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 2 February 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

Volume 6, Issue 2 Page 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.

Volume 6, Issue 2 Page 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)

Volume 6, Issue 2 Page 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)

Volume 6, Issue 2 Page 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

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 1 January 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)

Volume 6, Issue 1 Page 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)

Volume 6, Issue 1 Part II NORCB Page 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)

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.