PAGE 3 PAGE 1-2 PAGE 4 PAGE 5-6

PHARMACY N E W S L E T T E R

July– Sept 2017 (Volume 3)

Asthma & COPD

28TH JULY 2017 MAJLIS MERIAH KONGSI RAYA

PAGE 7-8

NEWS & ANNOUNCEMENTS: PAGE 11-12

TREATMENT ALGORITHM: PAGE 9-10

DISEASE (UPDATE)

Chronic Obstructive

Pulmonary Disease (COPD) COPD & Asthma

CURRENT ISSUE

SMART Therapy in Asthma

DRUG SAFETY NEW DRUG PROFILE DRUG REVIEW

Thrombocytopenia Risk of Montelukast

Bronchodilators and Inhaled Corticosteroid

5TH AUG 2017 SAMBUTAN HARI KELUARGA @ PHARM’ILY DAY 2017

6-8TH AUG 2017 KONVENSYEN INOVASI & KREATIIVITI FARMASI 2017

Hospital Melaka

PAGE 13

PHARMACY EDUCATION:

Respiratory Medications

Available in Hospital

Melaka

Seebri Breezhaler (Glycopyrronium)

Page 1 CURRENT ISSUE HOSPITAL MELAKA PHARMACY NEWSLETTER

The Role and Benefits of ‘SMART’

Therapy in Asthma Management

‘SMART’ therapy

(Single maintenance & reliever therapy for asthma)

‘SMART’ regimen allows patients to use only one combination inhaler (inhaled

corticosteroids & formoterol [LABA] ), for both maintenance and reliever therapy.1

The maintenance dose is adjustable, but should be a minimum of two doses per day.

CLINICAL EVIDENCE 2006 Significant reductions in the number of severe exacerbations and in the time elapsed before the first severe exac-

erbation, were seen using SMART regimen in STAY trial.2

2007 In COMPASS trial, SMART regimen resulted in a significant reduction in severe exacerbations of asthma in adults

and adolescents (aged 12 years) in comparison with either equivalent maintenance dose fluticasone/salmeterol with a

SABA as required or a maintenance dose budesonide/formoterol at twice the SMART dose with a SABA as required.3

2009 A Cochrane analysis concluded that SMART therapy reduces the risk of asthma exacerbations in comparison with

fixed dose maintenance inhaled corticosteroid. 4

2011 The post-hoc analysis of the results of 5 RCTs (>12000 patients) summarized that SMART therapy may be prefera-

ble options for patients on Step 2 to 4 of asthma guidelines (GINA) requiring a more effective treatment, compared with

other fixed dose alternatives.5

Page 2 CURRENT ISSUE HOSPITAL MELAKA PHARMACY NEWSLETTER

BENEFITS

Clinical results showed that SMART regimen prolongs the time to the first severe asthma exacerbation,

reduces the rate of exacerbations, and maintains day-to-day asthma control at a reduced load of cortico-

steroids (inhaled plus systemic) when compared with higher fixed maintenance doses of combination

inhalers.

Due to its simplicity, SMART regimen may help to improve adherence while reducing the overall ICS dos-

es required to achieve asthma control. This may have an impact on long-term management of side-

effects and their associated morbidity.1,6

Inhalers that can be used for SMART regimen

Turbuhaler Symbicort (Budesonide 160mcg/Formoterol 4.5mcg)

Maximum dose: 12 puffs/day (including of regular daily doses)

Do not take more than 6 puffs at any single occasion.7

MDI Foster (Beclomethasone dipropionate 100mcg/Formoterol fumarate dihydrate 6mcg)

Maximum dose: 8 puffs/day (including of regular daily doses)

Do not take more than 6 “reliever” puffs per day.8

MECHANISM OF ACTIONS

The synergism of ICS & LABA in asthma therapy is well-established but recent studies have also shown

the efficacy of combinations containing ICS & Formoterol in the relief of acute symptoms. LABA

Formoterol is a full -receptor agonist with a rapid onset of action but minimal tolerance that enables

repeated dosing. Therefore, formoterol can be used as a reliever therapy in acute asthma attack.1

It is important that the temporary reliever includes not only a bronchodilator but an ICS too as worsening

of asthma includes not only more airway narrowing, but also an increase in the airway inflammation.1

Thus, the SMART concept ensures that patients get an anti-inflammatory drug at the time of the first

signs of asthma worsening.1

Page 3 DRUG SAFETY HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 3 DRUG SAFETY HOSPITAL MELAKA PHARMACY NEWSLETTER

Montelukast & Thrombocytopenia

Montelukast is a selective leukotriene receptor antagonist that inhibits the effects of cysteinyl leukotrienes in the

airways. This drug is used for the prophylaxis and chronic treatment of asthma in adults and pediatric patients aged

12 months and above, and for the relief of daytime and night time symptoms of seasonal allergic rhinitis in patients

aged 2 years and older.9

Thrombocytopenia is defined as a platelet count of 150 x 103 per µL or less, that may increase the risk of bleeding

such as epistaxis, bruising, petechiae, and gingival bleeding. Drug-induced thrombocytopenia is relatively common; it

often occurs within 5 - 7 days of initiating therapy and the condition usually resolves within 7 - 14 days upon drug dis-

continuation.9

Safety Issue

In Japan, three thrombocytopenia cases linked with montelukast use were reported since 2012. In view of these

cases, the Pharmaceuticals and Medical Devices Agency of Japan conducted an investigation on the safety of

montelukast sodium which resulted in the update of product package insert (PI) by including ‘thrombocytopenia’

under the section of ‘Clinically significant adverse reactions’.9

Investigations by the product registration holder also revealed 109 post-marketing reports associated with

thrombocytopenia around the world since Singulair® was first marketed in 1998 until 28 October 2014. It was reported

that thrombocytopenia adverse event affected patients of all ages (range 1 - 93 years), and the median onset of

reaction was 16 days after starting treatment.9

Local Scenario

Since year 2000, NPRA has received 94 montelukast-related ADR reports with a sum of 160 adverse events. As of now,

no reports of thrombocytopenia have been received locally. 9

Most of the adverse events were made up of skin and appendages disorders (34 cases, 21%) such as rash and pruritus;

gastro-intestinal system disorders (31 cases, 19%) such as diarrhoea and vomiting; and psychiatric disorders (31 cases,

19%) such as insomnia, aggressive behavior and hallucination. Majority of the cases (78%) were caused as C3

(possibly-related to the drug) as there were concurrent medications which may have contributed to the ADRs.9

Nonetheless, healthcare professionals need to advise patients on montelukast to be on the lookout for signs of

bleeding (e.g. nose bleed, bleeding gums when brushing teeth, slow healing of wounds & bruising).

Page 4 NEW DRUG PROFILE HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 4 NEW DRUG PROFILE

SEEBRI BREEZHALER® 50 mcg19

HOSPITAL MELAKA PHARMACY NEWSLETTER

INDICATION

Used as a long term bronchodilator in the maintenance treatment of

adult patients with chronic obstructive pulmonary disease (COPD),

emphysema, and chronic bronchitis.

(Glycopyrronium 50mcg, Inhalation Powder Hard Capsules)

DOSE

Adults: The recommended dose is one capsule (50 mcg) inhaled once daily.

Administer at the same time each day. If a dose is missed, administer as soon as possible on that day and do not

take 2 doses on the same day. Do not swallow the capsule.

Pediatrics (< 18 years of age): Not recommended

MECHANISM OF ACTION

Glycopyrronium is a long-acting muscarinic receptor antagonist (LAMA) which causes bronchodilation by reversibly

inhibiting the action of acetycholine at muscarinic receptor subtypes 1 to 3 in bronchial smooth muscle.

PHARMACOKINETICS

A: Rapidly absorbed & reached peak plasma levels at 5 minute post-dose

D: Steady-state Vd 83L & terminal phase Vd 376 L (Protein binding 38-41%)

M:Multiple CYP isoenyzme contribute to the oxidative biotransformation

of glycopyrronium

E: 85% excreted unchanged in urine, 5% excreted in bile

CONTENT OF SEEBRI BREEZHALER PACK

RENAL IMPAIRMENT

Mild to Moderate renal impairment: Seebri breezhaler can be used at

the recommended dose

Severe renal impairment (ESRF with dialysis): Seebri Breezhaler

should only be used if the expected benefits outweighs the potential

risks.

HEPATIC IMPAIRMENT

No clinically relevant increase of systemic exposure

ADVERSE REACTIONS

Dry mouth

Urinary retention

Gastrointestinal effects (e.g. dyspepsia)

Throat irritation & Dysphonia

Nasophyaryngitis, Rhinitis, Sinusitis

Musculoskeletal pain

Comparisons of Inhaled Bronchodilators 10

Bronchodilators Onset of Action

Duration of Action (Hours)

Side effects Indication Dosing Frequency

Short-Acting β-agonist (SABA)

Salbutamol

5-15 mins 4-6 Tremor, palpitations, tachycardia

Reliever therapy in asthma, COPD & prevention of exercise-induced bronchoconstriction

1-2 puffs PRN basis

Long-Acting β-agonist (LABA)

Indacaterol

5 mins 24 Tremor, palpitations, tachycardia, headache

Once-daily Maintenance therapy in COPD

Olodaterol

5-10 mins 24 Once-daily

Salmeterol 10-30 mins 12 Maintenance therapy in asthma & COPD

Twice-daily

Formoterol 1-3 mins 12 Twice-daily Maintenance therapy in asthma & COPD (SMART therapy in combination)

Short-Acting Muscarinic Antagonists (SAMA)

Ipratropium 3-10 mins 6-8 Dry mouth, throat irritation

Reliever therapy in asthma & COPD

PRN & TDS

Long-Acting Muscarinic Antagonists (LAMA)

Tiotropium 15 min 24 Dry mouth, throat irritation

Maintenance therapy in COPD

Once-daily

Glycopyrronium 5 min 12-24 Maintenance therapy in COPD

Once-daily

Page 5 DRUG REVIEW HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 6 DRUG REVIEW HOSPITAL MELAKA PHARMACY NEWSLETTER

Inhaled Corticosteroid Doses for Asthma 11 Adults and adolescents (12 years and older)

Drug Daily dose (mcg)

Low Medium High

Beclometasone dipropionate (CFC) 200-500 >500-1000 >1000

Beclometasone dipropionate (HFA) 100-200 >200-400 >400

Budesonide (DPI) 200-400 >400-800 >800

Ciclesonide (HFA) 80-160 >160-320 >320

Fluticasone propionate (DPI) 100-250 >250-500 >500

Fluticasone propionate (HFA) 100-250 >250-500 >500

Children 6-11 years

Beclometasone dipropionate (CFC) 100-200 >200-400 >400

Beclometasone dipropionate (HFA) 50-100 >100-200 >200

Budesonide (DPI) 100-200 >200-400 >400

Budesonide (nebules) 250-500 >500-1000 >1000

Ciclesonide (HFA) 80 >80-160 >160

Fluticasone propionate (DPI) 100-200 >200-400 >400

Fluticasone propionate (HFA) 100-200 >200-500 >500

Differences between CFC & HFA inhalers

CFC: chlorofluorocarbon propellant; DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant

This is not table of equivalence, but of estimated clinical comparability. Most of the clinical benefits from ICS is seen at low dose

High doses are arbitrary, but for most ICS with prolonged use, are associated with increased risk of systemic side-effects.

CFC INHALERS HFA INHALERS

Propellant Chlorofluorocarbons Hydrofluoroalkanes

Performance Sharp burst of spray

Gentler & softer spray

Technique &

Maintenance

Easier to clean & maintain

Requires priming before use

Requires slow inhalation

Needs to be cleaned & cared for differently

Temperature Cold spray Warm spray

Precautions - Contain ethanol which may cause allergic reaction

Page 7 PHARMACY ACTIVITES/ ANNOUNCEMENT HOSPITAL MELAKA PHARMACY NEWSLETTER

Date: 28th July 2017

Time: 8pm-10.30pm

Location: Hotel La Boss, Melaka

Date: 6th – 8thAugust 2017

Location: Klana Resort, Negeri Sembilan

MAJLIS MERIAH KONGSI RAYA KONVENSYEN INOVASI & KREATIVITI FARMASI 2017

Page 8 PHARMACY ACTIVITES/ ANNOUNCEMENT HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 8 PHARMACY ACTIVITES/ ANNOUNCEMENT HOSPITAL MELAKA PHARMACY NEWSLETTER

Date: 5th August 2017

Time: 7.30am-2pm

Location: Bayou Lagoon Water Park

PHARM’ILY DAY 2017 (SAMBUTAN HARI KELUARGA)

Wan

NorSuhada

Siti Fatimah

Bt Samat

Lim Ai Pang Norhayati

Abu Jamal

Page 9 DISEASE UPDATE HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 9 DISEASE (UPDATE) HOSPITAL MELAKA PHARMACY NEWSLETTER

Chronic Obstructive Pulmonary Disease (COPD)

PATHOPHYSIOLOGY

Airflow limitation & gas trapping where the extent

of inflammation, fibrosis & luminal exudates in the

small airways correlates with the reduction in the

FEV1 & FEV1/FVC ratio.11,12

Gas exchange abnormalities result in hypoxemia &

hypercapnia, whereby gas transfer for oxygen &

carbon dioxide worsens as the COPD progresses.12

Pulmonary hypertension develops late in the

course of COPD due to hypoxic vasoconstriction of

small pulmonary arteries, which results in structural

changes & smooth muscle hypertrophy/

hyperplasia.13

Mucus hypersecretion resulting in a chronic pro-

ductive cough, is a feature of chronic bronchitis but

not necessarily associated with airflow limitation.10

Exacerbations may result in increased hyperinfla-

tion & gas trapping which reduced expiratory flow &

increased dyspnea in COPD patients.14

Systemic features as airflow limitation & hyperin-

flation may affect cardiac function & gas exchange.

Inflammatory mediators in circulation may contrib-

ute to skeletal muscle wasting or worsen ischemic

heart disease, heart failure, osteoporosis, anemia or

diabetes.10

DEFINITION 10

COPD is characterized by persistent respiratory symptoms & airflow limitation that is due to airway and/

or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. The chronic

airflow limitation is caused by a mixture of small airways disease (e.g. bronchiolitis) & parenchymal

destruction (emphysema).

SYMPTOMS10

Dyspnea

Cough

Sputum production

Wheezing/ chest tightness

Fatigue

Weight loss

DIAGNOSIS10

COPD should be considered in any patient who has dyspnea, chronic cough or

sputum production, and/or a history of exposure to risk factors for the disease.

Spirometry is required to make the diagnosis in this clinical context16; the pres-

ence of a post-bronchodilator FEV1/FVC < 0.70 confirms the presence of persis-

tent airflow limitation & thus of COPD in patients with appropriate symptoms

and significant exposures to noxious stimuli. COPD Assessment Test (CAT) is

used to measure the impact of COPD on person’s life.

Example 1: Patient A with FEV1<30% & CAT

scores of 18 with no exacerbations in the past

year is labelled as GOLD Grade 4, Group B.

Example 2: Patient A with FEV1<30% & CAT

scores of 18 with 3 exacerbations in the past

year is labelled as GOLD Grade 4, Group D.

Page 10 DISEASE UPDATE HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 10 DISEASE (UPDATE) HOSPITAL MELAKA PHARMACY NEWSLETTER

PHARMACOLOGICAL TREAMENT10,17

* Refer to Page 12 for ‘Management of Stable COPD

PARAMETER MONITORING 10

Measurement (FEV1, functional capacity based on timed walking test, oxygenation level in arterial

blood gas)

Symptoms (cough, sputum, breathlessness, fatigue, activity limitation, sleep disturbances)

Exacerbations (sputum volume, sputum purulence, frequency)

Imaging (chest x-ray)

Smoking status

Pharmacological Treatment Examples Mechanism of Actions

Short-Acting Beta2-agonists (SABA) Salbutamol Relax airway smooth muscle which keep the airway open

& makes breathing easier

Long-Acting Beta2-agonists (LABA) Formoterol, Salmeterol, Indacaterol ,

Olodaterol

Short-Acting Muscarinic

Agonists (SAMA)

Ipratropium Blocks the bronchoconstrictor effects of acetylcholine on

muscarinic receptors expressed in airway smooth muscle

& help clear mucus from lung

Long-Acting Muscarinic Agonists

(LAMA)

Tiotropium, Glycopyrronium

Methylxanthines Theophylline May act as non-selective phosphodiesterase inhibitors

Inhaled Corticosteroids (ICS) Budesonide, Fluticasone Reduce inflammation in the airways which leads to less

swelling & mucous production in the airways

Combination Medications SABA/SAMA

(e.g. Berodual-N)

LABA/ICS

(e.g. Symbicort/ Seretide)

*Combining medications with different mechanisms &

duration of action may increase the efficacy with lower

risk of side effects

Phosphodiesterase-4 Inhibitors Roflumilast Reduce inflammation by inhibiting the breakdown of

intracellular cyclic AMP

Antibiotics Azithromycin 500mg OD for 5-7 days

OR

Amoxicillin/Clavulanate 625mg TDS for 1 week

OR

Cefuroxime 500mg BD for 1 week

*Only in patients with acute exacerbations with at least 2

out of 3 symptoms (purulent sputum, increased sputum

volume, increased dyspnea)

Vaccinations Influenza Vaccine

Pneumococcal Vaccine

*Vaccination reduces serious

Illness (e.g. flu)

Page 11 TREATMENT ALOGRITHIM HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 11 TREATMENT ALGORITHM HOSPITAL MELAKA PHARMACY NEWSLETTER

Group D treatment algorithm

COPD MANAGEMENT10 (pharmacological treatment algorithms based on GOLD Grade, whereby

highlighted boxes & arrows indicate preferred treatment pathways)

For Group B patients, initial therapy should consist of a long-acting bronchodilator swhich is superior to short-acting bronchodilators taken as needed.

For patients with persistent breathlessness on monotherapy, the use of two bron-chodilators is recommended whereas for patients with severe breathlessness, initial therapy with 2 bronchodilators may be considered.

Group B patients are likely to have comorbidities that may add to their symptomology and impact their prognosis and these possibilities should be investigated.

For Group C patients, initial therapy should consist of a single long acting bron-chodilator. Based on head-to-head trials, LAMA was superior to LABA on exacer-bation prevention, and thus LAMA is the recommended starting therapy in this group.

Patients with present exacerbations may benefit from adding a 2nd long-acting bronchodilator or using a combination of LABA/ICS. As ICS increases risk of pneu-monia in COPD patients, the primary choice is LAMA/LABA.

For Group D patients, initiation therapy with a combination of LABA/LAMA is preferred as it has superior results compared to single substances or LABA/ICS combination. Initial therapy with LABA/ICS may be first choice in some patients that may have history and/or findings suggestive of asthma-COPD overlap If a single bronchodilator is chosen as initial treatment, a LAMA is preferred compared to LABAs. In patients who develop further exacerbations on LABA/LAMA therapy, two alternative pathways are suggested: 1. Escalation to LABA/LAMA/ICS. 2. Switch to LABA/ICS but if LABA/ICS therapy doesn’t positively impact

exacerbations/symptoms, a LAMA can be added. If patients treated with LABA/LAMA/ICS still have exacerbations, the following options may be considered 1. Add roflumilast 2. Add a macrolide (azithromycin) 3. Stop ICS due to lack of efficacy & increased adverse events

Group B treatment algorithm

Group C treatment algorithm

LAMA

LAMA + LABA

LAMA + LABA

LAMA +

LABA +

ICS

All Group A patients should be offered bronchodilator treatment based on its effect on breathlessness. This can be either a SABA or LABA and should be continued if symptomatic benefit is documented.

Group A treatment algorithm

A long-acting bronchodilator

(LABA or lama)

LAMA + LABA

A bronchodilator

LABA: long acting beta2 agonists; LAMA: long-acting muscarinic antagonists; ICS: inhaled corticosteroid

Page 12 TREATMENT ALOGRITHIM HOSPITAL MELAKA PHARMACY NEWSLETTER

Page 12 TREATMENT ALGORITHM HOSPITAL MELAKA PHARMACY NEWSLETTER

ASTHMA MANAGEMENT11 (Stepwise approach for adjusting treatment)

Symptoms

Exacerbations

Side-effects

Patient satisfaction

Lung function

Asthma medications

Non-pharmacological strategies

Treat modifiable risk factors

Diagnosis

Symptom control & Risk Factors

Inhaler technique & adherence

Patient preference

LABA: long-acting beta2 agonists; LAMA: long-acting muscarinic antagonists; ICS: inhaled corticosteroid; LRA/LRTA: leukotriene receptor antagonists; OCS: oral corticosteroids

Page 13 PHARMACY EDUCATION HOSPITAL MELAKA PHARMACY NEWSLETTER Page 13 PHARMACY EDUCATION HOSPITAL MELAKA PHARMACY NEWSLETTER

MDI Salbutamol

100mcg(VENTOLIN)

MDI Ipratropium

bromide/ Fenoterol

(BERODUAL-N)

Easyhaler Salbutamol

sulphate 200mcg

(BUVENTOL)

Respimat Tiotropium

2.5mcg

(SPIRIVA RESPIMAT)

Breezhaler Indacaterol

150mcg inhalation powder

hard capsule (ONBREZ)

Evohaler

Salmeterol/

Fluticasone

Proprionate

25/125mcg

(SERETIDE)

Turbuhaler

Budesonide/ Formoterol

160mcg/4.5mcg;

(SYMBICORT)

MDI Beclomethasone

Diproprionate/Formoterol

Fumarate Dihydrate

100/6mcg

(FOSTER)

MDI

Ciclesonide

160 mcg

(ALVESCO)

MDI

Budesonide

200 mcg

MDI Beclomethasone

Diproprionate

100 mcg

MDI Fluticasone

Proprionate

125 mcg

(FLIXOTIDE)

Easyhaler

Beclomethasone

Diproprionate 200

mcg

(BECLOMET)

Easyhaler-

Budesonide

200 mcg

(GIONA)

Handihaler Tiotropium

Bromide 18mcg inhalation

powder hard capsule

(SPIRIVA)

Accuhaler Salmeterol/

Fluticasone

Proprionate

50/500mcg

50/250mcg

(SERETIDE)

18

Glycopyronnium

50mcg inhalation pow-

der hard capsules

(SEEBRI)

Indacaterol/

Glycopyronnium

inhalation powder hard

capsule 110mcg/50mcg

(ULTIBRO)

MDI Fluticasone

Propionate/

Formoterol Fumarate

Dihydrate

250/10mcg

(FLUTIFORM)

Page 14 MISCELLANEOUS HOSPITAL MELAKA PHARMACY NEWSLETTER

1. Selroos, Olof. A smarter way to manage asthma with a combination of a long-acting β2-agonist and inhaled corticosteroid. Ther Clin Risk Manag. 2007 Jun; 3(2):349–359.

2. O'Byrne PM1, Bisgaard H, Godard PP, Pistolesi M, Palmqvist M, Zhu Y, Ekström T, Bate-man ED. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med. 2005 Jan 15; Vol. 171(2).

3. Kuna P, Peters M, Manjra A et al. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract 2007; 61 (5): 725-736.

4. Cates CJ, Lasserson TJ. Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2009;(2):CD007313

5. ED Bateman, TW Harrison, Santiago Quirce et al. Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps. Respiratory Research 2011. 2011 Dec 1; Vol. 12:38. doi.org/10.1186/1465-9921-12-38.

6. WM Storrar, AJ Chauhan. Benefits of SMART therapy. Wiley Online Library, 2015 Apr 1, Vol. 26.

7. PACKAGE LEAFLET:INFORMATION FOR THE. Symbicort® Turbohaler®. AstraZenica. 2015 July. [Cited: 2017 Aug 8.] Available from: https://www.hpra.ie/img/uploaded/swedocuments/Sym200%20PIL%20Cast%2004122015-2170544-18122015151702-635860486235941250.pdf.

8. Chiesi. Package Leaflet Information for the user. 2016 July. [Cited: 2017 Aug 8.] Available from: https://www.medicines.org.uk/emc/PIL.21474.latest.pdf.

9. Montelukast: Risk of Thrombocytopenia, MADRAC Newsletter December 2015. 10. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Global Strategy for

the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease 2017 Report. [Cited 2017 June 28]. Available from: http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/

11. Global Initiative for Asthma (GINA) 2017. Global Strategy for Asthma Management and Prevention 2017 Report. [Cited 2017 June 28] Available from: http://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/

12. AF Elbehairy, CE Ciavaglia, KA Webb et al. Pulmonary Gas Exchange Abnormalities in Mild Chronic Obstructive Pulmonary Disease. Implications for Dyspnea and Exercise Intolerance. Am J Respir Crit Care Med 2015; 191(12): 1384-94.

13. Sakao S, Voelkel NF, Tatsumi K. The vascular bed in COPD: pulmonary hypertension and pulmonary vascular alterations. Eur Respir Rev 2014; 23(133): 350-5.

14. Parker CM, Voduc N, Aaron SD, Webb KA, O'Donnell DE. Physiological changes during symptom recovery from moderate exacerbations of COPD. Eur Respir J 2005; 26(3): 420-8.

15. Miller J, Edwards LD, Agusti A, et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med 2013; 107(9): 1376-84.

16. Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet 2007; 370(9589): 741-50.

17. National Antibiotic Guideline 2014. Ministry of Health. 18. Melaka State Drug Formulary Committee. Melaka State Drug Formulary 2016/2017. 19. Seebri Breezhaler [product monograph]. Quebec, Canada: Novartis Pharmaceutical

Canada Inc; 2016

EDITORIAL

ADVISOR:

Pn Saidatul Raihan

EDITORIAL BOARD:

Syamsiah Hj Shariff

Tay Eek Poei

Ng Siok Shen

EDITOR:

Tan Mei Fang

CONTRIBUTORS:

Low Ming Joe Noor Syafiqah

Masturah Uma Shalene

Sumathi

REFERENCES

For more information or drug enquiries, please contact:

Pharmacy Resources and Information Centre (PRIC),

Department of Pharmacy,

Hospital Melaka

Ext 2583 (8am—5pm)