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asthma%20(pediatric)
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.

Principles of Therapy

Management Plans for Long-Term Asthma Control:

 Recommended Medications Based on Level of Control
 Treatment Steps  Daily Controller Medications
Children ≤5 years Children ≥6 years
Step 1
  • No daily medication required

Reliever

  • As needed beta2-agonist (inhaled, short-acting)
  • No daily medication required

Preferred controller

  • As needed corticosteroid (inhaled, low-dose) plus Formoterol1,4

Other controller options:

  • Corticosteroid (inhaled, low-dose) if taking beta2-agonist (inhaled, short-acting)3
  • Daily corticosteroid (inhaled, low-dose)5

Preferred reliever3

  • As needed corticosteroid (inhaled, low-dose) plus Formoterol1

Other reliever option

  • As needed beta2-agonist (inhaled, short-acting)
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  

  • Daily corticosteroid (inhaled, low-dose) plus as-needed beta2-agonist (inhaled, short-acting)
  • As needed corticosteroid (inhaled, low-dose) plus Formoterol1,4

Other controller options (any of the following):

  • Corticosteroid (inhaled, low-dose) if taking beta2-agonist (inhaled, short-acting)2
  • Leukotriene modifier
  • Daily corticosteroid (inhaled, low-dose) plus as-needed beta2-agonist (inhaled, short-acting)4

Preferred reliever & other reliever option same as Step 1
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)4
  • Corticosteroid (inhaled, medium-dose)5

Other controller options (any one of the following):

  • Corticosteroid (inhaled, medium-dose)4
  • Corticosteroid (inhaled, low-dose) plus leukotriene modifier

Preferred reliever & other reliever option same as Step 16
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)
    •  recept

Preferred Controller

  • Corticosteroid (inhaled, medium-dose) plus beta2-agonist (inhaled, long-acting)4,10

Other controller options (any of the following):

  • Corticosteroid (inhaled, high-dose)
    • Plus beta2-agonist (inhaled, long-acting)5
  • Add-on Tiotropium bromide7
  • Add-on leukotriene modifier

Preferred reliever & other reliever option same as Step 16
Step 5 N/A

Preferred Controller

  • Corticosteroid (inhaled, high-dose) plus beta2-agonist (inhaled, long-acting)4
  • Plus any of the following:
    • Tiotropium bromide7
    • Anti-IgE (SC Omalizumab8)
    • Anti-IL5 (SC Mepolizumab8)
    • Anti-IL5 receptor (SC Benralizumab9)
    • Anti-IL4α receptor (SC Dupilumab9)

Other controller options (any of the following):

  • Add-on corticosteroid (oral, low-dose)

Preferred reliever & other reliever option same as Step 16

Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2018 & Global Initiative for Asthma (GINA). Pocket guide for asthma management and prevention for adults and children older than 5 years. A pocket guide for healthcare professionals: Updated 2019.
1Used as off-label therapy.
2Short-acting inhaled beta2-agonists should be used as required to relieve symptoms. Other options for reliever medications include anticholinergic (inhaled), beta2-agonists (oral, short-acting), or Theophylline (≥12 years old).
3Low-dose inhaled corticosteroids may be used separately or in combination with short-acting inhaled beta2-agonists.
4Recommended option for patients ≥12 years of age.
5Recommended option for patients 6-11 years of age.
6For patients previously given low-dose Budesonide/Formoterol or low-dose Beclomethasone dipropionate/Formoterol combination as maintenance & reliever regimen.
7Tiotropium by mist inhaler is only to be given to patients ≥6 years of age with a history of exacerbations.
8Contraindicated in patients <6 years of age.
9Contraindicated in patients <12 years of age.
10Expert referral is recommended for patients 6-11 years old with disease progression despite good adherence & correct technique.

 
 
 
 
 
 
 
 
                                           
  • 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
Maintaining Control of Asthma
  • Step-wise approach to therapy is the advancement to the next step of therapy if control is not reached or obtained with the current treatment
  • Treatment should be individualized based on the availability of antiasthmatic medications, resources of healthcare system, individual patient circumstances & cost
Step Down
  • Once control is achieved & maintained for 3 months, gradual step-wise reduction in treatment may be attempted
  • Not applicable for patients at risk of exacerbations & fixed airflow limitation
  • Patients currently on inhaled corticosteroids:
    • Consider reducing dose by 25-50% at 2-3 months interval
  • Patients adequately controlled by low-dose inhaled corticosteroid or a leukotriene modifier:
    • May shift to as-needed low-dose inhaled corticosteroid-Formoterol therapy
Step Up
  • Consider step-up if control is not maintained (review patient medication techniques, compliance & non-pharmacological control, comorbidities)
  • Sustained step-up of 2-3 months duration may be considered in patients who are not responding to initial treatment regimen despite good treatment adherence & removal of modifiable risk factors
  • Short-term step-up involved increasing the dose of inhaled corticosteroid for 1-2 weeks for special situations such as in the presence of viral infections or seasonal allergens
  • Daily adjustment is needed for patients prescribed as-needed low-dose inhaled corticosteroid-Formoterol combination for mild asthma, or maintenance/reliever therapy using low-dose inhaled corticosteroid-Formoterol

Pharmacotherapy

Stepwise Therapy Based on Control

Step 1 - Use of as-needed controller

  • 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
  • Patient adherence to medication should be considered when prescribing corticosteroids

Step 2 - Use of daily or as-needed controller

  • 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 -Use of daily controller & reliever, plus as-needed reliever

  • 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 -Daily controller and reliever, plus as-needed reliever treatment continued

  • Reassess inhaler technique, medication adherence, trigger factors & reinvestigate diagnosis
  • If symptom control is still not achieved, may consider increasing the dose of inhaled corticosteroid from low to medium until improvement is seen 
  • Consider expert referral if increasing the dose of inhaled corticosteroids fails or if symptom control remains poor &/or flare-ups persist
  • Addition of oral leukotriene modifiers or Tiotropium for patients ≥6 years old with history of exacerbations, or increasing the dose of inhaled corticosteroids given with long-acting inhaled beta2-agonist may be considered if symptoms are still not controlled in Step 3
    • For patients being considered for high-dose inhaled corticosteroids, advise should be given about the increased risk for side effects

Step 5 -Add-on treatment and expert referral

  • If symptoms are not controlled by step 4 medications, patient should be referred to a specialist for further diagnostic evaluation including assessment of phenotype and additional treatment
  • Addition of Tiotropium or a monoclonal antibody may be considered if symptoms are still not controlled
    • Tiotropium via mist inhaler may be considered for adolescent patients ≥12 years old with history of exacerbations despite combination therapy in Step 3
    • Addition of anti-IgE Omalizumab may be considered in pediatric patients ≥6 years of age diagnosed with moderate-severe asthma when control is not achieved despite combination treatments
    • Additional anti-IL-5 Mepolizumab may be considered for patients ≥6 years of age, & anti-IL5 receptor Benralizumab & anti-IL4α receptor Dupilumab in patients ≥12 years of age with severe uncontrolled eosinophilic asthma despite adherence to step 4 regimen

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
    • Combination with Formoterol as initial treatment is preferred over daily inhaled corticosteroids monotherapy due to issues with treatment adherence 
    • Addition of long-acting inhaled beta2-agonist is preferred when daily low-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

Alternative or Add-On 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
    • May help improve lung function & decrease interval to next asthma exacerbation
    • Ipratropium bromide should only be considered for exacerbations and not for long-term 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 patients ≥6 years old with moderate to severe asthma with allergic component not controlled by inhaled corticosteroids
    • For patients with severe eosinophilic asthma not controlled by inhaled corticosteroids, Mepolizumab may be considered in patients ≥6 years of age & Benralizumab in patients ≥12 years of age
    • Add-on Dupilumab may be considered in patients ≥12 years old with 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

Reliever Medications

Preferred Therapy

  • Corticosteroids (Inhaled) with Formoterol
    • Combination of steroid with Formoterol is preferred for patients previously given Budesonide-Formoterol or Beclometasone-Formoterol maintenance & reliever therapy
    • Reliever-only initial treatment ie as-needed short-acting inhaled beta2-agonist is no longer recommended  due to accumulated reports of increased risk of exacerbations & lower lung function w/ short-acting inhaled beta2-agonist monotherapy

Alternative 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
      • Concomitant use with corticosteroid is recommended with every intake of a short-acting inhaled beta2-agonist to prevent side effects of short-acting inhaled beta2-agonist monotherapy
  • Beta2-Agonists (Oral, Short-Acting)
    • Reserved for children in whom inhaled therapy is not well-tolerated
    • More side effects than inhalation route

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 ≥6 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
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
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
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). Pocket guide for asthma management and prevention for adults and children older than 5 years. A pocket guide for healthcare professionals: Updated 2019. p21.


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
Carbocisteine (Carbocysteine) Syr
<2 yr: 50 mg PO 12-24 hrly
2-5 yr: 100-250 mg PO 12-24 hrly 
5-12 yr: Up to 250 mg PO 8 hrly
Tab
6-12 yr: 375 mg PO 8 hrly		 Adverse Reactions
  • GI disturbances, N/V; Hypersensitivity reactions (bronchospasm, rashes); Other effect (hypotension)
Special Instruction
  • Use w/ caution in patients w/ gastric or duodenal ulcer
Dried ivy leaf extract Syr
1-5 yr: 2.5 mL PO 8 hrly
6-10 yr: 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
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 PO
1-<9 yr: 20-24 mg/kg/day PO
9-<12 yr (including adolescent smokers): 16 mg/kg/day PO
12-16 yr (nonsmokers): 13 mg/kg/day PO
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 µmol/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 µmol/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 6-12 yr: 75-375 mg in 1-3 SC inj every 2 or 4 wk
≥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 <6 years old
  • Corticosteroids should be tapered gradually
  • Use w/ caution in patients at risk of parasitic infections
Interleukin Inhibitors
Benralizumab ≥12 yr: 30 mg SC every 4 wk x 3 doses, then every 8 wk Adverse Reactions
  • CNS effect (headache); Resp effects (cough, pharyngitis); Dermatologic effects (urticaria, rash, inj site reaction, erythema,pruritus, papule)
Special Instructions
  • Not for acute asthma treatment
  • Use w/ caution in patients w/ helminth infection, children <12 years old, abrupt steroid withdrawal
  • Monitor for hypersensitivity reaction
Dupilumab ≥12 yr:
Initial dose: (200 mg x 2 doses) SC followed by 200 mg SC every other week or 600 mg (300 mg x 2 doses) SC followed by 300 mg SC given every other week		 Adverse Reactions
  • Inj site reaction, eosinophilia, oropharyngeal pain
Special Instructions
  • Not for acute asthma treatment
  • Use w/ caution in patients w/ uncontrolled worsening asthma, helminth infection, children <12 years old, abrupt steroid withdrawal
  • Monitor for hypersensitivity reaction
  • Administer each of the 2 doses into different inj sites
Mepolizumab 6-12 yr: 40 mg SC 24 hrly every 4 wk
≥12 yr: 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, abrupt steroid withdrawal


OTHER DRUGS ACTING ON THE RESPIRATORY SYSTEM
Drug Dosage Remarks
Bacterial lysate (Lyophilized H. influenzae, D. pneumoniae, K. pneumoniae, K. ozaneae, S. aureus, S. pyogenes, S. viridans, N.catarrhalis)
 Acute treatment: 50 mg PO 24 hrly
Long-term treatment: 50 mg PO 24 hrly x 10 days		 Adverse Reactions
  • GI effects (nausea, diarrhea, upper abdominal pain, gastric upset); Other effects (skin itching, cutaneous reactions, urological problems)

Special Instructions

  • Contraindicated in patients w/ autoimmune disease, cardiopulmonary insufficiency, conditions w/ compromised immunity, active TB, rheumatic disease
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