Preferred Reliever: A Paradigm Shift in Asthma...

PREFERRED RELIEVER: A PARADIGM SHIFT IN ASTHMA MANAGEMENT

Hadiarto Mangunnegoro

ID1861/ ED Mar22

Pereda pilihan:

Pergeseran paradigma pada managemen asma

DEFINITION AND FACT OF ASTHMA

THE IMPACT OF REGULAR B2 AGONIST

ASTHMA STEPWISE GUIDELINE

BUDESONIDE/FORMOTEROL AS RELIEVER AND CONTROLER

ASSESSING & EVALUATE ASTHMA CONTROL

Definition and Fact of Asthma

Definisi Asma – Penyakit Inflamasi Kronis

Definisi asma – GINA 20021:Asthma is a chronic inflammatory disorder of theairways in which many cells and cellular elements play a role

Definisi asma – GINA 20142Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation.

Definisi asma – GINA 20193Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation.

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2002. Available from: www.ginashtma.org2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2014. Available from: www.ginashtma.org3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginashtma.org

A B CB C A

C B A

Inflamasi adalah fitur yang mendasari penyakit asma

InflamasiSaluran napas

Obstruksisaluran napas

Hiperesponsifbronkial

Gejala Asma

Currie, GP., Therapeutic modulation of allergic airways disease with leukotriene receptor antagonists., Q J Med 2005; 98: 171 – 182

The facts• Treatment guidelines for man

agement of asthma1 (GINA) are well stablished.

• Both recommend inhalertherapy as primary route to administer the medication.

1. GINA 2014 2.GOLD 2015 3. Virchow et al. Resp Med 2008

GINA-defined Asthma ControlREALISE Study

However even with effective inhaled therapy, asthma remain uncontrolled around the world.

n=2,467

1. Price, D. et.al., J Asthma & Allergy, 2015; 8: 93–1032. Price, D. et.al. Prim Care Respir Med, 2014; 24, Article no. 14009

n=8,000

(1) (2)

PresenterPresentation NotesUsing the GINA-defined criteria, 17.8% (440), 32.5% (802), and 49.7% (1,225) of patients had controlled, partially controlled, and uncontrolled asthma, respectively.

Chart1

UncontrolledUncontrolled

Partly controlledPartly controlled

ControlledControlled

ASIA

EUROPE

% patients

49.7

45.1

32.5

34.8

17.8

20.1

Sheet1

ASIAEUROPE

Uncontrolled49.745.1

Partly controlled32.534.8

Controlled17.820.1

To update the chart, enter data into this table. The data is automatically saved in the chart.

Studi MAGIC: Kontrol asma belum optimal di semua jenjang GINA

19,5 19,212,7

4,0

28,0

37,4 36,2

12,0

52,4

43,451,1

84,0

0

10

20

30

40

50

60

70

80

90

Step 1 Step 2 Steps 3 & 4 Step 5

Prop

ortio

n of

pat

ient

s (%

) Controlled asthma Partially controlled asthma

Uncontrolled asthma

*Based on 2006 GINA guidelines. GINA, Global Initiative for Asthma; GCS, glucocorticoids; ICS, inhaled corticosteroid; IgE, immunoglobulin E; LABA, long-acting β2-agonist; SABA, short-acting β2-agonist

GINA treatment step

Tingkat kontrol asma berdasarkan jenjang pengobatan (n=624)

Low-dose ICS ICS/LABA therapy Step 4 + Systemic GCS and/or

IgE antibodies

SABA as needed

Olaguibel JM, et al. Measurement of asthma control according to global initiative for asthma guidelines: a comparison with the asthma control questionnaire. Respir Res 2012;13:50

Despite treatment according to current guidelines, the Global Initiative for Asthma guidelines…..

Patient percentage

At least 40%

At least 40% of asthma patients remain symptomatic despite using maintenance therapy.

Bateman ED, et al. Am J Respir Crit Care Med. 2004;170

Eksaserbasi terjadi di semua jenjang GINA

Eksaserbasi didefinisikan sebagai perburukan asma yang membutuhkan perawatan UGD/RS atau steroid oral(US: steroid oral yang digunakan setara dengan 20 mg/hari prednison selama 3-28 hari; UK: peresepan steroid oral

apapun dalam 2 minggu)

Suruki et al. The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA. BMC Pulmonary Medicine; 2017:17:74

Penggunaan β2-agonist yang berlebihan vs ICS

ICS, inhaled corticosteroid; MI, mild intermittent; MP, mild persistent; MOP, moderate persistent; SABA, short-acting β2-agonist; SP, severe persistent.The AIRE survey was conducted in 1999. Of the 73,880 households screened, one or more current asthma patients were identified in 3,488 households.Full interviews were completed by 2,803 (80.4%) respondents.

Rabe KF et al. Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study. Eur Respir J 2000; 16: 802–7.

Dalam 4 minggu terakhir, lebih banyak pasien menggunakan β2-agonist (63%) dibanding ICS (23%)

The impact of regular β2-agonist

Kontriksi bronkus akibat alergenbermakna lebih tinggi pada pasien yang menerima Albuterol* vs plasebo

Pelarut

Albuterol + Alergen

Plasebo + Alergen

1. Gauvreau GM, et al. Effect of Regular Inhaled Albuterol on Allergen-induced Late Responses and Sputum Eosinophils in Asthmatic Subjects. Am J Respir Crit Care Med 1997; 156:1738-452. U.S. National Library of Medicine. National Center for Biotechnology Information. 2015. Available from: pubchem.ncbi.nlm.nih.gov/compound/Salbutamol

*Albuterol = Salbutamol2

Overuse SABA and Underuse ICS: Increase asthma mortality

Canister ICS per year2 (Suissa 2000/p4/fig1)

Rat

e ra

tiom

orta

litas

asm

a

10 2 3 4 5 6 7 8 9 1210 110.0

0.5

1.0

1.5

2.0

2.5

Canister (20,000 μg) SABA per month 1 (Suissa 1994/p6/col1/fig3)

Mor

talit

asas

ma/

10,0

00 ta

hun-

pasi

en

0 2 3 4 5 6 710.0

50

100

150

200

250

ICS, inhaled corticosteroid; SABA, short-acting β2-agonist. 1. Suissa S, et al. Am J Respir Crit Care Med 1994; 149:604–10; 2. Suissa S, et al. N Engl J Med 2000; 343:332–6; 3. Buhl R, et al. Respir Res 2012; 13:59.

SABA vs. asthma

mortality

ICS vs. asthma

mortality

Use of SABA >6 inhalation/day even just 1 day is prediction of increase asthma exacerbation3(Buhl 2012/p1/p3)

Kortikosteroid meningkatkan ekspresi β2-receptor danmencegah terjadinya down-regulation akibat pemakaian jangka panjang β2-agonis

Glucocorticoidreceptor

ß2-Adrenoceptor

• Efek kortikosteroid terhadap ß2-agonist reseptor

Corticosteroid

Anti-inflammatory effect

• Efek ß2-agonist terhadap kortikosteroid

ß2-Agonist

Bronchodilatation

+

+

Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting b2-agonists and corticosteroids Eur Respir J 2002;19:182-91

There are paradoxes in asthma stepwise guideline

PARADOX definition

Paradox (‘parədɒks) – a statement or proposition which, despite sound (or

apparently sound) reasoning from acceptable premises, leads to a conclusion that seems logically unacceptable or self-contradictory

O’Byrne PM et all. The paradoxes of asthma management: time for a new approach? Eur Respir J 2017; 50: 1701103

Paradox –sebuah pernyataan atau proposi yang meskipun beralasan masukakal dari premise yang dapat diterima, mengarah pada kesimpulan yang tampaknya secara logis tidak dapat diterima atau bertentangan dengan dirisendiri

PARADOXES IN ASTHMA MANAGEMENT

Ada dislokasi antara pemahaman pasien

tentang "kontrolasma" dan frekuensi,

dampak dan keparahan gejala

mereka.

Paradoks 5

Pesan tidakkonsisten darijenjang 1 ke 5

Jenjang 1 SABA as needed dengankendali pasien,

tetapi pada jenjangberikutnya pasien

perlu menggunakanterapi pengontrol

setiap hari

Paradoks 2

Adanya perubahanrekomendasi dari

SABA (as needed) pada step 1 menjadi

ICS (fixed dose) pada step 2, padahal

pasien percayaSABA adalah

pengobatan yang paling bermanfaattapi kini dianjurkan

untuk dikurangi

Paradoks 3

Adanya informasikeamanan yang berbeda untuk

penggunaan SABA dan LABA dalam

guideline; SABA jikadigunakan tunggal

dikatakan amansedangkan LABA yang digunakan

tunggal tidak aman.

Paradoks 4

Asma adalahpenyakit

inflamasi kronis, tetapi pengobatansejak awal adalah

bronkodilator

Paradoks 1


What’s new in GINA 2019?Steps 3-5 for adults and adolescents

Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginashtma.org

http://www.ginashtma.org/

DISCLAIMER

Indikasi Symbicort as-needed reliever with maintenance di Indonesia hanyadisetujui pada asma sedang hingga berat (GINA Step 3-5).

Indikasi off-label (asma ringan, GINA Step 1-2) tidak akan didiskusikan padameeting ini, dan apabila ada pertanyaan akan dialihkan kepada MedicalDepartment PT AZI.

Informasi yang disampaikan dalam pertemuan ini tidak boleh dikaitkandengan promosi penggunaan ataupun indikasi off-label.

Data – data yang ditampilkan dalam pertemuan ini ditujukan untuk edukasidan memberikan kesempatan bagi komunitas ilmiah dan medis untukmendapatkan informasi terkini terkait perkembangan di bidang kedokteran.

NEW GINA 2019 TREATMENT RECOMMENDATIONFOR MODERATE-TO-SEVERE PATIENTS (Steps 3-5)

DISCLAIMER: SYMBICORT AS-NEEDED RELIEVER WITH MAINTENANCE IS ONLY INDICATED IN MODERATE-TO-SEVERE ASTHMA PATIENTS. Symbicort for mild asthma (GINA Step 1-2) has not yet been approved by BPOM RI. The information should under no circumstances be regarded as a recommendation for use of Symbicort in mild asthma (GINA step 1-2)

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginashtma.org2. Symbicort Product Information BPOM-RI 2017

For patients prescribed maintenance and reliever therapy


Rekomendasi GINA 2019 mengenaiterapi PELEGA dengan PENGONTROL

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginashtma.org2. Symbicort Product Information BPOM-RI 2017

DISCLAIMER: SYMBICORT AS-NEEDED RELIEVER WITH MAINTENANCE IS ONLY INDICATED IN MODERATE-TO-SEVERE ASTHMA PATIENTS. Symbicort for mild asthma (GINA Step 1-2) has not yet been approved by BPOM RI. The information should under no circumstances be regarded as a recommendation for use of Symbicort in mild asthma (GINA step 1-2)

1. Untuk pasien dengan eksaserbasi ≥1 dalam 1 tahun terakhir, beclomethasone/formoterol atau budesonide/formoterol sebagai terapi pelega dengan pengontrol lebihefektif dalam menurunkan eksaserbasi berat dan memberikan tingkat kontrol gejalaserupa dengan dosis ICS yang relative rendah dibandingkan ICS/LABA+SABA as needed

2. Low dose ICS/formoterol (as needed) merupakan pelega pilihan pada pasien yang sudah menggunakan terapi pelega dengan pengontrol (GINA step 3-5)*

* pada pasien yang sudah menggunakan bud/form atau BDP/form sebagai pelega dengan pengontrol


ALL ASTHMA PATIENTS ARE AT RISK OF ATTACKSREGARDLESS OF DISEASE SEVERITY AND ADHERENCE

Asma adalah: Penyakit inflamasi kronis7

Ditandai dengan flare up secara tiba-tibaterlepas dari derajat keparahan dan kepatuhan1-3,7

Dimana pasien bergantung kepada SABA untukmengatasi gejala asma4,8

Penggunaan SABA yang tinggi beresiko bagi pasien: SABA tidak mengurangi inflamasi dan tidak melindungi

pasien dari kemungkinan serangan asma5,7

Penggunaan SABA yang tinggi adalah indikatorterhadap resiko: ≥3 kanister SABA per tahun dapat meningkatkan

kemungkinan rawat inap/ kunjungan UGD 2x lebih tinggi6-7*

*Relationship between 1-year SABA use with hospitalisation or ED visits. Group with 0–2 SABA canisters (n=441) had 2.4% hospitalisations or ED visits while the 3–6 SABA canisters group (n=587) had 5%. Hence a 2.1 OR. Study based on a survey completed by a random sample of 2,250 health maintenance organisation members aged 18 to 56 years with persistent asthma. Linked computerised pharmacy data provided SABA canister and oral corticosteroid dispensing. Number of hospitalisations and ED visits were compared against SABA canisters dispensed in 12 months.OR = odds ratio, SABA = short-acting beta-agonists, ED = emergency department

1. Demoly P, Annunziata K, Gubba E, et al. Eur Respir Rev 2012;21:66–74. 2. Papi A, Ryan D, Soriano JB, et al. J Allergy Clin Immunol Pract 2018;6:1989–1998. 3. Price D, Fletcher M, Van der Molen T, et al. NPJ Prim Care Respir Med 2014;24:14009. 4. O’Byrne PM, FitzGerald JM, Bateman ED, et al. N Engl J Med 2018;378:1865–1876. 5. Humbert M, Andersson TLG, Buhl R, et al. Allergy 2008;63:1567–1580. 6. Schatz M, Zeiger RS, Vollmer WM, et al. J Allergy Clin Immunol 2006;117:995–1000. 7. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2019. Available at: http://www.ginasthma.org/8. GINA Pocket guide For Health Professional - Difficult to treat & severe asthma in adolescent & adult patients 2018

DISCLAIMER: SYMBICORT AS-NEEDED RELIEVER WITH MAINTENANCE IS ONLY INDICATED IN MODERATE-TO-SEVERE ASTHMA PATIENTS. Symbicort for mild asthma (GINA Step 1-2) has not yet been approved by BPOM RI.The information should under no circumstances be regarded as a recommendation for use of Symbicort in mild asthma (GINA step 1-2)

http://www.ginasthma.org/

Intervensi dini (window of opportunity) dengan anti-inflamatoridapat menurunkan dan mencegah perburukan asma dan eksaserbasi

Balter M, et al. Asthma worsening: Approaches to prevention and management from the Asthma WorseningsWorking Group. Can Respir J. 2008;15 (Suppl B):1B-19B

As neededβ2

As neededSymbicort

Dai

ly m

edic

atio

n us

e(m

aint

enan

ce a

nd re

lief)

Traditional Approach Fixed Symbicort

+ prn SABA

Traditional approach and Symbicort maintenance and reliever therapy (SMART)

Days with symptoms

Maintenance

Symbicort

SMART

Maintenance

Time

Most days patients use no reliever

illustrative

ID/RESP/0002/15 – For HCP onlyAD. 06/03/2014 - ED. 06/03/2016

Budesonide/formoterol as RELIEVER and CONTROLLER

Formoterol turbuhaler bekerjaSECEPAT DAN SEEFEKTIF salbutamol pMDI

n=36-5

0

5

10

15

20

25

30

-5

0 3 5 10 15 20 25 30 35

Cha

nge

in F

EV1

from

bas

elin

e (%

)

Menit setelah penggunaan obat

Onset kerja formoterol bekerja secepat salbutamol

Formoterol TBH 9 µgFormoterol TBH 4.5 µg

Salbutamol pMDI 200 µg

Salbutamol pMDI 100 µg

Plasebo

Adaptasi dari Seberova

Formoterol 4.5 atau 9 µg via turbuhaler memperbaiki FEV1 secepat dan seefektifsalbutamol 100 atau 200 µg via pMDI

FEV1, forced expiratory volume in 1 second; TBH, turbuhaler; pMDI, pressurised metered dose inhaler

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.

Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations (COMPASS STUDY)

Penelitian acak, buta-gandaselama 6 bulan terhadap 3335 pasien asma > 12 tahun, diagnosaasma > 6 bulan, ICS > 3 bulan, FEV₁ > 50% prediksi, > 1 eksaserbasi asma dalam 1-12 bulan sebelumnya

Regular ICS ≥500 µg + terbutaline

sebagai pelega

Salmeterol/fluticasone 50/250 μg BID + terbutaline sebagai pelega (n=1123)

Run-in Randomisation Treatment

Week

Budesonide/formoterol 320/9 μg BID + terbutaline sebagai pelega (n=1105)

Budesonide/formoterol 160/4.5 μg BID + budesonide/formoterol sebagai pelega (n=1107)

-2 0 248 16

Enrolled n=4399; Randomised n=3335

Dengan dosis ICS harian 25% lebih rendahSymbicort® sebagai pelega dengan pengontrol,

menurunkan eksaserbasi berat lebih baik 39% vs salmeterol/fluticasone

39%(p< 0.001)

25%SAL/FLU 50/250 µg bid + SABA as needed (n = 1123)

BUD/FORM 160/4.5 µg bid + BUD/FORM as needed (n = 1107)

BUD/FORM 320/9 µg bid + SABA as needed (n = 1105)

Eksaserbasi Berat

200

300

100

125

173

208

39% reduction p

Studi AHEAD: Bud/form for maintenance and relief in uncontrolled asthma vs high dose salmeterol/fluticasone + as needed SABA

Budesonide/formoterol 2x 160/4.5 μg bid + as reliever (n=1154)

Run-in RandomisasiICS (800-1600 µg/hari) atau

ICS (400-1000 µg/hari) ±LABA

+ terbutaline sebagai pelega

Pengobatan

Minggu

Salmeterol/fluticasone 50/500 µg bid + terbutaline as reliever (n=1155)

-2 0 264 13

21%

31%

lebih rendah kejadian ekaserbasi berat vs. dosis tinggi SAL/FLU + SABA(95% CI,1-37, p=0.039)

lebih rendah kejadian hospitalisasi/ perawatanIGD vs. dosis tinggi SAL/FLU + SABA (95% CI,1-51, p=0.046)

38%p

Assessing & evaluate asthma control

FAKTOR RISIKO EKSASERBASI ASMA

Gejala asma yang tidak terkontrol – faktor risiko utama terjadi eksaserbasi

Faktor risiko yang dapat dimodifikasi• Penggunaan SABA yang tinggi (mortalitas asma meningkat jika >1 x 200 dosis tabung/bulan)• ICS yang tidak adekuat: tidak diresepkan ICS, ketidakpatuhan menggunakan ICS, atau salah teknik menggunakan inhaler• Penyakit penyerta: obesitas, rhinosinusitis kronis, GERD, alergi makanan, kehamilan• Paparan: merokok, pajanan allergen bila sensitif, polusi udara• Masalah psikologis dan sosioekonomi mayor• Fungsi paru: FEV1 rendah terutama jika 1 eksaserbasi berat dalam12 bulan terakhir

SABA: short-acting β2-agonist; ICS: inhaled corticosteroid; GERD: gastroesophageal reflux disease; FEV1: forced expiratory volume in 1 second; FENO: fractional exhaled nitric oxide



Bagaimana menilai tingkat kontrol asmapasien dewasa, remaja, dan anak ≥6 tahun?

Kontrol Gejala Asma Tingkat Kontrol Gejala Asma

Dalam 4 minggu terakhir, pasien mengalami:

• Gejala asma di siang hari > 2x/minggu □ Ya □ Tidak

• Apakah pernah terbangun malamhari karena asma? □ Ya □ Tidak

• Apakah pelega* dibutuhkan untukgejala >2x/minggu □ Ya □ Tidak

• Apakah ada pembatasan aktivitaskarena asma? □ Ya □ Tidak

SemuaTidak

1-2 Ya 3-4 Ya

TerkontrolBaik

TerkontrolSebagian

Tidakterkontrol


* Berdasarkan SABA pelega; tidak termasuk pelega yang digunakan sebelum olahraga


Personalisasi manajemen asma:Menilai, menyesuaikan, meninjau respon

Konfirmasi diagnosis bila diperlukanKontrol gejala dan faktor resiko yang dapat dimodifikasi (termasuk fungsi paru)Penyakit pernyertaTeknik penggunaan inhaler & kepatuhanTujuan pasien dan orang tua

Penatalaksanaan faktor risiko yang dapatdimodifikasi dan penyakit penyertaStategi non-farmakologiEdukasi dan latihan ketrampilanMedikasi untuk asma

GejalaEksaserbasiEfek sampingFungsi paruKepuasan pasien dan orang tua



Evaluasi respon pasien dan penyesuaian pengobatan

Seberapa sering pengobatan asma perlu dievaluasi? 1-3 bulan setelah pengobatan dimulai, selanjutnya tiap 3-12 bulan Selama kehamilan, tiap 4-6 minggu Setelah eksaserbasi, dalam 1 minggu

Meningkatkan pengobatan asma Pertahankan step-up, minimal 2-3 bulan jika asma tidak terkontrol

Penting: pertama cek dulu penyebab umum (misal: gejala bukan karena asma, teknik penggunaan inhaler yang salah, pasien tidakpatuh)

Step-up jangka pendek, selama 1-2 minggu, misal saat infeksi virus atau pajanan alergenDapat diinisiasi oleh pasien dengan asthma action plan tertulis

Penyesuaian hari ke hari Pasien yang diresepkan ICS/formoterol pelega dengan pengontrol: Pelega: pasien menyesuaikan dosis ICS/formoterol berdasarkan gejala harian Pengontrol: tetap digunakan

Menurunkan pengobatan asma Pertimbangkan pengurangan obat jika gejala asma terkontrol dan fungsi paru stabil selama 3 bulan atau lebih Temukan dosis minimum efektif untuk tiap pasien (mencapai asma terkontrol dan meminimalizir eksaserbasi)



KESIMPULAN

1. Pasien masih berisiko mengalami serangan asma dan angka mortalitas asma masih tinggi di dunia1,2

2. Faktor risiko penyebab eksaserbasi asma antara lain3

- Penggunaan SABA yang tinggi- Kurangnya penggunaan ICS

3. Terdapat paradoks pada pengobatan asma pada tatalaksana sebelumnya4

4. GINA 2019 mengubah paradigma dalam pengobatan asma, menempatkan ICS/formoterol sebagai pelegautama, dan menggeser SABA sebagai pelega alternatif di Step 3-53

5. Dengan dosis harian ICS 25% lebih rendah, pasien dengan budesonide/formoterol sebagai pelega denganpengontrol mengalami penurunan eksaserbasi berat 39% lebih rendah vs. salmeterol/flutikason + SABA5

6. Evaluasi pengobatan direkomendasikan 1-3 bulan sejak pengobatan dimulai, kemudian dilanjutkan tiap3-12 bulan3

1. The Global Asthma Report 2018. Available from www.globalasthmareport.org; 2. Pavord I et al. The Lancet Commissions. After asthma: redefining airways diseases. Lancet 2018; 391(10118):350–400; 3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginashtma.org; 4. O’Byrne PM et all. The paradoxes of asthma management: time for a new approach? Eur Respir J 2017; 50: 1701103; 5. Kuna P et al. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract. 2007;61(5):725-736

http://www.globalasthmareport.org/http://www.ginashtma.org/

THE MESSAGES

• Educate the people• Educate the patients• Established diagnosis• Follow guidelines• Use inhaled therapy• Use ICS LABA Formoterol ICS as main reliever in Step 3 – 5 • Train and recheck inhaled medication technique• Follow up your treatment

• The focus is now on asthma control !

Abbreviated Prescribing Information

SYMBICORT TURBUHALER (Budesonide and formoterol); Inhalation Powder 80/4.5 mcg/dose and 160/4.5 mcg/dose (delivered dose). See local Prescribing Information for full details prior to prescribing –Prescribing Information may vary from country to country. Indication: Asthma: For regular treatment of asthma where use of a combination (inhaled corticosteroid and long-acting beta2-agonist) is appropriate:patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting beta2- agonists, or patients already adequately controlled on both inhaled corticosteroids and long-actingbeta2-agonists. COPD (Symbicort 160/4.5 mcg/inhalation): Symptomatic treatment of patients with severe COPD (FEV1 < 50% predicted normal) and a history of repeated exacerbations, who have significantsymptoms despite regular therapy with long-acting bronchodilators. SYMBICORT (80/4.5 mcg/inhalation) is not appropriate in patients with severe asthma nor patients with COPD. Dosage: Asthma: there are 2alternatives therapies: Maintenance and reliever therapy: SYMBICORT is taken as both regular maintenance treatment, and as needed in response to symptoms without separate inhaler. Adults (≥12 years):80/4.5 and 160/4.5 mcg/inhalation: 2 inhalations/day, (1 inhalation in the morning and evening or 2 inhalations either in the morning or evening). A maintenance dose of 2 inhalations twice daily may beappropriate (for 160/4.5 mcg/inhalation only). Children (≥6 years): 80/4.5 mcg/inhalation: 1 inhalation/day. Patients should take 1 additional inhalation as needed in response to symptoms. If symptoms persistafter a few minutes, an additional inhalation should be taken. Not more than 6 inhalations (for adults & adolescents) and 4 inhalations (for children) should be taken on any single occasion. Consider reassessmentof therapy in patients using an increasing number of inhalations for symptom relief without improving asthma control within 2 weeks. A total daily dose >8 inhalations for adults and adolescents (both strength)and 4 inhalations for children (for 80/4.5 mcg/inhalation) is not normally needed, however a total daily dose of up to 12 inhalations for adults and adolescents (both strength) and 8 inhalations for children (for80/4.5 mcg/inhalation) could be used temporarily. Maintenance therapy: SYMBICORT taken as regular maintenance treatment, with a separate rapid-acting bronchodilator as rescue. Adults and Adolescents (≥12years): 80/4.5 mcg/inhalation& 160/4.5 mcg/inhalation: 1-2 inhalations twice daily. Children (≥6 years): 80/4.5 mcg/inhalation: 2 inhalations twice daily. COPD: Adults: 160/4.5 mcg/inhalation: 2 inhalations twicedaily. Contraindication: Hypersensitivity to budesonide, formoterol or inhaled lactose. Warnings and precautions: When long term treatment is discontinued, taper the dose, do not stop abruptly. Not for treatingsevere exacerbations. The patient must be advised to have their rescue inhaler available at all times & reminded to take maintenance dose as prescribed even when asymptomatic. I f paradoxical bronchospasmoccur, discontinue treatment. Possible systemic effects (adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma) may occur in long periodtreatment at high doses. It is recommended to regularly monitor the height of children receiving prolonged treatment. Rinse mouth out with water after inhaling to minimize the risk of oropharyngeal candidainfection. Use with caution in patients with thyrotoxicosis, phaeochromocytoma, untreated hypokalaemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension,aneurysm or other severe cardiovascular disorders, QTc-interval prolongation, active or quiescent pulmonary tuberculosis, fungal and viral infections in the airways. Potentially serious hypokalaemia may resultfrom high doses of beta2-agonists. Additional effect of hypokalaemia may happen in coadministration of beta2-agonists with drugs which induce hypokalaemia. Additional blood glucose controls should beconsidered in diabetic patients. Increased risk of pneumonia in treatment of COPD. During pregnancy, it should only be used when the benefits outweigh the potential risks, use the lowest effective dose. It is notknown whether budesonide or formoterol passes into human milk. Interactions: Concomitant use with potent inhibitors of CYP450 3A4 (e.g. itraconazole, ritonavir) can increase plasma levels of budesonide. Beta-adrenergic blockers can inhibit the effect of formoterol. Concomitant use with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors and tricyclic anti-depressantscan prolong QTcinterval and increase the risk of ventricular arrhythmias. In addition L-dopa, L-thyroxine, oxytoxin and alcohol can impair cardiac tolerance towards beta2-sympathomimetics. Concomitant usewith MAO inhibitors including furazolidone and procarbazine may precipitate hypertensive reactions. Elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.Potentially additive effect in use with other beta-adrenergic drugs. Hypokalemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides. Undesirable effects:Common (1% - 10%): Palpitations, candida infection in the oropharynx, headache, tremor, mild irritation in throat, coughing, hoarseness. Uncommon (0.1% - 1%): Tachycardia, nausea, muscle cramps, dizziness,agitation, restlessness, nervousness, sleep disturbances. Rare (0.01% - 0.1%): Cardiac arrhythmias e.g atrial fibrillation, supraventricular tachycardia, extrasystoles, immediate and delayed hypersensitivityreactions e.g. dermatitis, exanthema, urticaria, pruritus, angioedema and anaphylactic reaction, bronchospasm, skin bruising. Very rare (

Preferred Reliever: A Paradigm Shift in Asthma...

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