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 GINA 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.
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.