Asthma (Pediatric) Treatment

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ASTHMA (PEDIATRIC)

Asthma is a chronic inflammatory disease of the airways in the lungs of children and adults.
The patient usually complains of shortness of breath, chest tightness and coughing with wheezing.

A diagnosis of asthma in young children is more likely if they have symptom patterns, presence of risk factors for development of asthma and therapeutic response to controller treatment.
Goals of treatment are effective symptom control with minimal or no exacerbations, minimal or no nocturnal and daytime symptoms, no limitations on activities, minimal or no need for reliever treatment, and minimal adverse effects of medication.

Treatment

Principles of Therapy

Management Plans for Long-Term Asthma Control:

Recommended Medications Based on Level of Control¹
Treatment Steps	Daily Controller Medications
Treatment Steps	Children ≤5 years¹	Children ≥6 years¹
Step 1	No daily medication required Reliever As needed beta₂-agonist (inhaled, short-acting)	No daily medication required Reliever As needed beta₂-agonist (inhaled, short-acting)² Other controller options: Consider corticosteroid (inhaled, low-dose)
Step 2	Preferred Controller Corticosteroid (inhaled, low-dose) Reliever As needed beta₂-agonist (inhaled, short-acting) Other controller options: Leukotriene modifier Intermittent corticosteroid (inhaled)	Preferred Controller Corticosteroid (inhaled, low-dose) Reliever As needed beta₂-agonist (inhaled, short-acting)² Other controller options: Leukotriene modifier Theophylline (low-dose)³
Step 3	Preferred Controller Corticosteroid (inhaled, double low-dose) Reliever As needed beta₂-agonist (inhaled, short-acting)² Other controller options: Corticosteroid (inhaled, low-dose) plus leukotriene modifier	Preferred Controller Corticosteroid (inhaled, low-dose) plus beta₂-agonist (inhaled, long-acting)³ Reliever (any of the following): As needed beta₂-agonist (inhaled, short-acting)² Corticosteroid (inhaled, low-dose) plus Formoterol⁴ Other controller options (any one of the following): Corticosteroid (inhaled, high- or medium⁵-dose) Corticosteroid (inhaled, low-dose) Plus any one of the following: Leukotriene modifier Theophylline (low-dose, extended-release)³
Step 4	Continue controller treatment Specialist referral Reliever As needed beta₂-agonist (short-acting) Other controller options: Plus any one of the following: Leukotriene modifier Increase corticosteroid (inhaled) frequency Intermittent corticosteroid (inhaled)	Preferred Controller Corticosteroid (inhaled, medium-/high-dose) plus beta₂-agonist (inhaled, long-acting) Reliever (any one of the following) As needed beta₂-agonist (inhaled, short-acting)² Corticosteroid (inhaled, low-dose) plus Formoterol⁴ Other controller options: Tiotropium bromide⁵ Corticosteroid (inhaled, high-dose) Plus any one of the following: Leukotriene modifier Theophylline (extended-release, long-acting)³
Step 5	N/A	Step 4 therapy Plus any one of the following: Tiotropium bromide³ Corticosteroid (oral, lowest dose) Anti-IgE (Omalizumab), anti-IL-5 (Mepolizumab³), anti-IL5 receptor (SC Benralizumab³)
Notes: Patients with symptoms not controlled with step 3 treatment should be referred to a specialist for further management. Tiotropium by mist inhaler is only to be given to patients ≥12 years of age with a history of exacerbations. ¹Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2018. pp 43 & 111. ²Short-acting inhaled beta₂-agonists should be used as required to relieve symptoms. Other options for reliever medications include anticholinergic (inhaled), beta₂-agonist (oral, short-acting), or Theophylline (≥12 years old). ³Contraindicated in children <12 years of age. ⁴Preferred for patients previously given low-dose Budesonide/Formoterol or low-dose Beclomethasone/Formoterol combination as maintenance & reliever regimen. ⁵Medium-dose inhaled corticosteroids preferred in children 6-11 years old.

Goals of asthma management are achieved through a cycle of:
- Assess (diagnosis, symptom control, risk factors, inhaler technique, adherence, parent preference)
- Adjust treatment (medications, non-pharmacological strategies, treatment of modifiable risk factors)
- Review regularly response including medication effectiveness & side effects

Pharmacotherapy

Stepwise Therapy Based on Control

Step 1 - Use of Reliever, as Needed

For children who have infrequent viral wheezing episodes & no or few interval symptoms
Intermittent inhaled corticosteroids may be an option for children with intermittent viral-induced wheezing

Step 2 - Initial single controller treatment plus as needed beta₂-agonist (short-acting)

For patients who require controller medications everyday in order to maintain control of their asthma
For children whose symptoms are not adequately controlled asthma symptoms or ≥3 exacerbations/year
For children whose symptom pattern are inconsistent with asthma but with frequent wheezing episodes
May be used as initial therapy for treatment-naive patients with persistent symptoms
Low-dose daily inhaled corticosteroid is preferred for children ≤5 years old
- As needed inhaled corticosteroids may be considered in pre-schoolers with increased frequency of wheezing secondary to viral infections
It should be given for at least 3 months to achieve good asthma control
Leukotriene modifiers may reduce symptoms in pediatric patients with persistent asthma

Step 3 - Double the daily low-dose inhaled corticosteroids

Before stepping up, re-confirm asthma diagnosis, check inhaler technique & compliance to medications & inquire about exposure to risk factors
For patients whom symptoms were not controlled by low-dose inhaled corticosteroids after 3 months of initial therapy or if exacerbations persisted
If symptoms are not controlled by step 3 medications, patient should be referred to a specialist for further diagnostic evaluation
Addition of oral leukotriene modifiers to low-dose corticosteroids may be considered

Step 4 - Controller treatment continued

Reassess inhaler technique, medication adherence, trigger factors & reinvestigate diagnosis
Consider expert referral if doubling the dose of inhaled corticosteroids fails or if symptom control remains poor &/or flare-ups persist
If symptom control is still not achieved, may consider increasing the dose of inhaled corticosteroid for several weeks until improvement is seen
Addition of oral leukotriene modifiers, low-dose oral corticosteroids, or Theophylline in children >12 years old may be considered if symptoms are still not controlled

Step 5 - Use of Reliever, as needed & Additional Controller Options

For children ≥6 years of age
Tiotropium via mist inhaler may be considered for adolescent patients ≥12 years w/ a history of exacerbations despite combination therapy in Step 4
Addition of anti-IgE (Omalizumab) may be considered in pediatric patients ≥6 years of age diagnosed w/ moderate-severe asthma when control is not achieved despite combination treatments
Additional anti-IL-5 (Mepolizumab) or anti-IL receptor (Benralizumab) may be considered for patients ≥12 years of age w/ severe uncontrolled eosinophilic asthma despite adherence to step 4 regimen
Treatment may be reassessed based on the patient’s eosinophilia seen during sputum exam
- May be applied if w/ previous history of high-dose inhaled corticosteroid or inhaled corticosteroid w/ long-acting beta₂-agonist therapy

Reliever Medications

Preferred Therapy

Beta₂-Agonists (Inhaled, Short-Acting)
- Most effective bronchodilator
- Agents of choice for relief of bronchoconstriction during acute episodes of asthma & are useful for pre-treatment prior to exercise with effects lasting for 0.5 to 2 hours
- Used only when necessary; increased use indicates that management should be re-assessed

Alternative Therapy

Anticholinergic (Inhaled)
- Eg Tiotropium bromide, Ipratropium bromide
- Considered alternative to short-acting inhaled beta₂-agonists because they may have a slower onset of action &/or higher risk for side effects
- Have an additive effect when nebulized together with a short-acting beta₂-agonists for exacerbations of asthma
- Considered in patients who experience adverse effects (eg tachycardia, arrhythmia, tremor) from short-acting beta₂-agonists
- Tiotropium may help improve lung function & decrease interval to next asthma exacerbation
- Not for long term management of asthmatic children

Beta₂-Agonists (Oral, Short-Acting)
- Reserved for children in whom inhaled therapy is not well-tolerated
- More side effects than inhalation route

Controller Medications

Preferred Therapy

Corticosteroids (Inhaled)
- These are the most effective anti-inflammatory medications used for asthma & are the preferred controller medications for patients with persistent asthma of all levels of severity
- Discontinuation is followed by deterioration of control within weeks to months in some patients
- To minimize side effects, upon achievement of control, corticosteroids should be titrated carefully to lowest effective dose to maintain control
  - Ciclesonide, a prodrug that is activated only in the lungs, may be an alternative with decreased oropharyngeal side effect
- Addition of long-acting inhaled beta₂-agonist is preferred when medium-dose inhaled corticosteroid fails
  - Improves lung function & symptoms, reduces exacerbations, decreases need of short-acting beta₂-agonists, achieves faster clinical control of asthma, & may also be used to prevent exercise-induced asthma
- Combination inhalers are available which may increase compliance

Alternative or Add-On Therapy

Beta₂-Agonists (Inhaled, Long-acting)
- Has no effect on airway inflammation, hence not used as a monotherapy
- Most efficacious when given together with inhaled corticosteroids
  - Rapid clinical control of asthma is achieved than when inhaled glucocorticosteroids are given alone
  - Studies have shown increased mortality risk when given alone; should not be used as a substitute for corticosteroids
  - Causes improved symptom scores, decreased nocturnal asthma symptoms, improved lung function, decreased use of short-acting beta₂-agonists, & reduced number of exacerbations

Beta₂-Agonist (Oral, Long-acting)
- May be considered as an alternative add-on therapy & should always be given with inhaled corticosteroids
- Only used on rare occasions when more bronchodilation is needed
- Less effective than inhaled beta₂-agonists & poses increased risk of side effects

Corticosteroids (Oral)
- Long-term use (>2 weeks) may be required for severely uncontrolled asthma
- Long-term use should be used at the lowest possible dose

Cromones (Inhaled)
- Limited use in long-term treatment of asthma
- May be used for patients with mild persistent asthma & exercise-induced bronchoconstriction
- Weak anti-inflammatory effect, less effective than low-dose inhaled corticosteroids

Leukotriene Modifiers (Oral)
- When used as add-on therapy, may reduce the required dose of inhaled corticosteroid for patients with moderate to severe symptoms
  - When used as monotherapy for control of asthma, leukotriene modifiers are less effective than low-dose inhaled corticosteroids

Monoclonal Antibodies (eg Benralizumab, Dupilumab, Mepolizumab, Omalizumab)
- Reduces asthma symptoms & exacerbations, & the need for rescue medications
- Omalizumab is indicated for moderate to severe asthma w/ allergic component not controlled by inhaled corticosteroids
- Benralizumab & Mepolizumab may be considered for patients ≥12 years old w/ severe eosinophilic asthma not controlled by inhaled corticosteroids
- Add-on Dupilumab may be considered in patients ≥6 years old w/ severe asthma & atopic dermatitis
- Use of Reslizumab in patients <18 years of age w/ asthma has not been established

Theophylline (Oral, Extended-Release)
- Treatment option for patients >12 years of age
- Bronchodilator, which at low dose, has anti-inflammatory effects

Allergen-Specific Immunotherapy

Therapeutic option after strict avoidance of triggers & medical intervention have failed
May be given as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT)
- Life-threatening anaphylactic reactions have been reported with SCIT use
- SLIT has been associated with mild oral & gastrointestinal (GI) symptoms
May reduce symptoms, medication use, improve allergen-specific & non-specific airway hyperresponsiveness & can possibly prevent asthma development in children with allergic rhinoconjunctivitis
Benefits must be weighed against adverse effects & inconvenience of length of therapy
Efficacy of extracts or regimens based on clinical trials should be put into consideration before initiating therapy

Inhalation Devices

INHALATION DEVICES
Age	Device
0-3 years	Preferred: Pressurized metered-dose inhaler plus dedicated spacer w/ face mask Alternate: Nebulizer w/ face mask
4-5 years	Preferred: Pressurized metered-dose inhaler plus dedicated spacer w/ mouthpiece Alternate: Pressurized metered-dose inhaler plus dedicated spacer w/ face mask or nebulizer w/ mouthpiece or face mask

Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2018. p114.

Dosage Guidelines

ANTICHOLINERGICS (INHALED)¹
Drug	Available Strength	Dosage	Remarks
Long-Acting			Adverse Reactions Resp effects [upper respiratory tract infection (URTI), bronchitis, sinusitis]; CV effects (chest pain, palpitation); CNS effects (headache, dizziness); GI effects (dry mouth, bad taste, dyspepsia, nausea); Hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) Special Instructions Use w/ caution in patients w/ prostatic hyperplasia, patients predisposed to narrow-angle glaucoma, bladder neck obstruction, myasthenia gravis Avoid contact of eyes w/ inhalation soln Check patient's inhaler technique for optimum delivery of drug Not used as 1st-line treatment Should be added to beta₂-agonist therapy
Tiotropium bromide	1.25 mcg/puff	≥12 yr: 2 puffs 24 hrly
Short-Acting
Ipratropium bromide	20 mcg/puff MDI	2 puffs 6 hrly Max dose: 12 puffs/day
	250 mcg/2 mL & 500 mcg/2 mL inhalation soln unit dose	1 unit dose (250-500 mcg) via nebulizer 6-8 hrly as required
	0.025% inhalation soln	<6 yr: 0.4-1 mL (100-250 mcg) via nebulizer 6-8 hrly as required 6-12 yr: 1 mL (250 mcg) via nebulizer 6-8 hrly as required
¹Bronchodilator combinations are available. Please see the latest MIMS for specific formulations.

BETA₂-AGONISTS (BRONCHODILATORS) (INHALED)¹
Drug	Available Strength	Dosage*	Remarks
Short-Acting
Fenoterol	100 & 200 mcg/puff MDI	Approved in some countries for childn >6 yr: 1-2 puff 8 hrly as required	Adverse Reactions CV effects (tachycardia, palpitations, cardiac arrhythmias especially in susceptible patients); CNS effects (headache, hyperactivity); Resp effects (mouth & throat irritation, paradoxical bronchospasm); Other effect (fine skeletal muscle tremor) Potentially severe hypokalemia may result esp in acute severe asthma Orciprenaline is less selective for beta₂-receptors & therefore, side effects may be more common Special Instructions Use w/ caution in patients w/ hyperthyroidism, DM, myocardial insufficiency or arrhythmias Monitor K levels in acute severe asthma Check patient's inhaler technique for optimum delivery of drug
Fenoterol	1.25 mg/2 mL soln for inhalation	10-20 drops via nebulizer up to 6 hrly as required 6-14 yr: 10 drops 8 hrly 1-6 yr: 5-10 drops 8 hrly <1 yr: 3-7 drops 8 hrly
Orciprenaline (Metaproterenol)	750 mcg/puff MDI	1-2 puffs 8 hrly as required Max dose: 12 puffs/day
Procaterol	10 mcg/puff MDI	Approved in some countries for childn: 1 puff 6-12 hrly as required
Salbutamol (Albuterol)	100 mcg/dose (autohaler/evohaler)	Immediate relief/prior to exertion: 100 mcg as single dose For chronic or preventive treatment: 100 mcg 6-8 hrly May increase to 200 mcg 6-8 hrly if necessary Max dose: 1.2 mg/day
	100 & 200 mcg/dose easyhaler
	100 mcg/dose MDI
	100 & 200 mcg/dose DPI
	200 mcg/dose accuhaler DPI
	200 mcg/dose diskhaler DPI
	200 mcg/cap DPI
	1 mg/mL, 2.5 mg/2.5 mL, 5 mg/2.5 mL inhalation soln unit dose	2.5-5 mg via nebulizer 6-8 hrly as required
	5 mg/mL (0.5% soln) inhalation soln	10-15 kg: 0.25 mL (1.25 mg) >15 kg: 0.5 mL (2.5 mg) >12 yr: 0.5-1 mL (2.5-5 mg) Dilute required amount of soln w/ normal saline to final volume of 2-3 mL via nebulizer over 10 min as required
Terbutaline	250 mcg/puff MDI	1-2 puffs 6-8 hrly as required Max dose: 8 puffs/day
	500 mcg/dose DPI, turbuhaler DPI	3-12 yr: 1 dose inhaled 6 hrly as required For severe exacerbations: 2 doses Max dose: 8 doses/day
	2.5 mg/2 mL, 5 mg/2 mL inhalation soln	<20 kg: 2.5 mg via nebulizer up to 6 hrly as required >20 kg: 5 mg via nebulizer up to 6 hrly as required
Long-Acting²
Formoterol	4.5 mcg/dose turbuhaler DPI	Approved in some countries for childn ≥6 yr: 1-2 doses inhaled 12-24 hrly Max dose: 4 doses/day	Adverse Reactions CV effects (tachycardia, palpitations, cardiac arrhythmias especially in susceptible patients); CNS effects (headache, hyperactivity); Resp effects (mouth & throat irritation, paradoxical bronchospasm); Other effect (fine skeletal muscle tremor) Potentially severe hypokalemia may result especially in acute severe asthma Special Instructions Use w/ caution in patients w/ hyperthyroidism, DM, myocardial insufficiency or arrhythmias Monitor K levels in acute severe asthma Check patient's inhaler technique for optimum delivery of drug
	9 mcg/dose turbuhaler DPI	Approved in some countries for childn ≥6 yr: 1 dose inhaled 12-24 hrly Max dose: 2 doses/day
	12 mcg/cap DPI	Approved in some countries for childn ≥5 yr: 1 cap inhaled 12 hrly
Salmeterol	25 mcg/puff MDI	≥4 yr: 2 puffs 12 hrly
Salmeterol	50 mcg/dose accuhaler DPI, diskhaler DPI	≥4 yr: 1 dose inhaled 12 hrly
*Please note: Doses for acute exacerbations can be higher than the recommended maintenance doses listed here. ¹Inhaled bronchodilator combinations are available. Please see the latest MIMS for specific formulations. ²Should be used as an adjunct to inhaled corticosteroids in the management of asthma. Please see the latest MIMS for specific formulations of different combination products.

BETA₂-AGONISTS (BRONCHODILATORS) (ORAL)¹
Drug	Dosage	Remarks
Short-Acting		Adverse Reactions CNS effects (headache, sleep disturbances, agitation, hyperactivity & restlessness); CV effects (palpitations, cardiac arrhythmias especially in susceptible patients); Other effect (fine skeletal muscle tremor) Potentially severe hypokalemia may result especially in acute severe asthma Orciprenaline is less selective for beta₂ receptors & therefore side effects may be more common Special Instructions Use w/ caution in patients w/ hyperthyroidism, DM, myocardial insufficiency or arrhythmias Monitor K levels in acute severe asthma
Clenbuterol	1.2 mcg/kg/day PO divided 12 hrly
Fenoterol	Approved for use in some countries for childn: <1 yr: 1.25 mg PO 8-12 hrly 1-6 yr: 1.25-2.5 mg PO 8 hrly 6-14 yr: 2.5 mg PO 8 hrly
Hexoprenaline	Approved for use in some countries for childn: 3-6 mth: 0.125 mg PO 12-24 hrly 6-12 mth: 0.125 mg PO 8-24 hrly 1-3 yr: 0.125-0.25 mg PO 8-24 hrly 3-6 yr: 0.25 mg PO 8-24 hrly 6-10 yr: 0.5 mg PO 8-24 hrly
Orciprenaline (Metaproterenol)	3-10 yr: 10 mg PO 6 hrly
Procaterol	<6 yr: 1.25 mcg/kg/dose PO 12 hrly >6 yr: 25 mcg PO 12-24 hrly
Salbutamol² (Albuterol)	2-6 yr: 1-2 mg PO 6-8 hrly Max dose: 12 mg/day 6-12 yr: 2 mg PO 6-8 hrly Max dose: 24 mg/day >12 yr: 2-4 mg PO 6-8 hrly Max dose: 32 mg/day
Terbutaline	<12 yr: 0.05 mg/kg/dose PO 8 hrly Max dose: 5 mg/day ≥12 yr: 2.5-5 mg PO 8 hrly Max dose: 15 mg/day
Long-Acting
Bambuterol	Approved for use in some countries for childn 2-12 yr: 5-10 mg PO 24 hrly Max dose for childn 2-5 yr: 10 mg/day (Doses >10 mg/day PO is not recommended in Asian childn 2-12 yr)
Formoterol	4 mcg/kg/day PO divided 8-12 hrly
Salbutamol (Albuterol)	Extended-release: <12 yr: 0.3-0.6 mg/kg/day divided 12 hrly >12 yr: 4 mg PO 12 hrly
¹Oral bronchodilator combinations are available. Please see the latest MIMS for specific formulations. ²Combination w/ other cough preparation is available. Please see the latest MIMS for specific formulations.

BRONCHODILATORS (PARENTERAL)
Drug	Dosage	Remarks
Beta₂-Agonists
Hexoprenaline	5-10 mcg slow IV inj x 3-4 doses in 24 hr	Adverse Reactions Fine skeletal muscle tremor, palpitations, cardiac arrhythmias esp in susceptible patients, headache, sleep disturbances, agitation, hyperactivity & restlessness Potentially severe hypokalemia may result esp in acute severe asthma Epinephrine: Dyspnea, hyperglycemia, restlessness, palpitations, tachycardia, tremors, sweating, hypersalivation, weakness, dizziness, headache, coldness of extremities, hypertension, flushing, hypotension Special Instructions Use w/ caution in patients w/ hyperthyroidism, DM, myocardial insufficiency or arrhythmias Monitor K levels in acute severe asthma
Salbutamol	250 mcg slow IV inj, may repeat as required 500 mcg IM/SC, may repeat 4 hrly as required IV infusion: 3-20 mcg/min IV infusion
Terbutaline	2-15 yr: 10 mcg/kg/dose SC/slow IV up to 6 hrly as required Max dose: 300 mcg/dose IV infusion: 25 mcg/kg/day IV as a continuous infusion
Nonspecific Sympathomimetic
Epinephrine (Adrenaline)	10 mcg/kg up to 300-500 mcg SC/IM every 20 min x 3 doses

CORTICOSTEROIDS (INHALED)¹
Drug	Available Strength	Dosage	Remarks
Beclomethasone dipropionate	50, 100, 250 mcg/puff MDI	Childn <5 yr: HFA-based Low dose: 100 mcg³ Medium dose: >200-400 mcg High dose: >400 mcg Childn 6-11 yr: CFC-based Low dose: 100-200 mcg Medium dose: >200-400 mcg High dose: >400 mcg HFA-based Low dose: 50-100 mcg Medium dose: >100-200 mcg High dose: >200 mcg Childn >12 yr & Adults: *CFC-based* Low dose: 200-500 mcg Medium dose: >500-1000 mcg High dose: >1000 mcg HFA-based Low dose: 100-200 mcg Medium dose: >200-400 mcg High dose: >400 mcg	Adverse Reactions Local effects (oropharyngeal candidiasis, cough from upper airway irritation, dysphonia); paradoxical bronchospasm (rare) Long-term use of high-dose steroids may result in cataracts, glaucoma, skin thinning, easy bruising, adrenal suppression, increased bone loss & osteoporotic fractures Risk of systemic effects will depend on dose, potency of the corticosteroid, absorption from the gut, delivery system, the use of spacers & the drug’s pharmacokinetics Special Instructions Local effects may be minimized by using a spacer, gargling & spitting out w/ water, or gargling w/ 1:50 dilution of Amphotericin B
Beclomethasone dipropionate	100, 200 mcg/cap DPI; 100, 200 mcg/dose diskhaler DPI; 200 mcg/dose easyhaler DPI
Budesonide	100, 200 mcg/puff MDI	Childn <5 yr: Low dose: 200 mcg Medium dose: >200-400 mcg High dose: >400 mcg Nebules Low dose: 500 mcg⁴ Medium dose: >500-1000 mcg High dose: >1000 mcg Childn 6-11 yr: Low dose: 100-200 mcg Medium dose: >200-400 mcg High dose: >400 mcg Nebules Low dose: 250-500 mcg Medium dose: >500-1000 mcg High dose: >1000 mcg Childn >12 yr & Adults: Low dose: 200-400 mcg Medium dose: >400-800 mcg High dose: >800 mcg
	100, 200, 400 mcg/dose turbuhaler DPI; 200 mcg/dose swinghaler; 200 mcg/dose easyhaler; 100, 200, 400 mcg/cap DPI
	250 mcg/2 mL, 500 mcg/2 mL, 500 mcg/mL, 1 mg/2 mL soln for inhalation unit dose
Ciclesonide	80, 160 mcg/actuation MDI	Childn <5 yr: Low dose: 160 mcg Medium dose: >160-320 mcg High dose: >320 mcg Once-daily dosing in patients w/ mild severity of asthma Childn 6-11 yr: Low dose: 80 mcg Medium dose: >80-160 mcg High dose: >160 mcg Childn >12 yr & Adults: Low dose: 80-160 mcg Medium dose: >160-320 mcg High dose: >320 mcg
Flunisolide	500 mcg/puff MDI	Childn <5 yr: Low dose: 500-750 mcg Medium dose: >750-1250 mcg High dose: >1250 mcg
Fluticasone furoate	50, 100, 250 mcg/dose accuhaler DPI; 50, 250 mcg dose diskhaler DPI; 50, 125, 250 mcg/dose evohaler	Childn >12 yr & Adults: Low dose: 100 mcg High dose: 200 mcg
Fluticasone propionate	50, 125, 250 mcg/puff MDI	Childn <5 yr: Low dose: 100 mcg⁵ Medium dose: >200-500 mcg High dose: >500 mcg Childn 6-11 yr: Low dose: 100-200 mcg Medium dose: >200-500 mcg High dose: >400-500 mcg Childn >12 yr & Adults: Low dose: 100-250 mcg Medium dose: >250-500 mcg High dose: >500 mcg
	50, 100, 250 mcg/dose accuhaler DPI; 50, 250 mcg dose diskhaler DPI; 50, 125, 250 mcg/dose evohaler
	0.5 mg/2 mL, 2 mg/2 mL soln for inhalation unit dose
Mometasone furoate²	50, 100, 200 mcg/dose for inhalation unit dose	Childn 6-11 yr: Low dose: 100 mcg⁵ Medium dose: ≥220-<440 mcg High dose: ≥440 mcg Childn >12 yr & Adults: Low dose: 110-220 mcg Medium dose: >220-440 mcg High dose: >440 mcg
Triamcinolone acetonide²	75, 200 mcg/dose for inhalation unit dose	Childn 6-11 yr: Low dose: 400-800 mcg Medium dose: >800-1200 mcg High dose: >1200 mcg Childn >12 yr & Adults: Low dose: 400-1000 mcg Medium dose: >1000-2000 mcg High dose: >2000 mcg
¹Corticosteroids combined w/ bronchodilators are available. Please see the latest MIMS for specific formulations. ²Approved for once-daily dosing in patients w/ mild severity of asthma. ³Ages ≥5 years ⁴Ages ≥1 year ⁵Ages ≥4 years Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2018. p45, 112.

CORTICOSTEROIDS (SYSTEMIC)
Drug	Dosage	Remarks
Dexamethasone	Childn: 0.08-0.3 mg/kg BW/day IV/IM, divided 6-12 hrly	Adverse Reactions CNS effects (excessive mental stimulation, insomnia & psychic disturbances); CV effect (tachycardia); Other effects (increased appetite, wt gain, muscle weakness)
Hydrocortisone	Asthma exacerbations in emergency dept: 2-4 mg/kg/dose slow IV/IV infusion 6 hrly x 24 hr Adjust dose according to response & reduce over 4-5 days to oral dose when tolerated	Adverse Reactions GI effect (gastritis). If administered long-term: adrenocortical insufficiency, osteoporosis, muscle wasting, pain or weakness, increased susceptibility to infection, impaired wound healing, electrolyte imbalances, wt gain, DM, skin thinning leading to striae & easy bruising, cataracts, glaucoma Special Instructions Should be taken w/ food Patients on long-term corticosteroids should receive preventive treatment for osteoporosis
Methylprednisolone, Prednisolone, Prednisone	1-2 mg/kg/day PO divided 6-8 hrly x 3-10 days Max dose: 60 mg/day

COUGH & COLD PREPARATIONS
Drug	Dosage	Remarks
Ambroxol	≤6 mth: 1.25 mL PO 12 hrly 7 mth-2 yr: 2.5 mL PO 12 hrly 2-6 yr: 2.5 mL PO 8 hrly 7-12 yr: 5 mL PO 8-12 hrly	Adverse Reactions GI effect (N/V, diarrhea); Other effects (headache, polyuria, fatigue) Special Instruction Should not be taken in an empty stomach Use w/ caution in patients w/ gastric ulcer
Bromhexine	<5 yr: 2 mg PO 8 hrly 5-10 yr: 4 mg PO 8 hrly >10 yr: 8 mg PO 8 hrly	Adverse Reactions GI effect (GI irritation); Metabolic effect (transient increase of serum transaminases) Special Instruction Use w/ caution in patients w/ gastric ulcer
Dried ivy leaf extract	Syr 6-10 yr: 5 mL PO 8 hrly 1-5 yr: 2.5 mL PO 8 hrly Effervescent Tab 6-12 yr: 32.5 mg PO 12 hrly	Adverse Reactions Rarely, laxative effect due to sorbitol content Special Instructions Use w/ caution in patients w/ fructose/sorbitol intolerance
Dried ivy leaf extract
Guaifenesin	Infant: 25 mg PO 6 hrly 2-6 yr: 10-50 mg PO 4-6 hrly ≥7 yr: 20-100 mg PO 4-6 hrly Max Dose ≥6 yr: 600 mg/day	Adverse Reactions GI effects (GI discomfort; N/V); CNS effects (drowsiness; headache) Special Instruction Use w/ caution in childn <2 years old & in patients w/ persistent or chronic cough
Lagundi (Vitex negundo)	15 mg/kg/dose or 2.5 mL/kg/dose 8 hrly	Adverse Reactions GI effects (N/V, diarrhea); Dermatologic effect (rash) Special Instruction Use w/ caution in patients w/ hypersensitivity to Lagundi

CROMONE (INHALED)

Drug

Available Strength

Dosage

Remarks

Cromoglicic acid (Cromolyn Na, Na cromoglicate, Na cromoglycate)

5 mg/puff MDI

2 puffs 6 hrly
May increase to 2 puffs 6-8x/day in more severe cases & reduce to 1 puff 6 hrly once asthma has been stabilized

Adverse Reactions

Resp effects (transient bronchospasm, cough & irritation of throat, rarely, severe bronchospasm, angioedema, laryngea l edema & anaphylaxis); Other effects (unpleasant taste, nausea, headache)

Special Instructions

Should not be used for acute asthma attacks

LEUKOTRIENE MODIFIERS (ORAL)
Drug	Dosage	Remarks
5-Lipoxygenase
Zileuton	≥12 yr: 600 mg PO 6 hrly Extended-release: 1.2 g PO 12 hrly	Adverse Reactions CNS effect (headache); GI effects (GI upset, raised liver enzymes); Other effects (rashes, leukopenia has occurred in a few patients) Special Instructions Avoid in patients w/ hepatic impairment/disease Monitor liver enzymes before & periodically during therapy Should not be used for acute asthma attacks
Leukotriene Receptor Antagonists
Montelukast	6 mth-5 yr: 4 mg PO 24 hrly before bedtime 6-14 yr: 5 mg PO 24 hrly before bedtime ≥15 yr: 10 mg PO 24 hrly before bedtime	Adverse Reactions Generally well-tolerated: headache, GI upset Less commonly: generalized pain, arthralgia, myalgia, fever, dizziness; hypersensitivity reactions Zafirlukast: raised liver enzymes, rarely symptomatic hepatitis, hyperbilirubinemia Very rarely: agranulocytosis, bleeding, bruising & edema, systemic eosinophilia consistent w/ Churg-Strauss disease Special Instructions Should not be used for acute asthma attacks Zafirlukast: Avoid in patients w/ hepatic impairment or cirrhosis
Pranlukast	3.5 mg/kg PO 12 hrly Max dose: 10 mg/kg/day
Zafirlukast	5-11 yr: 10 mg PO 12 hrly ≥12 yr: 20 mg PO 12 hrly

MAST CELL STABILIZER/ANTIHISTAMINE (ORAL)

Drug

Dosage

Remarks

Ketotifen

6 mth-3 yr: 0.5 mg PO 12 hrly
>3 yr: 1 mg PO 12 hrly
Extended-release:
>3 yr: 2 mg PO at bedtime

Adverse Reactions

CNS effects (drowsiness, dizziness, CNS stimulation); GI effects (dry mouth, increased appetite, wt gain)

Special Instructions

Should not be used for acute asthma attacks

METHYLXANTHINES (ORAL)
Drug	Dosage	Remarks
Acefylline	500 mg-2 g/day PO in divided doses	Adverse Reactions GI effects (irritation, N/V, abdominal pain, diarrhea, gastroesophageal reflux); CNS effects (CNS stimulation, headache, anxiety, restlessness, dizziness, tremor); Other effect (palpitations) Serum concentration >15-20 mcg/mL (85-110 micromol/L) are associated w/ increased risk of adverse effects including lethal adverse reactions Special Instructions Use w/ caution in patients w/ peptic ulcer, hyperthyroidism, hypertension, cardiac arrhythmias or other CV disease, epilepsy, heart failure, hepatic dysfunction, acute febrile illness, in neonates Many drug interactions occur w/ Theophylline including smoking Increases Theophylline clearance Serum concentration monitoring is necessary to ensure that concentration are within therapeutic range Serum concentration needs to be measured if a patient is changed from one extended-release product to another Optimal therapeutic concentration: 5-15 mcg/mL (28-85 micromol/L)
Aminophylline	Dosage should be individualized
Choline Theophyllinate	100 mg PO 6-8 hrly
Diprophylline (Dyphylline)	15 mg/kg/dose PO 6 hrly
Doxofylline	<12 yr: 6-9 mg/kg/dose PO 12 hrly >12 yr: 200 mg PO 8-24 hrly
Heptaminol acefyllinate	>15 yr: 500 mg-1 g PO 8 hrly
Theophylline¹	Acute bronchospasm: Loading dose in patients not taking methylxanthine: 5 mg/kg PO Maintenance dose: 6 mth-<1 yr: 12-18 mg/kg/day 1-<9 yr: 20-24 mg/kg/day 9-<12 yr (including adolescent smokers): 16 mg/kg/day 12-16 yr (nonsmokers): 13 mg/kg/day
¹Different formulations for Theophylline are available. Please see the latest MIMS for specific formulations.

METHYLXANTHINES (PARENTERAL)
Drug	Dosage	Remarks
Acefylline	1.5-2 g/day IM 0.5-1 g/day IV	Adverse Reactions GI effects (irritation, N/V, abdominal pain, diarrhea, gastroesophageal reflux); CNS effects (CNS stimulation, headache, anxiety, restlessness, dizziness, tremor); Other effect (palpitations) Serum concentration >15-20 mcg/mL (85-110 µ/L) are associated w/ increased risk of adverse effects including lethal adverse reactions Special Instructions Administer IV inj very slowly to prevent dangerous CNS & CV side effects Use w/ caution in patients w/ peptic ulcer, porphyria, hyperthyroidism, hypertension, cardiac arrhythmias or other CV disease, epilepsy, heart failure, hepatic dysfunction, acute febrile illness, in neonates Serum concentration monitoring is necessary to ensure concentration are within therapeutic range Optimal therapeutic concentration: 5-15 mcg/mL (28-85 µ/L)
Aminophylline	Loading dose: 5 mg/kg IV infusion over 20-30 min Maintenance dose: 6 mth-9 yr: 1 mg/kg/hr 10-16 yr: 0.8 mg/kg/hr
Proxyphylline	400-800 mg IM or slow IV 8 hrly

MONOCLONAL ANTIBODIES
Drug	Dosage	Remarks
Anti-Immunoglobulin E (Anti-IgE) Antibody
Omalizumab	≥12 yr: 150-375 mg SC every 2 or 4 wk Max dose: 375 mg every 2 wk Dose depends on pretreatment IgE level & body wt	Adverse Reactions CNS effect (headache); Resp effects (resp infections, sinusitis, pharyngitis); Other effects (local site reaction, viral infection, anaphylaxis, malignancies) Special Instructions Max of 150 mg should be delivered per inj site Should not be used for the treatment of acute bronchospasm or status asthmaticus Contraindicated in patients w/ severe hypersensitivity to the drug & in children <12 years old Corticosteroids should be tapered gradually Use w/ caution in patients at risk of parasitic infections
Interleukin Inhibitor
Mepolizumab	≥12 yr, ≥45 kg: 100 mg SC 24 hrly every 4 wk	Adverse Reactions Dermatologic effects (pruritus, eczema, inj site reaction including erythema, swelling, itching, burning); Musculoskeletal effects (muscle spasm, back pain); Resp effects (nasal congestion, dyspnea, allergic rhinitis, bronchospasm); Misc effects (UTI, headache, toothache, infection) Special Instructions Not for acute asthma treatment Use w/ caution in patients w/ uncontrolled worsening asthma, helminth infection, children <12 years old, <45 kg, abrupt steroid withdrawal

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