PHARMACY NEWSLETTER

April-June 2016

Anti-

vaccination: Facts &

Drug Safety: AEFI &

Inside this issue:

Ankylosing Spondylitis

Dapagliflozin (Forxiga®)

Humour Corner

Activities

2

Anti-

vaccine

groups :

Facts

and

Myths

Anti-vaccine is a

person who is op-

posed to vaccina-

tion, typically a par-

ent who does not

wish to vaccinate

their child.

The anti vaccine

has existed as long

as vaccination it-

Anti Vaccine : Facts

Critics of vaccination have taken a variety of positions, including op-

position to the smallpox vaccine in England and the United States in

the mid to late 1800s, and the

resulting is an anti-vaccination

leagues. However, the modern

anti-vaccination movement has

its origins in a study published in

The Lancet, a highly influential peer-

reviewed medical journal, in 1998.

The study was widely

criticized as being “filled with

false and fraudulent data,” and was fully redacted in 2010. But once

the study was published in the first place, the damage was already

done. Vaccination rates plummeted, and have stayed lower ever

since, as anti-vaccination activists continue to cite the infamous

study. Decades of progress in vaccine research has been nullified by

anti-vaccination advocacy based largely on a redacted scientific

study.

So if the anti-vaccination movement does not have science behind it,

how exactly does it spread? One factor behind the spread of the

movement is that several celebrities in the west have participated in

anti-vaccine activism. These celebrities include a number of actors,

including Rob Schneider, who campaigned against a bill in California

that would have made it harder to get personal exemptions from vac-

cine requirements. Another infamous anti-vaccine activist is Jenny

McCarthy, who co-hosted the view for one season and spread her anti

-vaccine views through the show.

Another reason that the movement is able to persuade par-

ents is because it uses a lot of fear-mongering and scare tactics to

frighten parents into not vaccinating their children. These tactics

range from blatant fact denial and bad science to naming ingredients

in vaccines that seem harmful to those without a scientific back-

CURRENT ISSUES

3

Understandably, vaccine safety gets more public attention than vaccination effectiveness, but inde-

pendent experts and WHO have shown that vaccines are far safer than therapeutic medicines. Vaccines

have an excellent safety record and most “vaccine scares” have been shown to be false alarms. Mis-

guided safety concerns in some countries have led to a fall in vaccination coverage, causing the re-

emergence of diseases.

Conclusion

Efficacious vaccines not only protect the immu-nized, but can also reduce disease among unim-munized individuals in the community through “indirect effects” or “herd protection”. Hib vac-cine coverage of less than 70% in the Gambia was sufficient to eliminate Hib disease, with similar findings seen in Navajo populations.

Most vaccine-preventable diseases are spread from person to person. If one person in a community gets an infectious disease, he can spread it to others who are not immune. But a person who is immune to a disease because she

has been vaccinated can’t get that disease and can’t spread it to others.

The more people who are vaccinated, the fewer opportunities a disease has to spread.

Herd Protection: Consequences In Regards

http://www.cdc.gov/vaccines/vac-gen/whatifstop.htm

http://www.who.int/bulletin/volumes/86/2/07-040089/en/

“The History of Anti-Vaccination Movement.” (2016). Re-trieved from http://www.historyofvaccines.org/

Wakefield, A. et al. Ileal-lymphoid-nodular Hyperplasia, Non-specific Colitis, and Pervasive Developmental Disorder in Children. The Lancet 351, 637-641. (Feb., 1998).

Pearl, R. “A Doctor’s Take on the Anti-Vaccine Movement.” Forbes. (March, 2014).

“Anti-Vaccine Body Count.” (Sept, 2014). Retrieved from h t tp : / / w w w .j e n ny m cc a rt h yb o d yc o u nt .c o m / An t i-

References

4

“To catch the reader's attention, place an interesting sentence or quote from the story here.”

Play a part in reporting AEFI MADRAC via the National Pharmaceutical Control Bureau website (http://www.npra.gov.my)

1. Vaccine reactions

Individual’s response to inherent

properties of the vaccine.

Minor reactions includes local

pain, swelling or redness, fever,

malaise, headache which usually

occurs within a few hours of in-

fection and resolves spontane-

ously.

Severe reactions includes sei-

zures and allergic reactions

which can be life-threatening,

although, rare.

2. Immunization error-related reac-

tion

Preventable

Non-sterile injection: the reuse

of disposable syringe or needle,

or improperly sterilized syringe

Reconstitution error: inadequate

shaking of vaccine.

Injection at incorrect site: BCG

given subcutaneously, DTP/DT/

TT too superficial, injection into

buttocks.

Vaccine transported/stored in-

correctly: freezing vaccine dur-

ing transport, failure to keep

vaccine in cold chain.

Contraindication to vaccines

ignored due to unfamiliarity

3. Immunization anxiety-related

reactions

Patients react in anticipation to

and as a result of an injection.

Not related to the vaccine but to

fear of the injection.

Examples are fainting, hyperven-

tilation, vomiting or convulsions.

4. Coincidental events

Occurs after a vaccination has

been given but are not caused by

the vaccine or administration

errors.

Could be due to illness, congeni-

tal or early neurological condi-

tions.

Classifications of AEFI

How safe are vaccines?

Vaccines are the best defense we

have against serious, preventable

and sometimes, deadly contagious

diseases. However, like any other

medical products, there may be

risks.

The World Health Organization (WHO)

defines an AEFI as “a medical incident

that takes place after an immunization,

causes concern and believed to be

caused by immunization..”

Adverse events of vaccinations is not a

new news. It has been increasingly

popular in inciting anxiety and negativity

towards vaccination despite its crucial

benefits to the general population in

fighting certain infectious diseases.

Adverse events does not necessarily

have a causal relationship with the usage

of vaccine and can be temporarily asso-

ciated with immunization. As with other

medications, side effects are inevitable

but most of them such as fever and

injection site reactions are mild and clear

up quickly. More serious reactions like

anaphylaxis are rare and generally does

not result in long-term problems.

Play a part in reporting AEFI

MADRAC via the National Phar-

maceutical Control Bureau website

(http://www.npra.gov.my)

Adverse Events following Immunization (AEFI)

DRUG SAFETY/MADRAC NEWS

5

Stevens-Johnson

Syndrome ???

However there were 7 reports (12%) of Pal-

mar-plantar erythro-

dysaesthesia (PPE) or m o r e c o m m o n l y

known as hand-foot

syndrome, which is a

condition known and

documented in the

current approved pre-

scribing information of

Capecitabine (Xeloda®) is

a chemotherapy drug which

has been registered and

used in Malaysia since 2000.

Indication: Advanced or

metastatic breast cancer,

stage III colon cancer,

metastatic colorectal

c a r c i n o m a a n d

oesophagogastric cancer.

Capecitabine (Xeloda®) DRUG REVIEW

According to the Na-

tional Pharmaceutical Control Bureau (NPCB),

severe skin reactions

such as Stevens-

Johnson Syndrome

(SJS) and Toxic Epider-

mal Necrolysis (TEN),

in which some, with fa-

tal outcome has been

reported with the use

of Xeloda®. These

cases however, have

been classified as rare.

In June 2013, the Drug Safety Monitoring Centre, NPCB

has received 26 adverse drug reactions (ADR) reports

from the use of Xeloda® with 56 adverse events:

Fortunately, none of the reports in Malaysia involves

SJS nor TEN or with a fatal outcome.

16 events

of:

Nausea

Vomiting

Diarrhea

13 events

of:

Itching

Erythema

Maculo-

papular rash

12 events

of:

Back pain

Fever

Fatigue

PPE

Globally, WHO database contained 16 reports for SJS

and 13 reports of epidermal necrolysis associated

with Xeloda® from countries such as America , Africa and

Europe.

6

PATHOPHYSIOLOGY:

Primary pathology of the spondyl oarthropathies is

enthesitis with chronic inflammation, including

CD4+ and CD8+ T lymphocytes and macrophages.

Cytokines, particularly tumor necrosis factor-α

(TNF-α) and transforming growth factor-β (TGF-β),

are also important in the inflammatory process by

leading to fibrosis and ossification at sites of en-

thesitis -common genetic factors including the hu-

man leukocyte antigen (HLA) B27 gene.

ANKYLOSING SPONDYLITIS

DISEASES AND TREATMENT

DIAGNOSIS:

-Physical examination—eg: back pain and stiffness made

worse with immobility, pain for more than 3 months,

-Blood test to test for:

C-reactive protein (CRP), erythrocyte sedimentation

rate (ESR), plasma viscosity (PV). And/or HLA-B27 gene

-X-rays—for later stages .

-MRI) scans—for earlier stage of AS

-History of GI infection, uveitis, and family history of AS

TREATMENT: for active AS

A)NSAIDS (first line):

Naproxen— ORALLY; 250mg or 500mg BD. Max 1500mg/

day for 6 months .

Diclofenac—ORALLY; 150mg daily. Mild or long term: 75-

150mg daily in 2-3 divided doses.

Celecoxib—ORALLY; 200mg OD or 400mg OD max in di-

vided doses. If no improvement after 6 weeks, then 400mg/

day. Is a COX-2 inhibitor, given if patient has G1 distur-

bances when taking NSAIDs.

B) TNF-i Drugs (second line):

Golimumab— 50mg S/Q once a month

Infliximab— 5mg/kg IV over at least 2 hours given at week 0,

2 and 6, followed by maintenance therapy which 5mg/kg IV

over at least 2 hours every 6 weeks.

Etarnecept—50mg S/Q once a week .(not recommended in

pt with AS and inflammatory bowel disease)

C) Disease-modifying anti-rheumatic drugs (DMARDs)

(Conditionally recommended if TNF-s is contraindicated)

Sulfasalazine- ORALLY; initially 0.5 to 1g per day or in di-

vided doses not >8H. Maintenance, 2g/ day in divided dose

not >8H intervals.

Methotrexate– initially 7.5mg S/Q once weekly. Dose can

exceed 20mg/wk but with increase risk of toxicity. When

switching from oral to S/Q

must consider bioavailability

difference.

D) Physiotherapy and exercise.

PARAMETERS MONITORING:

Baseline serum levels of the following biomarkers were

examined: C-reactive protein (CRP), matrix metallopro-

teinase 3 (MMP3), sclerostin, Dickkopf 1 (DKK1), perio-

stin, bone morphogenetic protein (BMP) 2 and 7, osteo-

protegerin, vascular endothelial growth factor (VEGF),

procollagen type I and II N-propeptide (PINP and PIINP),

CTX-II, BALP, sRANKL, COPM, and bone sialoprotein.

7

Pharmacokinetic

Absorption

Cmax: within 2 hours

Bioavailability, oral: 78 %

Peak plasma time: 2 hrs (fasting), ~3 hrs (with high fat meal)

High fat meal decreases peak plasma concentration by up to 50 %

Distribution

Protein binding: 91 %

Metabolism

Extensive via UGT1A9 (an enzyme present in the liver and kidney)

3-O-glucuronide; to form an inactive metabolite

Excretion

Renal: 75 % (less than 2 % unchanged)

Fecal: 21%( 15 % unchanged)

Pharmacodynamic

Dapagliflozin is a highly potent, se-lective and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2).

The SGLT2 is selectively expressed in the kidney with no expression detected in > 70 other tissues in-cluding liver, skeletal muscle, adi-pose tissue, breast, bladder and brain.

SGLT2 is the predominant trans-porter responsible for reabsorption of glucose from the glomerulare filtrate back into the circulation.

Indication

Adjunct to diet and exercise to

improve glycaemic control in

adults ≥ 18 years old with type 2

DM as monotherapy, add-on

combination with metformin,

sulfonylurea, insulin, DPP4 in-

hibitor, in combination with

metformin and a sulfonylurea

and as initial combination ther-

apy with metformin (includes

poor respects for response to

metformin therapy)

Dose

Monotherapy and add-on com-bination therapy: 10 mg once daily

Initial combination therapy: 10 mg dapagliflozin + 500 mg met-formin once daily

Dosage modification

Renal impairment:

eGFR ≥60 ml/min/1.73 m2. No dosage adjustment needed

eGFR <60 ml/min/1.73 m2. Do not initiate

Not recommended with eGFR that declines persistently be-tween 30 to <60 ml/min/1.73 m2.

eGFR <30 ml/min/1.73 m2. Con-traindicated

Hepatic impairment:

Mild or moderate: No dosage adjustment needed

Severe: Not studied

Mechanism of Action

Inhibits sodium-glucose cotrans-

porter 2 (SGLT2), thereby reduc-

ing reabsorption of filtered glu-

cose, lowering the renal thresh-

old for glucose, and increasing

Dapagliflozin NEW DRUG PROFILE

8 HUMOUR CORNER

Two chemists go

into a restaurant.

The first one says "I

think I'll have an

H2O."

The second one

says "I think I'll have

an H2O too" -- and

he died.

9

BASIC STATISTICS COURSE

FOR MEDICAL

RESEARCH 2016

4TH JUNE 2016

PHARMILY TRIP TO

KUCHING, SARAWAK ON

15-17TH APRIL 2016

ACTIVITIES

Participants having hands-on experience

with SPSS Program

Group snap before dispersing.

Visiting the beautiful Fairy Cave as part

of the activities planned

Group photo when visiting the “Kampung

Kebudayaan Sarawak”

10

“To catch the reader's attention, place an interesting sentence or quote from the story here.”

If passion drives you, let reason hold the reins.”– Benjamin Franklin

KURSUS MOTIVASI ANJURAN JABATAN FARMASI HOSPITAL MELAKA

Participants enjoying the activity

Speaker sharing his experience and motivating the participants.

11

Jabatan Farmasi & Bekalan, Hospital Melaka, Jalan Mufti Hj Khalil, 57400 Melaka Phone: 06-2892583 Fax: 06-2837500 E-mail: prichospitalmelaka@gmail.com

Pharmacy Resources & Information Centre

ADVISOR:

Pn Saidatul Raihan Ibrahim

EDITORIAL BOARD:

Pn Syamsiah Hj Shariff

Cik Tay Eek Poei

Cik Umi Solehah binti Sa’ad

EDITOR:

Roshwini Muthiah

CONTRIBUTORS

Tan Jhii Lien

Nor Sa’adah binti Harun

References:

1.Malaysian clinical pharmacists knowledge regarding Adverse Events Following Immunization (AEFI). International Summit on Clinical Pharmacy & Dispensing. USA; Nov 2013.

2.Adverse events following immunization. World Health Organization; 2016.

3.Bulletin-MADRAC-December 2013. Xeloda® (Capecitabine): Association with Severe Skin Reac-tions such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).

4.Drug Safety Update. Medicines and Healthcare products Regulatory Agency, UK. Volume 7 Issue 6, January 2014.

5.Michael M. Ward, Atul Deodhar, Elie A. Akl, et al. American College of Rheumatology/Spondylitis

Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommenda-

tions for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthri-

tis. AMERICAN COLLEGE OF RHEUMATOLOGY 2015; DOI 10.1002/ART.39298(): . http://

www.rheumatology.org/Portals/0/Files/Recommendations%20for%20the%20Treatment%20of%

20Ankylosing%20Spondylitis.pdf (accessed 7th Octorber 2016).

6.Serum Biomarkers Predict Ankylosing Spondylitis Progression [Internet]. Medscape. 2016 [cited

13 June 2016]. Available from: http://www.medscape.com/viewarticle/765228

7.. Ankylosing spondylitis - Treatment - NHS Choices [Internet]. Nhs.uk. 2016 [cited 14 June 2016]. Available from: http://

8.MIMS Malaysia. 2016. [Internet] Available from : http://www.mims.com/malaysia/drug/info/forxiga

9.Medscape. 2016. [Internet] Available from : http://reference.medscape.com/drug/farxiga-dapagliflozin-999899

10.)Pharmacists Jokes at WorkJoke.com - Profession Jokes [Internet]. Workjoke.com. 2016 [cited 20 June 2016]. from: http://www.workjoke.com/pharmacists-jokes.html

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