Leukotriene receptor antagonists
ATC code: R03DC03 (Montelukast)
Selective CysLT1 receptor antagonist. Blocks leukotriene D4 activity in the airways – a mediator responsible for bronchoconstriction, mucosal edema, mucus secretion, and eosinophil recruitment. Taken orally once daily.
First line
Approved for prophylaxis of exercise-induced bronchoconstriction. Taken 2 hours before exercise or regularly in the evening. An alternative to pre-exercise SABA for patients preferring oral administration. RCTs demonstrate a 40-50% reduction in post-exercise FEV1 decline.
Second line
Second-line for allergic rhinitis when antihistamines are insufficient. Less effective than intranasal corticosteroids. Per ARIA, may benefit patients with coexisting asthma and rhinitis – one drug addresses both conditions.
Adjunct
Add-on to ICS when asthma is uncontrolled at step 2. As add-on therapy, it is inferior to LABAs (formoterol, salmeterol) per meta-analyses. Preferred in patients with comorbid allergic rhinitis or aspirin-exacerbated respiratory disease, where the leukotriene component of inflammation is more prominent.
In children 6-14 years, montelukast may be considered an alternative to low-dose ICS when parents firmly refuse inhalers.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Montelukast is a leukotriene receptor antagonist. It is prescribed for asthma (as a first-line alternative) and allergic rhinitis ( 2024 guidelines). For shortness of breath or allergy prevention outside asthma or allergic rhinitis, montelukast is not used. In 2020 the added a boxed warning to the label about severe neuropsychiatric side effects: depression, anxiety, insomnia, nightmares, aggression, and suicidal thoughts and attempts. The FDA recommended avoiding montelukast for mild allergic rhinitis when other options are available (antihistamines, intranasal corticosteroids). If montelukast was prescribed for shortness of breath without confirmed asthma, consider seeking a second opinion, especially in children and adolescents.
1 pair found. Sorted from critical to minor.
Mechanism
No clinically significant direct interaction. Montelukast is metabolised by CYP2C8 and CYP3A4; amiodarone moderately inhibits CYP3A4. Montelukast AUC may rise slightly, without clinical consequences.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. In asthma with atrial fibrillation, the combination is standard.
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Boxed warning
FDA black box (2020): serious neuropsychiatric events including suicidal thoughts and actions, depression, agitation, aggression, and sleep disturbances, including in children. Prescribers must weigh benefits and risks. Patients and caregivers are instructed to seek immediate medical attention for behavioral or mood changes.
FDA category B. Animal studies showed no teratogenicity. Human data are limited but available registries have not identified increased malformation risk.
Montelukast is evaluated for the following indications with varying evidence strength: Exercise-induced bronchoconstriction (evidence tier A), Allergic rhinitis (evidence tier B), Asthma (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Montelukast (≥ 1 in 100): Headache, Abdominal pain, Diarrhea, Upper respiratory infections (in pediatric trials). See the Safety section for uncommon and serious reactions.
FDA category B. FDA category B. Animal studies showed no teratogenicity. Human data are limited but available registries have not identified increased malformation risk.
Compatible. Hale L3. Transfers into milk in small amounts; RID about 0.7-3%. Observational data do not document clinical problems in breastfed infants. The 2020 AEMPS alert on neuropsychiatric reactions (behavioural change, depression, self-harm ideation) refers to the patient taking the drug, not to infants exposed through milk. Mild infant irritability or sleep disturbance is possible but rare and usually self-limited.
Montelukast is contraindicated in: Hypersensitivity to montelukast or any component. Full list in the Safety section.
Compatible. Hale L3. Transfers into milk in small amounts; RID about 0.7-3%. Observational data do not document clinical problems in breastfed infants. The 2020 AEMPS alert on neuropsychiatric reactions (behavioural change, depression, self-harm ideation) refers to the patient taking the drug, not to infants exposed through milk. Mild infant irritability or sleep disturbance is possible but rare and usually self-limited.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
FDA black box (2020): serious neuropsychiatric events including suicidal thoughts and actions, depression, agitation, aggression, and sleep disturbances, including in children. Prescribers must weigh benefits and risks. Patients and caregivers are instructed to seek immediate medical attention for behavioral or mood changes.