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