Peranan Budesonide (Pulmicort®)

Respules pada Tatalaksana

Eksaserbasi Asma Dewasa

Referensi:
1. Camargo et al. Association between common asthma therapies and recurrent asthma exacerbations in children enrolled in a state Medicaid plan. Am J Health-Syst Pharm. 2007;64:1054-1061
2. Michael J. Welch. Nebulization Therapy for Asthma: A Practical Guide for the Busy Pediatrician. Clinical Pediatrics. 2008;47:744-756
3. Saito et. Al. High-dose nebulized budesonide is effective for mild asthma exacerbations in children under 3 years of age. Eur Ann Allergy Clin Immunol. 2017;49: N1: 22-27
Gambar : dibeli dari shutterstocks_226532458
Asthma

heterogeneous disease, usually characterized by chronic airway inflammation.

history of respiratory symptoms such as wheeze, shortness of breath, chest

tightness and cough that vary over time and in intensity, together with variable
expiratory airflow limitation.

2
Derajat keparahan asma
Berdasarkan GINA Guideline 2019, derajat keparahan asma untuk anak >6
tahun dibagi menjadi 31:
Asma ringan (Mild Asthma)
Asma dapat terkontrol sepenuhnya dengan terapi Step 1 dan 2
Terapi pelega: SABA; Terapi pengontrol: Kortikosteroid dosis rendah

Asma sedang (Moderate Asthma)

Asma dapat terkontrol sepenuhnya dengan terapi Step 3.
Terapi pelega: SABA; Terapi pengontrol: Kortikosteroid dosis rendah/LABA

Asma berat (Severe Asthma)

Asma yang membutuhkan terapi step 4 atau 5 agar dapat terkontrol sepenuhnya.
Terapi pelega: SABA; Terapi pengontrol: Kortikosteroid dosis sedang atau tinggi/LABA.

3 Referensi : Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2018. Tersedia di: http://www.ginasthma.org/.
Asma Eksaserbasi
Asma eksaserbasi adalah episode akut atau sub akut, perburukan gejala sesak
napas, batuk, mengi, atau dada terasa berat dan penurunan fungsi paru yang lebih
buruk dari status hariannya.1

Pencetus:
Bronkospasme
- Infeksi virus, alergen, polusi udara, perubahan cuaca,
aderens terapi controler yg buruk

Asma eksaserbasi terjadi karena perburukan

Inflamasi
peradangan (inflamasi) di saluran napas2.

4 Referensi ; 1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2019. Tersedia di: http://www.ginasthma.org/.
2. Barnes. Pathophysiologyofasthma. Br J Clin Pharmacol ;42:3–10, 1996.
Manajemen Eksaserbasi (GINA, 2019)
1. Menilai severitas eksaserbasi (derajat sesak nafas, RR, HR, SO2, dan fungsi
paru. Terapi O2 dan SABA mulai diberikan.

2. Kebutuhan perawatan intensif bila : penurunan kesadaran, gelisah, silent

chest. Dapat diberikan SABA, kombinasi dengan ipratropium bromide, O2
controlled, dan kortikosteroid.
3. SABA dapat diberikan berulang, kombinasi dengan ipratropium bromida,
pemberian steroid sistemik direkomendasikan lebih awal, pertimbangkan
MgSO4.
4. Penilaian respon terapi
5. Menyiapkan terapi lanjutan apabila pasien membaik dan direncanakan rawat
jalan. Memulai terapi controller atau step up dosis controller dari sebelumnya
2-4 minggu, dan menurunkan dosis SABA menjadi as needed.

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Penggunaan High Dose budesonide pada Asma eksaserbasi
berdasarkan GINA

Pemberian ICS dosis tinggi yang diberikan dalam 1 jam pertama setelah gejala
klinis muncul dapat menurunkan kebutuhan rawat inap pada pasien yang
tidak menerima kortikosteroid sistemik (Evidence A)1

Dosis rekomendasi budesonide (Pulmicort® respules) berdasarkan GINA

2018: >1.000 mcg1

6 Referensi ; 1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2018. Tersedia di: http://www.ginasthma.org/.
Terapi Pada Asma Eksaserbasi1

SABA (Short Acting B2 agonist) Kortikosteroid

• Mengatasi gejala asma secara cepat • Diberikan dalam 1 jam pertama
• Dapat diberikan beberapa kali pada pasien • Terdapat 2 jenis kortikosteroid, yaitu
asma akut kortikosteroid sistemik dan kortikosteroid
• Contoh: Bricasma®, Salbutamol, etc inhalasi

Oksigen Ipratropium Bromide

• Untuk mencapai saturasi oksigen 93-95% (94- • Kombinasi SABA & ipratropium bromide
98% pada anak usia 6-11 tahun) menurunkan angka hospitalisasi dan
meningkatkan FEV1 dan PEF

Referensi ; 1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2018. Tersedia di: http://www.ginasthma.org/.
 Bricasma® Merupakan SABA yang memiliki efektivitas lebih lama dan
palpitasi yang lebih rendah dibandingkan salbutamol

Perubahan nilai PEFR setelah inhalasi menggunakan Kejadian efek samping palpitasi dan tremor setelah
dosis equipotent Bricasma® respules dan salbutamol1 pemberian Bricasma® vs. salbutamol secara
intravena2

Palpitasi Tremor
Terapi
% (n) % (n)
Change of PEFR (L/min)

Bricasma® 35%(7) 15%(3)

Salbutamol 70%(14)* 25%(5)

* p<0.05 vs bricasma

• Double-blind, crossover design, randomisasi, obat diadministrasikan

Dalam percobaan double-blind, pada 12 pasien dengan obstruksi saluran napas reversibel,
menilai efek pada obstruksi saluran nafas oleh spirometri dan pengukuran berulang dari laju dalam volume 10 mL melalui injeksi intravena selama 10 menit: 500 μg
aliran ekspirasi puncak (PEFR) selama 5 jam setelah inhalasi 0.l0 + 0,20 mg salbutamol dan bricasma, 250 μg salbutamol
0,25 + 0,50 mg terbutalin
8
Referensi: 1. Bo G. Sirnonsson,et al. Acta med. Scand ;192:371-376, 1972. 2. Sahay JN,et al. Curr Med Res Opin ;9(1):1-6, 1984.
 Apakah terapi SABA saja cukup pada pasien
eksaserbasi asma?

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Peranan Kortikosteroid Pada Tatalaksana Eksaserbasi Asma

 GINA merekomendasikan pemberian kortikosteroid pada semua tingkat

keparahan eksaserbasi asma, baik pada ringan-sedang dan berat1

 Peran utama kortikosteroid berfungsi sebagai anti inflamasi (efek genomik)

dengan onset kerja > 6 jam2

 ICS dosis tinggi, bekerja dengan dua mekanisme yaitu genomic dan non-
genomic dengan onset kerja cepat dalam hitungan detik atau menit 3

Referensi; 1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2018. Tersedia di: http://www.ginasthma.org/. 2. Rodrigo GJ
10 CHEST 2004;130:1301-1311 3. Rodrigo GJ. Arch bronchoneumol 2006; 42(10):5 33-40
Kombinasi Pulmicort® + Bricasma® Signifikan meningkatkan
efektivitas terapi dan Fungsi Paru dibandingkan Bricasma® saja

Pulmicort® 2 kali sehari

+ Bricasma®*

• Pasien asma akut di Rumah

Sakit
• 19-56 tahun

Bricasma®*

7 hari

*Terapi lain yang diberikan: aminofiline IV dan kortikosteroid sistemik diberikan sesuai dengan kondisi pasien
11
Referensi ; Xu, Z. et al. Effects of Nebulized Inhalation of Terbutaline and Budesonide on Acute Bronchial Asthma. Medical China & Medical Foreign Treatment ;2013
Kombinasi Pulmicort® + Bricasma® Signifikan meningkatkan
efektivitas terapi dan Fungsi Paru dibandingkan Bricasma® saja

Signifikan Penggunaan Pulmicort® +

Kelompok Efektif Tidak Efektif Total Efisiensi* SABA
Efektif
Terapi N (%) N (%) (N (%)
N (%)

Pulmicort® +
18(62.07) 10(34.48) 1(3.45) 28 (96.55)
Bricasma®

Bricasma® 15(51.72) 8(27.59) 6(20.69) 23 (73.31)

32%
Efisiensi dibandingkan SABA
*P=0.044 saja
32%?

Total efisiensi signifikan efektif + efektif

Parameter efikasi klinis meliputi mengi, sesak, dada terasa berat

12 Referensi ; Xu, Z. et al. Effects of Nebulized Inhalation of Terbutaline and Budesonide on Acute Bronchial Asthma. Medical China & Medical Foreign Treatment ;2013
Pemberian ICS di UGD memberikan efek cepat sehingga menurunkan risiko
hospitalisasi
• Meta Analisis 17 randomize control trial
• Total 1.133 pasien asma eksaserbasi sedang – berat di UGD*
• Membandingkan pasien yang diberi ICS dosis tinggi vs. Plasebo, ICS dosis tinggi vs. SCS, ICS dosis tinggi +SCS vs SCS
• ICS yang digunakan adalah Budesonide, beclomethasone, dexamethasone, flunisolide, fluticasone, triamcinalon

Dalam 2-3 jam, pasien yang dipulangkan dari Pemberian ICS vs. plasebo
UGD dengan pemberian ICS

4,7 kali
Signifikan lebih tinggi dibandingkan dengan pasien
70%
yang mendapatkan plasebo atau kortikosteroid Tingkat Hospitalisasi
sistemik

Pemberian high dose ICS menunjukkan efektivitas yang cepat (1-2 jam) jika diberikan dalam multiple dosis
dengan interval waktu ≤30 sampai 90 -120 menit di UGD. Hal ini disebabkan adanya efek non genomic
pada pemberian ICS dosis tinggi

*447 dewasa dan 663 anak

13
Referensi; Rodrigo J Gustavo, 2006. CHEST 2006; 130:1301–1311
 Berapa lama rekomendasi pemberian Pulmicort®
respules pada Eksaserbasi Asma?

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Berdasarkan GINA 2019

Pada eksaserbasi asma yang lebih ringan, pemberian ICS setelah pasien
dipulangkan dari Rumah Sakit memiliki efikasi yang setara dengan
kortikosteroid sistemik (evidence B)

Pemberian kortikosteroid sistemik pada pasien eksaserbasi dewasa diberikan

selama 5-7 hari (evidence B)

15 Referensi; Global Initiative for asthma. Global strategy for asthma management and prevention, 2018. Available from: www.ginasthma.org.
Pulmicort® respules 4 mg/hari selama 5 hari pemberian memiliki
efektivitas yang setara dengan kortikosteroid sistemik

Studi retrospektif, multisenter

Pulmicort® respules® (2 mg/nebulisasi,

dua kali sehari)*

• pada 28 pasien rawat inap dengan

asma eksaserbasi ringan-berat
• Pasien sudah tidak menggunakan
steroid ≥1 tahun

Oral Prednisolon (15 mg, dua kali sehari)*

days
0 1 2 3 4 5
*Kedua kelompok mendapatkan fenoterol as needed
Referensi ; Chian CF et al. Five-day course of budesonide inhalation suspension is as effective as oral prednisolone in the treatment of mild
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to severe acute asthma exacerbations in adults ; Pulmonary Pharmacology & Therapeutics 24: 256-260, 2011.
Pulmicort® respules 4 mg/hari selama 5 hari pemberian memiliki
efektivitas yang setara dengan kortikosteroid sistemik
Rata-rata PEF

Pulmicort Respules®
Oral Prednisolon

Waktu (Hari)

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Referensi ; Chian CF et al. Five-day course of budesonide inhalation suspension is as effective as oral prednisolone in the treatment of mild
to severe acute asthma exacerbations in adults ; Pulmonary Pharmacology & Therapeutics 24: 256-260, 2011.
 Efek Samping Pemberian Kortikosteroid Sistemik Jangka Pendek
Menjadi Pertimbangan Penggunaan ICS

Pemberian Pulmicort® respules hingga 4 mg/hari, tidak menurunkan kadar serum kortisol dan
osteokalsin secara signifikan, berbeda dengan pemberian kortikosteroid sistemik.
Study double-blind, double-dummy, placebo-controlled, randomized crossover.

Referensi ; Wilson AM, McFarlane LC, Lipworth BJ. Systemic bioactivity profiles of oral prednisolone and nebulized budesonide in
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adult asthmatics. Chest ;114:1022–7, 1998.
For IPAD presentation only
 Bagaimanakah perbedaan Pulmicort®
dibandingkan ICS lainnya (flutikason)?

19
Pulmicort® respules memiliki waktu disolusi yang lebih cepat
dibandingkan fluticasone

2,7

No significance data

• Waktu disolusi Pulmicort®: >80 kali lebih cepat dibandingkan fluticasone

• Kelarutan yang tinggi dalam air meningkatkan penyerapan di paru3
• Pulmicort® memiliki efek vasokontriksi paru yang kuat dalam 30 menit
20 Referensi; 1. Edsbacker S et al., Basic Clin Pharmacol Toxicol 2006;98(6):523-36 2. Mendes ES et al., Eur Respir J 2003;21:989–993, n=10. 3. Horvath G, Wanner A. Eur Respir J
2006;27(1):172-87;
Informasi Produk, Dosis dan Cara Pemakaian1,2

 Pulmicort® respules (budesonide) terdapat dalam 2 sediaan: 0,5 mg/mL dan 0,25 mg/mL

Dosis Awal selama 5 Hari

Hari Anak dan Dewasa ≥ Anak 3 Bulan -12

12 Tahun Tahun

Ke-1 s/d ke-5 4 mg/hari 2 mg/hari

21 Referensi ; 1. Produk informasi Pulmicort Respules, Nop 2017,2. KMK No.HK.01.07-MENKES-659-2017 ttg Formularium Nasional
Informasi Produk, Dosis dan Cara Pemakaian
 Pulmicort® respules dapat langsung dikombinasikan dengan berbagai terapi asma
lainnya, seperti:
 Terbutaline
 Salbutamol
 Ipatropium bromide
 Fenoterol hydrobromide
 Sodium cromoglicate
 Acetylcysteine
 Nebulisasi Pulmicort® respules direkomendasikan dengan jet nebulizer. Penggunaan
ultrasound nebulizer tidak dianjurkan

Refrensi ; 1. W. Kamin et al. Journal of Cystic Fibrosis 5 ; 205–213, 2006. 2. Produk informasi Pulmicort Respules Nop 2017
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Kesimpulan
 Perburukan inflamasi menjadi dasar penyebab utama eksaserbasi asma sehingga terapi
SABA saja tidak cukup hanya mengatasi bronkospasmusnya saja.1
 ICS Dosis Tinggi dapat digunakan untuk penanganan eksaserbasi asma berdasarkan
GINA 20192

 Pemberian Pulmicort® + SABA meningkatkan efisiensi terapi sebesar 32%,

meningkatkan jumlah pasien yang dipulangkan dalam 2-3 jam pertama sebesar 4,7
kali, menurunkan 70% risiko hospitalisasi 3,4

Referensi ; 1. Barnes. Pathophysiologyofasthma. Br J Clin Pharmacol ;42:3–10, 1996. 2. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2019. Tersedia di:
http://www.ginasthma.org/. 3. Xu, Z. et al. Effects of Nebulized Inhalation of Terbutaline and Budesonide on Acute Bronchial Asthma. Medical China & Medical Foreign Treatment ;2013 4. Rodrigo J
Gustavo. CHEST ; 130:1301–1311, 2006.
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 Thank you

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 PULMICORT ABBREVIATED PRESCRIBING INFORMATION

Budesonide; PULMICORT® RESPULES® Sterile;Nebulising suspension for inhalation 0.25 mg/ml & 0.5 mg/ml. See local Prescribing Information for full details prior to prescribing –
Prescribing Information may vary from country to country. Presentation: White to off-white sterile nebuliser suspension in plastic single dose units. One single dose unit contains 0.5
mg or 1.0 mg budesonide per 2 mL.. Indication: Treatment of bronchial asthma. Dosage: PULMICORT RESPULES should be administered from a suitable nebuliser. The dose
delivered to the patient varies between 40 – 60% of the nominal dose depending on the nebulising equipment used. The nebulisation time and the dose delivered is dependent on
flow rate, volume of nebuliser chamber and volume fill. A suitable fill for most nebulisers is 2-4 ml. Some sedimentation may occur during storage of PULMICORT RESPULES. If this
does not readily resuspend completely upon shaking, the RESPULE should be discarded. Dosage initially or during periods of severe asthma or while reducing oral corticosteroids:
Adults & Children ≥12 years: 1 – 2 mg twice daily. Children 3 months - 12 years: 0.5 – 1 mg twice daily. Maintenance: The maintenance dose should be individualized and should be
the lowest dose which keep the patient symptom-free. Recommended doses are: Adults: 0.5 – 1 mg twice daily. Children 3 months - 12 years: 0.25 – 0.5 mg twice daily.
Contraindication: Hypersensitivity to budesonide or any other ingredients. Warnings and precautions: PULMICORT is not indicated for rapid relief of bronchospasm and not
suitable as sole therapy for status asthmaticus or other acute exacerbations of asthma where intensive measures are required. The patient should seek medical advice if previous
effective dosage regimen no longer gives the same relief. Particular care is needed in patients who are being transferred from oral corticosteroids to PULMICORT since they may
remain at risk of impaired adrenal function for some considerable time. Dose-dependent HPA axis suppression has been observed. Bone mineral density measurement in children
should be interpreted with caution. The growth of children taking glucocorticosteroids in long- term treatment should be monitored and the benefits of the therapy weighed against the
possibility of growth suppression. Decreased liver function may affect the ability to eliminate budesonide. Special care in patients with active or quiescent pulmonary tuberculosis or
fungal, bacterial or viral infections of the respiratory system. Respiratory drugs should not be used with positive pressure delivery systems in pulmonary conditions involving
pneumothorax, air cysts or mediastinal emphysema unless special drainage is performed. Inhibitors of CYP3A4 (e.g. ketoconazole and itraconazole) may increase systemic exposure
to PULMICORT. Interactions: Inhibitors of CYP3A4 (see warnings and precautions). Pregnancy and lactation: Administration during pregnancy should be avoided unless there are
compelling reasons. Budesonide is excreted in breast milk. However, at therapeutic doses of PULMICORT RESPULES no effects on the suckling child are anticipated. PULMICORT
RESPULES can be used during breast feeding. Undesirable effects: Common (>1%): hoarseness, sore, throat irritation, tongue and mouth irritation, dry mouth, oral candidiasis and
cough. Uncommon (˂1%): larynx irritation, bad taste, diarrhoea, nausea, immediate and delayed hypersensitivity reactions such as skin reactions (e.g. rash, dermatitis, urticaria),
angioedema and bronchospasm, headache, lightheadedness, thirst, tiredness, weight gain. Candida infection in the oropharynx. In rare cases signs or symptoms of systemic
glucocorticosteroid effect, including hypofunction of the adrenal gland and reduction of growth velocity, may occur. Possible systemic effects in higher than recommended doses
include depression of the HPA axis, reduction of bone density and retardation of growth rate in children. Rare reports of skin bruising. Psychiatric symptoms such as behavioural
disturbances, nervousness, restlessness and depression. Facial skin irritation. Rarely, may provoke bronchoconstriction in hyperreactive patients. Packsize: PULMICORT
RESPULES 0.25 mg/ml: Box of 4 packs @ 5 respules @ 2 ml (Reg. No.: DKI1151302568A1), PULMICORT RESPULES 0.50 mg/ml: Box of 4 packs @ 5 respules @ 2 ml (Reg. No.:
DKI1151302568B1). HARUS DENGAN RESEP DOKTER Nopember 2017

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 BRICASMA ABBREVIATED PRESCRIBING INFORMATION
Terbutaline sulphate; BRICASMA® RESPULES®; Sterile Solution for nebulization 2.5 mg/ml See local Prescribing Information for full details prior to prescribing – Prescribing Information
may vary from country to country. Presentation: Solution for nebulization in single dose unit of 2 ml. BRICASMA solution for nebulization is isotonic and contains no preservatives.
Indication: For the release of bronchospasm in chronic bronchitis, emphysema and other lung diseases where bronchospasm is a complicating factor. Dosage: Inhaled bronchodilators
should, as initial therapy, be used as required rather than regularly. BRICASMA solution for nebulization is to be used in nebulizers with or without assisted breathing in acute or sub-acute
disorders where conventional inhalers prove unsatisfactory and in maintenance therapy in severe broncho-obstructive conditions. Dosage should be individual. Body weight > 25 kg: 5 mg
(1 single dose unit @ 2 ml) is inhaled 2-4 times in a 24 hour period. Contraindication: Hypersensitivity to any of the ingredients. Warnings and precautions: The patient’s inhalation
technique should be regularly checked. The patient should seek medical advice if a previously effective dosage regimen no longer gives the same relief. BRICASMA should be used with
caution when an increased susceptibility to sympathomimetic amines can be expected, for instance in patients with hyperthyroidism not yet under adequate control. Caution should be
observed in patients with thyrotoxicosis and severe heart disease. Due to the hyperglycaemic effect of β2-agonist, additional blood glucose controls are recommended initially in diabetic
patients. Due to the positive inotropic effect of β2-agonist, BRICASMA should not be used in patients with hypertrophic cardiomyopathy. BRICASMA has an arrhythmogenic potential which
must be considered in the treatment of individual lung patient. BRICASMA is not indicated and should not be used for the management of preterm labor. Particular caution is recommended
in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalemic effect may be potentiated by concomitant treatment and monitoring serum potassium levels
is recommended. Immediate hypersensitivity reactions and exacerbation of bronchospasm have been reported after BRICASMA administration. Safety and effectiveness in children below
the age of 12 have not been established. Lactic acidosis has been reported in association with high therapeutic doses of parenteral and nebulised shortacting beta-agonist therapy, mainly
in patients being treated for an acute asthma exacerbation (see Undesirable effects and Overdose). In patients not adequately responding to acute Bricasma therapy, consideration should
be given to the presence of lactic acidosis as a possible contributing factor to ongoing respiratory symptoms. Interactions: β2-receptor blocking agents (including eye drops) especially
those which are non-selective, may partly or totally inhibit the effect of β2-receptor stimulant. Hypokalemia may result from β2-agonist therapy and may be potentiated by concomitant
treatment with xanthine derivatives, steroids and diuretics. Pregnancy and lactation: No teratogenic effects have been observed in patients or in animals. However, caution is recommended
during the first trimester of pregnancy. BRICASMA passes over to breast milk but an influence on the child is unlikely withtherapeutic doses. Transient hypoglycaemia has been reported in
newborn preterm infants after maternal 2-agonist treatment. Undesirable effect: Very common (≥ 1/10): Tremor, headache. Common (<1/10 and ≥ 1/100): Tachycardia, palpitations, tonic
muscle cramps, hypokalaemia. Rare (<1/1000 and≥1/10000) and frequency unknown: Cardiac arrhythmias e.g. atrial fibrillation, supraventricular tachycardia and extrasystoles myocardial
ischemia, nausea, sleep disturbances and behavioural disturbances such as agitation, hyperactivity and restlessness,
lactic acidosis, urticaria and exanthema. Date of preparation: 13th August 2018 Date of expiry : 13th August 2020

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