Leukotrienes are inflammatory substances in the body that produce allergy-like effects. Aspirin Exacerbated Respiratory Disease (AERD, Samter's Triad) patients have been found to produce high levels of leukotrienes, especially after ingestion of aspirin or NSAIDs. These substances contribute to both asthma and sinus symptoms in AERD. It is recommended that AERD patients be prescribed a leukotriene modifier regardless of the severity of their asthma. 

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Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) are often helpful in managing the symptoms of AERD. These drugs come in tablet form and work by blocking or altering the action of leukotrienes. In addition to reducing the severity of asthma, leukotriene modifiers may have benefit in the treatment of nasal polyps.

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Singulair (montelukast) is usually one of the first drugs prescribed after an AERD diagnosis is made. Singulair has also been shown to reduce the severity of reactions during aspirin desensitization. Another leukotriene modifier, Zyflo (zileuton) appears to be even more effective. In a 2015 survey, 28% of AERD patients reported that Zileuton (Zyflo) was "extremely effective," but only 24% of patients had ever had it prescribed.  In comparison, only 15% of patients found Singulair "extremely effective," but almost 90% of patients had tried it. Zyflo is not prescribed as often for several reasons. First, it is necessary to have liver enzymes monitored while taking Zyflo. Also, it may not be safe for those with chronic liver disease or the elderly. Additionally, it is not recommended to consume alcohol while taking Zyflo. Despite this, Zyflo is a good option for many patients and should be considered when Singulair is ineffective. 

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Leukotriene modifiers are generally well-tolerated, but do have an array of potential side effects. Research has found that neuropsychiatric side effects such as depression, aggression, suicidal ideation, abnormal behavior and nightmares are commonly reported in both children and adults taking Singulair. For some patients, these side effects lessen after taking the medication for a few weeks. If you experience side effects that seem intolerable, be sure to talk to your doctor before stopping the medication.