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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: montelukast (mon te LOO kast)
Brand name(s): SINGULAIR
GENERIC: not available FAMILY: Leukotriene Inhibitors
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: zafirlukast (za fer LOO kast)
Brand name(s): ACCOLATE
GENERIC: not available FAMILY: Leukotriene Inhibitors
Find the drug label by searching at DailyMed.

Safety Warnings For This Drug [top]

FDA BLACK-BOX WARNING for montelukast (SINGULAIR)

WARNING: SERIOUS NEUROPSYCHIATRIC EVENTS

Serious neuropsychiatric (NP) events have been reported with the use of SINGULAIR. The types of events reported were highly variable, and included, but were not limited to, agitation, aggression, depression, sleep disturbances, and suicidal thoughts and behavior (including suicide). The mechanisms underlying NP events associated with SINGULAIR use are currently not well understood.

Because of the risk of NP events, the benefits of SINGULAIR may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies. Reserve use of SINGULAIR for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies. In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and risks before prescribing SINGULAIR.

Health care providers should discuss the benefits and risks of SINGULAIR with patients and caregivers when prescribing SINGULAIR. They should advise patients and/or caregivers to be alert for changes in behavior or new NP symptoms when taking SINGULAIR. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts and/or behavior occur, patients should be advised to discontinue SINGULAIR and contact a healthcare provider immediately.

Important Warnings in the Product Labeling for Montelukast and Zafirlukast

 

  • Do not use to treat acute asthma attacks.
  • Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking these drugs. These events include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, stuttering, hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, sleepwalking, suicidal thinking and behavior (including suicide), and tremor.
  • Uses of these drugs rarely has been associated a serious inflammatory conditions known as systemic eosinophilia, eosinophilic pneumonia, and Churg-Strauss syndrome. These condition often are treated with systemic (oral or injected) corticosteroids.
  • Cases of life-threatening liver failure have been reported in patients using zafirlukast.

 

Do not stop any asthma medication without first consulting your physician. Abruptly stopping a medication may result in acutely deteriorating asthma control.

Additional Precautions for Asthma

Avoid exposure to things that trigger your allergies or asthma, such as animals, bedding, chemicals, cosmetics, drugs, dust, mold, foods, pollens, or smoke. Wearing a mask reduces inhalation of drugs, pollens, and smoke.

Aspirin can trigger asthma in people who are aspirin-allergic, as can beta-blockers. Infections aggravate lung problems. During epidemics of respiratory illnesses, avoid crowded places and wash your hands frequently to help prevent infection. If you have asthma, get a flu vaccination.

Note: The information in this profile addresses the care of asthma that is not serious enough to need emergency treatment.

Facts About This Drug [top]

The Food and Drug Administration (FDA) approved montelukast (SINGULAIR) and zafirlukast (ACCOLATE) for the prevention and long-term treatment of asthma in patients aged one year and older and five years and older, respectively.[1],[2] These drugs are taken orally.

Montelukast also is approved for the treatment of seasonal allergic rhinitis (hay fever) — a collection of symptoms affecting the nose that are typically caused by inhaled allergens such as tree pollen — in adults and children...

The Food and Drug Administration (FDA) approved montelukast (SINGULAIR) and zafirlukast (ACCOLATE) for the prevention and long-term treatment of asthma in patients aged one year and older and five years and older, respectively.[1],[2] These drugs are taken orally.

Montelukast also is approved for the treatment of seasonal allergic rhinitis (hay fever) — a collection of symptoms affecting the nose that are typically caused by inhaled allergens such as tree pollen — in adults and children two years of age and older and perennial allergic rhinitis (a year-round allergic condition commonly caused by indoor allergens such as mold and pet dander) in patients six months of age and older.[1] It is additionally approved for the prevention of exercise-induced bronchoconstriction (narrowing of the airways) in patients 15 years of age and older.[3]

Montelukast and zafirlukast are members of the leukotriene inhibitor family of asthma drugs. Leukotrienes are chemicals produced by the immune system that can lead to bronchoconstriction, increased mucus production and inflammation. Leukotriene inhibitors work by blocking the function or preventing the production of these chemicals, which are thought to play a role in asthma and allergic rhinitis. However, clinical trials have shown that these drugs are less effective than other asthma drugs.[4]

Because montelukast and zafirlukast have only limited benefits, none of which are unique, but pose some unique risks, such as psychiatric adverse reactions, we have designated these drugs as Do Not Use since their approval.

The effectiveness of montelukast for treatment of asthma was assessed in several large preapproval randomized, double-blind clinical trials that compared this oral drug to use of a placebo or the inhaled corticosteroid beclomethasone (QVAR REDIHALER).[5] These trials, which together enrolled a few thousand subjects, overall showed that montelukast was better than placebo for improving measures of lung function and asthma symptoms. However, the trials also demonstrated that inhaled corticosteroids were superior to montelukast for treating asthma.

Similarly, approval of zafirlukast for treating asthma was based primarily on three trials that enrolled nearly 1,400 subjects.[2] These trials were randomized, double-blind, placebo-controlled and lasted 13 weeks. These trials showed that zafirlukast improved asthma symptoms and measures of lung function compared with placebo. However, a fourth trial that compared zafirlukast with inhaled cromolyn (generic only), another type of asthma drug, found that zafirlukast was no better than cromolyn in reducing rescue asthma inhaler use.

The evidence on the effectiveness of leukotriene inhibitors also was reviewed by the Cochrane Collaboration, an independent organization that examines published studies. The review looked at 65 randomized clinical trials that compared the safety and effectiveness of leukotriene inhibitors with those of inhaled corticosteroids for four weeks or longer in patients with asthma aged two years or older.[4] The review found that inhaled corticosteroids were superior to leukotriene inhibitors in improving lung function. It also found that compared with the use of inhaled corticosteroids, the use of leukotriene inhibitors was associated with an enhanced risk of exacerbations (worsening of asthma symptoms) that required systemic (oral or injectable) corticosteroids, more frequent hospital admissions for asthma exacerbations and an increased risk of withdrawal from the trials due to poor asthma control. The review concluded that inhaled corticosteroids should remain the first-choice drug in adults and children with persistent asthma.

Overall, montelukast is an unremarkable treatment for hay fever. Clinical trials of the leukotriene inhibitors have shown that when used alone, these drugs are inferior to inhaled steroids in preventing and treating asthma, and their use to help reduce exposure to steroids is questionable. Thus, the lack of a documented therapeutic advantage over current treatment and the chance of some serious adverse effects should rule out the use of these drugs.

Adverse effects

Particularly concerning, both montelukast and zafirlukast have been associated with a wide range of adverse neuropsychiatric effects. These reactions include aggression, agitation, anxiety, depression, nightmares, hallucinations, insomnia, attention or memory disturbances, and suicidal thinking or behavior, among many other behavioral abnormalities.[6],[1],[2],[7] Because of these adverse neuropsychiatric effects, the FDA in March 2020 required the addition of a black-box warning — the strongest warning that the agency can require — about these effects to the product labeling for montelukast.[8] The new warning advises that for allergic rhinitis, the drug should only be used by patients who are not treated effectively with or cannot tolerate other allergy medicines.

These drugs also have been linked to liver injury. Cases of life-threatening liver failure have been reported with zafirlukast use,[2] and the labeling for this drug includes a liver toxicity warning. Likewise, the labeling for montelukast indicates that postmarketing cases of hepatitis (inflammation of the liver) and other types of liver injury have been reported in patients using the drug.[1] Most of these cases occurred in patients who had underlying liver disease or risk factors for liver injury, such as alcohol use.

Both drugs also rarely can cause a condition known as systemic eosinophilia, which is characterized by a marked increase in a type of white blood cells called eosinophils in the blood and inflammation in organs such as the lungs or liver. Sometimes, this condition can develop into Churg-Strauss syndrome, a serious disorder in which blood vessels become inflamed, leading to restricted blood flow to vital organs and tissues.[9],[10]

Montelukast may cause severe hypersensitivity allergic reactions, including life-threatening anaphylaxis — a type of allergic reaction characterized by throat tightness, drop in blood pressure, swelling of the upper airways that impairs breathing, and hives.[10]

In addition to the aforementioned adverse events, zafirlukast can have a dangerous interaction with the blood thinner warfarin (COUMADIN, JANTOVEN). Studies have shown that concomitant use of zafirlukast with warfarin can increase blood levels of warfarin and, thus, increase the risk of bleeding.

last reviewed February 28, 2021