1. SINGULAIR HISTORY
How was Singulair discovered?

Singulair is a product of Merck & Co.

Singulair received U.S. Food and Drug Administration (FDA) approval in February 1998.

Note: World-drugs.net sells generic version of Singulair

2.SINGULAIR FACTS

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.

Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories.

Merck & Co. aims at helping to improve the health and well-being of people everywhere by discovering, developing and bringing to market breakthrough medicines. Their priorities are focused on turning cutting-edge science into breakthrough medicines that address significant unmet needs, and thus have the potential to become important medical advances.  

3.ABOUT SINGULAIR MEDICATION

Singulair is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies.

Singulair blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1, thus inhibiting bronchoconstriction.

What Is Asthma?
Asthma (AZ-muh) is a chronic disease that affects your airways, which are the tubes that carry air in and out of your lungs.

In asthma the inside walls of your airways get inflamed (swollen). The inflammation makes the airways very sensitive, and they tend to react strongly to things to which you are allergic or find irritating. When the airways react, they get narrower and less air flows through to your lung tissues. This causes symptoms like wheezing (a whistling sound when you breathe), coughing, chest tightness, and trouble breathing.

Asthma cannot be cured, but for most patients it can be controlled so that you have only minimal and infrequent symptoms and you can live an active life. So, if you have asthma, taking care of it is an important part of your life. Controlling your asthma means staying away from things that bother your airways and taking medicines as directed by your doctor. By controlling your asthma every day, you can prevent serious symptoms and take part in all activities.

When you experience a worsening of your asthma symptoms, it is called an asthma episode or attack. In an asthma attack, muscles around the airways tighten up, making the airway openings narrower so less air can flow through. Inflammation increases and the airways become more swollen and narrow. Cells in the airways also make more mucus than usual. This extra mucus also narrows the airways. These changes cause the symptoms of asthma and make it harder to breathe. Asthma attacks are not all the same-some are worse than others. In a severe asthma attack, the airways can close so much that not enough oxygen gets to vital organs. This condition is a medical emergency. People can die from severe asthma attacks.

What Causes Asthma?
It is not clear exactly what makes the airways of people with asthma inflamed in the first place. Your inflamed airways may be due to a combination of things. We know that if other people in your family have asthma, you are more likely to develop it. New research suggests exposures early in your life (like tobacco smoke, infections, and some allergens) may be important.

What Causes Asthma Attacks?
There are things that can make asthma symptoms worse and lead to asthma attacks. Some of the more common things that can worsen your asthma symptoms are exercise, allergens, irritants, and viral infections. Some people only have asthma with exercise or a viral infection. The lists below give some examples of things that can worsen asthma symptoms.

Allergens

• Animal dander (from the skin, hair, or feathers of animals)

• Dust mites (contained in house dust)

• Cockroaches
• Pollen from trees and grass

• Mold (indoor and outdoor)

Irritants

• Cigarette smoke
• Air pollution
• Cold air or changes in weather
• Strong odors from painting or cooking
• Scented products
• Strong emotional expression (including crying or laughing hard), and stress

Others

• Medications such as aspirin and beta-blockers
• Sulfites in food (dried fruit) or beverages (wine)
• A condition called gastroesophageal reflux disease (GERD) that causes heartburn and can worsen asthma symptoms, especially at night.
• Irritants or allergens that you may be exposed to at your work such as special chemicals or dusts
• Infections.

This is not a complete list of all the things that can worsen asthma. People can have trouble with one or more of these. It is important for you to learn which ones are problems for you. Your doctor can help you identify which things affect your asthma and ways to avoid them. 

Who Gets Asthma?
In the United States, about 15 million people have asthma. Nearly 5 million of them are children. Asthma is closely linked to allergies. Most, but not all, people with asthma have allergies. Children with a family history of allergy and asthma are more likely to have asthma.

Although asthma affects people of all ages, it often starts in childhood and is more common in children than adults. More boys have asthma than girls, but in adulthood, more women have asthma than men.

Although asthma is a problem among all races, blacks have more asthma attacks and are more likely than whites to be hospitalized for asthma attacks and to die from asthma. 

What Are the Symptoms of Asthma?

Common asthma symptoms include:

• Coughing. Coughing from asthma is often worse at night or early in the morning, making it hard to sleep.
• Wheezing. Wheezing is a whistling or squeaky sound when you breathe.
• Chest tightness. This can feel like something is squeezing or sitting on your chest.
• Shortness of breath. Some people say they can't catch their breath, or they feel breathless or out of breath. You may feel like you can't get enough air in or out of your lungs.
• Faster breathing or noisy breathing.

People with asthma may have:

• Wheezing when they have a cold or other illness
• Frequent coughing, especially at night (sometimes this is the only sign of asthma in a child)
• Asthma symptoms brought on by exercises such as running, biking, or other brisk activity, especially during cold weather
• Coughing or wheezing brought on by prolonged crying or laughing
• Coughing or wheezing when they are near an allergen or irritant
• If you notice that you or your child has these symptoms, talk to your doctor or your child's doctor.

Not all people have these symptoms, and symptoms may vary from one asthma attack to another. Symptoms can differ in how severe they are: sometimes symptoms can be mildly annoying; other times they can be serious enough to make you stop what you are doing, and sometimes symptoms can be so serious that they are life threatening. Symptoms also differ in how often they occur. Some people with asthma only have symptoms once every few months, others have symptoms every week, and still other people have symptoms every day. With proper treatment, however, most people with asthma can expect to have minimal or no symptoms. 

How Is Asthma Diagnosed?

Some things your doctor will ask about include:

• Periods of coughing, wheezing, shortness of breath, or chest tightness that come on suddenly or occur often or seem to happen during certain times of year or season
• Colds that seem to "go to the chest" or take more than 10 days to get over
• Medicines you may have used to help your breathing
• Your family history of asthma and allergies
• What things seem to cause asthma symptoms or make them worse

Your doctor will listen to your breathing and look for signs of asthma or allergies.

Your doctor will probably use a device called a spirometer to check your airways. This test is called spirometry. The test measures how much air and how fast you can blow air out of your lungs after taking a deep breath. The results will be lower than normal if your airways are inflamed and narrowed, as in asthma, or if the muscles around your airways have tightened up. As part of the test, your doctor may give you a medication that helps open up narrowed airways to see if it changes or improves your test results. Spirometry is also used to check your asthma over time to see how you are doing.

If your spirometry results are normal but you have asthma symptoms, your doctor will probably want you to have other tests to see what else could be causing your symptoms. One test commonly used is a bronchial challenge test. A substance such as methacholine, which causes narrowing of the airways in asthma, is inhaled. The effect is measured by spirometry. Children under age 5 usually cannot use a spirometer successfully. If spirometry cannot be used, the doctor may decide to try medication for a while to see if the child's symptoms get better.

Besides spirometry, your doctor may also recommend that you have:

• Allergy testing to find out if and what allergens affect you
• A test that uses a hand-held peak flow meter every day for 1-2 weeks to check your breathing (a peak flow meter is a device that shows how well you are breathing)
• A test to see how your airways react to exercise
• Tests to see if you have gastroesophageal reflux disease (GERD)
• Test to see if you have sinus disease.

Other tests, such as a chest x-ray or an electrocardiogram, may be needed to find out if a foreign object, or other lung diseases or heart disease could be causing asthma symptoms. A correct diagnosis is important because asthma is treated differently from other diseases with similar symptoms.

Depending on the results of your physical exam, medical history, and lung function tests, your doctor can determine how severe your asthma is. This is important because your asthma severity will determine how your asthma should be treated. A general way to classify severity is to consider how often a person has symptoms when that person is not taking any medicine or when his or her asthma is not well controlled. Based on symptoms, the four levels of asthma severity classification are:

• Mild Intermittent (comes and goes)-- when your asthma is not well controlled, you have asthma symptoms twice a week or less, and you are bothered by symptoms at night twice a month or less.
• Mild persistent asthma --when your asthma is not well controlled, you have asthma symptoms more than twice a week, but no more than once in a single day. You are bothered by symptoms at night more than twice a month. You may have asthma attacks that affect your activity.
• Moderate persistent asthma --when your asthma is not well controlled, you have asthma symptoms every day, and you are bothered by nighttime symptoms more than once a week. asthma attacks may affect your activity.
• Severe persistent asthma --when your asthma is not well controlled, you have symptoms throughout the day on most days, and you are bothered by nighttime symptoms often. In severe asthma, your physical activity is likely to be limited.

Anyone with asthma can have a severe attack-even those who have intermittent or mild persistent asthma. 

How is Asthma Treated?
You and your doctor together can decide about your treatment goals and what you need to do to control your asthma. Asthma treatment includes:

• Avoiding things that bring on your asthma symptoms or make symptoms worse. Doing so can reduce the amount of medicine you need to control your asthma.
• Allergy medicine and allergy shots in some cases may help your asthma.

With proper treatment, you should ideally have these results:

• Your asthma should be controlled.
• You should be free of asthma symptoms.
• You should have fewer attacks.
• You should need to use short-acting bronchodilators less often.
• You should be able to do normal activities without having symptoms.

Your doctor will fill out an action plan for your asthma. Your action plan will tell you what medications you should take and other things you should do to keep your asthma under control.

Medications for asthma. There are two main types of medicines for asthma:

1. Quick Relief medicines give rapid, short-term treatment and are taken when you have worsening asthma symptoms that can lead to asthma episodes or attacks. You will feel the effects of these medicines within minutes.

2. Long-term Control medicines are taken every day, usually over long periods of time, to control chronic symptoms and to prevent asthma episodes or attacks. You will feel the full effects of these medicines after taking them for a few weeks. People with persistent asthma need long-term control medicines. 

Quick relief medicines are used only when needed. A type of quick relief medicine is a short-acting inhaled bronchodilator. Bronchodilators work by relaxing tightened muscles around the airways. They help open up airways quickly and ease breathing. They are sometimes called "rescue" or "relief" medicines because they can stop an asthma attack. These medicines act quickly but their effects only last for a short period of time. You should take quick relief medicines when you first begin to feel asthma symptoms like coughing, wheezing, chest tightness, or shortness of breath. Anyone who has asthma should always have one of these inhalers in case of an attack. For severe attacks, your doctor may use steroids to treat the inflammation.

• Long-term control medicines . The most effective, long-term control medication for asthma is an inhaled corticosteroid because this medicine reduces the swelling of airways that makes sthma attack more likely.
• Inhaled corticosteroids (or steroids for short) are the preferred treatment for controlling mild, moderate, and severe persistent asthma. They are safe when taken as directed by your doctor. Inhaled medicines go directly into your lungs where they are needed. There are many kinds of inhalers that require different techniques, and it is important to know how to use your inhaler correctly. In some cases, steroid tablets or liquid are used for short times to bring asthma under control. The tablet or liquid form may also be used to control severe asthma.
• Long-acting beta-agonists are another kind of long-term control medication. They are bronchodilators, not anti-inflammatory drugs. These medicines are used to help control moderate and severe asthma and to prevent nighttime symptoms. Long-acting beta-agonists are taken together with inhaled corticosteroid medicine.
• Leukotriene modifiers (montelukast, zafirlukast, and zileuton) are long-term control medicines used either alone to treat mild persistent asthma or together with inhaled corticosteroids to treat moderate persistent asthma or severe persistent asthma.

Cromolyn and nedocromil are also long-term control medicines used to treat mild persistent asthma.

• Theophylline is a long-term control medication used either alone to treat mild persistent asthma or together with inhaled corticosteroids to treat moderate persistent asthma. People who take theophylline should have their blood levels checked to be sure the dose is appropriate.

If you stop taking long-term control medicines, your asthma will likely worsen again. 

Many people with asthma need both a short-acting bronchodilator to use when symptoms worsen and long-term daily asthma control medication to treat the ongoing inflammation. Over time, your doctor may need to make changes in your asthma medication. You may need to increase your dose, lower your dose, or try a combination of medications. Be sure to work with your doctor to find the best treatment for your asthma. The goal is to use the least amount of medicine necessary to control your asthma.

Use a peak flow meter. As part of your asthma action plan, you may use a hand-held device called a peak flow meter at home to measure lung function. To use it, you take a deep breath and blow hard into a tube to find out how fast you can blow out. This gives you a peak flow number. You will need to find out your "personal best" peak flow number by recording the peak flow number daily for a few weeks until your asthma is under control. The highest number you get during that time is your personal best peak flow. Then you can compare future peak flow measurements to your personal best peak flow, and that will show if your asthma is staying under control or not.

Your doctor will tell you how and when to use your peak flow meter and how to use your medication based on the results. You may be asked to use your peak flow meter each morning to keep track of how well you are breathing. The peak flow meter can help warn of a possible asthma attack even before you notice symptoms. If your peak flow meter shows that your breathing is getting worse, you should follow your action plan. Take your quick relief or other medication as your doctor directed. Then you can use the peak flow meter to see how your airways are responding to the medication.

Ask your doctor about how you can help take care of your own asthma. You should know:

• How to take your long-term daily medication correctly
• What things tend to make your asthma worse and ways to avoid them
• Early signs to watch for that mean your asthma is starting to get worse (like a drop in your peak flow number or an increase in symptoms)
• How and when to use your peak flow meter
• What medication and how much to take to stop an asthma attack and how to use it correctly
• When to call or see your doctor
• When you should get emergency treatment  

Treating asthma in children. Children with asthma, like adults with asthma, should see a doctor for treatment. Treatment may include allergy testing, finding ways to limit contact with things that cause asthma attack, and taking medication.

Young children will need help from their parents and other caregivers to keep their asthma under control. Older children can learn to care for themselves and follow their asthma action plan with less supervision.

Medications for asthma in children are like those adults use, but doses are smaller. Children with asthma may need both a quick-relief (or "rescue") inhaler for attacks and daily medication to control their asthma. Children with moderate or severe asthma should learn to use a peak flow meter to help keep their asthma under control. Using a peak flow meter can be very helpful because children often have a hard time describing their symptoms.

Parents should be alert for possible signs of asthma in children, such as coughing at night, frequent colds, wheezing, or other signs of breathing problems. If you suspect asthma or that your child's asthma is not in good control, take your child to a doctor for an exam and testing.

Your doctor will choose medication for your child based on the child's symptoms and test results. If your child has asthma, you will need to go to the doctor for regular followup visits and make sure that your child uses the medication properly.

Treating asthma in older adults. Older adults may need to have adjustments in their asthma treatment because of other diseases or conditions they have. Some medicines (like beta blockers used for treating high blood pressure and glaucoma, aspirin, and nonsteroidal anti-inflammatory drugs) can interfere with asthma medications or even cause asthma attacks. Be sure to tell your doctor about all medications that you take, including over-the-counter ones. Using steroids may affect bone density in adults, so ask your doctor about taking calcium and vitamin D supplements and other ways to help keep your bones strong.

Treating asthma in pregnancy. If you are pregnant, it is very important to both you and your baby to control your asthma. Uncontrolled asthma can lower the oxygen level in your blood, which means that your baby gets less oxygen too. Most asthma medications are safe to take during pregnancy. If you are pregnant or thinking about becoming pregnant, talk to your doctor about your asthma and how to have a healthy pregnancy.

Treating exercise-induced asthma. Regular physical exercise is important for good health. If exercise brings on asthma symptoms, work with your doctor to find the best way to avoid having symptoms when you exercise. Some people with asthma use inhaled quick relief medication before exercising to keep symptoms under control. If you use your asthma medication as directed and learn how to pace yourself, you should be able to take part in any physical activity or sport you choose. Many Olympic athletes have asthma. 

4.SINGULAIR EFFECTIVENESS
When is Singulair best taken?

Absorption
Singulair is rapidly absorbed following oral administration. After administration of the 10-mg film-coated tablet to fasted adults, the mean peak montelukast plasma concentration (C max ) is achieved in 3 to 4 hours (T max ). The mean oral bioavailability is 64%. The oral bioavailability and C max are not influenced by a standard meal in the morning.

For the 5-mg chewable tablet, the mean C max is achieved in 2 to 2.5 hours after administration to adults in the fasted state. The mean oral bioavailability is 73% in the fasted state versus 63% when administered with a standard meal in the morning.

For the 4-mg chewable tablet, the mean C max is achieved 2 hours after administration in pediatric patients 2 to 5 years of age in the fasted state.

The safety and efficacy of Singulair in patients with asthma were demonstrated in clinical trials in which the 10-mg film-coated tablet and 5-mg chewable tablet formulations were administered in the evening without regard to the time of food ingestion. The safety of Singulair in patients with asthma was also demonstrated in clinical trials in which the 4-mg chewable tablet and 4-mg oral granule formulations were administered in the evening without regard to the time of food ingestion.

The comparative pharmacokinetics of Singulair when administered, as two 5-mg chewable tablets versus one 10-mg film-coated tablet have not been evaluated. 

Distribution
Singulair is more than 99% bound to plasma proteins. The steady-state volume of distribution of Singulair averages 8 to 11 liters.

Metabolism
Singulair is extensively metabolized. In studies with therapeutic doses, plasma concentrations of metabolites of Singulair are undetectable at steady state in adults and pediatric patients.

In vitro studies using human liver microsomes indicate that cytochromes P450 3A4 and 2C9 are involved in the metabolism of Singulair. Clinical studies investigating the effect of known inhibitors of cytochromes P450 3A4 (e.g., ketoconazole, erythromycin) or 2C9 (e.g., fluconazole) on montelukast pharmacokinetics have not been conducted. Based on further in vitro results in human liver microsomes, therapeutic plasma concentrations of montelukast do not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6. 

Elimination
The plasma clearance of Singulair averages 45 mL/min in healthy adults. Following an oral dose of radiolabeled montelukast, 86% of the radioactivity was recovered in 5-day fecal collections and <0.2% was recovered in urine. Coupled with estimates of Singulair oral bioavailability, this indicates that Singulair and its metabolites are excreted almost exclusively via the bile.

In several studies, the mean plasma half-life of Singulair ranged from 2.7 to 5.5 hours in healthy young adults. The pharmacokinetics of Singulair is nearly linear for oral doses up to 50 mg. During once daily dosing with 10-mg Singulair, there is little accumulation of the parent drug in plasma (14%). 

5.SINGULAIR EFFECTS ON SPECIAL POPULATION
How do different people react to Singulair?

Gender:
The pharmacokinetics of Singulair is similar in males and females.

Elderly:
The pharmacokinetic profile and the oral bioavailability of a single 10-mg oral dose of Singulair are similar in elderly and younger adults. The plasma half-life of Singulair is slightly longer in the elderly. No Singulair dosage adjustment in the elderly is required.

Race:
Pharmacokinetic differences due to race have not been studied. 

Nursing Mothers
Studies in rats have shown that montelukast is excreted in milk. It is not known if Singulair is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Singulair is given to a nursing mother.

Pediatric Use
Safety and efficacy of Singulair have been established in adequate and well-controlled studies in pediatric patients with asthma 6 to 14 years of age. Safety and efficacy profiles in this age group are similar to those seen in adults.

The safety of Singulair 4-mg chewable tablets in pediatric patients 2 to 5 years of age with asthma has been demonstrated by adequate and well-controlled data. Efficacy of Singulair in this age group by extrapolation from the demonstrated efficacy in patients 6 years of age and older with asthma and is based on similar pharmacokinetic data, as well as the assumption that the disease course, pathophysiology and the drug's effect are substantially similar among these populations. Efficacy in this age group is supported by exploratory efficacy assessments from a large, well controlled safety study conducted in patients 2 to 5 years of age.

The safety of Singulair 4-mg oral granules in pediatric patients 12 to 23 months of age with asthma has been demonstrated in an analysis of 172 pediatric patients, 124 of whom were treated with Singulair, in a 6-week, double-blind, placebo-controlled study. Efficacy of Singulair in this age group is extrapolated from the demonstrated efficacy in patients 6 years of age and older with asthma based on similar mean systemic exposure (AUC), and that the disease course, pathophysiology and the drug's effect are substantially similar among these populations, supported by efficacy data from a safety trial in which efficacy was an exploratory assessment.

The safety and effectiveness in pediatric patients below the age of 12 months have not been established. Long-term trials evaluating the effect of chronic administration of Singulair on linear growth in pediatric patients have not been conducted. 

6.SINGULAIR EFFECTS ON MEDICAL CONDITIONS
(How does Singulair affect your existing condition/ailment?

Hepatic Insufficiency : Patients with mild-to-moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of Singulair resulting in 41% (90% Cl=7%, 85%) higher mean Singulair area under the plasma concentration curve (AUC) following a single 10-mg dose. The elimination of Singulair was slightly prolonged compared with that in healthy subjects (mean half-life, 7.4 hours). No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency. The pharmacokinetics of Singulair in patients with more severe hepatic impairment or with hepatitis has not been evaluated.

Renal Insufficiency : Since Singulair and its metabolites are not excreted in the urine, the pharmacokinetics of Singulair were not evaluated in patients with renal insufficiency. No dosage adjustment is recommended in these patients. 

7.OTHER/ALTERNATE USES OF SINGULAIR
What else does Singulair treat?

Singulair is also indicated in adults and pediatric patients 2 years of age and older for the relief of daytime and nighttime symptoms of seasonal allergic rhinitis and perennial allergic rhinitis.

8.ADVERSE/SIDE EFFECTS of SINGULAIR
What are the side effects of Singulair?

Adults and Adolescents 15 Years of Age and Older with Asthma

Singulair has been evaluated for safety in approximately 2600 adult and adolescent patients 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with Singulair occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo, regardless of causality assessment:

Adverse Experiences Occurring in >/=1% of Patients

The frequency of less common adverse events was comparable between Singulair and placebo.

Cumulatively, 569 patients were treated with Singulair for at least 6 months, 480 for one year, and 49 for two years in clinical trials. With prolonged treatment, the adverse experience profile did not significantly change.

Pediatric Patients 6 to 14 Years of Age with Asthma

Singulair has been evaluated for safety in 321 pediatric patients 6 to 14 years of age. Cumulatively, 169 pediatric patients were treated with Singulair for at least 6 months, and 121 for one year or longer in clinical trials. The safety profile of Singulair in the 8-week, double blind, pediatric efficacy trial was generally similar to the adult safety profile. In pediatric patients 6 to 14 years of age receiving Singulair, the following events occurred with a frequency >/=2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: pharyngitis, influenza, fever, sinusitis, nausea, diarrhea, dyspepsia, otitis, viral infection, and laryngitis. The frequency of less common adverse events was comparable between Singulair and placebo. With prolonged treatment, the adverse experience profile did not significantly change.

Pediatric Patients 2 to 5 Years of Age with Asthma

Singulair has been evaluated for safety in 573 pediatric patients 2 to 5 years of age in single and multiple dose studies. Cumulatively, 426 pediatric patients 2 to 5 years of age were treated with Singulair for at least 3 months, 230 for 6 months or longer, and 63 patients for one year or longer in clinical trials. Singulair 4 mg administered once daily at bedtime was generally well tolerated in clinical trials. In pediatric patients 2 to 5 years of age receiving Singulair, the following events occurred with a frequency >/=2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: fever, cough, abdominal pain, diarrhea, headache, rhinorrhea, sinusitis, otitis, influenza, rash, ear pain, gastroenteritis, eczema, urticaria, varicella, pneumonia, dermatitis, and conjunctivitis.

Pediatric Patients 12 to 23 Months of Age with Asthma

Singulair has been evaluated for safety in 124 pediatric patients 12 to 23 months of age. The safety profile of Singulair in a 6-week, double blind, placebo-controlled clinical study was generally similar to the safety profile in adults and pediatric patients 2 to 14 years of age. Singulair administered once daily at bedtime was generally well tolerated. In pediatric patients 12 to 23 months of age receiving Singulair, the following events occurred with a frequency >/=2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: upper respiratory infection, wheezing; otitis media; pharyngitis, tonsillitis, cough. The frequency of less common adverse events was comparable between Singulair and placebo.

Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing use: hypersensitivity reactions (including anaphylaxis, angioedema, pruritus, urticaria, and very rarely, hepatic eosinophilic infiltration), dream abnormalities and hallucinations, drowsiness, irritability, agitation including aggressive behavior, restlessness, insomnia, paraesthesia/hypoesthesia, and very rarely seizures; nausea, vomiting, dyspepsia, diarrhea, very rarely pancreatitis, and very rarely cholestatic hepatitis; arthralgia, myalgia including muscle cramps; increased bleeding tendency, bruising; palpitations; and edema.

In rare cases, patients with asthma on therapy with Singulair may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition, which is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between Singulair and these underlying conditions has not been established.