The Relationship between AD and DM

PAGE 3 PAGE 1-2 PAGE 4 PAGE 5

Empagliflozin

N E W S L E T T E R

JAN—MAR 2017 (Volume 1)

14th January Bengkel Pelan Tindakan

PAGE 7-8

NEWS & ANNOUNCEMENTS: PAGE 9 - 10 DRUG PROFILE :

Diazoxide (Proglicem)

CURRENT ISSUE DRUG SAFETY DRUG REVIEW DISEASE UPDATE DPP4 Inhibitors: risk of severe joint pain

Neonatal Hypoglycemia

PAGE 6

PHARMACY EDUCATION 25th February 2017

Kursus Pengurusan Stress

5th January 2017

Majlis Hi-Tea Akhir Tahun & Perpisahan

Hospital Melaka

PAGE 11

TREAMENT ALOGRITHIM:

Type 2 Diabetes Mellitus

PAGE 12-13

PHARMACY JOKES/PUZZLES

Page 1 CURRENT ISSUE HOSPITAL MELAKA PHARMACY NEWSLETTER

The Relationship

Between Alzheimer’s

Disease and Diabetes

Mellitus

Over the recent years, there are increasing

evidences supporting a possible connection be-

tween Alzheimer's disease (AD) and diabetes

mellitus (DM). It was repor ted that a diabetic

patient has a greater incidence of cognitive decline

and an increased risk of acquiring all types of de-

mentia including AD.1,2,3 Generally, DM is charac-

terized by impairment in insulin actions and sig-

naling which leads to chronic hyperglycemia. DM

can be further categorized into Type 1 (T1DM)

and Type 2 (T2DM). T2DM is caused by insulin

resistance in peripheral tissues which subsequently

result in hyperglycemia.1,4 Conversely, T1DM is

caused by destruction of pancreatic islet beta cells

and attendant insulin deficiency.4 De la Monte pro-

posed AD as Type 3 DM, whereby AD may repre-

sent a form of diabetes that selectively involves the

brain and has both molecular and biochemical fea-

tures that overlap with both T1DM and T2DM.4

AD is a neurodegenerative disorder, in which the

exact pathological defects are still not clear but

most studies have suggested that the deposits of

amyloid-beta peptide formed from abnormal pro-

cessing of amyloid-beta precursor protein (amyloid

cascade hypothesis), may initiate and contribute to

the pathogenesis of AD.1,2

Introduction

The Rotterdam Study reported that DM al-

most doubled the risk of dementia and AD. This

study consisted of 6370 elderly subjects, followed

up for 2.1 years and 126 patients developed de-

mentia with 89 of them had AD.5 The

Kungsholmen study conducted in Sweden reported

that DM increased the risk of dementia (260 AD

and 49 vascular dementia cases) in 1301 very old

people (aged ≥75 years).7

Besides that, a systematic review of 14

studies found that the incidence of ‘any dementia’

was greater in diabetic subjects than in non-

diabetic subjects in majority studies.6 Another lon-

gitudinal cohort study involving 824 subjects up to

9 years, found that patients with DM had a 65%

higher risk of developing AD than those without

DM.8 In addition, a 2008 Swedish study also that

reported that men who develop T2DM in midlife

has significant increased risk of developing AD.9

In 2014, a nationwide population based co-

hort study conducted by Huang CC et al. in Tai-

wan found that newly diagnosed diabetic patients

was associated with greater risk of future AD de-

velopment compared to non-diabetic subjects over

a maximum 11 years of follow up. This study in-

cluded a total of 71,433 patients with newly diag-

nosed diabetes and another group of non-diabetic

subjects as non-exposure control after matching

using propensity score. There were 68,462 T2DM

patients and 2791 T1DM patients.

Epidemiological evidences

Page 2 CURRENT ISSUE HOSPITAL MELAKA PHARMACY NEWSLETTER

This study reported that both T1DM (hazard ratio,

1.89; 95% CI: 1.23–2.89, p= 0.004) and T2DM

(hazard ratio, 1.57; 95% CI: 1.34–1.85, p=0.001)

increased the risk of AD. This study also showed

that those with DM had significantly higher inci-

dence of AD than non-diabetic subjects (0.48% vs

0.37%,

p=0.001) (Figure 1). Moreover, this study also

found that the risk of developing AD increased

gradually in association to longer duration of DM

since diagnosis (Figure 2).10

Figure 1: Kaplan-Meier estimates of survival free of AD events in

subjects categorized by DM.10 Figure 2: The trend of incidence of AD according to the duration

of DM.10

Pathophysiological link Many recent studies have focused on the role of

insulin as possible link between AD and T2DM.1There

is a rapid growth in the literature pointing toward insu-

lin deficiency and insulin resistance as mediators of

AD.4Insulin has significant neurotrophic properties in

the brain and crosses blood brain barrier (BBB) through

insulin receptors mainly located in areas of brain re-

sponsible for cognitive function (the hippocampus, en-

torhinal cortex and frontal areas) .1,3 Insulin activates

signaling pathway associated with long term memory

and learning.2,3 According to de la Monte, insulin also

helps to regulate processes such as neuronal survival,

energy metabolism, and plasticity which are required

for learning and memory.4

In diabetic patient, due to insulin resistance and

hyperinsulinemia, insulin levels in the brain are initially

elevated and then down-regulated.10 Initial elevated

insulin concentrations in the brain interfere with β-

amyloid peptides clearance by competing for insulin

degrading enzyme (IDE) as both are degraded by IDE.

However, IDE is more selective for insulin than for β-

amyloid peptides, thus brain hyperinsulinemia may de-

prive β-amyloid peptides of its main clearance mecha-

nism, accumulate in the brain and subsequently result

in neurotoxic effects.1,3

Furthermore, insulin also modulates -amyloid

peptides metabolism by regulating expression of the

IDE.10 At chronic state of hyperinsulinemia, insulin

receptors at the BBB are down-regulated, and thus

transport of insulin into the brain decreased resulting in

low levels.1,3 Low insulin levels in the brain may reduce

IDE in brain and thereby reduce -amyloid peptide

clearance. The aggregation of beta amyloid peptides is a

fundamental neuropathological hallmark of AD.10

Moreover, insulin is also involved in the synthesis of

acetylcholine (Ach) by stimulating the expression of

choline acetyltransferase (ChAT). Therefore, low insu-

lin levels and insulin resistance may reduce Ach levels,

which represents a possible chemical link between AD

and DM.1,2,3

In a nutshell, current evidences available sug-

gest a possible association between AD and DM.1,2,3,10

However, those findings are not without controver-

sy.11,12 Hence, further study is still warranted to prove

the existence or the extent of a connection between DM

and AD das well as to clarify the mechanistic link and

to provide a clearer pathophysiological link.1,2

Figure 3: Insulin's role in the cholin-

ergic hypothesis3

Page 3 DRUG SAFETY HOSPITAL MELAKA PHARMACY NEWSLETTER

DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS:

RISK OF SEVERE JOINT PAIN

Overview

DPP-4 inhibitors group is one of the oral antidiabetic drugs that are used in the pharmaco-

logical therapy of Type 2 Diabetes Mellitus. It acts by prolonging the half-life of endoge-

nously produced glucagon-like peptide-1 (GLP-1). It then reduces the inappropriately ele-

vated post-prandial glucagon and stimulate glucose-dependent insulin secretion. The aver-

age reduction in HbA1c is approximately 0.7% to 1% at maximum dose.13

Safety Issue

In August 2015, United States Food and Drug Administration (US FDA) announced that DPP

-4 inhibitors may cause joint pain that can be severe and disabling. The FDA Adverse Event

Reporting System database identified 33 cases of severe arthralgia reported with the use

of DPP-4 inhibitors between October 2006 to December 2013.

All 33 patients experienced arthralgia that impaired their level of activity, including 10 pa-

tients who were hospitalized due to disabling joint pain. Onset of the joint pain symptoms

may start from day one to years after initial consumption of DPP-4 inhibitors. Symptoms

usually resolve in less than a month upon drug discontinuation. However, when patients

are restarted on a similar medication or an alternate DPP-4 inhibitor, a few of them en-

counter a repeat of manifestations.14

Local Scenario

In Malaysia, the National Pharmaceutical Regulatory Agency (NPRA) has received 291 re-

ports with 461 adverse events suspected to be associated with DPP-4 inhibitors.15 The ad-

verse events reported were mostly mild, such as rash, nausea, itching, diarrhea and head-

ache. There are three cases related to joint pain involving sitagliptin:-

A 45-year old male experienced lethargy, joint pain and fever-like feeling with chills

after taking the drug. He was unable to work throughout the day but recouped after

discontinuation of the drug.

The other two reports involved women aged 70 and 72 years respectively. Both doses

were 10 mg daily and were claimed to experience joint pain and body ache. Therapy

was continued despite of suspected adverse events and no further information was

provided by the reporter.

Page 4 DRUG REVIEW HOSPITAL MELAKA PHARMACY NEWSLETTER

Indication

An adjunct to diet and exercise to improve glycemic

control in adults with Type 2 Diabetes Mellitus (T2DM)

(approved by FDA in Aug, 2014)

Reduce the risk of cardiovascular death in adult patients

with T2DM and cardiovascular disease (CVD) (approved

by FDA in Dec, 2016)

Clinical Trial Result

The EMPA-REG trial reported a 38% relative risk

reduction for death from cardiovascular causes in

the empagliflzoin group (3.7% vs 5.9% in the pla-

cebo group), 35% relative risk reduction from hos-

pitalization for heart failure (2.7% vs 4.1% respec-

tively) and 32% relative risk reduction for death

from any causes (5.7% vs 8.3% respectively) .

Adverse Events

Urinary tract infection

Genital infection in females (e.g. Vag moniliasis, vul-

vovaginitis, balanitis)

Dehydration, hypotension, ketoacidosis, acute kid-

ney injury and impairment in renal function

Hypoglycemia

Contraindication

Patients with Type 1 Diabetes Mellitus

To treat diabetic ketoacidosis

Hypersensitivity reactions to the drug

Severe renal impairment, end-stage renal

disease, or dialysis

Empagliflozin tablet

Availability in Malaysia:

Jardiance® 10 mg and 25 mg Tablet

by Boehringer Ingelheim is registered

in Malaysia, but not listed in FUKKM

(Blue Book) yet.

Dosing: Initially PO 10

mg OD; may increase to

PO 25 mg OD

Drug Review

Empagliflozin (Jardiance) 16,17

Page 5 DISEASE (UPDATE) HOSPITAL MELAKA PHARMACY NEWSLETTER

HIGH RISK INFANTS

High risk infants will be frequently screened for asympto-matic hypoglycemia. 19

To date, no study has shown that asymptomatic hypoglyce-mia will benefit from treatment whereby frequent feeding and repeated glucose measurements is the current standard treatment. 19,22

Continuous IV dextrose infusion may be indicated if hypogly-cemia persists despite frequent milk feeding. 19,22

Investigational new approach for treatment of asymptomatic hypoglycemia: Buccal 40% dextrose gel (200mg/kg massaged into infant’s dried buccal mucosal) is recommended as first-line agent to manage hypoglycemia in late preterm and term babies within 48 h after birth. 19

Neonatal Hypoglycemia INTRODUCTION

Hypoglycemia definitions and threshold for treat-ment remain controversial with little data to sup-port a definitive breakpoint for serum glucose level (SGL). 18,19,20

At current, there is no established consensus defi-nition or treatment strategy for neonatal hypogly-cemia.20

However, it is widely accepted among clinicians that hypoglycemia is defined as < 2.6 mmol/L, re-quiring intervention.18,19,21,22

It is vital to distinguish between transitional neona-tal glucose regulation in normal newborns and persistent hypoglycemia to avoid serious conse-quences such as seizures and permanent brain injury.23

Persistent hypoglycemia is often caused by congen-ital or genetic defect in regulating secretion of in-sulin, deficiency of cortisol and/or growth hor-mone, or defects in the metabolism of glucose, glycogen and fatty acids.23

Treatment goals are to prevent poor neurodevel-opmental outcomes and to encourage normal feeding behavior.18

SYMPTOMS OF HYPOGLYCEMIA23

Autonomic symptoms: adrenergic responses (eg. palpitations, tremor, anxiety); cholinergic responses (eg. sweating, hunger, paresthesia)

Neuroglycopenic symptoms: confusion, coma and seizure.

AVAILABLE TREATMENT OPTIONS Table 2: Pharmacological agents for treatment of neonatal hypoglycemia.

Agent MOA Dosing Side Effects18

Hypoglycemia

Dextrose 18,21

Administration of glucose titrated to achieve euglyce-mia

IV bolus dextrose 10% 2mL-3mL/kg, fol-lowed by continuous infusion 4-8 mg/kg/min (max:20-30mg/kg/min)

Venous throm-bosis, phlebitis, hyperosmolar syndrome

Persistent hypoglycemia despite glucose delivery > 8-10mg/kg/min

Glucagon18,21 As a counter-regulatory hormone of insulin helps to regulate gluconeogenesis and promotes hepatic gly-cogenolysis to raise serum glucose levels

IV or IM 0.04mg/kg stat, then 10-50mcg/kg/hr (0.5mg/kg in 50ml at 1-5ml/hr)

**not for small gestational age babies or adrenal insufficiency

Hyponatremia; thrombocytopenia (rare)

Hydrocorti-sone18,21

Reduce insulin secretion, increase insulin resistance, enhancing both gluconeogenesis and glycogenolysis

IV 2.5-5mg/kg/dose BD, especially small gestational age babies

Growth suppres-sion; hypertension

Diazoxide18,21 A potent β-cell KATP channel opener. Stabilize open KATP channel leads to inhibition of insulin secretion.

PO 10-25mg/kg/day in 3 divided doses (max:30mg/kg/day)

Hirsutism; heart failure; fluid reten-tion; nausea, vom-iting

Octreotide 18,21

Indicated when diazoxide therapy failed. Somatostatin inhibits insulin secretion by hyperpolarization of β-cell and direct inhibition of voltage gated calcium chan-nels.

SC or IV 2-10mcg/kg/day in 2 or 3 divided doses (max:40mcg/kg/day)

Cholelithiasis

Nifedipine18 Investigational therapy with variable success for whom failed diazoxide therapy. Calcium channels located on pancreatic β-cells are blocked by calcium channel blocker (CCB), inhibiting influx of calcium and thus decreased intracellular calcium and subsequently in-hibits insulin secretion.

PO initial: 0.25-0.3mg/kg/day divided every 8 hours titrated up to final: 0.5-0.8mg/kg/day divided every 8 hours

None reported by case studies. Com-mon side effects of CCB (nausea, dizziness, flushing, headaches.

Neonatal at increased risk of hypoglycemia: 23

1) Symptoms of hypoglycemia

2) Large for gestational age (even without maternal diabetes)

3) Perinatal stress (birth asphyxia/ ischemia, maternal pre-eclampsia or hypertension, intrauterine growth restriction, meconium aspiration syndrome, erythroblastosis fetalis, polycythemia, hypothermia)

4) Premature or post-mature delivery

5) Infant of diabetic mother

6) Family history of a genetic form of hypoglycemia

7) Congenital syndrome & abnormal physical features

Page 6 PHARMACY EDUCATION HOSPITAL MELAKA PHARMACY NEWSLETTER

Images adapted from: http://www.diabetesed.net/page/_files/HyperHypo-handout.pdf

Hypoglycemia Symptoms

Hyperglycemia Symptoms

Page 7 PHARMACY ACTIVITES/ ANNOUNCEMENT HOSPITAL MELAKA PHARMACY NEWSLETTER

Date : 14th January 2017

Location : Impian Ballrom, Bayview Hotel

Participants : 33 people

Objectives :

To discuss 2016 achievements for pharmacy department

To propose 2017 action plans for pharmacy department

Date : 25th February 2017

Location : Auditorium Sri Baiduri, Hosp Melaka

Participants : 50 people

Objectives : To expose participants to stress man-agement techniques and effective ways to handle stress

Page 8 PHARMACY ACTIVITES/ ANNOUNCEMENTS HOSPITAL MELAKA PHARMACY NEWSLETTER

Date : 5th January 2017

Location : Main Pharmacy Department

Organizers : Share & Care Of Pharmacy Depart-ment, Hospital Melaka

Agenda :

Farewell Party for Pharmacy Staffs

New Year 2017 Celebration

Page 9 NEW DRUG PROFILE HOSPITAL MELAKA PHARMACY NEWSLETTER

INDICATION

Useful in the management of hyopgylcemia due to hyperinsulinism associated with the following conditions:

Adults: inoperable islet cell adenoma or carci-noma or extra-pancreatic malignancy

Infants & Children: Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extra-pancreatic malignancy, islet cell adenoma or adenomatosis

DOSE

ADULT & CHILDREN

The usual daily dosage is 3 to 8 mg/kg/day divided in 2 or 3 equal doses. In certain in-stances, patients with refractory hypoglyce-mia may require higher dosages.

Ordinarily, an appropriate initial dosage is 3mg/kg/day, divided into 3 equal doses eve-ry 8 hours. Thus, an average adult would receive a starting dosage of approximately 200mg daily

INFANTS & NEWBORNS

The usual daily dosage is 8 to 15mg/kg, di-vided into 2 or 3 equal doses every 8 or 12 hours.

An appropriate starting dosage is 10mg/kg/day, divided into 3 equal doses every 8 hours

MECHANISM OF ACTION

Increase the blood glucose level by inhibiting insulin release from the -cells of the pancre-as and also to an extra-pancreatic (catecholamine-induced) effect

Decrease the excretion of sodium & water, resulting in fluid retention which may be clini-cally significant

Produces arteriolar vasodilation and decreases peripheral resistance which possibly result in anti-hypertensive effects

N ew Dr ug i n Ho sp i ta l Me la ka :

D IAZOXIDE (Progl i cem® ) 100mg C apsule 25,26

Chemical structure of diazoxide.

Page 10 NEW DRUG PROFILE HOSPITAL MELAKA PHARMACY NEWSLETTER

A D M E

Absorption: Readily absorbed from the GI tract

Distribution: Crosses the placenta & blood brain barrier

Protein Binding: >90%

Metabolism: Partially metabolized in liver by oxidation and sulfate conjugation

Excretion: Via urine filtration as un-changed drug (50%) and metabolites; feces (small amount)

Half-Life: 9-24 hr (children); 24-36 hr (adults), increases in patients with renal im-pairment

Dialyzable: HD: yes, PD: yes; no supple-mental dose is required

RENAL

IMPAIRMENT

Dose reductions may be necessary.

PREGNANCY/

LACTATION

Pregnancy Category: C

Lactation: Excretion in milk unknown;

not recommended

ADVERSE DRUG

REACTIONS

Hypotension

Hyperglycemia including diabetic ketoacido-

sis

Edema or body fluid retention

Congestive heat failure

Gastrointestinal disturbances (abdominal

pain, loss of appetite, nausea or vomiting)

Dermatological effects (hirsutism, alopecia)

Thrombocytopenia & eosinophilia

Dizziness & tinnitus

Page 11 TREATMENT ALOGRITHIM HOSPITAL MELAKA PHARMACY NEWSLETTER

Figure 5: Treatment alogarithm of type 2 diabetes mellitus. 24

Page 12 PHARMACY JOKES HOSPITAL MELAKA PHARMACY NEWSLETTER

Pharmacy Humour

Page 13 PHARMACY PUZZLE HOSPITAL MELAKA PHARMACY NEWSLETTER

Rx Word Search

Answer:

Page 14 MISCELLANEOUS HOSPITAL MELAKA PHARMACY NEWSLETTER

1. Barbagallo M and Dominguez LJ. Type 2 diabetes mellitus and Alzheimer’s disease.

World J of diabetes 2014 Dec; 5(6):889-893.

2. Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M and Raffa RB. Diabetes mellitus and

Alzheimer’s disease: shared pathology and treatment? Br J Clin Pharmacol 2011; 71

(3):365-376.

3. Kroner Z. The relationship between Alzheimer’s disease and diabetes: type 3 diabetes? Altern Med Rev 2009; 14(4):373–9.

4. de la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes-evidence reviewed. J

Diabetes Sci Technol 2008; 2(6):1101-1113

5. Ott A, Stolk RP, van Harskamp F, et al. Diabetes mellitus and the risk of dementia: The

Rotterdam Study. Neurology 1999; 53:1937-1942.

6. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabe-

tes mellitus: a systematic review. Lancet Neurol 2006; 5: 64-74.

7. Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L. Diabetes mellitus and risk of de-mentia in the Kungsholmen project: a 6-year follow-up study. Neurology 2004; 63: 1181–

1186.

8. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk

of Alzheimer disease and decline in cognitive function. Arch Neurol 2004; 61: 661-666

9. Rönnemaa E, Zethelius B, Sundelöf J, et al. Impaired insulin secretion increases the risk of

Alzheimer disease. Neurology 2008; 71:1065-1071.

10. Huang CC, Chuang CM, Leu HB, et al. Diabetes mellitus and the risk of Alsheimer’s disease: a nationwide population- based study. PLOS ONE 2014; 9(1):e87095.

11. MacKnight C, Rockwood K, Awalt E, McDowell I. Diabetes mellitus and the risk of

dementia, Alzheimer’s disease and vascular cognitive impairment in the Canadian Study

of Health and Aging. Dement Geriatr Cogn Disord 2002; 14: 77–83.

12. Akomolafe A, Beiser A, Meigs JB, Au R, Green RC, et al. Diabetes mellitus and risk of

developing Alzheimer disease: results from the Framingham Study. Arch Neurol 2006; 63:

1551–1555.

13. Barbara G Wells et al, Pharmacotherapy Handbook, 2012. 14. FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes

may cause severe joint pain, Aug 2015.

15. Malaysian Adverse Drug Reactions Newsletter, Dec 2015.

16. US Food & Drug Administration. (2016). FDA approves Jardiance to reduce cardiovascu-

lar death in adults with type 2 diabetes [Press release]. Retrieved from https://

www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm531517.htm

17. Miriam E Tucker, FDA Approves Empagliflozin for Reducing CVD Death, Medscape, [Updated December 2016], Available: http://www.medscape.com/viewarticle/872697

18. Sweet CB, Grayson S and Polak M. Management strategies for neonatal hypoglycemia:

review article. I Pediatr Pharmacol Ther 2013; 18(3):199-208.

19. Rozance PJ and Hay Jr WW. New approaches to management of neonatal hypoglycemia.

Maternal Health, Neunatology, and Perinatology 2016; 2(3):1-7

20. Rozane PJ. Update on Neonatal hypoglycemia. Curr Opin Endocrinol Diabetes Obes 2014;

21(1):45-50.

21. Hj Muhammad Ismail HI, Ng HP, and Thomas T. Paediatric protocols for Malaysian hospitals. 3rd ed. Malaysia: Ministry of Health. 2014.

22. Hegarty JE, Harding JE, Crowther CA, Brown J and Alsweiler J. Oral dextrose gel for the

prevention of hypoglycemia newborn infants (protocol). Cochrane Database of Systematic

Reviews 2016; 4: CD012152.

23. Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the pediatric endo-

crine society for evaluation and management of persistent hypoglycemia in neonates,

infants, and children. The Journal of Pediatrics 2015; 167(2):238-245.

24. American Diabetes Association. Standards of medical care in diabetes– 2016. Diabetes Care 2016; 39(Suppl. 1):S1-S111.

25. Medscape. Drug & Disease: Diazoxide. Accessed 2017 Mar 10. Available from URL:

http://reference.medscape.com/drug/proglycem-diazoxide-342311

26. MIMS. Patient Medinfo: Diazoxide. Accessed 2017 Mar 10. Available from: URL:http://

www.mims.com/malaysia/drug/info/diazoxide?mtype=generic

EDITORIAL

ADVISOR:

Pn Saidatul Raihan

EDITORIAL BOARD:

Syamsiah Hj Shariff

Tay Eek Poei

Ng Siok Shen

EDITOR:

Loh Wan Ting

CONTRIBUTORS:

Soraya Binti Rosli Thanarupini A/P Giamasraw Siti Nur Aisyah Binti Razali

REFERENCES

NEW STAFFS Pn Chew Soo Piing (FRP TDM)

Pn Azlin Shahida Bt Mohd Noor (EO Stor)

For more information or drug enquiries, please contact: