EPVC newsletter sixty one -february 2015

1. Part I of II
EPVC Newsletter
Egyptian
Pharmaceutical
Vigilance Center
(EPVC)
Pharmacovigilance
Department
Inside this issue:
E p i d e m i o l o g y
Training organized
by EPVC
1
Solgar ABC Dophi-
lus Powder: Recall -
Risk of Infection
1
Nitrofurantoin -
Case Of Abortion
Due To Maternal
Exposure During
Pregnancy In Cairo
2
Levoxin - Case of
QT Prolongation
with a History of
Hypokalemia in
Cairo
3
Ziprasidone Drug
safety communica-
tion-Rare but po-
tentially fatal skin
Reactions
5
Volume 6, Issue 2February 2015
Epidemiology Training organized by EPVC
Kindly note that ABC Dophilus is not
registered in Egypt, however; because
some batches are illegally imported
and distributed against law, the
Pharmacovigilance department recom-
mended informing the public with this
safety information through this news-
letter.
This recommendation is based on
the FDA announcement on
11/17/2014 that Solgar, Inc. is vol-
untarily recalling Solgar ABC Doph-
ilus Powder. Testing conducted by
the Centers for Disease Control re-
vealed the presence of Rhizopus
oryzae in 50 g containers of Solgar
ABC Dophilus Powder, which may
cause Mucormycosis. This is a rare
infection that may cause health prob-
lems to consumers, particularly pre-
mature infants/infants, children,
and those with weakened immune
systems. It may also occur rarely in
people who are otherwise healthy.
Mucormycosis is any fungal infec-
tion caused by fungi in the or-
der Mucorales. Generally, species in
the Mucor, Rhizopus,Absidia,
and Cunninghamella genera are
most often implicated.
This disease is often characterized
Solgar ABC Dophilus Powder: Recall - Risk of
Infection
At the interval from 20 to 22 Janu-
ary, the Egyptian Pharmaceutical
vigilance center (EPVC) conducted
an epidemiology training under the
umbrella of AUPAM (Arab Union
of the Manufacturers of Pharmaceu-
ticals and Medical Appliances) and
Arab League and was attended by 48
attendees.
The covered topics in this workshop
were:
• Principles of Pharmacoepidemiolo-
gy
• Appropriate Literature Review
• Systematic Review and Meta-
analysis
• Evidence Based Medicine
• Study designs
• Essential Statistics for the Pharma-
ceutical Sciences
• Evidence Based Medicine in Phar-
macy Practice

2. Volume 6, Issue 2Page 2 Part I EPVC
by hyphae growing in and around vessels.
Risk factors for developing Mucormycosis include: uncontrolled diabetes; cancer; organ transplant;
neutropenia (low white blood cells); skin trauma (cuts, scrapes, punctures, or burns).
Product recalled has UPC Code: 0 33984 00010 0; Lot# 074024-01R1, 074024-01, 074024-02; Expira-
tion Date 7/31/15
RECOMMENDATION: Do not consume this product. Susceptible consumers should consult with
their physician or health care provider if they have used this product.
It is important to mention that the Ministry of health at Australia is working to stop future shipments of
affected batches of Solgar ABC Dophilus powder from entering the country.
References
1. FDA safety alert (Click here)
2. Recall firm press release (Click here)
3. TGA safety information (Click here)
The regional center in Cairo received an ICSR
concerning a thirty years old pregnant female,
with a history of threatened abortion, who re-
ceived Nitrofurantoin 100 mg (one tablet every
12 hours) during the third month of pregnancy
as per her physician’s prescription. This led to
Abortion.
Background:
Nitrofurantioin is used for the treatment of and
prophylaxis against acute of recurrent, uncom-
plicated lower urinary tract infections or pyelitis
either spontaneous or following surgical proce-
dures. (1)
Animal studies with Nitrofurantoin have shown
no teratogenic effects. Nitrofurantoin has been
in extensive clinical use since 1952 and its suita-
bility in human pregnancy has been well docu-
mented. However as with all drugs, the maternal
side effects may adversely affect the course of
pregnancy. The drug should be used at the low-
est dose appropriate for the specific indication,
only after careful assessment. (1)
Nitrofurantoin - Case Of Abortion Due To Maternal Exposure During
Pregnancy In Cairo
Urinary tract infections are among the most com-
mon bacterial infections during pregnancy due to
hormonal and mechanical changes. (2)
Labeled information:
According to Nitrofurantoin Summary of prod-
uct Characteristics (SmPC)(1)
it was stated under
section (4.3 Contraindications) that: “In infants
under three months of age as well as pregnant
patients at term (during labour and delivery) be-
cause of the theoretical possibility of haemolytic
anaemia in the foetus or in the new-born infant,
due to immature erythrocyte enzyme systems.” (1)
According to Nitrofurantoin (PIL) it was stated
under section (Contraindications) that:
“Caution is indicated in any impairment of excretion
and during the first three months of pregnancy.”
However in this case, with a history of threat-
ened abortion, Nitrofurantoin caused severe ab-
dominal pain and vaginal bleeding after the first
tablet then spontaneous abortion after the second
tablet.

3. Volume 6, Issue 2Page 3 Part I EPVC
The regional center in Cairo received an ICSR
concerning a fifty years old female that received
Levofloxacin 500 mg IV (Once daily) for
COPD, and Potassium Chloride 15% (W/V) IV
(Once daily) for hypokalemia as per her physi-
cian’s prescription. This led to QT Prolonga-
tion.
Background:
Some fluoroquinolones, including Levofloxa-
cin, have been associated with prolongation of
the QT interval on the electrocardiogram
Levoxin - Case of QT Prolongation with a History of Hypokalemia in
Cairo
"ECG" and infrequent cases of arrhythmia. (1)
Rare cases of torsade de pointes have been spon-
taneously reported during postmarketing surveil-
lance in patients receiving fluoroquinolones, in-
cluding Levofloxacin. (1)
Levofloxacin should be avoided in patients with
known prolongation of the QT interval, patients
with uncorrected hypokalemia, and patients re-
ceiving Class IA (quinidine, procainamide), or
Class III (amiodarone, sotalol) antiarrhythmic
agents. (1)
Another case with a history of threatened abor-
tion was reported previously in a study in 1956
of 11 pregnant women, nausea and vomiting
occurred in five of the pregnant patients. One
patient with a previous diagnosis of threatened
abortion had fetal loss after 1 day of Nitrofu-
rantoin therapy. (3)
By searching the UMC database (VigiLyze),
the following was found:
Nitrofurantoin caused 15 cases of abortion, 11
cases of miscarriage, and 9 cases of premature
labor.
Recommendations for Healthcare Profession-
als:
Nitrofurantoin has been assigned to be catego-
ry B in pregnancy by the FDA, but: Nitrofu-
rantoin should be used at the lowest dose as
appropriate only after careful assessment, due
to the following:
a. The risk of “Spontaneous Abortion” if the preg-
nant woman had a medical history of threat-
ened abortion.
b. The possibility of hemolytic anemia in neonates
and children under 3 months due to immature
erythrocyte enzyme systems (glutathione instabil-
ity). So:
 Nitrofurantoin is contraindicated in the first 6
months of pregnancy and during the last 4
weeks before the expected date.
 Nitrofurantoin is contraindicated in pregnant
patients at term (during labour and delivery),
infants under three months of age and when
breast feeding
References:
1. MHRA Medicines and Healthcare Products Reg-
ulatory Agency. Nitrofurantoin SmPC [cited 26
January 2015]. (Click Here)
2. Emedicine.medscape.com. [cited 26 January
2015]. (Click Here)
3. DIGGS ES e. - PubMed - NCBI [cited 26 Janu-
ary 2015]. (Click Here)

4. Volume 6, Issue 2Page 4 Part I EPVC
Elderly patients may be more susceptible to drug-associated effects on the QT interval. (1)
The QT interval is the time between onset of ventricular depolarization and end of ventricular repolari-
zation. (2)
Other possible causes of prolonged QT interval include: MI, myocarditis, hypocalcemia, hypokalemia,
hypomagnesemia, hypothyroidism, subarachnoid or intracerebral hemorrhage, stroke, congenital long
QT syndrome, antiarrhythmics, tricyclic antidepressants, phenothiazines, other drugs. (2)
Labeled information:
According to Levofloxacin Summary of product Characteristics (SmPC) (3)
it was stated under section (4.4
Special warnings and precautions for use) that: Caution should be taken when using fluoroquinolones,
including levofloxacin in patients with known risk factors for prolongation of the QT interval such as, for
example:
 congenital long QT syndrome
 concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhyth-
mics, tricyclic antidepressants, macrolides, antipsychotics)
 uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
 cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
 Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution
should be taken when using fluoroquinolones, including levofloxacin, in these populations. (3)
Recommendations for Healthcare Professionals:
Do NOT use levofloxacin if there is:
 Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia):
Hypokalemia must be corrected first. Monitor potassium level to avoid such serious Medication Error that led to
QT prolongation in this case. N.B: Normal adult serum potassium level is (3.5 - 5.2 mmol/L). (3, 4)
 Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia), or cardiac disorder (e.g. congenital long
QT syndrome).(3, 5)
 Certain type of irregular heartbeat (QT prolongation, long QT syndrome) or low blood potassium levels. (5)
 History of myasthenia gravis. (5)
 Elderly patients and women may be more sensitive to fluoroquinolones related QTc-prolongation. (3)
 Patients receiving drugs known to prolong the QT interval (e.g class IA and III antiarrhythmics, tricyclic antide-
pressants, macrolides, antipsychotics). (3)
 Allergy to any ingredient in levofloxacin or to any other quinolone antibiotic (e.g., ciprofloxacin). (5)
References:
1. Drugs.com. Levofloxacin (Click Here)
2. Merckmanuals.com. [cited 28 January 2015]. (Click Here)
3. Medicines.org.uk. [cited 28 January 2015]. (Click Here)
4. Webmd.com. [cited 28 January 2015]. (Click Here)
5. Drugs.com. [cited 28 January 2015]. (Click Here)

5. Volume 6, Issue 2Page 5 Part I EPVC
Ziprasidone is an atypical antipsychot-
ic approved by the U.S. Food and Drug Admin-
istration (FDA) for the treatment of schizophre-
nia, and acute mania and mixed states associated
with bipolar disorder. Its intramuscular injection
form is approved for acute agitation in schizo-
phrenic patients for whom treatment with just
ziprasidone is appropriate. Ziprasidone is also
used off-labelfor depression, bipolar mainte-
nance, mood disorders, anxiety, aggression, de-
mentia, attention deficit hyperactivity disor-
der,obsessive compulsive disorder, autism,
and post-traumatic stress disorder.
On 11/12/2014 FDA warned that the antipsy-
chotic drug ziprasidone (marketed under the
brand name, Geodon, and its generics) is associ-
ated with a rare but serious skin reaction that can
progress to affect other parts of the body. A new
warning has been added to the Geodon drug la-
bel to describe the serious condition known as
Drug Reaction with Eosinophilia and Systemic
Symptoms (DRESS).
DRESS may start as a rash that can spread to all
parts of the body. It can include fever, swollen
lymph nodes, and inflammation of organs such
as the liver, kidney, lungs, heart, or pancreas.
DRESS also causes a higher-than-normal num-
ber of a particular type of white blood cell called
eosinophils in the blood. DRESS can lead to
death.
FDA reviewed information from six patients in
whom the signs and symptoms of DRESS ap-
peared between 11 and 30 days after ziprasidone
treatment was started.
None of these patients died.
Based on this information, FDA required the
manufacturer of Geodon to add a new warning
for DRESS to the Warnings and Precautions sec-
tion of the drug labels for the capsule, oral sus-
pension, and injection formulations.
RECOMMENDATIONS:
 Treatment with ziprasidone may cause you
to have a rash. The rash can be severe, cover-
ing much of the body. You may also have a
fever and other symptoms associated with a
serious condition known as Drug Reaction
with Eosinophilia and Systemic Symptoms
(DRESS).
 Call your health care professional(s) and seek
immediate care if you develop any of the fol-
lowing signs or symptoms:
 Skin rash
 Fever
 Swollen face
 Swollen lymph glands
 For ziprasidone to work properly, it should be
taken every day as prescribed.
 Do not stop taking ziprasidone or change your
dose without first talking to your health care
professional.
 Discuss any questions or concerns about
ziprasidone with your health care professional.
References
1. FDA article published on 11/12/2014 (Click here)
2. FDA Drug Safety Communication (Click here)
Ziprasidone Drug safety communication-Rare but potentially fatal skin
Reactions

6. Inhalable vaccines for lung diseases on the horizon
National Organization
for Research &
Control of Biologicals
Post Marketing
Surveillance and
Adverse Event
Following
immunization
Department
Inside this issue:
Inhalable vaccines for
lung diseases on the
horizon
1
Vaccine testing for inop-
erable pancreatic cancer
1
New research shows HPV
vaccine not a cause for
MS
2
Shingles vaccine shows
promise in test subjects
age 50 and older
2
New antiretroviral drug
shows promise as HIV
vaccine
3
Ebola treatments could
be affected by virus
mutations
3
NORCB Newsletter
Volume 6 , Issue 1January 2015
Researchers at the University of North
Carolina at Chapel Hill and North Car-
olina State University recently discov-
ered a unique approach to creating in-
halable vaccines for pneumonia and
influenza. The vaccines are made using
nanoparticles and also show promise
for curing lung-specific diseases, in-
cluding tuberculosis.
When delivered through the lungs, par-
ticles with a positive surface charge
were shown to elicit antibody respons-
es, both in the lung and in the body.
By contrast, negatively charged parti-
cles of the same composition led to
weaker immune responses and in some
cases, undetectable immune responses.
This suggests that particle charge is an
important consideration in pulmonary
vaccination.
Reference
Vaccine news daily : (Click Here)
A biopharmaceutical oncology com-
pany based in Norway, recently re-
cruited 18 patients with inoperable
pancreatic cancer for the Phase I/II
clinical trial of its TG01 vaccine.
The CT TG01-01 trial is testing the
efficacy and safety of combining TG01
with chemotherapy to treat nonopera-
ble pancreatic cancer.
TG01 is a leading candidate for pan-
creatic cancer treatments. Researchers
believe it teaches the body’s immune
system to detect and destroy cancer
cells that show RAS mutations, one of
the first signs of a normal cell becom-
ing cancerous.
Vaccine testing for inoperable pancreatic cancer
The company will present interim re-
sults for the study during the first quar-
ter of 2016, with final results due in
the second quarter of 2017.
Reference
Vaccine news daily : (Click Here)

7. Volume 6, Issue 1Page 2 Part II NORCB
New research shows HPV vaccine not a cause for MS
Some research has linked the human papilloma-
virus vaccination (HPV) to the development of
multiple sclerosis (MS), but a recent study in
Scandinavia shows this isn’t the case.
The findings, found that girls and women ages
10 to 44 who received the HPV vaccination in
Sweden and Denmark had no increased risk for
MS or other central nervous system disorders.
The study conducted between 2006 and 2013 a
total of 3,983,824 girls and women were eligible
for inclusion in the study group. Of those,
789,082 were vaccinated during the study period
with a total of 1,927,581 quadrivalent human
papillomavirus (qHPV) vaccine doses.
During the follow-up process, 4,322 MS cases
and 3,300 cases of other central nervous system
diseases were discovered, but the researchers
determined that the qHPV vaccine was not the
cause.
Since the approval and licensure of the qHPV
vaccine in 2006, and the subsequent approval and
licensure of the bivalent HPV vaccine, more than
175 million doses have been distributed globally.
“These findings do not support concerns about a
causal relationship between qHPV vaccination and
demyelinating diseases.”
Reference
Vaccine news daily : (Click Here)
Shingles vaccine shows promise in test subjects age 50 and older
A new vaccine has been created that in a re-
cent Zoster Efficacy study demonstrated the
ability to reduce shingles in people 50 and
older .
The Zoster Efficacy study, which started in
August 2010 and was conducted with more
than 16,000 adult participants age 50 and
over, remains ongoing in 18 countries. Re-
sults of the study showed that during the
four years of the study, the new vaccine HZ/
su reduced the risk of shingles by 97.2 per-
cent compared with a placebo.
This candidate vaccine may offer an im-
portant option for the prevention of shingles,
a painful disease that negatively impacts health and
quality of life.
Reference
Vaccine news daily : (Click Here)

8. Volume 6, Issue 1Part II NORCBPage 3
New antiretroviral drug shows promise as HIV vaccine
HIV researchers hope the new antiretroviral drug,
can make dosing easier for some because the drug
would be administered by injection once every
three months. A clinical trial looking at the safety
and efficacy already has started at several U.S.
labs.
Antiretroviral drugs can interfere with HIV’s abil-
ity to duplicate itself using host cells and are used
to treat HIV infections or to prevent those at high
risk from acquiring the virus initially.
Ebola treatments could be affected by virus mutations
Reference
(Click Here)Vaccine news daily :
A recent study identified genetic mutations in the
strain of Ebola virus behind the current outbreak
in West Africa that could hinder potential se-
quence-based treatment options.
The research dates back four decades and traces
the genetic mutations that have taken place in the
virus. The findings conclude experimental, se-
quence-based therapeutic treatments could possi-
bly be affected due to changes in the composition
of the strain
A number of drugs currently being developed to
combat Ebola bind to and target a segment of the
genetic or protein sequence of the virus. The
drugs may not be as effective if the sequence
changes because of genetic drift.
The study compared the complete genomic se-
quence of the current outbreak strain EBOV/Mak
with the EBOV/Yam-May alternation from an
outbreak in Yambuku, Zaire, in 1976 and the
EBOV/Kik-9510621 strain from an outbreak in
Kikwit, Zaire, in 1995. Research revealed single
nucleotide polymorphisms in more than 600
spots, or roughly 3 percent of the genome.
Research was confined to those mutations that
altered the genetic sequences. Ten new mutations
were discovered that interfere with the actions of
monoclonal antibody, siRNA (small-interfering
RNA) or PMO (phosphorodiamidate morpholino
oligomer) drugs that are currently in the testing
phase.
Reference
Vaccine news daily : (Click Here)

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.