Montelukast: Clinical Overview
Indications
Montelukast is FDA-approved for chronic asthma prophylaxis, exercise-induced bronchoconstriction (EIB), and allergic rhinitis, but it is not a first-line therapy for asthma and carries a significant FDA black box warning for neuropsychiatric adverse effects. 1
FDA-Approved Indications by Age:
- Asthma prophylaxis: Ages ≥6 months 1
- Exercise-induced bronchoconstriction: Ages ≥6 years (adolescents and adults) 2
- Perennial allergic rhinitis: Ages ≥6 months 1
- Seasonal allergic rhinitis: Ages ≥2 years 1
Clinical Positioning:
- Alternative therapy for mild persistent asthma when inhaled corticosteroids (ICS) cannot be used or compliance is problematic 1, 3
- Not recommended as monotherapy for moderate-to-severe persistent asthma; ICS are superior 1, 3
- Less effective than ICS for asthma control in children, with ICS showing a number needed to treat (NNT) of approximately 6.5 1, 3
- Inferior to long-acting beta-agonists (LABAs) when used as add-on therapy to ICS 3
- Do not use for acute asthma exacerbations or as rescue therapy 1, 3
Age-Specific Dosing
Infants (6-23 months):
- 4 mg oral granules once daily 1
Preschool children (2-5 years):
- 4 mg chewable tablet once daily 1
School-age children (6-14 years):
- 5 mg chewable tablet once daily 1, 4, 5
- This dose provides systemic exposure comparable to the adult 10 mg dose 4, 5
Adolescents and adults (≥15 years):
- 10 mg film-coated tablet once daily 5
- Selected based on flat dose-response curve; doses >10 mg provide no additional efficacy 1, 5
Administration:
- Can be taken at any time of day, though evening dosing is traditional practice 1
- Onset of action: 1-2 hours after oral administration, with maximum protection within 24 hours 2
- Clinical effect: Improvements typically observed by the second day of daily treatment 1
- Must be taken continuously daily to maintain efficacy; not for intermittent use 1
Contraindications
Montelukast has no absolute contraindications listed in FDA labeling, but the 2020 FDA black box warning establishes a strong relative contraindication in patients with pre-existing neuropsychiatric disorders. 2, 3
Relative Contraindications:
- History of neuropsychiatric disorders (depression, anxiety, suicidal ideation, behavioral disorders) 2, 3
- Active suicidal thoughts or behaviors 1, 3
- Severe mood disturbances 3
Clinical Decision Algorithm:
- Before prescribing to any patient, explicitly counsel about neuropsychiatric risks 1, 3
- Consider safer alternatives first (intranasal corticosteroids for allergic rhinitis, ICS for asthma) 1
- If prescribing despite risks, ensure close monitoring is feasible 3
- Avoid in patients with psychiatric history unless benefits clearly outweigh risks 3
Neuropsychiatric Adverse Effects
The FDA issued a black box warning in March 2020 for serious neuropsychiatric events with montelukast, making mandatory surveillance at every clinical encounter essential. 2, 1, 3
Specific Neuropsychiatric Events:
- Suicidal thoughts and actions 1, 3
- Depression 1, 3
- Anxiety (11% increased risk compared to placebo) 6
- Sleep disturbances 1
- Behavioral changes (agitation, aggressive behavior) 1, 3
- Mood disturbances 3
Mandatory Monitoring Protocol:
- Counsel parents/patients explicitly about neuropsychiatric risks before initiating therapy 1
- Monitor for unusual behavioral or mood changes, particularly in the first weeks of therapy 1
- Assess at every clinical encounter for depression, anxiety, agitation, aggressive behavior, and suicidal ideation 3
- Discontinue immediately if any neuropsychiatric symptoms develop 3
Common Non-Psychiatric Adverse Events (Infants 6-23 months, ≥2% frequency):
Hepatic Monitoring
Monitor liver enzymes periodically during long-term therapy and instruct patients to discontinue use if signs of liver dysfunction develop. 3
Efficacy Considerations
Exercise-Induced Bronchoconstriction:
- Attenuates EIB in approximately 50% of patients (30-80% attenuation range) 2
- Does not lead to tolerance with long-term use, unlike beta-agonists 2
- Provides incomplete protection; most patients do not experience complete protection 2
- Not effective for reversing airway obstruction 2
Asthma Control:
- Variable response: 17% respond to both montelukast and ICS, 23% to ICS alone, 5% to montelukast alone, and 55% to neither 2
- Higher exhaled nitric oxide (eNO) levels predict better differential response to ICS over montelukast 2
- ICS improve clinical outcomes significantly more than montelukast (asthma control days, albuterol use, lung function) 2
Combination Therapy:
- Adding montelukast to ICS shows a trend toward improved lung function and allows 50% steroid dose reduction without loss of efficacy 3
- ICS + LABA combinations are preferred over ICS + montelukast at Steps 3-4 based on superior efficacy 3
- Montelukast as add-on to ICS + LABA is an alternative option (not preferred) for Step 4-5 care, with modest clinical benefits 3
Treatment Duration and Reassessment
- Reassess asthma control every 2-6 weeks after initiating or adjusting therapy 3
- Consider stepping down if well-controlled for ≥3 consecutive months 2, 3
- Discontinue if neuropsychiatric adverse events emerge 3
Common Pitfalls to Avoid
- Do not use for acute asthma exacerbations 1, 3
- Do not increase dose beyond recommended amounts; flat dose-response curve means no additional benefit 3
- Do not use as monotherapy when ICS therapy is appropriate and feasible 3
- Do not overlook neuropsychiatric monitoring even in stable patients 3
- Do not prescribe without counseling about black box warning 1, 3
Allergic Rhinitis: Positioning Relative to Other Therapies
Intranasal corticosteroids are strongly preferred over montelukast as first-line treatment for both seasonal and persistent allergic rhinitis. 1
- Oral H1-antihistamines are also preferred over montelukast for seasonal allergic rhinitis 1
- Conditional recommendation for montelukast in preschool children with persistent allergic rhinitis when first-line options are unsuitable 1
- Dual benefit: Montelukast may be advantageous in patients with both asthma and allergic rhinitis 1