Understanding Montelukast (Singulair)
Montelukast, commonly known by its brand name Singulair, is a prescription oral medication used for the long-term management of asthma and to relieve symptoms of allergic rhinitis (hay fever) [1.3.1, 1.3.6]. It belongs to a class of drugs called leukotriene receptor antagonists [1.3.2]. Leukotrienes are chemicals your body releases in response to allergens or during an asthma attack, causing inflammation, bronchoconstriction (tightening of the airways), and mucus production [1.3.6]. Montelukast works by blocking the action of these leukotrienes, which helps to reduce inflammation, relax smooth muscle in the lungs, and make breathing easier [1.3.2, 1.3.6].
It's approved for preventing asthma attacks in adults and children as young as one year old and for preventing exercise-induced bronchospasm in those aged six and older [1.5.1]. For allergic rhinitis, its use is often reserved for patients who have not responded to or cannot tolerate other treatments, due to its potential for side effects [1.4.3]. It is important to note that montelukast is a maintenance medication and should not be used to treat a sudden, acute asthma attack [1.3.3].
FDA Boxed Warning: Neuropsychiatric Events
In March 2020, the U.S. Food and Drug Administration (FDA) mandated a boxed warning, its most serious alert, for montelukast [1.4.2, 1.4.4]. This warning highlights the risk of serious mental health side effects. These neuropsychiatric events have been reported in patients with and without a pre-existing history of mental illness [1.5.1]. Reports include agitation, aggressive behavior, anxiety, depression, sleep disturbances (like vivid dreams and nightmares), hallucinations, and, in rare cases, suicidal thoughts and actions [1.4.3, 1.5.1]. The FDA advises that for patients with mild symptoms, particularly allergic rhinitis, the risks of montelukast may outweigh the benefits [1.4.1]. Patients and caregivers should immediately report any mood or behavior changes to their healthcare provider [1.4.3].
Major and Moderate Drug Interactions
While montelukast is considered to have a relatively safe profile, it is metabolized by enzymes in the liver, primarily CYP2C8, CYP2C9, and CYP3A4 [1.3.1, 1.7.3]. Therefore, other drugs that induce or inhibit these enzymes can alter the concentration of montelukast in the blood, affecting its efficacy or increasing the risk of side effects. Always inform your doctor and pharmacist of all medications, herbs, and supplements you are taking [1.2.5].
Medications That Decrease Montelukast's Effectiveness
Certain medications, known as enzyme inducers, can speed up the metabolism of montelukast, lowering its levels in the bloodstream and making it less effective [1.7.4]. If you are taking one of these medications, your doctor may need to monitor your asthma or allergy symptoms more closely [1.7.1].
- Phenobarbital, Primidone, and Phenytoin: These anticonvulsant medications, used to treat seizures, are known to decrease montelukast levels. Studies have shown that phenobarbital can reduce the systemic exposure (AUC) of montelukast by about 40% [1.2.2, 1.7.3].
- Rifampin: This antibiotic, primarily used to treat tuberculosis, is a potent enzyme inducer and can significantly reduce the effectiveness of montelukast [1.2.2, 1.2.5].
- Carbamazepine: Another anticonvulsant that can decrease the effectiveness of montelukast [1.2.5, 1.7.2].
- St. John's Wort: This herbal supplement, often used for depression, can also induce liver enzymes and may make montelukast less effective [1.2.3, 1.2.5].
Medications That Increase Montelukast Levels
Conversely, drugs that inhibit the CYP2C8 enzyme can slow down the metabolism of montelukast, leading to higher concentrations in the blood. This can increase the risk of montelukast-related side effects [1.6.1, 1.6.5].
- Gemfibrozil (Lopid): Used to treat high cholesterol, gemfibrozil is a potent inhibitor of CYP2C8. Taking gemfibrozil with montelukast can increase the blood concentration of montelukast by as much as 4.4-fold [1.6.3]. While a dose adjustment isn't always required, your doctor should monitor for potential side effects [1.6.3]. Increased side effects could include headache, stomach pain, or the more serious neuropsychiatric events mentioned in the boxed warning [1.6.1].
Other Considerations
- Prednisone: Generally, no direct interaction is found between montelukast and corticosteroids like prednisone [1.8.1]. They are often prescribed together. However, a rare case report described severe peripheral edema when both drugs were used together, which resolved when prednisone was stopped [1.8.3].
- Warfarin: Montelukast may make the blood thinner warfarin less effective [1.2.5]. If taken together, more frequent blood tests may be necessary to ensure the warfarin dosage is correct [1.2.5].
- Aspirin/NSAIDs: Patients with a known allergy or sensitivity to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) that worsens their asthma should continue to avoid these medications while taking montelukast [1.2.1].
Drug Interaction Comparison Table
| Interacting Drug | Drug Class | Effect on Montelukast | Clinical Management Recommendation |
|---|---|---|---|
| Phenobarbital [1.7.1] | Anticonvulsant | Decreases blood levels | Monitor for reduced effectiveness of montelukast. Doctor may consider alternatives. |
| Rifampin [1.2.5] | Antibiotic | Decreases blood levels | Monitor for reduced effectiveness. |
| Gemfibrozil [1.6.1, 1.6.3] | Cholesterol-lowering (Fibrate) | Increases blood levels (4.4-fold) | Monitor for increased side effects. Dose adjustment is not typically required but should be considered. |
| Carbamazepine [1.2.5] | Anticonvulsant | Decreases blood levels | Monitor for reduced montelukast efficacy. |
| St. John's Wort [1.2.5] | Herbal Supplement | Decreases blood levels | Inform your doctor; monitor for reduced effectiveness. |
| Warfarin [1.2.5] | Anticoagulant | May make warfarin less effective | More frequent blood monitoring may be needed to adjust warfarin dose. |
Conclusion
While montelukast is an effective medication for many people with asthma and allergies, it's essential to be aware of its potential interactions with other drugs and its significant boxed warning regarding mental health side effects. The most notable interactions involve medications that affect its metabolism in the liver, such as phenobarbital and gemfibrozil. Always maintain an open dialogue with your healthcare provider about all medications and supplements you are taking to ensure the safe and effective use of montelukast. Never start or stop a medication without consulting your doctor.
For more information from the manufacturer, you can visit the official Singulair® website.
