Asuhan Kefarmasian pada

Pasien Asma & PPOK

LOUISA ENDANG BUDIARTI
AGENDA
01 PENDAHULUAN

02 Apoteker dan DTP pasien asma, PPOK

03 Multiple Inhaler Devices - Adherence

04 Pemantauan Apoteker

05 Kesimpulan
 PATIENT CENTERED CARE - pHARMACIST

AKSES
Nothing about me , without me
CONFIDEN “care that is respectful of and responsive
TIAL to individual patient preferences, needs,
KOLABORA
and values.”
TIF The Institute of Medicine (IOM)
 MEDICATION SAFETY

4
CASE COPD / PPOK

6
medication adherence was considered to be a problem in
nearly 60% of adolescents (age 12-15 years) with asthma.

Approximately 40% of patients had severe denial regarding

their asthma and its severity.

Nearly 80% of patients had preventable asthma

exacerbations
Apoteker dan DTP
pasien asma, PPOK
11
 PHARMACIST INTERVENTION
35

30

25

20

15

10

0
Drug Changed Dosage change Drug stop New drug started Others
Prospective Retrospective

12
 emergency

13
 Selektifitas, potensi, mula kerja, durasi

14
 PK/PD kortikosteroid

15
GINA 2019 – landmark changes in asthma management
▪ For safety, GINA no longer recommends SABA-only treatment for Step 1
▪ This decision was based on evidence that SABA-only treatment increases the risk of severe
exacerbations, and that adding any ICS significantly reduces the risk
▪ GINA now recommends that all adults and adolescents with asthma should
receive
ICS-containing controller treatment, to reduce the risk of serious exacerbations
▪ The ICS can be delivered by regular daily treatment or, in mild asthma, by as-needed low
dose ICS-formoterol
▪ This is a population-level risk reduction strategy
▪ Other examples: statins, anti-hypertensives
▪ Individual patients may not necessarily experience (or be aware of) short-term clinical
benefit
▪ The aim is to reduce the probability of serious adverse outcomes at a population level
 Opsi perawatan berevolusi
Perawatan Penambahan
ICS LAßA pada terapi ICS
Penggunaan ß2- diperkenalkan Kips et al, AJRCCM 2000
pada Pauwels et al, NEJM 1997 Terapi
agonis kerja
Greening et al, Lancet 1992 inhaler
pendek secara 1972
luas 1975 tunggal
(Budesonide
/formoterol)
“Ketakutan”
1980 akan ß2-agonis
kerja pendek

1985

2000
1990 1995
Bronkospasme inflamasi Pemodelan ulang

17 Adapted from Prof Bateman symposium on 2018, April 22nd

 Trend penggunaan SABA sebelum kunjungan ke rumah sakit
karena asma eksaserbasi berat

Permasalahan kritis:
o Penggunaan SABA yang berlebih
o Keterlambatan memperoleh tinjauan medis
terhadap SABA

Penggunaan konsep Pelega dengan Pengontrol

menurunkan ketidak-patuhan terhadap kortikosteroid
inhalasi selama eksaserbasi berat

Analisis post hoc uji klinik selama 6 bulan pada 303 pasien acak
antara bud/form pelega dengan pengontrol dan fixed dose bud/form +
SABA seperlunya. Pola penggunaan SABA inhaler dilakukan dengan
pemantauan elektronik

18 Patel M, et al. The use of β2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis. NPJ Prim Care Respir Med. 2015; 25: 14099.
 Satisfaction level and asthma control among Malaysian asthma
patients on Budesonide/formoterol as Reliever and Controller
Therapy in the primary care setting
Chin-Kin Liam, Yong-Kek Pang and Keong-Tiong Chua

Conclusions: Budesonide/formoterol as Reliever and

Controller resulted in a high satisfaction level and asthma
control among Malaysian patients treated in the primary
care setting and it is an effective and appealing treatment
for asthmatic patients. (Asian Pac J Allergy Immunol
2013;32:145-52)

Budesonide/formoterol as reliever and controller therapy is an example of reducing

number and type of inhalers

19
19
 Formoterol Secepat dan Seefektif SABA

20 1. PDPI, Pedoman Diagnosis dan Penatalaksanaan Asma di Indonesia 2018; 2. Seberová E and Andersson A. Oxis1 (formoterol given by Turbuhaler1) showed as rapid an onset of
action as salbutamol given by a pMDI. Respir Med 2000; 94(6):607–11.
 KORTIKOSTEROID

Kortikosteroid sintetis (hormon steroid) yang digunakan untuk mengontrol inflamasi.

21 Reference:
1. Lynn and Kushto-Reese. Understanding Asthma Pathophysiology, Diagnosis and Management. American Nurse Today 2015; 10(7): 49-51
2. Currie et al. Therapeutic Modulation of Allergic Airways Disease with Leukotriene Receptor Antagonists. Q J Med 2015 98: 171-182
 MEKANISME KERJA KORTIKOSTEROID
Kompleks GCS-
Reseptor bergerak
menuju inti sel GCS-Reseptor
mengubah
transkripsi

GCS mengikat
receptor

Efek anti-inflamasi

Glukokoritikosteroid ↓inflamasi & pembengkakan

(GCS) bergerak ke ↓ produksi mukus
dalam sel

22 References: https://www.aic.cuhk.edu.hk/web8/corticosteroids.htm
 Bagaimana?
Ketebalan Dinding Ketebalan Dinding

Tidak ada pemendekan

CONTROLLER

R
E
L
I
E
Pemendekan

V
E
R

23 McGeachie et al. 2017 Genomic and Precision Medicine (Third Ed, 2017)
 Karakter ICS yang berbeda sebagai rasionalitas perbedaan efikasi terhadap
eksaserbasi antara budesonide/formoterol vs flutikason/salmeterol
Hipotesis Imunosupresi / Infeksi
Budesonid Kolonisasi Bakteri di ≈50% Flutikason
/formoterol pasien PPOK1-3 /salmeterol

ELF = Epithelial lining fluid Kolonisasi Bakteri

Budesonid ELF Flutikason
Budesonid/GCS-receptor Flutikason/GCS-receptor

Mucosa/Jaringan Paru-paru
• Kelarutan air FLU yang lebih rendah dapat
• Potensi imunosupresan yang menyebabkan waktu tinggal yang lebih
lebih tinggi, FLU> BUD pada lama di mukus
imunitas manusia4 • Meningkatnya konsentrasi lokal FLU vs
BUD 4,5
Proliferasi bakteri lokal selama infeksi,
yang dapat meningkatkan kejadian infeksi

Eksaserbasi Infeksi paru-paru

(Tracheobronchitis)

Eksaserbasi yang berkepanjangan

1. Wedzicha JA, et al. Am J Respir Crit Care Med 2008;177:19–26;

2. Calverley PM, et al. Chest 2011;139:505–12;
3. Patterson C, et al. Respir Res 2012,13:40; 4. Ek A, et al. Allergy 1999;54:691–9;
4. Miller-Larsson A, et al. Am J Respir Crit Care Med 2000;162:1455–61;
5. Johnsson M, et al. Allergy 1995;50:s11–14; 7. Dalby C, et al. Respir Res 2009;10:104

24
 Mengapa menambahkan formoterol ke budesonide?

* Efek stabilisasi sel mast, mengurangi eksudasi plasma/pelepasan mediator inflamasi

AHR: Airway Hyperresponsiveness

25 Ref: Barnes PJ ERJ 2002; 19: 182-191

 Dosis Terapi Budesonide/formoterol 160/4.5mcg
Untuk Pasien ≥12 Tahun

Untuk Asma : Untuk PPOK :

1. Asma ringan digunakan jika dibutuhkan Dewasa: 160/4.5 mcg: 2 inhalasi 2x sehari
1 inhalasi jika dibutuhkan untuk mengatasi gejala. Tidak
lebih dari 6 inhalasi dalam 1 kejadian. Total 8 inhalasi dalam
1 hari (12 inhalasi bisa untuk sementara).

2. Dosis Terapi sebagai Pengontrol & Pelega

Untuk Pengontrol: 2 inhalasi/hari atau sebagai 2 inhalasi
pada pagi atau sore hari, atau sesuai petunjuk dokter.
Untuk pelega: inhalasi dan tunggu beberapa menit. Jika
tidak merasa lebih baik, lakukan inhalasi lagi. Maksimum 6
inhalasi dalam satu waktu.
Maksimum 12 inhalasi/hari

Symbicort Product Information 2019

Budesonide-Formoterol 160/4.5 mcg (Symbicort 160/4.5)
PERUBAHAN: FORNAS 2019
1. Penambahan indikasi “ untuk terapi pelega
pada asma persisten sedang – berat ”.

2. Jumlah peresepan maksimum.

FORNAS 2017
ADHERENCE
29 Gillissen, Andrian. Patient’s adherence in asthma. Journal of Physiology and Pharmacology. 2007. Suppl 5, 205-222
 POOR MEDICATION ADHERENCE IN ASTHMA

Factors contributing to poor adherence How to identify poor adherence in clinical practice
Medication/regimen factors Ask an empathic question
• Difficulties using inhaler device (e.g. arthritis) • Acknowledge the likelihood of incomplete adherence
• Burdensome regimen (e.g. multiple times per day) and encourage an open non-judgmental discussion.
• Multiple different inhalers Examples are:
Unintentional poor adherence o ‘Many patient don’t use their inhaler as
• Misunderstanding about instructions prescribed. In the last 4 weeks, how many days a
• Forgetfulness week have you been taking it – not at all, 1,2,3 or
• Absence of a daily routine more days a week?’
• Cost o ‘Do you find it easier to remember your inhaler in
Intentional poor adherence the morning or the evening?’
• Perception that treatment is not necessary Check medication usage
• Denial or anger about asthma or its treatment • Check the date of the last controller prescription
• Inappropriate expectations • Check the date and dose counter on the inhaler
• Concerns about side-effect (real or perceived) • In some health systems, prescribing and dispensing
• Dissatisfaction with health care providers frequency can be monitored electronically by
• Stigmatization clinicians and/or pharmacist
• Cultural or religious issues • See review articles for more detail.
• Cost

30 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2020. Available from: www.ginashtma.org;
30
 INTERVENSI – ADHERANCE (SYSTEMATIC REVIEW)

31
Kripalani S, Yao X, Haynes B, Intervention to enhance medication adherence in chronic medical condition, Arch Int Med 2007;167:540-550
32
Kripalani S, Yao X, Haynes B, Intervention to enhance medication adherence in chronic medical condition, Arch Int Med 2007;167:540-550
TEKNIK PENGGUNAAN YANG BURUK → OUTCOME

Usmani et al. Respiratory Research (2018) 19:10

34
 TIDAK DISUKAI PASIEN - ANAK

35
36 Gillissen, Andrian. Patient’s adherence in asthma. Journal of Physiology and Pharmacology. 2007. Suppl 5, 205-222
 Multiple Inhaler berkaitan dengan ketidakpatuhan pasien
asma & PPOK

Always try to minimize number of inhalers or type of inhalers

37
Makela, et al. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD.2013. 107,1481-1490
Multiple Inhaler Devices
- Adherence
 Why inhaler devices matter
▪ The efficiency with which inhaler devices deliver
medications depends upon a range of factors:1,2
▪ Their design and characteristics
▪ The formulation (i.e. solution, suspension) “It is clearly pointless to prescribe an
▪ The particle size and velocity of the aerosol inhaler device which the patient will not, or
▪ How easy it is to use the device correctly cannot use correctly.
Thus, choosing the correct inhaler for each
patient is just as important as choosing the
▪ Even with correct inhalation technique, lung most appropriate medication”1
deposition for different inhalers varies greatly1,2
▪ Many patients treated with potentially effective
inhaled therapy continue to report symptoms due
to incorrect inhaler technique2
▪ Patient preference is clearly important because it
may influence their adherence1,2

39 1. Lavorini F et al. Expert Opin. Drug Deliv. 2013; 10(12):1597-1602; 2. Lavorini F et al. Respir Med 2011;
 PARTICLE SIZE RANGE MATTERS FOR OPTIMAL LUNG DEPOSITION
▪ Particles 1–5 µm are optimal for lung deposition, with those 1–3 µm
Optimal lung
most likely to be deposited in central and peripheral airways1 deposition

▪ Particles <1 µm are most likely to be exhaled again but some will
reach the alveoli and then enter the systemic circulation1,2 <1 µm
1–5 µm
>5 µm

▪ Particles > 5 µm mainly impact on the oropharynx and are then

swallowed1,2
Exhaled or
▪ Oropharyngeal impaction increases at higher inspiratory flow rates1,2 alveolar
deposition
▪ Turbuhaler was the only DPI of 4 tested* that compensated for higher <1 µm

oropharyngeal losses and the shift in deposition to upper airways at 1–5 µm

>5 µm

higher flow rates1

▪ Turbuhaler delivered the highest fine particle fraction (FPF) 1–3 µm of

the 4 DPIs tested* as percent of label claim in vitro1 Oropharyngeal
impact

<1 µm
* Symbicort Turbuhaler, Seretide Diskus, Rolenium Elpenhaler and Foster NEXThaler 1–5 µm
>5 µm

1. De Boer AH, et al. Eur J Pharm Biopharm 2015; 96:14351; 2. Demoly P, et al. Respir Med 2014; 108: 1195-203;
 Switching devices may lead to reduced asthma control and an increase in
exacerbations
▪ In an observational, real-world, matched cohort Outcomes in asthma patients* following switching1
study in Sweden switching from a budesonide-
containing DPI to a generic equivalent, particularly in
patients with asthma who did not see their primary
care HCP at the time, was associated with:1
▪ decreased asthma control
▪ a higher exacerbation rate (0.40 vs 0.32; p=0.047)
▪ more outpatient hospital visits (2.01 vs. 0.81;
p<0.001)

▪ Similar effects were noted in the Icelandic

population, when switching from ICS/LABA
combinations to single component inhalers was p values
enforced for both asthma and COPD patients2

* Two matched cohorts of 463 patients

41 1. Ekberg-Jansson A et al. Int J Clin Prac 2015; 69, 10, 1171–78; 2. Björnsdóttir U et al. Int J Clin Prac 2014; 68, 7, 812–19.
Note: RWE is subject to the potential confounding bias
usually associated with observational research
 ‘Switching’ legislation in Iceland led to increased need for OCS, SABA and
healthcare visits
Medications dispensed (A, B and C) and healthcare visits (D)
▪ Reimbursement of fixed ICS/LABA per 100 patients years in pre- (2009) and post index (2010) periods1
combinations was limited on 01 Jan
2010 (index date)1

▪ 47.8% fewer fixed ICS/LABA

combinations were dispensed after
the index date (A)

▪ Prescriptions were increased for:

▪ OCS 76% (B)
▪ SABA 51% (C)

▪ There was also a 44% increase in

healthcare visits for any reason (D)

42 ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; OCS, oral corticosteroids; SABA, short-acting β2-agonists
1. Björnsdóttir U et al. Int J Clin Prac 2014; 68(7), 812–19.
 Brands/devices might not be easily interchangeable
▪ Substitution without consultation/training could potentially threaten COPD control,
safety, patient preference, and adherence and increase health care resource utilisation1–3

Potential implications and concerns with non-consensual switching

of inhalers in the treatment of COPD:

Negative impact on therapeutic effect and COPD control1

Increased confusion when operating a new device1

Negative impact on adherence1–2

Increased health care resource utilisation3

1. Williams AE, Chrystyn H. Pharm World Sci 2007;29(3):221–27; 2. Schulte M et al. J Aerosol Med Pulm Drug Deliv 2008;21(4):321–28; 3. Bjermer L. Respiration 2014;88:346–52
 Turbuhaler – effective across ages and severities
▪ Patients of most ages and severity of asthma and COPD
have been shown to be able to generate sufficient inspiratory
flow (30 L/min) to use a Turbuhaler effectively.1–4
▪ Severe COPD1
Patients with very low lung function (FEV1 0.7 L/min, PEF 182 L/min)
on average generated an inspiratory flow rate of 53 L/min, i.e. well
above the required 30 L/min. All 100 patients generated above 28
L/min, which is sufficient for effective drug delivery.

▪ Children with asthma2

Children aged 3-6 yrs generated an average 60 L/min and 7-10 year
olds generated an average of 70 L/min. All 82 children with asthma
generated above the recommended 30 L/min.

▪ Patients with acute asthma3

Acute asthma patients generated an average 60 L/min PIF through
Turbuhaler. Only two of the 99 patients generated below 30 L/min
(both 26 L/min, which is still adequate).

▪ Patients with asthma4 Figures adapted from references stated

Able to generate at least 40 L/min PIF in a study at their homes Study population details on Notes page
1. budesonide/formoterol; 2. terbutaline; 3. empty Turbuhaler; 4. budesonide
L/min, litres/minute; PIF, peak inspiratory flow Turbuhaler M2 may have been used in these studies. Current Turbuhaler is M3

1. Dewar MH, et al. Respir Med 1999; 93: 342-44; 2. Ståhl E, et al. Pediatric Pulm 1996; 22: 106-10.
3. Brown PH, et al. Eur Respir J 1995; 8:1940–41; 4. Meijer Thorax 1996;51:433-434
 The importance of storage conditions to dry powder inhalers

• The conditions dry powder inhaler (DPI) are stored in may affect their aerosol characteristics
and the resulting lung deposition1
• In particular, inhalers are sensitive to humidity, particularly at high room temperatures1
• Most patients are unaware of this and store their DPI in humid locations, such as their
bathroom cupboard, when not in use2
• Different manufacturers adopt different approaches to protect against humidity and prolong
shelf-life1
• Sealed humidity resistant packs – these only protect until the patient opens the pack
• Individual doses sealed in laminated foil – again, protection ends when the foil is opened

• The Turbuhaler contains a desiccant within the inhaler body and has a tightly fitting cover to
keep out moisture when not in use1

1. Jansson C et al. Prim Care Respir Med 2016; 26, 16053; 2. Norderud Laerum B et al. Multidid Respir Med 2016; 11:21.
 How the current Turbuhaler works to deliver inhalable particles

Each dose is initially in the form of loosely

packed powder consisting of spherical
particle aggregates of ∼5–20 μm1,2

Turbulence, generated first

in the circulation chamber
and then in the helical region
and mouthpiece, breaks up
the powder aggregate into
optimally sized particles
for lung deposition1 (1–5 μm)3

1. Milenkovic J, et al. Int J Pharmaceut 2013;448:205–13; 2. Hoppentocht M et al. Adv Drug Deliv Rev. 2014; 75:18–31; 3. De Boer A, et al. Eur J Pharm Biopharm 2015;96:143–51.
Turbuhaler technology – simple outside, sophisticated inside
 SIMPEL DENGAN INHALER YANG MUDAH PENGGUNAANNYA

KLIK

Putar dan lepaskan Putar grip merah ke kedua Hisap Tutup kembali
penutup Turbuhaler arah sampai terdengar Turbuhaler
• Hembuskan napas (jangan mengenai mouthpiece)
bunyi KLIK! • Tempatkan mouthpiece diantara gigi, rapatkan bibir
dan hisap dengan kuat dan dalam
• Lepaskan inhaler dari mulut, lalu hembuskan napas
• Berkumurlah dengan air. Jangan ditelan

96% Pasien pada studi multi senter

menyatakan Turbuhaler mudah
dari n = 138 penggunaannya*1

48
*Study of 140 patients (47% were aged 6 to 16 years and 6% were over 65 years) designed to assess how easy it was for the physician to instruct the patient to use the ‘Bricanyl Turbohaler’ correctly, how well the patient
continued to use it over 1 month, the improvement in peak expiratory flow rate and forced expiratory volume in 1 second on first using the device and after 1-month’s use, and patients’ and physicians’ impressions of it.
1. Watson J. Curr Med Res Opin. 1990;11(10)654–660.
LANGKAH PENGGUNAAN

Devices Kenali bagian alat dengan benar

• Mouthpiece
• Indikator dosis
• Pemutar/pembuka dosis

Use Gunakan dengan Teknik yang benar

• Awal penggunaan dengan 2 klik
• Lanjutan penggunaan hanya 1 klik

Storage Simpan di suhu ruang

• Upayakan di tempat yang sama

Hal penting Kumur setelah menggunakan

• Bersihkan mouthpiece dgn tissue kering
• Ulang pemutar jika turbohaler terjatuh

49
50
 Pemantauan Apoteker

51
 PEMANTAUAN TERAPI OBAT

▪ ALTHOUGH ALL PRACTITIONERS PROVIDE DRUG THERAPY ADVICE AND

INSTRUCTIONS WITH THE BEST INTENTIONS, THESE WELL-MEANING ACTIVITIES
DO NOT ALWAYS HAVE POSITIVE OUTCOME.

▪ FOLLOWED-UP EVALUATION ACTIVITIES REPRESENT A NEW STEP IN THE HEALTH

CARE SYSTEM THAT DOES NOT ROUTINELY OCCUR WITHIN THE DISPENSING
PROCESS AND FREQUENTLY DOES NOT OCCUR EVEN IN PATIENT CARE PROCESS

52
 AKTIVITAS TANGGUNG JAWAB
mendapatkan data klinis maupun data EVALUASI EFEKTIVITAS TERAPI OBAT PASIEN
laboratorium sebagai fakta aktual outcome
dibandingkan dengan tujuan yang diharapkan
mengumpulkan bukti klinis maupun evaluasi terhadap safety terapi obat pasien
laboratorium terhadap kejadian efek
samping, toksisitas sebagai gambaran
keselamatan pasien (safety of drug)
dokumentasi status klinis dan adanya membuat keputusan terapi terhadap kondisi
perubahan farmakoterapi yang diperlukan klinis dalam proses pengelolaan
farmakoterapi pasien
asesmen pasien terhadap masalah terapi evaluasi kepatuhan pengobatan pasien dan
obat yang baru identifikasi adanya masalah terapi obat yang
baru
menjadwalkan pemantauan terpai obat kontinuitas pelayanan
selanjutnya
53
 Key areas of the WHO Global Patient Safety Challenge on medication safety

1. Reads slowly RISIKO PASIEN – LOW LITERACY

2. Has difficulty telling a coherent story
3. Fills out forms incorrectly or incompletely
4. Uses excuses such as, “I forgot my glasses,” “I’ll read this later,” or “I don’t have
time to read this now. Can I take it home?”
5. Brings along a friend or family member for assistance
6. Fails to show up for appointments or is late for refills
7. Does not ask questions for clarification
8. Has difficulty following instructions
9. Nods in agreement or expresses understanding but does not truly understand
information

(WHO 2017, adopted from Schepel 201812)

Pasien dgn gangguan pernafasan kronis
(GOLD)

MODIFIKASI FAKTOR RISIKO MANAJEMEN DIRI

PENATALAKSANAAN
KOMORBID PEMANTAUAN RUTIN

NON FARMAKOLOGI : OR,

VAKSINASI, REHAB
PEMANTAUAN

KEPATUHAN
Morisky Medication Adherence Scale (MMAS-8)

Medication Possession Ratio (MPR)

QUALITY of LIFE
Asthma Quality of Life Questionnaire (Elizabeth F. Juniper)
 ICS-formoterol is the
preferred reliever for
patients prescribed
maintenance and reliever
therapy. For other
ICS-LABAs, the reliever
is SABA

GINA 2020, Box 3-5A © Global Initiative for Asthma, www.ginasthma.org

KLAS FEV1/FVC <0.7

GOLD1 MILD FEV1 < 80%

GOLD2 MODERATE 50%< =FEV1 <80%

GOLD3 SEVERE 30%<=FEV1<50 %

GOLD4 VERY SEVERE FEV1 <30%

https://www.guidelinesinpractice.co.uk/respiratory/key-
learning-points-gold-copd-2020-report/455218.article
Asesmen PPOK
Asthma Quality of Life Questionnaire (Elizabeth F. Juniper)
 KESIMPULAN

apoteker melanjutkan penatalaksanaan obat pasien

asthma dan ppok dengan edukasi komprehensif pada
pemahaman dan teknik penggunaan alat yang
digunakan pengobatan dengan pemantauan
berkelanjutan