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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.

Asthma%20(pediatric) Treatment

Principles of Therapy

  • Goals of long-term management of asthma includes:
    • Effective symptom control with minimal or no exacerbations
    • Minimal or no daytime and nocturnal symptoms
    • No limitations on activities, including exercise
    • Minimal or no need for reliever treatment
    • Normal or near normal pulmonary function
    • Minimal adverse effects of medication 
  • These 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 and side effects
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 Formoterol1,2

Other controller options:

  • Corticosteroid (inhaled, low-dose) if taking beta2-agonist (inhaled, short-acting)1,3
  • Daily corticosteroid (inhaled, low-dose)

Preferred reliever3

  • As needed corticosteroid (inhaled, low-dose) plus Formoterol2

Other reliever option

  • As needed beta2-agonist (inhaled, short-acting)
Step 2

Preferred Controller 

  • Daily corticosteroid (inhaled, low-dose)

Other controller options:

  • Leukotriene modifier
  • Intermittent corticosteroid (inhaled) 

Reliever

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

Preferred Controller  

  • Daily corticosteroid (inhaled, low-dose)
  • As needed corticosteroid (inhaled, low-dose) plus Formoterol1,2

Other controller options (any of the following):

  • Leukotriene modifier 
  • Corticosteroid (inhaled, low-dose) if taking beta2-agonist (inhaled, short-acting)1,3
  • Daily corticosteroid (inhaled, low-dose) plus as-needed beta2-agonist (inhaled, short-acting)2

Preferred reliever and other reliever option same as Step 1
Step 3 Preferred Controller
  • Corticosteroid (inhaled, double low-dose)

Other controller options:

  • Corticosteroid (inhaled, low-dose) plus leukotriene modifier5

Reliever

  • As needed beta2-agonist (inhaled, short-acting)6

Preferred Controller 

  • Corticosteroid (inhaled, low-dose) plus beta2-agonist (inhaled, long-acting)2
  • Corticosteroid (inhaled, medium-dose)4

Other controller options (any one of the following):

  • Corticosteroid (inhaled, medium-dose)2
  • Corticosteroid (inhaled, low-dose) plus leukotriene modifier

Preferred reliever and other reliever option same as Step 17
Step 4
  • Continue controller treatment
  • Specialist referral

Other controller options

  • Any of the following 
    • Add leukotriene modifier
    • Increase corticosteroid (inhaled) frequency
    • Add intermittent corticosteroid (inhaled)

Reliever

  • As needed beta2-agonist (short-acting) 

Preferred Controller

  • Corticosteroid (inhaled, medium-dose) plus beta2-agonist (inhaled, long-acting)5

Other controller options (any of the following):

  • Corticosteroid (inhaled, high-dose)
    • Plus beta2-agonist (inhaled, long-acting)4
  • Add-on Tiotropium bromide
  • Add-on leukotriene modifier

Preferred reliever and other reliever option same as Step 17
Step 58 N/A

Preferred Controller

  • Corticosteroid (inhaled, high-dose) plus beta2-agonist (inhaled, long-acting)2
  • Plus any of the following:
    • Tiotropium bromide
    • Anti-IgE (SC Omalizumab)
    • Anti-IL5 (SC Mepolizumab)
    • 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 and other reliever option same as Step 17

Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2019.
1Used as off-label therapy.
2Recommended option for patients ≥12 years of age.
3Low-dose inhaled corticosteroids may be used separately or in combination with short-acting inhaled beta2-agonists.
4Recommended option for patients 6-11 years of age.
5Expert referral is recommended for patients 6-11 years old when asthma is not controlled despite treatment with moderate-dose inhaled corticosteroids.
6Short-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).
7For patients previously given low-dose Budesonide/Formoterol or low-dose Beclomethasone dipropionate/Formoterol combination as maintenance and reliever regimen.
8Refer patients for phenotypic assessment.
9Contraindicated in patients <12 years of age.
 
 
 
 
 
 
 
 
                                           

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 and cost
Step Down
  • Once control is achieved and maintained for ≥3 months, gradual step-wise reduction in treatment may be attempted
  • Not applicable for patients at risk of exacerbations or persistent and fixed airflow limitation
  • Patients currently on inhaled corticosteroids:
    • Consider reducing dose by 25-50% at 2-3 months interval
    • If given with long-acting beta2-agonist and add-on agents, specialist referral is advised
  • Patients adequately controlled by low-dose inhaled corticosteroid or a leukotriene modifier:
    • Inhaled low-dose corticosteroids may be reduced to once-daily dosing
    • May shift to as-needed low-dose inhaled corticosteroid-Formoterol therapy
    • Addition of leukotriene modifiers may be considered when stepping down inhaled corticosteroids dose
    • Discontinuation of inhaled corticosteroid therapy in adolescents is not advised
  • In patients ≥12 years on inhaled corticosteroid-Formoterol combination therapy: Reduce maintenance inhaled corticosteroid-Formoterol therapy from medium-dose to low-dose or low-dose to once-daily dose and continue as-needed low-dose corticosteroid-Formoterol reliever regimen
Step Up
  • Consider step-up if control is not maintained (review patient medication techniques, compliance and 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 and removal of modifiable risk factors
  • Short-term step-up of 1-2 weeks 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 reliever

  • For children who have infrequent viral wheezing episodes and no or few interval symptoms, use of inhaled short-acting beta2-agonist is recommended for relief of 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 initial controller plus as-needed reliever 

  • For patients who require controller medications everyday in order to maintain control of their asthma
  • For children whose symptom pattern is consistent with asthma, and asthma symptoms are inadequately controlled or with ≥3 exacerbations/year
  • For children whose symptom pattern are inconsistent with asthma but with frequent wheezing episodes requiring reliever medication
  • May be used as initial therapy for treatment-naive patients ≤5 years old to control asthma 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 after initial treatment with daily inhaled corticosteroids
  • It should be given for at least 3 months to achieve good asthma control
  • Leukotriene modifiers may reduce symptoms and oral corticosteroid use in pediatric patients with persistent asthma
  • Use of daily low-dose inhaled corticosteroid with long-acting beta2-agonist as initial maintenance controller treatment is an option for patients ≥12 years given controller medications for the first time

Step 3 -Use of additional controller, plus as-needed reliever and expert referral

  • Before stepping up, re-confirm asthma diagnosis, check inhaler technique and compliance to medications and 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
  • Moderate-dose inhaled corticosteroid is preferred
  • Addition of oral leukotriene modifiers to low-dose corticosteroids may be considered

Step 4 -Daily controller and reliever therapy continued and expert referral

  • Reassess inhaler technique, medication adherence, trigger factors and reinvestigate diagnosis
  • If symptom control is still not achieved, may consider increasing the dose of inhaled corticosteroid until improvement is seen 
  • Consider expert referral if increasing the dose of inhaled corticosteroids fails or if symptom control remains poor and/or flare-ups persist
  • Add-on therapy with the following until symptom control is achieved: Oral leukotriene modifiers, long-acting inhaled beta2-agonist in combination with inhaled corticosteroid, Theophylline, or low-dose oral corticosteroid
    • May add intermittent inhaled corticosteroid to daily corticosteroid dose if main concern is exacerbation
    • Tiotropium by mist inhaler is only to be given to patients ≥6 years old with a history of exacerbations
    • Routine use of Theophylline as a controller is not recommended and may only be considered as an add-on therapy until asthma control is achieved if approved by a specialist
  • For patients ≥6 years old, being considered for high-dose inhaled corticosteroids, advise should be given about the increased risk for side effects and should be referred for expert assessment

Step 5 -Add-on treatment and expert referral

  • For patients ≥6 years old, Step 5 is recommended 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 ≥6 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, and anti-IL5 receptor Benralizumab in patients ≥12 years of age with severe uncontrolled eosinophilic asthma despite adherence to step 4 regimen
    • Add-on anti-IL4α receptor subcutaneous Dupilumab in patients ≥12 years of age with severe type 2 asthma or those on maintenance oral corticosteroid

Controller Medications

Preferred Therapy

  • Corticosteroids (Inhaled)
    • These are the most effective anti-inflammatory medications used for asthma and 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 and symptoms, reduces exacerbations, decreases need of short-acting beta2-agonists, achieves faster clinical control of asthma, and 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 and/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 and 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, and reduced number of exacerbations
  • Beta2-Agonist (Oral, Long-acting)
    • May be considered as an alternative add-on therapy and should always be given with inhaled corticosteroids
    • Only used on rare occasions when more bronchodilation is needed
    • Less effective than inhaled beta2-agonists and 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 and 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)
    • Treatment option for patients ≥12 years of age 
    • Reduces asthma symptoms and exacerbations, and 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 and Benralizumab in patients ≥12 years of age
    • Add-on Dupilumab may be considered in patients ≥12 years old with severe asthma and atopic dermatitis
    • Use of Reslizumab in patients <18 years of age with 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

  • Beta2-Agonists (Inhaled, Short-Acting)
    • Preferred reliever for patients <12 years of age; alternative reliever to inhaled corticosteroid-Formoterol combination in patients ≥12 years of age 
    • Most effective bronchodilator
    • Agents of choice for relief of bronchoconstriction during acute episodes of asthma and 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
  • Corticosteroids (Inhaled) with Formoterol
    • Preferred reliever for patients ≥12 years of age
    • Combination of steroid with Formoterol is preferred for patients previously given Budesonide-Formoterol or Beclometasone-Formoterol maintenance and 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 and lower lung function with short-acting inhaled beta2-agonist monotherapy

Alternative Therapy

  • 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 and 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 and gastrointestinal (GI) symptoms
  • May reduce symptoms, medication use, improve allergen-specific and non-specific airway hyperresponsiveness and can possibly prevent asthma development in children with allergic rhinoconjunctivitis
  • Benefits must be weighed against adverse effects and inconvenience of length of therapy
  • Efficacy of extracts or regimens based on clinical trials should be put into consideration before initiating therapy

Difficult-to-treat Asthma

  • Defined as asthma with persistent symptoms and/or exacerbations despite adherence to high-dose asthma regimens (eg Step 4-5 of the management plan for long-term asthma, high-dose inhaled corticosteroids in adults or medium-dose inhaled corticosteroids in children with a long-acting inhaled beta2-agonist or leukotriene modifier, continuous/frequent therapy with oral corticosteroids)
  • Risk factors include: Incorrect inhaler technique, poor adherence, comorbidities, exacerbation triggers, over-use of a long-acting inhaled beta2-agonist, psychosocial factors, adverse effects of medications
  • Steps to optimize management:
    • Check, review, correct and demonstrate inhaler technique every visit
    • Confirm if patient has a written asthma action plan and confirm if the patient understands what is included
    • Treat comorbidities and modifiable risk factors
    • Consider lifestyle modifications, avoidance of triggers and other non-pharmacologic treatments
    • Consider the following if not previously given: Nonbiologic therapies (eg Tiotropium bromide, Azithromycin, long-acting beta2-agonist), biologic therapies (eg Mepolizumab, Dupilumab, Benralizumab, etc), high-dose inhaled corticosteroids
  • Advise patient to follow-up after 3-6 months to assess patient's response to treatment changes
    • Referral to a specialist or to a severe asthma clinic is recommended if asthma is still with uncontrolled even with modifications and optimization of treatment
    • If with uncontrolled symptoms and/or exacerbations after treatment step-down, return previous regimen and refer to a specialist or to a severe asthma clinic
  • Assess patient's inflammatory phenotype and considered add-on biologic treatments once identified
    • Review patient response after 3-4 months

Preferred Inhalation Devices

PREFERRED INHALATION DEVICES 
 Age  Device
 0-3 years Preferred: Pressurized metered-dose inhaler plus dedicated spacer with face mask
Alternate: Nebulizer with face mask
 4-5 years Preferred: Pressurized metered-dose inhaler plus dedicated spacer with mouthpiece
Alternate: Pressurized metered-dose inhaler plus dedicated spacer with face mask or nebulizer with mouthpiece or face mask
Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2019. p145.

Treatment of Acute Exacerbations in Primary Care

  • Treatment of patients with mild/moderate asthma exacerbation and PEF >50% predicted/best:
    • Salbutamol 2-10 puffs depending on age every 20 minutes for 1 hour
    • Consider Prednisolone
    • Administer O2
  • Treatment of patients with severe/life-threatening asthma exacerbation and PEF <50% predicted/best:
    • Transport to emergency department
    • While waiting, administer:
      • Salbutamol 6-10 puffs every 20 minutes as needed
      • O2 therapy 
      • Oral/IV Prednisolone
      • Ipratropium bromide
  • Dose of Salbutamol should be based on patient's age:
    • ≥6 years old: 4-10 puffs by pMDI with spacer and mask or mouthpiece
    • ≤5 years old: 2 puffs (100 mcg/puff) by pMDI with spacer and mask or mouthpiece, or 2.5 mg by air-driven nebulizer or oxygen-driven nebulizer if with low SaO2
      • If unresponsive to initial dose after 1 hour, may give 2-6 more puffs 20 minutes after the 1st dose and may repeat at 20-minute intervals for 1 hour
  • In patients with poor response or worsening condition after 1st-line treatment, continue therapy while arranging hospital admission

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 with caution in patients with prostatic hyperplasia, patients predisposed to narrow-angle glaucoma, bladder neck obstruction, myasthenia gravis
  • Avoid contact of eyes with inhalation solution
  • 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 and throat irritation, paradoxical bronchospasm); Other effect (fine skeletal muscle tremor)
  • Potentially severe hypokalemia may result especially in acute severe asthma
  • Orciprenaline is less selective for beta2-receptors and therefore, side effects may be more common
Special Instructions
  • Use with caution in patients with 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 solution with 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 and throat irritation, paradoxical bronchospasm); Other effect (fine skeletal muscle tremor)
  • Potentially severe hypokalemia may result especially in acute severe asthma
Special Instructions
  • Use with caution in patients with 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 and 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 and therefore side effects may be more common
Special Instructions
  • Use with caution in patients with 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 with 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 especially in susceptible patients, headache, sleep disturbances, agitation, hyperactivity and restlessness
  • Potentially severe hypokalemia may result especially 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 with caution in patients with 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 mcg2
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 and 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 and osteoporotic fractures
  • Risk of systemic effects will depend on dose, potency of the corticosteroid, absorption from the gut, delivery system, the use of spacers and the drug’s pharmacokinetics
Special Instructions
  • Local effects may be minimized by using a spacer, gargling and spitting out with water, or gargling with 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 mcg3
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 and 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 with mild severity of asthma

Childn 6-11 yr:
Low dose: 80 mcg
Medium dose: >80-160 mcg
High dose: >160 mcg

Childn >12 yr and 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 and Adults:
Low dose: 100 mcg
High dose: 200 mcg
Fluticasone propionate 50, 125, 250 mcg/puff MDI

Childn <5 yr:
Low dose: 50 mcg4 
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 and 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 furoate 50, 100, 200 mcg/dose for inhalation unit dose

Childn <5 yr:
Low dose: 110 mcg4 

Childn 6-11 yr:
Low dose: 110 mcg 
Medium dose: ≥220-<440 mcg
High dose: ≥440 mcg

Childn >12 yr and Adults:
Low dose: 110-220 mcg
Medium dose: >220-440 mcg
High dose: >440 mcg

Triamcinolone acetonide 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 and Adults:
Low dose: 400-1000 mcg
Medium dose: >1000-2000 mcg
High dose: >2000 mcg

1Corticosteroids combined with bronchodilators are available. Please see the latest MIMS for specific formulations.
2Ages ≥5 years
3Ages ≥1 year
4Ages ≥4 years
Modified from: Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: Updated 2019. p48,144.


CORTICOSTEROIDS (SYSTEMIC)
Drug Dosage Remarks
Dexamethasone Childn: 0.08-0.3 mg/kg/day IV/IM, divided 6-12 hrly
 Adverse Reactions
  • CNS effects (excessive mental stimulation, insomnia and psychic disturbances); CV effect (tachycardia); Other effects (increased appetite, weight 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 and 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, weight gain, DM, skin thinning leading to striae and easy bruising, cataracts, glaucoma
Special Instructions
  • Should be taken with 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 AND 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 effects (N/V, diarrhea); Other effects (headache, polyuria, fatigue)
Special Instruction
  • Should not be taken in an empty stomach
  • Use with caution in patients with 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 with caution in patients with 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 effects (GI disturbances, N/V); Hypersensitivity reactions (bronchospasm, rashes); Other effect (hypotension)
Special Instruction
  • Use with caution in patients with 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 with caution in patients with 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 with caution in children <2 years old and in patients with persistent or chronic cough
Lagundi (Vitex negundo) 15 mg/kg PO 8 hrly Adverse Reactions
  • GI effects (N/V, diarrhea); Dermatologic effect (rash)
Special Instruction
  • Use with caution in patients with 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 and reduce to 1 puff 6 hrly once asthma has been stabilized		 Adverse Reactions
  • Resp effects (transient bronchospasm, cough and irritation of throat, rarely, severe bronchospasm, angioedema, laryngeal edema and 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 with hepatic impairment/disease
  • Monitor liver enzymes before and 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 and edema, systemic eosinophilia consistent with Churg-Strauss disease
Special Instructions
  • Should not be used for acute asthma attacks
  • Zafirlukast: Avoid in patients with 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, weight 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 with increased risk of adverse effects including lethal adverse reactions
Special Instructions
  • Use with caution in patients with peptic ulcer, hyperthyroidism, hypertension, cardiac arrhythmias or other CV disease, epilepsy, heart failure, hepatic dysfunction, acute febrile illness, in neonates
  • Many drug interactions occur with 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 with increased risk of adverse effects including lethal adverse reactions
Special Instructions
  • Administer IV inj very slowly to prevent dangerous CNS and CV side effects
  • Use with caution in patients with 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 6-11 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
Dose depends on pretreatment IgE level and body weight		 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 with severe hypersensitivity to the drug and in children <6 years old
  • Corticosteroids should be tapered gradually
  • Use with 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 with caution in patients with 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 with caution in patients with 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 with caution in patients with 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 with autoimmune disease, cardiopulmonary insufficiency, conditions with compromised immunity, active TB, rheumatic disease
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