These Highlights Do Not Include All The Information Needed To Use Montelukast Sodium Safely And Effectively. See Full Prescribing Information For Montelukast Sodium.

Pediatric Patients 6 to 23 Months of Age with Asthma

Safety and effectiveness in pediatric patients younger than 12 months of age with asthma have not been established.

Montelukast sodium has been evaluated for safety in 175 pediatric patients 6 to 23 months of age. The safety profile of montelukast sodium 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. In pediatric patients 6 to 23 months of age receiving montelukast sodium, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo: upper respiratory infection, wheezing; otitis media; pharyngitis, tonsillitis, cough; and rhinitis. The frequency of less common adverse events was comparable between montelukast sodium and placebo.

Teratogenic Effect: No teratogenicity was observed in rats and rabbits at doses approximately 100 and 110 times, respectively, the maximum recommended daily oral dose in adults based on AUCs [see Nonclinical Toxicology (13.2)].

During worldwide marketing experience, congenital limb defects have been rarely reported in the offspring of women being treated with montelukast sodium during pregnancy. Most of these women were also taking other asthma medications during their pregnancy. A causal relationship between these events and montelukast sodium has not been established.

Adults and Adolescents 15 Years of Age and Older with Asthma

Montelukast sodium has been evaluated for safety in approximately 2950 adult and adolescent patients 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with montelukast sodium occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo:

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

The safety profile of montelukast sodium, when administered as a single dose for prevention of EIB in adult and adolescent patients 15 years of age and older, was consistent with the safety profile previously described for montelukast sodium.

Cumulatively, 569 patients were treated with montelukast sodium 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.

Patient Information

Montelukast Sodium

(MON-te-LOO-kast SOE-dee-um)

Tablets

Montelukast Sodium

Chewable Tablets

CIA76025G

Rev. 01/2017

Read the Patient Information Leaflet that comes with montelukast sodium before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is Montelukast Sodium?

• •
  Montelukast sodium is a prescription medicine that blocks substances in the body called leukotrienes. This may help to improve symptoms of asthma and allergic rhinitis. Montelukast sodium does not contain a steroid.

Montelukast sodium is used to:

• 1.
  Prevent asthma attacks and for the long-term treatment of asthma in adults and children ages 12 months and older.
•  
  Do not take montelukast sodium if you need relief right away for a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.
• 2.
  Prevent exercise-induced asthma in people 6 years of age and older.
• 3.
  Help control the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose). Montelukast sodium is used to treat:
  • 1.
    outdoor allergies that happen part of the year (seasonal allergic rhinitis) in adults and children ages 2 years and older, and
  • 2.
    indoor allergies that happen all year (perennial allergic rhinitis) in adults and children ages 6 months and older.

Who should not take Montelukast Sodium?

Do not take montelukast sodium if you are allergic to any of its ingredients.

See the end of this leaflet for a complete list of the ingredients in montelukast sodium.

What should I tell my healthcare provider before taking Montelukast Sodium?

Before taking Montelukast Sodium, tell your healthcare provider if you:

• •
  are allergic to aspirin
• •
  have any other medical conditions
• •
  are pregnant or plan to become pregnant. Talk to your doctor if you are pregnant or plan to become pregnant, as montelukast sodium may not be right for you.
• •
  are breast-feeding or plan to breast-feed. It is not known if montelukast sodium passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking montelukast sodium.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how montelukast sodium works, or montelukast sodium may affect how your other medicines work.

How should I take Montelukast Sodium?

For anyone who takes Montelukast Sodium:

• •
  Take montelukast sodium exactly as prescribed by your healthcare provider. Your healthcare provider will tell you how much montelukast sodium to take, and when to take it.
• •
  Do not stop taking montelukast sodium or change when you take it without talking with your healthcare provider.
• •
  You can take montelukast sodium with food or without food.
• •
  If you or your child misses a dose of montelukast sodium, just take the next dose at your regular time. Do not take 2 doses at the same time.
• •
  If you take too much montelukast sodium, call your healthcare provider or a Poison Control Center right away.

For adults and children 12 months of age and older with asthma:

• •
  Take montelukast sodium 1 time each day, in the evening. Continue to take montelukast sodium every day for as long as your healthcare provider prescribes it, even if you have no asthma symptoms.
• •
  Tell your healthcare provider right away if your asthma symptoms get worse, or if you need to use your rescue inhaler medicine more often for asthma attacks.
• •
  Do not take montelukast sodium if you need relief right away from a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.
• •
  Always have your rescue inhaler medicine with you for asthma attacks.
• •
  Do not stop taking or lower the dose of your other asthma medicines unless your healthcare provider tells you to.

For patients 6 years of age and older for the prevention of exercise-induced asthma:

• •
  Take montelukast sodium at least 2 hours before exercise.
• •
  Always have your rescue inhaler medicine with you for asthma attacks.
• •
  If you take montelukast sodium every day for chronic asthma or allergic rhinitis, do not take another dose to prevent exercise-induced asthma. Talk to your healthcare provider about your treatment for exercise-induced asthma.
• •
  Do not take 2 doses of montelukast sodium within 24 hours (1 day).

For adults and children 2 years of age and older with seasonal allergic rhinitis, or for adults and children 6 months of age and older with perennial allergic rhinitis:

• •
  Take montelukast sodium 1 time each day, at about the same time each day.

What is the dose of montelukast sodium?

The dose of montelukast sodium prescribed for your or your child's condition is based on age:

• •
  2 to 5 years: one 4-mg chewable tablet.
• •
  6 to 14 years: one 5-mg chewable tablet.
• •
  15 years and older: one 10-mg tablet.

What should I avoid while taking montelukast sodium?

If you have asthma and aspirin makes your asthma symptoms worse, continue to avoid taking aspirin or other medicines called non-steroidal anti-inflammatory drugs (NSAIDs) while taking montelukast sodium.

What are the possible side effects of montelukast sodium?

Montelukast sodium may cause serious side effects.

• •
  Behavior and mood-related changes. Tell your healthcare provider right away if you or your child have any of these symptoms while taking montelukast sodium:
  • •
    agitation including aggressive behavior or hostility
  • •
    attention problems
  • •
    bad or vivid dreams
  • •
    depression
  • •
    disorientation (confusion)
  • •
    feeling anxious
  • •
    hallucinations (seeing or hearing things that are not really there)
  • •
    irritability
  • •
    memory problems
  • •
    restlessness
  • •
    sleep walking
  • •
    suicidal thoughts and actions ( including suicide )
  • •
    tremor
  • •
    trouble sleeping
  • •
    uncontrolled muscle movements
• •
  Increase in certain white blood cells (eosinophils) and possible inflamed blood vessels throughout the body (systemic vasculitis). Rarely, this can happen in people with asthma who take montelukast sodium. This sometimes happens in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered.
  
  Tell your healthcare provider right away if you get one or more of these symptoms:
  • •
    a feeling of pins and needles or numbness of arms or legs
  • •
    a flu-like illness
  • •
    rash
  • •
    severe inflammation (pain and swelling) of the sinuses (sinusitis)

The most common side effects with montelukast sodium include:

• •
  upper respiratory infection
• •
  fever
• •
  headache
• •
  sore throat
• •
  cough
• •
  stomach pain
• •
  diarrhea
• •
  earache or ear infection
• •
  flu
• •
  runny nose
• •
  sinus infection

Other side effects with montelukast sodium include:

• •
  increased bleeding tendency, low blood platelet count
• •
  allergic reactions [including swelling of the face, lips, tongue, and/or throat (which may cause trouble breathing or swallowing), hives and itching]
• •
  dizziness, drowsiness, pins and needles/numbness, seizures (convulsions or fits)
• •
  palpitations
• •
  nose bleed, stuffy nose, swelling (inflammation) of the lungs 
• •
  heartburn, indigestion, inflammation of the pancreas, nausea, stomach or intestinal upset, vomiting
• •
  hepatitis
• •
  bruising, rash, severe skin reactions (erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis) that may occur without warning
• •
  joint pain, muscle aches and muscle cramps
• •
  bedwetting in children
• •
  tiredness, swelling

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of montelukast sodium. For more information ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088.

How should I store montelukast sodium?

• •
  Store montelukast sodium at 59°F to 86°F (15°C to 30°C).
• •
  Keep montelukast sodium in the container it comes in.
• •
  Keep montelukast sodium in a dry place and away from light.

General Information about the safe and effective use of montelukast sodium

Medicines are sometimes prescribed for purposes other than those mentioned in Patient Information Leaflets. Do not use montelukast sodium for a condition for which it was not prescribed. Do not give montelukast sodium to other people even if they have the same symptoms you have. It may harm them. Keep montelukast sodium and all medicines out of the reach of children.

This leaflet summarizes information about montelukast sodium. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about montelukast sodium that is written for health professionals. For more information, call 1-844-834-0530.

What are the ingredients in montelukast sodium?

Active ingredient: montelukast sodium

Inactive ingredients:

• •
  4-mg and 5-mg chewable tablets: butylated hydroxyanisole, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, mannitol, microcrystalline cellulose, natural and artificial orange flavor, red ferric oxide, sodium stearyl fumarate and sucralose.
• •
  10-mg tablets: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium stearyl fumarate, talc and titanium dioxide.

Rx only

Distributed by:

Lannett Company, Inc.

Philadelphia, PA 19154

Made in the USA

Repackaged by:

Proficient Rx LP

Thousand Oaks, CA 91320

CIA76025G

Rev. 01/2017

Storage

Store montelukast 4-mg chewable tablets, 5-mg chewable tablets and 10-mg film-coated tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original package.

Storage for Bulk Bottles

Store bottles of 1000 montelukast 4-mg chewable tablets, 5-mg chewable tablets and 10-mg film-coated tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original container. When product container is subdivided, repackage into a well-closed, light-resistant container.

PRINCIPAL DISPLAY PANEL - 5 mg Tablet Bottle Label

NDC 63187-896-30

Montelukast

Sodium

CHEWABLE TABLETS

5 mg*

For Pediatric Patients

6-14 Years of Age

Pharmacist- Dispense attached patient leaflet to each patient

Rx Only

30 TABLETS

Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older.

Montelukast sodium should be taken once daily in the evening. The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.

There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion.

No specific information is available on the treatment of overdosage with montelukast sodium. In chronic asthma studies, montelukast has been administered at doses up to 200 mg/day to adult patients for 22 weeks and, in short-term studies, up to 900 mg/day to patients for approximately a week without clinically important adverse experiences. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.

There have been reports of acute overdosage in post-marketing experience and clinical studies with montelukast sodium. These include reports in adults and children with a dose as high as 1000 mg. The clinical and laboratory findings observed were consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of overdosage reports. The most frequently occurring adverse experiences were consistent with the safety profile of montelukast sodium and included abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity.

It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis.

Montelukast sodium, the active ingredient in montelukast sodium tablets, is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT₁ receptor.

Montelukast sodium is described chemically as [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid, monosodium salt.

The empirical formula is C₃₅H₃₅CINNaO₃S, and its molecular weight is 608.18. The structural formula is:

Montelukast sodium is a hygroscopic, optically active, white to off-white powder. Montelukast sodium is freely soluble in ethanol, methanol, and water and practically insoluble in acetonitrile.

Each 10-mg film-coated montelukast sodium tablet contains 10.4 mg montelukast sodium, which is equivalent to 10 mg of montelukast, and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium stearyl fumarate, talc and titanium dioxide.

Each 4-mg and 5-mg chewable montelukast sodium tablet contains 4.2 and 5.2 mg montelukast sodium, respectively, which are equivalent to 4 and 5 mg of montelukast, respectively. Both chewable tablets contain the following inactive ingredients: butylated hydroxyanisole, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, mannitol, microcrystalline cellulose, natural and artificial orange flavor, red ferric oxide, sodium stearyl fumarate and sucralose.

Montelukast sodium is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Patients should be advised to have appropriate rescue medication available. Therapy with montelukast sodium can be continued during acute exacerbations of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled β-agonist.

Safety and efficacy of montelukast sodium 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 [see Adverse Reactions (6.1), Clinical Pharmacology, Special Populations (12.3), and Clinical Studies (14.1, 14.2)].

The efficacy of montelukast sodium for the treatment of seasonal allergic rhinitis in pediatric patients 2 to 14 years of age and for the treatment of perennial allergic rhinitis in pediatric patients 6 months to 14 years of age is supported by extrapolation from the demonstrated efficacy in patients 15 years of age and older with allergic rhinitis as well as the assumption that the disease course, pathophysiology and the drug's effect are substantially similar among these populations.

The safety of montelukast sodium 4-mg chewable tablets in pediatric patients 2 to 5 years of age with asthma has been demonstrated by adequate and well-controlled data [see Adverse Reactions (6.1)]. Efficacy of montelukast sodium in this age group is extrapolated 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 montelukast sodium 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 montelukast sodium, in a 6-week, double-blind, placebo-controlled study [see Adverse Reactions (6.1)]. Efficacy of montelukast sodium 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 of montelukast sodium 4-mg and 5-mg chewable tablets in pediatric patients aged 2 to 14 years with allergic rhinitis is supported by data from studies conducted in pediatric patients aged 2 to 14 years with asthma. A safety study in pediatric patients 2 to 14 years of age with seasonal allergic rhinitis demonstrated a similar safety profile [see Adverse Reactions (6.1)].

The safety of montelukast sodium 4-mg oral granules in pediatric patients as young as 6 months of age with perennial allergic rhinitis is supported by extrapolation from safety  data  obtained  from  studies  conducted  in  pediatric  patients  6  months  to 23 months of age with asthma and from pharmacokinetic data comparing systemic exposures in patients 6 months to 23 months of age to systemic exposures in adults.

The safety and effectiveness in pediatric patients below the age of 12 months with asthma, 6 months with perennial allergic rhinitis, and 6 years with exercise-induced bronchoconstriction have not been established. 

Of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetic profile and the oral bioavailability of a single 10-mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required.

• •
  Hypersensitivity to any component of this product.

Most common adverse reactions (incidence ≥ 5% and greater than placebo listed in descending order of frequency): upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No dose adjustment is needed when montelukast sodium is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3)].

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

Montelukast sodium is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 6 months of age and older. 

Montelukast causes inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD₄ in asthmatics. Doses as low as 5 mg cause substantial blockage of LTD₄-induced bronchoconstriction. In a placebo-controlled, crossover study (n=12), montelukast sodium inhibited early- and late-phase bronchoconstriction due to antigen challenge by 75% and 57%, respectively.

The effect of montelukast sodium on eosinophils in the peripheral blood was examined in clinical trials. In patients with asthma aged 2 years and older who received montelukast sodium, a decrease in mean peripheral blood eosinophil counts ranging from 9% to 15% was noted, compared with placebo, over the double-blind treatment periods. In patients with seasonal allergic rhinitis aged 15 years and older who received montelukast sodium, a mean increase of 0.2% in peripheral blood eosinophil counts was noted, compared with a mean increase of 12.5% in placebo-treated patients, over the double-blind treatment periods; this reflects a mean difference of 12.3% in favor of montelukast sodium. The relationship between these observations and the clinical benefits of montelukast noted in the clinical trials is not known [see Clinical Studies (14)].

For allergic rhinitis, montelukast sodium should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs.

The following doses for the treatment of symptoms of seasonal allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.

The following doses for the treatment of symptoms of perennial allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established.

Montelukast sodium tablets is a leukotriene receptor antagonist indicated for:

• •
  Prophylaxis and chronic treatment of asthma in patients 12 months of age and older (1.1).
• •
  Acute prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older (1.2).
• •
  Relief of symptoms of allergic rhinitis (AR): seasonal allergic rhinitis (SAR) in patients 2 years of age and older, and perennial allergic rhinitis (PAR) in patients 6 months of age and older (1.3).

Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium. Although montelukast sodium is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to truncate bronchoconstrictor response to aspirin and other non-steroidal anti-inflammatory drugs in aspirin-sensitive asthmatic patients [see Clinical Studies (14.1) ].

No dosage adjustment is recommended in patients with renal insufficiency [see Clinical Pharmacology (12.3)].

The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene (CysLT) receptors. The CysLT type-1 (CysLT₁) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both early-and late-phase reactions and are associated with symptoms of allergic rhinitis.

Montelukast is an orally active compound that binds with high affinity and selectivity to the CysLT₁ receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or β-adrenergic receptor). Montelukast inhibits physiologic actions of LTD₄ at the CysLT₁ receptor without any agonist activity.

No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency [see Clinical Pharmacology (12.3)].

• •
  Do not prescribe montelukast sodium to treat an acute asthma attack (5.1).
• •
  Advise patients to have appropriate rescue medication available (5.1).
• •
  Inhaled corticosteroid may be reduced gradually. Do not abruptly substitute montelukast sodium for inhaled or oral corticosteroids (5.2).
• •
  Patients with known aspirin sensitivity should continue to avoid aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium (5.3).
• •
  Neuropsychiatric events have been reported with montelukast sodium. Instruct patients to be alert for neuropsychiatric events. Evaluate the risks and benefits of continuing treatment with montelukast sodium if such events occur (5.4 and 6.2).
• •
  Systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, has been reported. These events have been sometimes associated with the reduction of oral corticosteroid therapy (5.5 and 6.2).

Administration (by indications):

• •
  Asthma (2.1): Once daily in the evening for patients 12 months and older.
• •
  Acute prevention of EIB (2.2): 10 mg tablet at least 2 hours before exercise for patients 6 years of age and older.
• •
  Seasonal allergic rhinitis (2.3): Once daily for patients 2 years and older.
• •
  Perennial allergic rhinitis (2.3): Once daily for patients 6 months and older.

Dosage (by age) (2):

• •
  15 years and older: one 10-mg tablet.
• •
  6 to 14 years: one 5-mg chewable tablet.
• •
  2 to 5 years: one 4-mg chewable tablet.

Patients with both asthma and allergic rhinitis should take only one dose daily in the evening (2.4).

Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking montelukast sodium. Post-marketing reports with montelukast sodium use include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor. The clinical details of some post-marketing reports involving montelukast sodium appear consistent with a drug-induced effect.

Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with montelukast sodium if such events occur [see Adverse Reactions (6.2) ].

Patients with asthma on therapy with montelukast sodium 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 have been sometimes 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 montelukast sodium and these underlying conditions has not been established [see Adverse Reactions (6.2) ].

• •
  Montelukast sodium Tablets, 10-mg are round, white, film-coated, convex tablets, debossed with "KU" on one side and "210" on the other.
• •
  Montelukast sodium Chewable Tablets, 5-mg are round, light pink, convex tablets, debossed with "KU" on one side and "205" on the other.
• •
  Montelukast sodium Chewable Tablets, 4-mg are round, light pink, convex tablets, debossed with "KU" on one side and "204" on the other.

The following adverse reactions have been identified during post-approval use of montelukast sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: increased bleeding tendency, thrombocytopenia.

Immune system disorders: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration.

Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor [see Warnings and Precautions (5.4) ].

Nervous system disorders: drowsiness, paraesthesia/hypoesthesia, seizures.

Cardiac disorders: palpitations.

Respiratory, thoracic and mediastinal disorders: epistaxis, pulmonary eosinophilia.

Gastrointestinal disorders: diarrhea, dyspepsia, nausea, pancreatitis, vomiting.

Hepatobiliary disorders: Cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury have been reported in patients treated with montelukast sodium. Most of these occurred in combination with other confounding factors, such as use of other medications, or when montelukast sodium was administered to patients who had underlying potential for liver disease such as alcohol use or other forms of hepatitis.

Skin and subcutaneous tissue disorders: angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticarial.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps.

Renal and urinary disorders: enuresis in children.

General disorders and administration site conditions: edema.

Patients with asthma on therapy with montelukast sodium 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 have been sometimes 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 [see Warnings and Precautions (5.5) ].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the following description of clinical trials experience, adverse reactions are listed regardless of causality assessment.

The most common adverse reactions (incidence ≥ 5% and greater than placebo; listed in descending order of frequency) in controlled clinical trials were: upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis.

Patients with both asthma and allergic rhinitis should take only one montelukast sodium dose daily in the evening.

•  
  See FDA-approved patient labeling (Patient Information).

While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, montelukast sodium should not be abruptly substituted for inhaled or oral corticosteroids.

Montelukast sodium Chewable Tablets, 5-mg, are round, light pink, convex tablets, debossed with "KU" on one side and "205" on the other.

They are supplied as follows:

Montelukast sodium is indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older.

For prevention of EIB, a single dose of montelukast should be taken at least 2 hours before exercise.

The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

An additional dose of montelukast should not be taken within 24 hours of a previous dose. Patients already takingmontelukast sodium daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting ß-agonist. Safety and efficacy in patients younger than 6 years of age have not been established. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB. 

No evidence of tumorigenicity was seen in carcinogenicity studies of either 2 years in Sprague-Dawley rats or 92 weeks in mice at oral gavage doses up to 200 mg/kg/day or 100 mg/kg/day, respectively. The estimated exposure in rats was approximately 120 and 75 times the AUC for adults and children, respectively, at the maximum recommended daily oral dose. The estimated exposure in mice was approximately 45 and 25 times the AUC for adults and children, respectively, at the maximum recommended daily oral dose.

Montelukast demonstrated no evidence of mutagenic or clastogenic activity in the following assays: the microbial mutagenesis assay, the V-79 mammalian cell mutagenesis assay, the alkaline elution assay in rat hepatocytes, the chromosomal aberration assay in Chinese hamster ovary cells, and in the in vivo mouse bone marrow chromosomal aberration assay.

In fertility studies in female rats, montelukast produced reductions in fertility and fecundity indices at an oral dose of 200 mg/kg (estimated exposure was approximately 70 times the AUC for adults at the maximum recommended daily oral dose). No effects on female fertility or fecundity were observed at an oral dose of 100 mg/kg (estimated exposure was approximately 20 times the AUC for adults at the maximum recommended daily oral dose). Montelukast had no effects on fertility in male rats at oral doses up to 800 mg/kg (estimated exposure was approximately 160 times the AUC for adults at the maximum recommended daily oral dose).

Pediatric Patients 6 to 23 Months of Age with Asthma

Safety and effectiveness in pediatric patients younger than 12 months of age with asthma have not been established.

Montelukast sodium has been evaluated for safety in 175 pediatric patients 6 to 23 months of age. The safety profile of montelukast sodium 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. In pediatric patients 6 to 23 months of age receiving montelukast sodium, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo: upper respiratory infection, wheezing; otitis media; pharyngitis, tonsillitis, cough; and rhinitis. The frequency of less common adverse events was comparable between montelukast sodium and placebo.

Teratogenic Effect: No teratogenicity was observed in rats and rabbits at doses approximately 100 and 110 times, respectively, the maximum recommended daily oral dose in adults based on AUCs [see Nonclinical Toxicology (13.2)].

During worldwide marketing experience, congenital limb defects have been rarely reported in the offspring of women being treated with montelukast sodium during pregnancy. Most of these women were also taking other asthma medications during their pregnancy. A causal relationship between these events and montelukast sodium has not been established.

Adults and Adolescents 15 Years of Age and Older with Asthma

Montelukast sodium has been evaluated for safety in approximately 2950 adult and adolescent patients 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with montelukast sodium occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo:

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

The safety profile of montelukast sodium, when administered as a single dose for prevention of EIB in adult and adolescent patients 15 years of age and older, was consistent with the safety profile previously described for montelukast sodium.

Cumulatively, 569 patients were treated with montelukast sodium 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.

Patient Information

Montelukast Sodium

(MON-te-LOO-kast SOE-dee-um)

Tablets

Montelukast Sodium

Chewable Tablets

CIA76025G

Rev. 01/2017

Read the Patient Information Leaflet that comes with montelukast sodium before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is Montelukast Sodium?

• •
  Montelukast sodium is a prescription medicine that blocks substances in the body called leukotrienes. This may help to improve symptoms of asthma and allergic rhinitis. Montelukast sodium does not contain a steroid.

Montelukast sodium is used to:

• 1.
  Prevent asthma attacks and for the long-term treatment of asthma in adults and children ages 12 months and older.
•  
  Do not take montelukast sodium if you need relief right away for a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.
• 2.
  Prevent exercise-induced asthma in people 6 years of age and older.
• 3.
  Help control the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose). Montelukast sodium is used to treat:
  • 1.
    outdoor allergies that happen part of the year (seasonal allergic rhinitis) in adults and children ages 2 years and older, and
  • 2.
    indoor allergies that happen all year (perennial allergic rhinitis) in adults and children ages 6 months and older.

Who should not take Montelukast Sodium?

Do not take montelukast sodium if you are allergic to any of its ingredients.

See the end of this leaflet for a complete list of the ingredients in montelukast sodium.

What should I tell my healthcare provider before taking Montelukast Sodium?

Before taking Montelukast Sodium, tell your healthcare provider if you:

• •
  are allergic to aspirin
• •
  have any other medical conditions
• •
  are pregnant or plan to become pregnant. Talk to your doctor if you are pregnant or plan to become pregnant, as montelukast sodium may not be right for you.
• •
  are breast-feeding or plan to breast-feed. It is not known if montelukast sodium passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking montelukast sodium.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how montelukast sodium works, or montelukast sodium may affect how your other medicines work.

How should I take Montelukast Sodium?

For anyone who takes Montelukast Sodium:

• •
  Take montelukast sodium exactly as prescribed by your healthcare provider. Your healthcare provider will tell you how much montelukast sodium to take, and when to take it.
• •
  Do not stop taking montelukast sodium or change when you take it without talking with your healthcare provider.
• •
  You can take montelukast sodium with food or without food.
• •
  If you or your child misses a dose of montelukast sodium, just take the next dose at your regular time. Do not take 2 doses at the same time.
• •
  If you take too much montelukast sodium, call your healthcare provider or a Poison Control Center right away.

For adults and children 12 months of age and older with asthma:

• •
  Take montelukast sodium 1 time each day, in the evening. Continue to take montelukast sodium every day for as long as your healthcare provider prescribes it, even if you have no asthma symptoms.
• •
  Tell your healthcare provider right away if your asthma symptoms get worse, or if you need to use your rescue inhaler medicine more often for asthma attacks.
• •
  Do not take montelukast sodium if you need relief right away from a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.
• •
  Always have your rescue inhaler medicine with you for asthma attacks.
• •
  Do not stop taking or lower the dose of your other asthma medicines unless your healthcare provider tells you to.

For patients 6 years of age and older for the prevention of exercise-induced asthma:

• •
  Take montelukast sodium at least 2 hours before exercise.
• •
  Always have your rescue inhaler medicine with you for asthma attacks.
• •
  If you take montelukast sodium every day for chronic asthma or allergic rhinitis, do not take another dose to prevent exercise-induced asthma. Talk to your healthcare provider about your treatment for exercise-induced asthma.
• •
  Do not take 2 doses of montelukast sodium within 24 hours (1 day).

For adults and children 2 years of age and older with seasonal allergic rhinitis, or for adults and children 6 months of age and older with perennial allergic rhinitis:

• •
  Take montelukast sodium 1 time each day, at about the same time each day.

What is the dose of montelukast sodium?

The dose of montelukast sodium prescribed for your or your child's condition is based on age:

• •
  2 to 5 years: one 4-mg chewable tablet.
• •
  6 to 14 years: one 5-mg chewable tablet.
• •
  15 years and older: one 10-mg tablet.

What should I avoid while taking montelukast sodium?

If you have asthma and aspirin makes your asthma symptoms worse, continue to avoid taking aspirin or other medicines called non-steroidal anti-inflammatory drugs (NSAIDs) while taking montelukast sodium.

What are the possible side effects of montelukast sodium?

Montelukast sodium may cause serious side effects.

• •
  Behavior and mood-related changes. Tell your healthcare provider right away if you or your child have any of these symptoms while taking montelukast sodium:
  • •
    agitation including aggressive behavior or hostility
  • •
    attention problems
  • •
    bad or vivid dreams
  • •
    depression
  • •
    disorientation (confusion)
  • •
    feeling anxious
  • •
    hallucinations (seeing or hearing things that are not really there)
  • •
    irritability
  • •
    memory problems
  • •
    restlessness
  • •
    sleep walking
  • •
    suicidal thoughts and actions ( including suicide )
  • •
    tremor
  • •
    trouble sleeping
  • •
    uncontrolled muscle movements
• •
  Increase in certain white blood cells (eosinophils) and possible inflamed blood vessels throughout the body (systemic vasculitis). Rarely, this can happen in people with asthma who take montelukast sodium. This sometimes happens in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered.
  
  Tell your healthcare provider right away if you get one or more of these symptoms:
  • •
    a feeling of pins and needles or numbness of arms or legs
  • •
    a flu-like illness
  • •
    rash
  • •
    severe inflammation (pain and swelling) of the sinuses (sinusitis)

The most common side effects with montelukast sodium include:

• •
  upper respiratory infection
• •
  fever
• •
  headache
• •
  sore throat
• •
  cough
• •
  stomach pain
• •
  diarrhea
• •
  earache or ear infection
• •
  flu
• •
  runny nose
• •
  sinus infection

Other side effects with montelukast sodium include:

• •
  increased bleeding tendency, low blood platelet count
• •
  allergic reactions [including swelling of the face, lips, tongue, and/or throat (which may cause trouble breathing or swallowing), hives and itching]
• •
  dizziness, drowsiness, pins and needles/numbness, seizures (convulsions or fits)
• •
  palpitations
• •
  nose bleed, stuffy nose, swelling (inflammation) of the lungs 
• •
  heartburn, indigestion, inflammation of the pancreas, nausea, stomach or intestinal upset, vomiting
• •
  hepatitis
• •
  bruising, rash, severe skin reactions (erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis) that may occur without warning
• •
  joint pain, muscle aches and muscle cramps
• •
  bedwetting in children
• •
  tiredness, swelling

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of montelukast sodium. For more information ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088.

How should I store montelukast sodium?

• •
  Store montelukast sodium at 59°F to 86°F (15°C to 30°C).
• •
  Keep montelukast sodium in the container it comes in.
• •
  Keep montelukast sodium in a dry place and away from light.

General Information about the safe and effective use of montelukast sodium

Medicines are sometimes prescribed for purposes other than those mentioned in Patient Information Leaflets. Do not use montelukast sodium for a condition for which it was not prescribed. Do not give montelukast sodium to other people even if they have the same symptoms you have. It may harm them. Keep montelukast sodium and all medicines out of the reach of children.

This leaflet summarizes information about montelukast sodium. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about montelukast sodium that is written for health professionals. For more information, call 1-844-834-0530.

What are the ingredients in montelukast sodium?

Active ingredient: montelukast sodium

Inactive ingredients:

• •
  4-mg and 5-mg chewable tablets: butylated hydroxyanisole, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, mannitol, microcrystalline cellulose, natural and artificial orange flavor, red ferric oxide, sodium stearyl fumarate and sucralose.
• •
  10-mg tablets: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium stearyl fumarate, talc and titanium dioxide.

Rx only

Distributed by:

Lannett Company, Inc.

Philadelphia, PA 19154

Made in the USA

Repackaged by:

Proficient Rx LP

Thousand Oaks, CA 91320

CIA76025G

Rev. 01/2017

Storage

Store montelukast 4-mg chewable tablets, 5-mg chewable tablets and 10-mg film-coated tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original package.

Storage for Bulk Bottles

Store bottles of 1000 montelukast 4-mg chewable tablets, 5-mg chewable tablets and 10-mg film-coated tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original container. When product container is subdivided, repackage into a well-closed, light-resistant container.

PRINCIPAL DISPLAY PANEL - 5 mg Tablet Bottle Label

NDC 63187-896-30

Montelukast

Sodium

CHEWABLE TABLETS

5 mg*

For Pediatric Patients

6-14 Years of Age

Pharmacist- Dispense attached patient leaflet to each patient

Rx Only

30 TABLETS

Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older.

Montelukast sodium should be taken once daily in the evening. The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.

There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion.

No specific information is available on the treatment of overdosage with montelukast sodium. In chronic asthma studies, montelukast has been administered at doses up to 200 mg/day to adult patients for 22 weeks and, in short-term studies, up to 900 mg/day to patients for approximately a week without clinically important adverse experiences. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.

There have been reports of acute overdosage in post-marketing experience and clinical studies with montelukast sodium. These include reports in adults and children with a dose as high as 1000 mg. The clinical and laboratory findings observed were consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of overdosage reports. The most frequently occurring adverse experiences were consistent with the safety profile of montelukast sodium and included abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity.

It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis.

Montelukast sodium, the active ingredient in montelukast sodium tablets, is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT₁ receptor.

Montelukast sodium is described chemically as [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid, monosodium salt.

The empirical formula is C₃₅H₃₅CINNaO₃S, and its molecular weight is 608.18. The structural formula is:

Montelukast sodium is a hygroscopic, optically active, white to off-white powder. Montelukast sodium is freely soluble in ethanol, methanol, and water and practically insoluble in acetonitrile.

Each 10-mg film-coated montelukast sodium tablet contains 10.4 mg montelukast sodium, which is equivalent to 10 mg of montelukast, and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium stearyl fumarate, talc and titanium dioxide.

Each 4-mg and 5-mg chewable montelukast sodium tablet contains 4.2 and 5.2 mg montelukast sodium, respectively, which are equivalent to 4 and 5 mg of montelukast, respectively. Both chewable tablets contain the following inactive ingredients: butylated hydroxyanisole, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, mannitol, microcrystalline cellulose, natural and artificial orange flavor, red ferric oxide, sodium stearyl fumarate and sucralose.

Montelukast sodium is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Patients should be advised to have appropriate rescue medication available. Therapy with montelukast sodium can be continued during acute exacerbations of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled β-agonist.

Safety and efficacy of montelukast sodium 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 [see Adverse Reactions (6.1), Clinical Pharmacology, Special Populations (12.3), and Clinical Studies (14.1, 14.2)].

The efficacy of montelukast sodium for the treatment of seasonal allergic rhinitis in pediatric patients 2 to 14 years of age and for the treatment of perennial allergic rhinitis in pediatric patients 6 months to 14 years of age is supported by extrapolation from the demonstrated efficacy in patients 15 years of age and older with allergic rhinitis as well as the assumption that the disease course, pathophysiology and the drug's effect are substantially similar among these populations.

The safety of montelukast sodium 4-mg chewable tablets in pediatric patients 2 to 5 years of age with asthma has been demonstrated by adequate and well-controlled data [see Adverse Reactions (6.1)]. Efficacy of montelukast sodium in this age group is extrapolated 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 montelukast sodium 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 montelukast sodium, in a 6-week, double-blind, placebo-controlled study [see Adverse Reactions (6.1)]. Efficacy of montelukast sodium 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 of montelukast sodium 4-mg and 5-mg chewable tablets in pediatric patients aged 2 to 14 years with allergic rhinitis is supported by data from studies conducted in pediatric patients aged 2 to 14 years with asthma. A safety study in pediatric patients 2 to 14 years of age with seasonal allergic rhinitis demonstrated a similar safety profile [see Adverse Reactions (6.1)].

The safety of montelukast sodium 4-mg oral granules in pediatric patients as young as 6 months of age with perennial allergic rhinitis is supported by extrapolation from safety  data  obtained  from  studies  conducted  in  pediatric  patients  6  months  to 23 months of age with asthma and from pharmacokinetic data comparing systemic exposures in patients 6 months to 23 months of age to systemic exposures in adults.

The safety and effectiveness in pediatric patients below the age of 12 months with asthma, 6 months with perennial allergic rhinitis, and 6 years with exercise-induced bronchoconstriction have not been established. 

Of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetic profile and the oral bioavailability of a single 10-mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required.

• •
  Hypersensitivity to any component of this product.

Most common adverse reactions (incidence ≥ 5% and greater than placebo listed in descending order of frequency): upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No dose adjustment is needed when montelukast sodium is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3)].

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

Montelukast sodium is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 6 months of age and older. 

Montelukast causes inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD₄ in asthmatics. Doses as low as 5 mg cause substantial blockage of LTD₄-induced bronchoconstriction. In a placebo-controlled, crossover study (n=12), montelukast sodium inhibited early- and late-phase bronchoconstriction due to antigen challenge by 75% and 57%, respectively.

The effect of montelukast sodium on eosinophils in the peripheral blood was examined in clinical trials. In patients with asthma aged 2 years and older who received montelukast sodium, a decrease in mean peripheral blood eosinophil counts ranging from 9% to 15% was noted, compared with placebo, over the double-blind treatment periods. In patients with seasonal allergic rhinitis aged 15 years and older who received montelukast sodium, a mean increase of 0.2% in peripheral blood eosinophil counts was noted, compared with a mean increase of 12.5% in placebo-treated patients, over the double-blind treatment periods; this reflects a mean difference of 12.3% in favor of montelukast sodium. The relationship between these observations and the clinical benefits of montelukast noted in the clinical trials is not known [see Clinical Studies (14)].

For allergic rhinitis, montelukast sodium should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs.

The following doses for the treatment of symptoms of seasonal allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.

The following doses for the treatment of symptoms of perennial allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established.

Montelukast sodium tablets is a leukotriene receptor antagonist indicated for:

• •
  Prophylaxis and chronic treatment of asthma in patients 12 months of age and older (1.1).
• •
  Acute prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older (1.2).
• •
  Relief of symptoms of allergic rhinitis (AR): seasonal allergic rhinitis (SAR) in patients 2 years of age and older, and perennial allergic rhinitis (PAR) in patients 6 months of age and older (1.3).

Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium. Although montelukast sodium is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to truncate bronchoconstrictor response to aspirin and other non-steroidal anti-inflammatory drugs in aspirin-sensitive asthmatic patients [see Clinical Studies (14.1) ].

No dosage adjustment is recommended in patients with renal insufficiency [see Clinical Pharmacology (12.3)].

The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene (CysLT) receptors. The CysLT type-1 (CysLT₁) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both early-and late-phase reactions and are associated with symptoms of allergic rhinitis.

Montelukast is an orally active compound that binds with high affinity and selectivity to the CysLT₁ receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or β-adrenergic receptor). Montelukast inhibits physiologic actions of LTD₄ at the CysLT₁ receptor without any agonist activity.

No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency [see Clinical Pharmacology (12.3)].

• •
  Do not prescribe montelukast sodium to treat an acute asthma attack (5.1).
• •
  Advise patients to have appropriate rescue medication available (5.1).
• •
  Inhaled corticosteroid may be reduced gradually. Do not abruptly substitute montelukast sodium for inhaled or oral corticosteroids (5.2).
• •
  Patients with known aspirin sensitivity should continue to avoid aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium (5.3).
• •
  Neuropsychiatric events have been reported with montelukast sodium. Instruct patients to be alert for neuropsychiatric events. Evaluate the risks and benefits of continuing treatment with montelukast sodium if such events occur (5.4 and 6.2).
• •
  Systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, has been reported. These events have been sometimes associated with the reduction of oral corticosteroid therapy (5.5 and 6.2).

Administration (by indications):

• •
  Asthma (2.1): Once daily in the evening for patients 12 months and older.
• •
  Acute prevention of EIB (2.2): 10 mg tablet at least 2 hours before exercise for patients 6 years of age and older.
• •
  Seasonal allergic rhinitis (2.3): Once daily for patients 2 years and older.
• •
  Perennial allergic rhinitis (2.3): Once daily for patients 6 months and older.

Dosage (by age) (2):

• •
  15 years and older: one 10-mg tablet.
• •
  6 to 14 years: one 5-mg chewable tablet.
• •
  2 to 5 years: one 4-mg chewable tablet.

Patients with both asthma and allergic rhinitis should take only one dose daily in the evening (2.4).

Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking montelukast sodium. Post-marketing reports with montelukast sodium use include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor. The clinical details of some post-marketing reports involving montelukast sodium appear consistent with a drug-induced effect.

Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with montelukast sodium if such events occur [see Adverse Reactions (6.2) ].

Patients with asthma on therapy with montelukast sodium 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 have been sometimes 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 montelukast sodium and these underlying conditions has not been established [see Adverse Reactions (6.2) ].

• •
  Montelukast sodium Tablets, 10-mg are round, white, film-coated, convex tablets, debossed with "KU" on one side and "210" on the other.
• •
  Montelukast sodium Chewable Tablets, 5-mg are round, light pink, convex tablets, debossed with "KU" on one side and "205" on the other.
• •
  Montelukast sodium Chewable Tablets, 4-mg are round, light pink, convex tablets, debossed with "KU" on one side and "204" on the other.

The following adverse reactions have been identified during post-approval use of montelukast sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: increased bleeding tendency, thrombocytopenia.

Immune system disorders: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration.

Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor [see Warnings and Precautions (5.4) ].

Nervous system disorders: drowsiness, paraesthesia/hypoesthesia, seizures.

Cardiac disorders: palpitations.

Respiratory, thoracic and mediastinal disorders: epistaxis, pulmonary eosinophilia.

Gastrointestinal disorders: diarrhea, dyspepsia, nausea, pancreatitis, vomiting.

Hepatobiliary disorders: Cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury have been reported in patients treated with montelukast sodium. Most of these occurred in combination with other confounding factors, such as use of other medications, or when montelukast sodium was administered to patients who had underlying potential for liver disease such as alcohol use or other forms of hepatitis.

Skin and subcutaneous tissue disorders: angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticarial.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps.

Renal and urinary disorders: enuresis in children.

General disorders and administration site conditions: edema.

Patients with asthma on therapy with montelukast sodium 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 have been sometimes 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 [see Warnings and Precautions (5.5) ].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the following description of clinical trials experience, adverse reactions are listed regardless of causality assessment.

The most common adverse reactions (incidence ≥ 5% and greater than placebo; listed in descending order of frequency) in controlled clinical trials were: upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis.

Patients with both asthma and allergic rhinitis should take only one montelukast sodium dose daily in the evening.

•  
  See FDA-approved patient labeling (Patient Information).

While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, montelukast sodium should not be abruptly substituted for inhaled or oral corticosteroids.

Montelukast sodium Chewable Tablets, 5-mg, are round, light pink, convex tablets, debossed with "KU" on one side and "205" on the other.

They are supplied as follows:

Montelukast sodium is indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older.

For prevention of EIB, a single dose of montelukast should be taken at least 2 hours before exercise.

The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

An additional dose of montelukast should not be taken within 24 hours of a previous dose. Patients already takingmontelukast sodium daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting ß-agonist. Safety and efficacy in patients younger than 6 years of age have not been established. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB. 

No evidence of tumorigenicity was seen in carcinogenicity studies of either 2 years in Sprague-Dawley rats or 92 weeks in mice at oral gavage doses up to 200 mg/kg/day or 100 mg/kg/day, respectively. The estimated exposure in rats was approximately 120 and 75 times the AUC for adults and children, respectively, at the maximum recommended daily oral dose. The estimated exposure in mice was approximately 45 and 25 times the AUC for adults and children, respectively, at the maximum recommended daily oral dose.

Montelukast demonstrated no evidence of mutagenic or clastogenic activity in the following assays: the microbial mutagenesis assay, the V-79 mammalian cell mutagenesis assay, the alkaline elution assay in rat hepatocytes, the chromosomal aberration assay in Chinese hamster ovary cells, and in the in vivo mouse bone marrow chromosomal aberration assay.

In fertility studies in female rats, montelukast produced reductions in fertility and fecundity indices at an oral dose of 200 mg/kg (estimated exposure was approximately 70 times the AUC for adults at the maximum recommended daily oral dose). No effects on female fertility or fecundity were observed at an oral dose of 100 mg/kg (estimated exposure was approximately 20 times the AUC for adults at the maximum recommended daily oral dose). Montelukast had no effects on fertility in male rats at oral doses up to 800 mg/kg (estimated exposure was approximately 160 times the AUC for adults at the maximum recommended daily oral dose).