VOL34: JANUARY - MARCH 2016 EDITION

Pharmacy Update

Advisors:

Pn Saidatul Raihan

Chief Editor:

Miss Tay Eek Poei

Pn Syamsiah Shariff

Editor:

Tan Jien Lee

Contributors:

Yap Ren Ai

Sarah Nazurah

Siti Jannah Ibrahim

El-Nino is ‘turning up the heat’!

“During El-Nino, the Western atmosphere

becomes hot and dry resulting in drought.”

- more on page 2

Current Issue: El-Nino Page

2-3

Drug Safety: Cellcept® Page

4-5

Management of Tha-

lassemia

Page

6

New Drug Profile: Pici-

banil

Page

7-8

Pharmacy Jokes:

Laughter the Best

Medicine! :)

Page

9

Activities/

Announcements: Janu-

ary — March 2016

Page

10-11

Inside this issue:

New evidences have dem-

onstrated that the drug

may be associated with

birth defects and even

pregnancy loss.

- More on page 4

Cellcept®: A Powerful Human Teratogen

El Nino, translated from Spanish means ‘The Little Boy’ or ‘The Christ

Child’. This phenomenon was first discovered by Benjamín Vicuña

MacKenna in 1877. In 1960, Gilbert Walker and Jacob Bjerknes success-

fully identified a periodic variation predicting this weather phenomenon.

THE 5-W’S OF EL-NINO PHENOMENON

Page 2 Pharmacy Update

World weather event during which

the warm “trade” wind, normally

flowing from East to West, weakens

allowing the spreading of hot and

wet area toward West side.

This phenomenon is also know as

El -Nino/Southern Oscillation

(ENSO)

In normal conditions, Asia and Aus-

tralia are warm and wet while the

Eastern part stay cool and dry.

During ENSO, due to shift of warm region, rain occurs more commonly in

South and Central America (Peru) causing flood.

Meanwhile, the Western atmosphere (Indonesia or India) becomes hot

and dry resulting drought.

2. WHAT

1. WHO

3. WHERE

Central equatorial line on South Pacific

Ocean between East (South and Central

America) and West side (Asia and Austra-

lia)

By: Yap Ren Ai

Page 3 Pharmacy Update

ENSO happens every 2 to 7 years

Normally starts from December and ends in September on the fol-

lowing year

THE 5-W’S OF EL-NINO PHENOMENON

This is important to predict ENSO as it help preventing damage

from natural disasters in different regions of the world.

Change in weather also affects population balance of fish and ma-

rine species hence, in turn, alternating other mammals’ demo-

graphic, such as seals.

Agriculture and other weather-dependent jobs, e.g. fishing, would

be more productive.

During El Nino, the heat surrounding South Pacific Ocean emit to

the atmosphere contributing to global warming.

5. WHY

4. WHEN

REFERENCES

1. h t t p s : / / w w w . g o o g l e . c o . u k / s e a r c h ?

q=fisherman&rlz=1C5CHFA_enGB503GB503&espv=2&biw=1920&bih=957&source=lnms&tbm=isch&sa=X&

ved=0ahUKEwj6sJKd4rHLAhWIShQKHY2XDxwQ_AUIBigB#imgrc=YxVTgJbwfKDbxM%3A

2. https://ams.confex.com/ams/annual2003/techprogram/paper_58909.htm

3. h t t p s : / / w w w . g o o g l e . c o . u k / s e a r c h ?

q=seal&rlz=1C5CHFA_enGB503GB503&source=lnms&tbm=isch&sa=X&ved=0ahUKEwimkITU3bHLAhUD1hQ

KHfM4BEEQ_AUIBygB&biw=1920&bih=957#imgdii=_V42bHa_ToryBM%3A%3B_V42bHa_ToryBM%3A%

3Bbha9kG4RWOPkdM%3A&imgrc=_V42bHa_ToryBM%3A

4. http://www.cpc.ncep.noaa.gov/products/analysis_monitoring/enso_advisory/ensodisc.html

5. https://www.wildlife.ca.gov/Conservation/Marine/El-Nino#26072341-what-effects-does-el-nio-have-on-world-

climate

6. http://oceanservice.noaa.gov/facts/ninonina.html

7. https://www.youtube.com/watch?v=WPA-KpldDVc

8. http://www.walesonline.co.uk/news/wales-news/el-nino-forecasters-predict-70-9298059

9. http://www.listland.com/top-10-facts-about-the-weather-phenomenon-el-nino/

Page 4 Pharmacy Update

DRUG SAFETY: CELL-

CEPT®

BACKGROUND

Cellcept® (mycophenolate mofetil) is an immunosuppresant agent currently indi-

cated for the prophylaxis of solid organ rejection in adults receiving allogeneic or-

gan transplants in Malaysia. The drug is also indicated for induction and mainte-

nance treatment of lupus nephritis and used concomitantly with corticosteroids.

However, recent studies have shown that Cellcept® may present as a powerful

human teratogen. The increased risk of spontaneous abortions and congenital

malformations following exposure during pregnancy has led to the drug being con-

traindicated for use in certain population:

During pregnancy due to its mutagenic and teratogenic potential

In women of childbearing potential not using highly effective contraceptive

methods

In women who are breastfeeding

EVIDENCES

A study conducted by Sifontis et. al reported that approximately one quarter

(~25%) of live births in women exposed to mycophenolate mofetil during preg-

nancy had some form of structural malformation. This is significant as compared

to malformations occuring in 2-3% of live births in the overall population and ap-

proximately 4-5% in solid organ transplant patients treated with immunosuppre-

sants other than mycophenolate mofetil.

By: Tan Jien Lee

Page 5 Pharmacy Update

DRUG SAFETY: CELLCEPT®

EVIDENCES (CONTINUED)

Another separate study done by Hoeltzenbein et. al found that

exposure to mycophenolate during the first trimester of preg-

nancy also contributed to a high incidence of major malforma-

tions (26%). These include:

Congenital heart diseases;

Facial malformations, ie. cleft lip and cleft palate;

Eye abnormalities;

Finger malformations;

Tracheo-oesophageal malformations;

Nervous system malformations, ie. spina bifida;

Renal abnormalities

CONTRACEPTION ADVICE FOR BOTH MEN AND WOMEN

Women of childbearing age are advised to use 2 reliable forms of contra-

ception simultaneously before starting Cellcept® therapy, during therapy and for

at least 6 weeks after cessation of therapy, unless the individual is sexually in-

active.

Sexually active men are advised to use con-

doms during treatment and for 3 months after dis-

continuing treatment, even if vasectomy had been

done due to the risks involved with the transfer of

seminal fluid. Moreover, the female partner of the

male patients is encouraged to use reliable contra-

ception during Cellcept® therapy and also for 90

days after termination of therapy.

Baby with spina bifida

Contraceptive methods

RISK VS. BENEFIT

Female and male patients of reproductive potential must be notified of the

increased risk of pregnancy loss and congenital malformations. Healthcare pro-

fessionals play a key role in ensuring that individuals on Cellcept® understand

the risk of foetal harm, the need for effective contraception, and the need to

seek a physician immediately in cases of possible pregnancy.

Baby with cleft palate

REFERENCES

1. Medicines and Healthcare products Regulatory Agency. 14 Dec 2015. Mycophenolate mofetil, mycophenolic acid: new pregnancy-

prevention advice for women and men.

2. Sifontis NM, Coscia LA, Constantinescu S, Lavelanet AF, Moritz MJ and Armenti VT. Pregnancy outcomes in solid organ transplant recipi-

ents with exposure to mycophenolate mofetil or sirolimus. Journal of Transplantation. Dec 2006;82(12):pp.1698-702.

3. Hoeltzenbein M, Elefant E, Vial T. et al. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Tera-

tology Information Services. American Journal of Medical Genetics Part A. Mar 2012;158A(3):588-96.

4. Therapeutic Goods Administration of Australia. 26 November 2015. Consumer Medicine Information : Cellcept® Mycophenolate Mofetil.

Page 6 Pharmacy Update

INTRODUCTION

Thalassemia is increasingly becoming a worldwide problem as there are approximately

350,000 births per year associated with thalassemia. Thalassemia is a genetical disorder

caused by abnormal synthesis of one or more globin chains. The impairment alters

production of haemoglobin (Hb) by decreasing Hb synthesis and red cell survival .

MANAGEMENT OF THALASSEMIA

PATHOPHYSIOLOGY

Thalassemia is an autosomal recessive disorder caused by mutations in the alpha or beta globulin

genes, leading to an imbalanced production of adult hemoglobulin (HbA) α2β2 tetramers. A de-

crease in the amount of one globulin chain leads to relative overproduction and aggregation of the

others. In α-thalassemia, production of the α globin chain is affected, whereas in β-thalassemia,

production of the β globin chain is affected.

1. Deferoxamine (Desferal)

A heavy metal antagonist.

Works by helping the kidney

and gall bladder get rid of extra

iron. It will bind to trivalent

(ferric) iron forming ferrioxam-

ine (stable) which is eliminated

via kidney.

S/C 30 to 60 mg/kg for eight to

fifteen hours, five to seven days or nights per week.

Run over a minimum of six hours (or longer) at a

maximum of 15 mg/kg per hour.

Deferoxamine at 60 mg/kg per day, 24 hours per day,

7 days per week, may be indicated with patients with

severe hemosiderosis and vital organ dysfunction

2. Deferasirox (Exjade)

Good oral bioavailabil-

ity and a long half-life

Suitable for once-daily

dosing taken as dis-

persible tablet

Tablet can be suspended in water, apple

juice, or orange juice and should be taken

on an empty stomach.

Starting dose is 20 mg/kg per day and

may be increased to 30 mg/kg per day,

and in certain cases, to 40 mg/kg per day

After starting therapy, increase the dose by

5 to 10 mg/kg every three to six months

based on iron stores

TREATMENTS

3. Deferiprone (L1/Ferriprox)

Approved by FDA for patients not effectively chelated with standard therapy.

Reduces or maintains total body iron stores in the majority of patients

Studies suggest that deferiprone may be more effective than deferoxamine in

reducing cardiac iron.

Deferiprone in combination with deferoxamine may decrease the risk of cardiac

disease and improve cardiac function.

Side effects include gastrointestinal symptoms, joint pain

References

1. Sandard of Care Guidelines for Thalassemia. 2012. http://thalassemia.com/documents/SOCGuidelines2012.pdf

2. Guidelines for the Clinical Care of Patients with Thalassemia in Canada. http://www.thalassemia.ca/wp-content/uploads/Thalassemia-Guidelines_LR.pdf

3. Clinical Practise Guideline. 2009. Management of Transfusion Dependent Thalassaemia.

4. Ministry Of Health Management of Thalassemia. http://www.moh.gov.my/attachments/727.pdf

By: Siti Jannah Ibrahim

Page 7 Pharmacy Update Written by: Sarah Nazurah

INTRODUCTION

Picibanil is a a lyophilized incubation mixture of the low virulent Su strain of Group A Strepto-

coccus pyogenes of human origin which has lost its streptolysin S-producing ability and peni-

cillin G potassium. In Japan, Picibanil has been used as a biological response modifier, mainly

in the treatment of alimentary tract cancer, lung cancer, head and neck cancer and thyroid

cancer with no serious adverse effects.

INDICATIONS DOSAGE AND ADMINISTRATION

1. Prolongation of survival time in

patients with gastric cancer

(postoperative cases) or primary

lung cancer in combination with

chemotherapy

Suspend in the accompanying isotonic NaCl solution and

administer IM, SC or intradermally. The usual initial dosage

is 0.2—0.5KE OD or EOD. While monitoring the patient's

condition, the dosage is gradually increased to 2-5KE over a

2-3 week period. The maintenance dosage is 2-5KE once or

twice a week.

2. Reduction of cancerous pleural

effusion or ascites in patients

with gastrointestinal cancer or

lung cancer

Administer 5-10KE into the serous cavity once or twice a

week.

3. Head and neck cancer (maxillary

cancer, laryngeal cancer, pharyn-

geal cancer, and tongue cancer)

and thyroid cancer that are resis-

tant to other drugs

Inject 5-10KE into a tumor or the marginal area of a tumor

daily or once every several days. However, this product

should not be administered by more than one route to the

same patient on the same day.

4. Lymphangioma Suspend in isotonic NaCl solution to prepare 0.05-0.1KE/

mL solutions. As a general rule, the dosage equals the

amount of aspirated fluid collected from lymphangioma. The

maximum dosage is 2KE/injection, and the dosage may be

adjusted depending on the patient's age and symptoms.

MECHANISM OF ACTION 1. Effect on tumor cells

This product has been shown to directly suppress the proliferation of tumor cells.

2. Effect on biophylaxis The administration of this product increased neutrophils, macrophages and lymphocytes (humans); activated

neutrophils (rats), macrophages (humans) and NK cells (humans); and caused the induction of CTL cells

(rats). This product also induced the production of various cytokines, such as IL-1, IL-2 (mice), IL-8 (humans),

IL-12 (mice), IFN-γ (mice), TNF-α (humans), G-CSF (humans) and GM-CSF (humans), that are involved in the

proliferation and activation of the aforementioned cells, suggesting that the antitumor effect of this product

is manifested through various types of host biophylaxis activated by the product.

Page 8 Pharmacy Update

MECHANISM OF ACTION (continued on from Page 7)

3. Mechanism of action in lymphangioma The local administration of this product into lymphangioma induced inflammatory reactions caused the induc-

tion of macrophages, and induced the production of cytokines such as TNF. (This compound increases the

permeability of endothelial cells.) This series of events accelerates the excretion of lymph, thus reducing the

size of lymphatic vascular lumen (humans).

PHARMACOLOGY 1. Effect on autologous tumors

In experiments using mice with spontaneously induced tumors or methylcholanthrorene-induced tumors, the

intratumor/intramuscular administration of this product suppressed tumorous proliferation.

2. Effect on isogeneic tumors

In experiments using mice and rats with isogeneic tumors, the intraperitoneal administration of this product

prolonged survival time and shrank tumors. Furthermore, in a study using guinea pigs with isogeneic tumors,

the intratumor administration of this product shrank tumors.

3. Effect of PICIBANIL® in combination with chemotherapy

The co-administration of this product and fluorouracil (antineoplastic agent) to mice with L1210 tumors pro-

longed survival time when compared to the sole administration of fluorouracil.

ADVERSE DRUG REACTIONS

Malignant tumor: 13,092 adverse reactions to this product were reported in 8,312 (31.9%) of 26,027 pa-

tients treated. The major adverse reactions were fever 6,019 events (23.1%), injection site pain 2,893

events (11.1%), injection site redness (induration, swelling) 1,198 events (4.6%), general malaise 848

events (3.3%), and anorexia 789 events (3.0%)

Lymphangioma: 207 adverse reactions to this product were reported in 93 (98.9%) of 94 patients treated.

The major adverse reactions were swelling and redness 80 events (85.1%), fever 79 events (84.0%), pain

13 events (13.8%), and tenderness pain 10 events (10.6%). And the major abnormal laboratory values

were increased WBC in 57 (64.0%) of 89 and increased CRP in 56 (71.8%) of 78 patients treated.

Clinically significant adverse reactions: Shock: Since shock may occur, patients should be closely monitored. If any abnormalities are observed,

the administration of this product should be discontinued and appropriate measures taken.

Interstitial pneumonia: Since interstitial pneumonia may occur or be exacerbated, patients should be

closely monitored. If abnormalities such as fever, cough, dyspnea and abnormal chest X-ray findings, are

observed, the administration of this product should be discontinued and appropriate measures (e.g., ad-

ministration of adrenocorticotropic hormone) taken.

Acute renal failure: Since acute renal failure may occur, patients should be closely monitored. When ab-

normalities such as increased BUN or creatinine, or decreased urinary output are observed, the admini-

stration of this product should be discontinued and appropriate measures should be taken.

REFERENCES

1. Package insert of Picibanil, Chugai Pharmaceutical Co., Ltd. May 2003

2. Swiss society of Neonatalogy; intralesional injection therapy with OK-432 (Picibanil®) in a full term infant with multicysticlymphangio-

macolli; April 2006

Page 9 Pharmacy Update

By: Yap Ren Ai

Pharmacist: Mam, I think your uncontrolled asthma might be due to

your poor inhaler technique….

Patient (cut off): No way! I’m so sure I have been using it right all these

while! I’ve used this type of inhaler many times before!

Doctor (surprised): Huh? I thought this is the first time you’ve been prescribed

Ventolin? Okay, there is no harm in showing it again right?

Patient took her inhaler, sprayed to her wrist, then sniffed it and said:

Just like testing any other perfume!

Pharmacist: ….O_o….

Page 10 Pharmacy Update

Compiled by: Siti Jannah Ibrahim and Sarah Nazurah

Group photo of all participants of ‘Seminar Retreat Farmasi Gemilang 2016’ held at

Akademi Kastam Malaysia, Bukit Baru, Melaka.

SEMINAR FARMASI RETREAT GEMILANG 2016 (9 JANUARY 2016)

KURSUS PENDISPENSAN ASEPTIK (6 APRIL 2016)

Emcee — Miss Karen Low introducing the speakers for the day

Page 11 Pharmacy Update

KURSUS KESELAMATAN DAN KESIHATAN PEKERJA

(27 FEBRUARY 2016)

Participants eager to kick-

start the day!

Emcees for the day —

Mr. Shahrul Azhan and

Ms. Tan Jhii Lien

Mdm Loh Lai Yee as chairman

of the committee, presenting a

gift pack to one of the present-

ers of the course as a token of

appreciation