2 Bloktiene Actavis Montelukast DR Budhi Antariksa
2 Bloktiene Actavis Montelukast DR Budhi Antariksa
(GINA, 2019)
BRONKOKONTRIKSI
2019 GINA Pocket guide for Asthma Management and Prevention, Global Initiative for Asthma, 2019. Available from:
https://ginasthma.org/gina-reports/. Accessed July 2019.
ASMA: PATOFISIOLOGI
ASMA = INFLAMASI & REMODELING
3
Low dose ICS Leukotriene receptor antagonist (LTRA), Medium dose High dose Add low dose
Other controller taken whenever or low dose ICS taken whenever SABA ICS, or low dose ICS, add-on OCS, but
options consider
SABA is taken † taken † ICS+LTRA # tiotropium, or
add-on LTRA # side-effects
* Off-label; data only with budesonide-formoterol (bud-form) ‡ Low-dose ICS-form is the reliever for patients prescribed
† Off-label; separate or combination ICS and SABA inhalers bud-form or BDP-form maintenance and reliever therapy
# Consider adding HDM SLIT for sensitized patients with
allergic rhinitis and FEV >70% predicted
1
© Global Initiative for Asthma, www.ginasthma.org
ASMA: TATALAKSANA
Haughney J, Price D, Kaplan A, et al. Achieving asthma control in practice: understanding the reasons for poor control. Respir Med 2008;102:1681-93
ASMA: Studi INSPIRE
• Subjek: 3,415 pasien asma dewasa ≥16 thn dari 11 negara yang diresepkan
ICS atau ICS+LABA
• Hasil:
– 74% masih menggunakan SABA setiap hari;
– 51% pasien memiliki asma yang tidak terkontrol;
– 21% pasien memiliki asma yang tidak terkontrol dengan baik; dan
– hanya 28% pasien yang diklasifikasikan memiliki asma yang terkontrol dengan baik.
ASMA: Studi AIRIAP
=
“Perlu perubahan dalam manajemen terapi asma”
Leukotriene
• Diproduksi oleh leukosit dan memiliki struktur tiga rantai ganda (triena)
• Mediator pro-inflamasi, hasil dari aktivasi sel-sel imun pada membran sel
akibat adanya alergen
• Vora AC. Montelukast – place in therapy. Supplement to Journal of The Association of Physicians of India 2014(62):46-50.
• Benninger MS & Waters H. Montelukast: Pharmacology, safety, tolerability and efficacy. Therapeutics 2009(1):1253-61.
Leukotriene
Phospholipase A2 5-HPETE
Phospolipid
Asam Arakhidonat
pada
(arachidonic acid)
membran sel
Prostaglandins
Cyclo-oxygenase Thromboxanes
LTB4
LTC4 synthase
LT4 hydrolase
5-lipoxygenase/FLAP
*
9.4
10.0
8.0
6.4
6.0
perlu anti-
leukotrien /
4.0 antagonis reseptor
2.0
leukotrien (LTRA).
* p<0.02 vs normal control
0.0 # p<0.05 vs normal control
Normal control Subjects with Treated with ICS Acute severe
(n=10) asthma (n=20) (n=10) asthma (n=6)
Diadaptasi dari: Pavord ID, et al. Induced sputum eicosanoid concentrations in asthma. AM J Respir Crit Care Med
1999;160:1905–1909.
LT-Receptor Antagonist dan LT-Synthesis Inhibitor
• Drakatos, et. al., Targeting Leukotrienes for the teratment COPD?. Inflammation & Allergy – Drugs Targets, 2009;8:297-306.
Bagaimana LTRA pada GINA 2019 ?
STEP 5
High dose
ICS-LABA
Asthma medication options: Refer for
Adjust treatment up and down for STEP 4
phenotypic
individual patient needs assessment
Medium dose
STEP 3 ± add-on
ICS-LABA therapy,
STEP 2 Low dose e.g.tiotropium,
PREFERRED STEP 1 ICS-LABA anti-IgE,
CONTROLLER Daily low dose inhaled corticosteroid (ICS), anti-IL5/5R,
to prevent exacerbations As-needed or as-needed low dose ICS-formoterol * anti-IL4R
and control symptoms low dose
ICS-formoterol *
Low dose ICS Leukotriene receptor antagonist (LTRA), Medium dose High dose Add low dose
Other controller taken whenever or low dose ICS taken whenever SABA ICS, or low dose ICS, add-on OCS, but
options consider
SABA is taken † taken † ICS+LTRA # tiotropium, or
add-on LTRA # side-effects
* Off-label; data only with budesonide-formoterol (bud-form) ‡ Low-dose ICS-form is the reliever for patients prescribed
† Off-label; separate or combination ICS and SABA inhalers bud-form or BDP-form maintenance and reliever therapy
# Consider adding HDM SLIT for sensitized patients with
allergic rhinitis and FEV >70% predicted
1
© Global Initiative for Asthma, www.ginasthma.org
GINA 2019
STEP 3
STEP 2 Low dose ICS-
PREFERRED LABA
CONTROLLER Daily low dose inhaled corticosteroid (ICS),
to prevent exacerbations
and control symptoms or as-needed low dose ICS-formoterol *
PREFERRED
RELIEVER
As-needed low dose ICS-formoterol *
Preferred option:
Other options:
High dose ICS, add-on tiotropium, or add-on LTRA
• Vora AC. Montelukast – place in therapy. Supplement to Journal of The Association of Physicians of India 2014(62):46-50.
• Benninger MS & Waters H. Montelukast: Pharmacology, safety, tolerability and efficacy. Therapeutics 2009(1):1253-61.
MONTELUKAST – Studi MONICA
Virchow JC, et al. Add-on montelukast in inadequately controlled asthma patients in a 6-month open-label study: the montelukast in chronic
asthma (MONICA) study. Respiratory Medicine 2010;104:644-51.
MONTELUKAST – Studi MONICA
Improvements in ACT Scores With Add-On Montelukast in ICS and ICS + LABA Subgroups
ACT Scores
25 (Completely controlled) 16–19 (Poorly controlled)
20–24 (Well controlled) <16 (Uncontrolled)
2.1 0.9
100
9.4 6.0 9.6
Patients in Each ACT Category, %
Improvements in Mini AQLQ With Add-On Montelukast in ICS and ICS + LABA Subgroups
Baseline ICS
Baseline ICS + LABA
Montelukast + baseline therapy
7
5.90
6 5.53 5.43
5.32
5.11
4.86
5
4.18
3.80
4
Score
0
Baseline Month 3 Month 6 Month 12 Baseline Month 3 Month 6 Month 12
(n=379) (n=345) (n=309) (n=228) (n=1,137) (n=983) (n=883) (n=613)
Virchow JC, et al. Add-on montelukast in inadequately controlled asthma patients in a 6-month open-label study: the montelukast in
chronic asthma (MONICA) study. Respiratory Medicine 2010;104:644-51.
MONTELUKAST – Studi MONICA
3 7
2.61a 6.20a 6.22a
2.60a
2.46 5.76
6
5
2
4
PEF, L/s
FEV1, L
3
1
2
0 0
Baseline Month 3 Month 6 Baseline Month 3 Month 6
(n=1,445) (n=1,057) (n=914) (n=967) (n=669) (n=563)
aP<0.0001 vs baseline.
Lung function measurements were performed at the investigator’s discretion; thus, not all patients had data for these
parameters.
Virchow JC, et al. Add-on montelukast in inadequately controlled asthma patients in a 6-month open-label study: the montelukast in chronic
asthma (MONICA) study. Respiratory Medicine 2010;104:644-51.
Conclusion:
The efficacy of 12-week treatment with MON-400BUD in older asthmatics was comparable to that
of 800BUD on asthma control but associated with reduced frequency of asthma
exacerbations requiring oral steroids and sore throat events.
Changes in ACT and PFS can be useful predictors of asthma control status in older patients.
MONTELUKAST vs Other LTRAs
Sanak M. Antileukotrienes in the treatment of allergic rhinitis. Global Atlas Of Allergic Rhinitis and Chronic Rhinosinusitis. In: Akdis CA, Hellings P, Agache I, editors.
Published by the European Academy of Allergy and Clinical Immunology; 2015, pp 197–199. http://eaaci.org/globalatlas/ENT_Atlas_web.pdf.
Seidman MD, Gurgel RK, Lin SY, Schwartz SR, Baroody FM, Bonner JR, et al. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg. 2015;152(1)
Suppl;S1–43
MONTELUKAST DAN ASMA PADA KEHAMILAN