopenia,
bone marrow depression, thrombocytopenia, leukopenia, leukocytosis,
eosinophilia, anemia, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda.
Patients who have exhibited hypersensitivity reactions to carbamazepine should be informed that ap-
Page 2
Part I EPVC
Volume 6, Issue 6
proximately 25-30% of these patients may experience hypersensitivity reactions with oxcarbazepine
(Trileptal®). Cross-hypersensitivity can occur between carbamazepine and phenytoin
In general, if signs and symptoms suggests hypersensitivity reactions occured, Tegretol should be withdrawn
immediately.
References:
 Tegretol label –FDA database (Click here)
 Tegretol label-TGA (Click here)
3. Tegretol Consumer Medicine Information (Click here)
Vaginal itching and inflammation induced by off label use of Sildenafil
tablets-Case Reports
The Egyptian Pharmaceutical Vigilance Regional Center in Sohag had received three reports about Sildenafil tablets which were described by a physician to be administrated as
vaginal suppository once daily for 10 days, one
of them refused to take it as a vaginal suppository and other two cases took it then, they suffered from vaginal itching and inflammation.
The reporter asked if Sildenafil tablet is approved to be administered as vaginal suppository.
Recommendations:
Upon search at EPVC –Sohag we found that:

We found No Conducted Research and Experiments on the use of Sildenafil as vaginal suppository

Use of the substance Sildenafil in the treatment of thin endometrial lining is still on probation, so it falls under the “Off Label Use”.

The effectiveness of the substance Sildenafil
in the treatment of thin endometrial lining is
set up in the scientific sites, But There Is No
Pharmaceutical Preparation Available.
Sildenafil: acts as selective inhibitor of cyclic
guanosine monophosphate (cgmp) specific
phosphodiesterase type-5 (pde-5) which enhanced platelet anti-aggregatory activity of nitric oxide observed in vitro, and the mild peripheral arterial-venous dilatation in vivo because of this action sildenafil used for erectile
dysfunction.
Page 3
Part I EPVC
Conclusions:

The treatment of infertility with Sildenafil in
women, intravaginal Sildenafil citrate tablets
used as suppositories in the treatment of
threatened miscarriage in patients with a history of unexplained recurrent spontaneous miscarriage (ursm).

Vaginal Sildenafil might be an interesting therapeutic option before conception in women
with histories of reproductive failure.

Vaginal administration of Sildenafil enhanced
endometrial development in 70% of patients
studied.
Volume 6, Issue 6

High implantation and ongoing pregnancy
rates were achieved in a cohort with a poor
prognosis for success.

Previous endometritis may decrease the response to Sildenafil.
References:
 FDA database search (Click here)
 EMA Website search (Click here)
WHO Calls for Worldwide Use of “Smart” Syringes
“Millions of people could be protected from infections acquired through unsafe injections if all
healthcare programmes switched to syringes that
cannot be used more than once.”
For these reasons, WHO is launching a new policy
on injection safety to help all countries tackle the
pervasive issue of unsafe injections.
WHO also stresses the need to reduce the number
of unnecessary injections as a critical way of reducing risk. as in many cases these injections are
unnecessary or could be replaced by oral medication.
“Adoption of safety-engineered syringes is absolutely critical to protecting people worldwide from
becoming infected with HIV, hepatitis and other
diseases. This should be an urgent priority for all
countries”
The new “smart” syringes WHO recommends for
injections into the muscle or skin have features
that prevent re-use. Some models include a weak
spot in the plunger that causes it to break if the
user attempts to pull back on the plunger after
the injection. Others have a metal clip that
blocks the plunger so it cannot be moved back,
while in others the needle retracts into the syringe barrel at the end of the injection
Syringes are also being engineered with features
to protect health workers from “needle stick” injuries and resulting infections. A sheath or hood
slides over the needle after the injection is com-
Part I EPVC
Page 4
Volume 6, Issue 6
pleted to protect the user from being injured accidentally by the needle and potentially exposed to an infection
WHO is urging countries to transition, by 2020, to the exclusive use of the new “smart” syringes.
Syringes without safety features cost US$ 0.03 to 0.04 when procured by a UN agency for a developing
country. The new “smart” syringes cost at least twice that much.
References:
The medical observer article (Click here)
“Batches” Recall of some pharmaceutical products from the Egyptian
market
The Drug Factories Inspection Department at the Central Administration of Pharmaceutical Affairs
(CAPA) has decided to recall some batches of the following Pharmaceutical products:
Pharmaceutical Product
MAH
Batch numbers
Reason
Metformin HCL 850mg
CID
03140892
03140891
Non conformity of physical
properties
Erythrokin 20%
El Arabia
419910
419911
140587
Non conformity of physical
properties
Ramallerge
Rameda
Non conformity of physical
properties
This decision was circulated to the Manufacturers, Marketing Authorization Holders (MAH) and
Distributers of these products to discontinue distribution of stocks and recall the amount sold of these
batches ONLY to pharmacies.
Necessary measures would be taken against the violators.
Recall from the Egyptian market due to counterfeit
The department of Pharmacies & Warehouse Inspection at CAPA has decided to recall the imitated
packages of Betadine antiseptic solution 10% 200 ml, Batch no. 1114121 with expiry date 5/2017.
The original packages are manufactured by El-Nile Company under license of Mundipharma Switzerland.
These counterfeited packages can be differentiated from the fake ones as follows:
Part I EPVC
Page 5
Original packages
The outer Package:
 The e-mail is written down as
[email protected]
 The Word “El Nile” in the logo is clear
The plastic bottle:
 The logo of Mundipharma is written as
one word without spaces
“Mundipharma”.
 The ARABIC Word “El Nile” in the
logo is clear.
Volume 6, Issue 6
Fake Packages
The outer Package:
 The e-mail is written down as
[email protected]
 The Word “El Nile” in the logo is not clear
The plastic bottle:
 The logo of Mundipharma is written as two
words with a space in between “Mundi pharma”
 The ARABIC Word “El Nile” in the logo is
not clear “without any dots”
Also, the department of Dietary Supplements Inspection at CAPA has decided to recall the following:

All the batches of the product “DVIRON CAPSULES” which have the following info on the external
package:

Reg. No. 1613/1996

Manufactured by The Egyptian Pharmaceutical Industries Co. for IBN SINA trading co.
This recall is for the reason that the previous registration number belongs to another product.

The imitated packages of “SHARK LIVER OIL soft gelatin capsules” Manufactured by Ibn Sina with
reg. no. 1890/1997.
The counterfeited packages can be differentiated from the fake ones as follows:
Point of Comparison
The Expiry date
The Method of writing the registration number on the package
The Method of writing the composition on the package
The ® symbol beside the product name
Bar Code
The back of the strip
Original packages
2 years from the production
date
Reg. MHN: 1890/97
Each capsules contains:
Shark Liver Oil 1000mg
None
Available
Opaque (White)
Fake Packages
3 years from the production
date
M.O.H. Reg. No.:
189C0/1997
Composition:
Shark Liver Oil 1000mg
Written
Not Available
Transparent
Moreover, the Local cosmetics and insecticide department at the Inspection department has decided the
following recalls:

Epirosa Lotion 120ml (International Pharma Group-Manufactured by Hi Care) with reg. no.
9519/2007. The last batch date was 03/2013 and since this date the factory didn’t manufacture any
packages.
Part I EPVC
Page 6
Volume 6, Issue 6
Therefore any package sold having a manufacture date beyond March 2013, is counterfeited.

The imitated packages of Vividol Hair Oil 250ml, Reg. No. 6871/2010
Original packages
 The colors on the outer packages are
dark and the writing is clear.
 The square found on the package has a
white frame then a silver frame.
Fake Packages
 The colors on the outer packages are pale
and the writing is not clear.
 The square found on the package has only
a silver frame.
One of the upper lids of the outer package
contains the name of the printing house
“Dot printing house”
The upper lid of outer package contains
letter M in a circle.
 The lower lid of the outer package
contains the batch no., production
date and expiry date in an Italian font
 The watermark on the lower lid is in
light color and clear writing
Not written
The batch no., production date and expiry
date are written on the inner package.
Not written
The cap of the plastic package has prominent lines
There is a circle below the package having
a flower and word “Botanical Origin”
The cap of the plastic package is flat
Not written


The lower lid of the outer package contains
the batch no., production date and expiry
date in an Bold, straight font
The watermark on the lower lid is in dark
color and the writing is not clear
There is a circle below the package having a
flower with nothing written.
EPVC – “ICSRs Processing” workshop in Cairo
The Egyptian Pharmaceutical Vigilance center (EPVC) has organized a training workshop on the New
Arab Guidelines for ICSR (Individual Case safety Reports) Processing which was held at Hilton RamsesCairo.
The training included ICSRs submission, Causality assessment and the MedDRA (Medical Dictionary
for Regulatory Activities) coding as well.
50 Marketing Authorization Holders from all Arab countries has attended this training from 24 th to 26th
of May 2015.
Page 7
Part I EPVC
Volume 6, Issue 6
EPVC regional center in Cairo - Hospitals QPPVs Pharmacovigilance
training workshop
During the period from 3rd to 4th of May 2015, The regional center in Cairo has organized the fourth
“Hospitals QPPVs Pharmacovigilance training workshop” which was held at the National Training Institute (NTI).
320 pharmacists "QPPVs" from 100 hospitals and health care institutions in Cairo, Giza, Qalyubia,
Menoufia and Port Said were highly selected by their managers to act as QPPV representatives and contact points at their work places.
This wave was the fourth “Hospitals QPPVs training workshop” organized by regional center in Cairo,
in order to introduce and apply the Pharmacovigilance system to all Cairo hospitals and health care institutions.
Memorandum among the Egyptian Pharmaceutical Vigilance Centre at
Sohag (EPVC-Sohag) and DIC of Faculty of Pharmacy, Assiut University
The desire of the parties to the mutual cooperation in the field of pharmaceutical sciences upgrade and in line with the policy of the Ministry of
Health for modernization and exchange of information in order to ensure the safe and secure use
of medicines and pharmaceuticals; EPVC- Sohag
signed a memorandum of mutual understanding
in the field of scientific monitoring of the adverse
effects of medications with (DIC) Drug Information Center Faculty of Pharmacy, Assiut University, represented by Prof. Amr Saad, the Associate Minister of Health of Pharmaceutical Affairs
and the Head manager of The Egyptian Pharmaceutical Vigilance Centre (EPVC) and Prof. Zidan
Ibraheim, Dean of Faculty of Pharmacy, Assiut
University.
NORCB Newsletter
May 2015
Volume 6 , Issue 5
National Organization
Genital herpes vaccine succeeds in Ph II.
for Research &
Control of Biologicals
Post Marketing
Surveillance and
Adverse Event
Following
immunization
Department
Inside this issue:
Genital herpes vaccine
succeeds in Ph II.
1
Advance made in pursuit
of vaccine for E. coli
1
Breast cancer vaccines
may work better with
silicon micro-particles.
2
Measles may weaken
immune system up to 3
years .
3
Potential vaccine may
lower blood pressure.
3
There is no cure for genital herpes, but a
company is getting closer to marketing an
immunotherapy that could control herpes
symptoms. The company announced that it
met its goals in a Phase II study of its investigational GEN-003 vaccine. The candidate
consists of a protein and adjuvant, and
works by targeting a T cell response against
the HSV-2 virus. The study's aim was to find
the best combination of the protein and adjuvant to reduce viral activity, measured in
the viral shedding rate and the genital lesion
rate. The study put 310 herpes-infected patients into 7 groups, administering 6 different dosages as well as a placebo. Every dose
of GEN-003 showed a statistically significant improvement in the viral shedding rate
vs. baseline, and compared to placebo, every dose but the weakest of GEN-003
showed a statistically significant improvement in the viral shedding rate, the rate at
which the virus, which lives in nerve cells,
makes its way to the skin and physically
shed.
Reference
Fierce vaccines : (Click Here)
Advance made in pursuit of vaccine for E. coli strains.
Researchers have discovered an antibody
with unusual characteristics that may inspire improvements for scientists to create
more effective vaccines for pathogens.
The antibody, which may inhibit bacteria
from bonding to human cell surfaces, may
stop E. coli bacteria cells from attaching
to human cells. If E. coli cannot bond to
human cells, then the bacteria cannot
cause an infection. E. coli is particularly
interesting to researchers because it causes
approximately 12 percent of urinary tract
infections in men and half of urinary tract
infections in women. The E. coli strains
cause up to 90 percent of these urinary
tract infections by irritating the urinary
tract. While its hairlike structures, known
as fimbriae, have pocket-shaped proteins
that attach to sugarlike molecules on human cells, the new antibody may stop this
adhesion, called FimH, and stop E. coli
from causing urinary tract infections. To
begin an infection, E. coli implements
FimH along the cells that compose the bladder wall and urinary tract.
Reference
Vaccine News Daily: (Click Here)
Page 2
Part II NORCB
Volume 6, Issue 5
Breast cancer vaccines may work better with silicon micro-particles.
nize the cancer cells overproducing HER2 and destroy them, leaving healthy cells more or less alone.
But so far, vaccines against HER2 have seen only
Model studies showed that micro-particles load- moderate success.
Vaccines targeting the HER2 onco-protein have
ed with an antigen, HER2, not only protected
the antigen from premature destruction, but al- been tried But these vaccines have mostly not been
very potent because of inefficient vaccine delivery, a
so stimulated the immune system to recognize
and relentlessly attack cancer cells overexpress- poor immune response at the site of the tumor, and
other factors. We have shown that the PSMing the HER2 antigen.
"We could completely inhibit tumor growth af- mediated vaccine is not only potent enough to trigger tumor cell killing, but also modifies the tumor
ter just one dose of the cancer vaccine in the
animal model," said principal investigator Haifa microenvironment in a way that favors tumor treatment.
Shen, M.D., Ph.D. "This is the most amazing
The effectiveness of cancer vaccines could be
dramatically boosted by first loading the cancer
antigens into silicon micro-particles.
result we have ever seen in a tumor treatment
study."
Shen said the use of PSMs could work for any variety of cancer antigens and cancers, and that the
PSMs could be loaded with multiple antigens for a
single vaccine target, or multiple antigens for several
targets, possibly enhancing the approach's effectiveness further.
The success of the treatment, appears to be the
porous silicon micro-particles (PSMs) themselves. In vivo and in vitro studies confirmed the
micro-particles stimulated a strong, sustained
Before human clinical trials can begin, the researchinnate immune response at local sites of tumor
activity and growth with or without any antigen ers must evaluate the toxicity of antigen-loaded
PSMs.
loaded.
"We have shown for the first time that a microparticle can serve as a carrier for sustained release and processing of tumor antigens, But just
as importantly, we learned the micro-particles
themselves appear to be enough to stimulate a
type I interferon response, and were even transferred from one antigen-presenting cell to another to maintain a long-lasting antigenreleasing effect."
Cancer vaccines are designed to turn a patient's
own immune system more strongly against cancer cells, and have been an area of recent and
intense interest among oncologists.
A vaccine against HER2 would train the immune system's more destructive agents to recog-
Reference
Science Daily :
(Click Here)
Page 3
Part II NORCB
Volume 6, Issue 5
Measles may weaken immune system up to 3 years.
The measles virus is known to cast a deadly shadow
upon children by temporarily suppressing their immune systems. While this vulnerability was previously thought to have lasted a month or two, a new study
shows that children may actually live in the immunological shadow of measles for up to three years leaving them highly susceptible to a host of other deadly
diseases.
the study Published in the journal Science provides
epidemiologic evidence that measles may throw the
body into a much longer-term state of "immune amnesia," where essential memory cells that protect the
body against infectious diseases are partially wiped
out.
Reference
Vaccine news daily : (Click Here)
Potential vaccine may lower blood pressure.
According to new research from Hypertension, a
journal from the American Heart Association, a
future vaccine may help to lower blood pressure
over the long term.
The DNA vaccine has been designed to target
angiotensin II, a hormone responsible for constricting blood vessels and therefore raising blood
pressure. Constricting the blood vessels also
makes a person’s heart work harder than it
should.
The study, which involved rats as test subjects,
suggests that a future vaccine may be a novel alternative for treating people with high blood pressure for up to six months. This new vaccine
would eliminate the need to take a daily blood
pressure pill.
The hypertensive rates received the vaccine
through needle-less injections three times every
two weeks. Not only did the vaccine lower blood
pressure for six months, but the rats also showed
a decrease in tissue damage to the heart as well as
blood vessels commonly linked to hypertension.
There did not appear to be any damage to the liver or kidneys.
"The potential of a vaccine for hypertension offers an innovative treatment that could be very
effective for the control of non-compliance which
is one of the major problems in the management
of hypertensive patients," Hironori Nakagami,
study co-author and professor at Osaka University in Japan, said. "Further research on this DNA
vaccine platform, including increasing the longevity of blood pressure reduction, may eventually
provide a new therapeutic option to treat hypertensive patients."
Reference
Vaccine news daily : (Click Here)
What is Pharmacovigilance
According to the WHO, Pharmacovigilance is
A call for reporting
the science and activities relating to the de-
Please remember that you can report suspected adverse
tection, assessment, understanding and pre-
reaction of medicines to EPVC, and adverse reaction
vention of adverse effects or any other medicine-related problem.
following immunization to NORCB using the following communication information
What is the Egyptian Pharmaceutical Vigilance Center
With the increasing demand for patient's
safety which is becoming more stringent, the
Communications information
regulatory authorities are facing an increased demand for patient welfare and
Central Administration of Pharmaceutical Affairs
safety. Thus, The Egyptian Pharmaceutical
Egyptian Pharmaceutical Vigilance Center
Vigilance Center (EPVC) is constructed within
Pharmacovigilance Department
The Central Administration of Pharmaceutical Affairs (CAPA) Ministry of Health to be
21 Abd El Aziz Al Soud Street. El-Manial, Cairo, Egypt, PO Box: 11451
Phone: +202 – 23684288,
responsible for the collection and evaluation
Fax: +202 – 23610497
of information on pharmaceutical products
Email: [email protected]
marketed in Egypt with particular reference
to adverse reactions. Furthermore, EPVC is
taking all appropriate measures to:
1.Encourage physicians and other healthcare
www.epvc.gov.eg
professionals to report the suspected adverse reactions to EPVC.
2.Necessitate the pharmaceutical companies to systematically collect information
on risks related to their medical products
National Organization for Research & Control of Biologicals
and to transmit them to EPVC.
Post Marketing Surveillance and Adverse Event Following
3.Provide information to end-users through
immunization Department
adverse drug reaction news bulletins, drug
51 Wezaret El Zeraa Street, Agouza, Giza P.O. Box: 354 Dokki
alerts and seminars.
Phone: +202 – 37 480 478
Fax: +202 – 37480472
Email: [email protected]
ext. 118