Can montelukast (leukotriene receptor antagonist) cause pedal edema?

Montelukast and Pedal Edema

Montelukast has not been established as a cause of pedal edema, and there is conflicting evidence regarding its association with various adverse events. 1

Evidence on Montelukast and Edema

• The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) mentions that various neuropsychiatric events have been reported as adverse events of anti-leukotrienes, but the evidence of this association is conflicting 1
• There is no specific mention of pedal edema as a known side effect of montelukast in the available guidelines 1
• While calcium channel blockers are well-known to cause pedal edema, leukotriene receptor antagonists like montelukast are not typically associated with this adverse effect 2

Known Adverse Effects of Montelukast

• The most commonly reported adverse effects of montelukast include neuropsychiatric events, though the evidence for this association remains conflicting 1, 3
• There have been rare case reports of angioedema associated with montelukast use, but this differs from pedal edema in pathophysiology and presentation 4
• Churg-Strauss syndrome has been reported in patients receiving montelukast, though this is thought to be related to unmasking of an underlying vasculitic syndrome rather than a direct drug effect 5

Potential Mechanisms

• Montelukast is a leukotriene receptor antagonist that interferes with molecular signaling pathways produced by leukotrienes 6
• Some studies suggest montelukast may actually have protective effects against certain types of edema through its anti-inflammatory properties 7
• In experimental models, montelukast has shown protective effects against reperfusion injury and associated edema in skeletal muscle 7

Clinical Implications

• Single-dose exposures of montelukast up to 445 mg are rarely associated with any adverse events in children aged 5-17 years 8
• When evaluating a patient with pedal edema who is taking montelukast, clinicians should consider other more common causes of edema before attributing it to montelukast 2
• The EPOS2020 steering group does not recommend montelukast for chronic rhinosinusitis unless in situations where patients do not tolerate nasal corticosteroids, but this recommendation is not related to edema concerns 1

Management Approach

• If pedal edema develops in a patient taking montelukast, consider other common causes such as venous insufficiency, heart failure, renal disease, or other medications 2
• A trial of montelukast discontinuation could be considered if no other cause is identified, with monitoring for resolution of edema 4
• If montelukast is being used for asthma or allergic rhinitis and needs to be discontinued, appropriate alternative therapy should be instituted 1