Side Effects of Leukotriene Blocking Agents
Leukotriene modifiers are generally considered safe medications with no specific adverse effects identified for montelukast, though rare but serious neuropsychiatric events and hepatotoxicity have been reported with certain agents in this class. 1
Safety Profile by Agent Type
Leukotriene Receptor Antagonists (LTRAs)
Montelukast:
- No specific adverse effects have been identified in the majority of patients 1
- Rare cases of Churg-Strauss syndrome have occurred, though the association remains unclear 1
- The FDA has issued warnings about serious neuropsychiatric events, including suicidal thoughts or actions, requiring monitoring for unusual behavioral or mood changes 2
- Visual hallucinations have been reported in pediatric patients, with symptoms resolving within 48 hours of discontinuation 3
- The drug is recognized for its exceptional safety profile and ease of administration 4
Zafirlukast:
- Postmarketing surveillance has documented cases of reversible hepatitis and, rarely, irreversible hepatic failure resulting in death and liver transplantation 1
- This hepatotoxicity risk distinguishes zafirlukast from montelukast in terms of safety considerations 1
5-Lipoxygenase Inhibitors
Zileuton:
- Elevation of liver enzymes has been reported as the primary concern 1
- Limited case reports document reversible hepatitis and hyperbilirubinemia 1
- The drug is contraindicated in patients with active liver disease or persistent ALT elevations ≥3 times the upper limit of normal 5
- Dosing adjustment is not necessary for renal impairment or hemodialysis patients 5
Clinical Context and Comparative Safety
The safety advantage of leukotriene modifiers is their primary clinical benefit, particularly when compared to other asthma medications 1. These agents demonstrate both anti-inflammatory and bronchodilatory effects with minimal systemic adverse effects 1.
Common Pitfalls to Avoid:
- Do not overlook neuropsychiatric monitoring: All patients, especially children and adolescents starting montelukast, require surveillance for mood or behavioral changes 2
- Hepatic monitoring is essential for zafirlukast and zileuton: Unlike montelukast, these agents require liver function monitoring due to documented hepatotoxicity risk 1, 5
- Distinguish between agent-specific risks: The safety profiles differ significantly between montelukast (neuropsychiatric), zafirlukast (hepatic), and zileuton (hepatic) 1
Mechanism-Related Considerations
Leukotrienes are potent proinflammatory mediators that induce bronchoconstriction, increase vascular permeability, and promote leukocyte migration 6, 7. Blocking these pathways through receptor antagonism or synthesis inhibition provides therapeutic benefit in asthma and allergic conditions 4, 8. The generally favorable safety profile reflects the targeted nature of leukotriene pathway inhibition, though rare idiosyncratic reactions can occur 1.