MONTELUKAST SODIUM- montelukast tablet, chewable

United States - English - NLM (National Library of Medicine)

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Active ingredient:
MONTELUKAST SODIUM (UNII: U1O3J18SFL) (MONTELUKAST - UNII:MHM278SD3E)
Available from:
Bryant Ranch Prepack
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Montelukast sodium tablets, chewable tablets and oral granules are indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older. Montelukast sodium tablets and chewable tablets are indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older. Montelukast sodium tablets, chewable tablets and oral granules are 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. - Hypersensitivity to any component of this product. Risk Summary Available data from published prospective and retrospective cohort studies over decades with montelukast use in pregnant women have not established a drug-associated risk of major birth defects [see Data] . In animal reproduction studies, no adverse developmental effects were observed with oral administration of montelukast to pregnant rats and rabbits during org
Product summary:
Product: 63629-8235 NDC: 63629-8235-1 30 TABLET, CHEWABLE in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
63629-8235-1

MONTELUKAST SODIUM - montelukast tablet, chewable

Bryant Ranch Prepack

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use MONTELUKAST SODIUM TABLETS,

CHEWABLE TABLETS AND ORAL GRANULES safely and effectively. See full prescribing information for

MONTELUKAST SODIUM TABLETS, CHEWABLE TABLETS AND ORAL GRANULES.

MONTELUKAST sodium tablets, chewable tablets and oral granules

Initial U.S. Approval: 1998

RECENT MAJOR CHANGES

Warnings and Precautions, Neuropsychiatric Events (5.4) 12/2018

INDICATIONS AND USAGE

Montelukast sodium tablets, chewable tablets, and oral granules are 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).

DOSAGE AND ADMINISTRATION

Administration (by indications):

Asthma (2.1): Once daily in the evening for patients 12 months and older.

Acute prevention of EIB (2.2): One 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 or one sachet of 4-mg oral granules.

6 to 23 months: one sachet of 4-mg oral granules.

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

administer within 15 minutes after opening the sachet (with or without mixing with food) (2.5).

DOSAGE FORMS AND STRENGTHS

Montelukast sodium 10-mg Film-Coated Tablets

Montelukast sodium 5-mg and 4-mg Chewable Tablets

Montelukast sodium 4-mg Oral Granules (3)

CONTRAINDICATIONS

Hypersensitivity to any component of this product (4).

WARNINGS AND PRECAUTIONS

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).

Inform patients with phenylketonuria that the 4-mg and 5-mg chewable tablets contain phenylalanine (5.6).

ADVERSE REACTIONS

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 Ajanta Pharma USA Inc. at 855-664-7744 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 9/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Asthma

1.2 Exercise-Induced Bronchoconstriction (EIB)

1.3 Allergic Rhinitis

2 DOSAGE AND ADMINISTRATION

2.1 Asthma

2.2 Exercise-Induced Bronchoconstriction (EIB)

2.3 Allergic Rhinitis

2.4 Asthma and Allergic Rhinitis

2.5 Instructions for Administration of Oral Granules

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Acute Asthma

5.2 Concomitant Corticosteroid Use

5.3 Aspirin Sensitivity

5.4 Neuropsychiatric Events

5.5 Eosinophilic Conditions

5.6 Phenylketonuria

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post-Marketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Insufficiency

8.7 Renal Insufficiency

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

14 CLINICAL STUDIES

14.1 Asthma

14.2 Exercise-Induced Bronchoconstriction (EIB)

14.3 Allergic Rhinitis (Seasonal and Perennial)

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Asthma

Montelukast sodium tablets, chewable tablets and oral granules are indicated for the prophylaxis and

chronic treatment of asthma in adults and pediatric patients 12 months of age and older.

1.2 Exercise-Induced Bronchoconstriction (EIB)

Montelukast sodium tablets and chewable tablets are indicated for prevention of exercise-induced

bronchoconstriction (EIB) in patients 6 years of age and older.

1.3 Allergic Rhinitis

Sections or subsections omitted from the full prescribing information are not listed.

Montelukast sodium tablets, chewable tablets and oral granules are 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.

2 DOSAGE AND ADMINISTRATION

2.1 Asthma

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 or one sachet of 4-mg oral

granules.

For pediatric patients 12 to 23 months of age: one sachet of 4-mg oral granules.

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.

2.2 Exercise-Induced Bronchoconstriction (EIB)

For prevention of EIB, a single dose of montelukast sodium tablets 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 sodium tablets or chewable tablets should not be taken within 24

hours of a previous dose. Patients already taking montelukast 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 β-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.

2.3 Allergic Rhinitis

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 or one sachet of 4-mg oral

granules.

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 or one sachet of 4-mg oral

granules.

For pediatric patients 6 to 23 months of age: one sachet of 4-mg oral granules.

Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic

rhinitis have not been established.

2.4 Asthma and Allergic Rhinitis

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

evening.

2.5 Instructions for Administration of Oral Granules

Montelukast sodium 4-mg oral granules can be administered either directly in the mouth, dissolved in 1

teaspoonful (5 mL) of cold or room temperature baby formula or breast milk, or mixed with a spoonful

of cold or room temperature soft foods; based on stability studies, only applesauce, carrots, rice, or ice

cream should be used. The sachet should not be opened until ready to use. After opening the sachet, the

full dose (with or without mixing with baby formula, breast milk, or food) must be administered within

15 minutes. If mixed with baby formula, breast milk, or food, montelukast sodium oral granules must not

be stored for future use. Discard any unused portion. Montelukast sodium oral granules are not intended

to be dissolved in any liquid other than baby formula or breast milk for administration. However, liquids

may be taken subsequent to administration. Montelukast sodium oral granules can be administered

without regard to the time of meals.

3 DOSAGE FORMS AND STRENGTHS

Montelukast sodium 10-mg Film-Coated Tablets are beige colored, circular, biconvex tablets, with

code 'MO1' engraved on one side and plain on the other side.

Montelukast sodium 5-mg Chewable Tablets are pink colored, slightly mottled, circular, biconvex,

uncoated tablets, with code 'MT2' engraved on one side and plain on the other side.

Montelukast sodium 4-mg Chewable Tablets are pink colored, slightly mottled, circular, biconvex,

uncoated tablets, with code 'MT1' engraved on one side and plain on the other side.

Montelukast sodium 4-mg Oral Granules are white granules with 500 mg net weight, packed in a

child-resistant foil sachet.

4 CONTRAINDICATIONS

Hypersensitivity to any component of this product.

5 WARNINGS AND PRECAUTIONS

5.1 Acute Asthma

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.

5.2 Concomitant Corticosteroid Use

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.

5.3 Aspirin Sensitivity

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)].

5.4 Neuropsychiatric Events

Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking

montelukast sodium. Post-marketing reports with montelukast sodium use include, but are not limited to,

agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in

attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, obsessive-

compulsive symptoms, 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)].

5.5 Eosinophilic Conditions

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)].

5.6 Phenylketonuria

Phenylketonuric patients should be informed that the 4-mg and 5-mg chewable tablets contain

phenylalanine (a component of aspartame), 0.449 and 0.561 mg per 4-mg and 5-mg chewable tablet,

respectively.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

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.

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:

Table 1: Adverse Experiences Occurring in ≥1% of Patients with an Incidence Greater than that in Patients Treated with

Placebo

Montelukast Sodium

10 mg/day (%)

(n=1955)

Placebo

(%)

(n=1180)

*Number of patients tested (Montelukast sodium tablets and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924,

1159.

Body As A Whole

Pain, abdominal

Asthenia/fatigue

Fever

Trauma

Digestive System Disorders

Dyspepsia

Pain, dental

Gastroenteritis, infectious

Nervous System/Psychiatric

Headache

18.4

18.1

Dizziness

Respiratory System Disorders

Influenza

Cough

Congestion, nasal

Skin/Skin Appendages Disorder

Rash

Laboratory Adverse Experiences*

ALT increased

AST increased

Pyuria

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.

Pediatric Patients 6 to 14 Years of Age with Asthma

Montelukast sodium has been evaluated for safety in 476 pediatric patients 6 to 14 years of age.

Cumulatively, 289 pediatric patients were treated with montelukast sodium for at least 6 months, and 241

for one year or longer in clinical trials. The safety profile of montelukast sodium 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 montelukast sodium, the following events occurred with a

frequency ≥2% and more frequently than in pediatric patients who received placebo: pharyngitis,

influenza, fever, sinusitis, nausea, diarrhea, dyspepsia, otitis, viral infection, and laryngitis. The

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

With prolonged treatment, the adverse experience profile did not significantly change.

The safety profile of montelukast sodium, when administered as a single dose for prevention of EIB in

pediatric patients 6 years of age and older, was consistent with the safety profile previously described

for montelukast sodium.

In studies evaluating growth rate, the safety profile in these pediatric patients was consistent with the

safety profile previously described for montelukast sodium. In a 56-week, double-blind study

evaluating growth rate in pediatric patients 6 to 8 years of age receiving montelukast sodium, the

following events not previously observed with the use of montelukast sodium in this age group

occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo:

headache, rhinitis (infective), varicella, gastroenteritis, atopic dermatitis, acute bronchitis, tooth

infection, skin infection, and myopia.

Pediatric Patients 2 to 5 Years of Age with Asthma

Montelukast sodium 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

montelukast sodium for at least 3 months, 230 for 6 months or longer, and 63 patients for one year or

longer in clinical trials. In pediatric patients 2 to 5 years of age receiving montelukast sodium, the

following events occurred with a frequency ≥2% and more frequently than in pediatric patients who

received placebo: fever, cough, abdominal pain, diarrhea, headache, rhinorrhea, sinusitis, otitis,

influenza, rash, ear pain, gastroenteritis, eczema, urticaria, varicella, pneumonia, dermatitis, and

conjunctivitis.

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.

Adults and Adolescents 15 Years of Age and Older with Seasonal Allergic Rhinitis

Montelukast sodium has been evaluated for safety in 2199 adult and adolescent patients 15 years of age

and older in clinical trials. Montelukast sodium administered once daily in the morning or in the evening

had a safety profile similar to that of placebo. In placebo-controlled clinical trials, the following event

was reported with montelukast sodium with a frequency ≥1% and at an incidence greater than placebo:

upper respiratory infection, 1.9% of patients receiving montelukast sodium vs. 1.5% of patients

receiving placebo. In a 4-week, placebo-controlled clinical study, the safety profile was consistent with

that observed in 2-week studies. The incidence of somnolence was similar to that of placebo in all

studies.

Pediatric Patients 2 to 14 Years of Age with Seasonal Allergic Rhinitis

Montelukast sodium has been evaluated in 280 pediatric patients 2 to 14 years of age in a 2-week,

multicenter, double-blind, placebo-controlled, parallel-group safety study. Montelukast sodium

administered once daily in the evening had a safety profile similar to that of placebo. In this study, the

following events occurred with a frequency ≥2% and at an incidence greater than placebo: headache,

otitis media, pharyngitis, and upper respiratory infection.

Adults and Adolescents 15 Years of Age and Older with Perennial Allergic Rhinitis

Montelukast sodium has been evaluated for safety in 3357 adult and adolescent patients 15 years of age

and older with perennial allergic rhinitis of whom 1632 received montelukast sodium in two, 6-week,

clinical studies. Montelukast sodium administered once daily had a safety profile consistent with that

observed in patients with seasonal allergic rhinitis and similar to that of placebo. In these two studies,

the following events were reported with montelukast sodium with a frequency ≥1% and at an incidence

greater than placebo: sinusitis, upper respiratory infection, sinus headache, cough, epistaxis, and

increased ALT. The incidence of somnolence was similar to that of placebo.

Pediatric Patients 6 Months to 14 Years of Age with Perennial Allergic Rhinitis

The safety in patients 2 to 14 years of age with perennial allergic rhinitis is supported by the safety in

patients 2 to 14 years of age with seasonal allergic rhinitis. The safety in patients 6 to 23 months of age

is supported by data from pharmacokinetic and safety and efficacy studies in asthma in this pediatric

population and from adult pharmacokinetic studies.

6.2 Post-Marketing Experience

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: including, but not limited to, agitation, aggressive behavior or hostility,

anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations,

insomnia, irritability, memory impairment, obsessive-compulsive symptoms, 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, urticaria.

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)].

7 DRUG INTERACTIONS

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)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from published prospective and retrospective cohort studies over decades with

montelukast use in pregnant women have not established a drug-associated risk of major birth defects

[see Data]. In animal reproduction studies, no adverse developmental effects were observed with oral

administration of montelukast to pregnant rats and rabbits during organogenesis at doses approximately

100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based

on AUCs [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In

the U.S. general population, the estimated background risk of major birth defects and miscarriage in

clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Poorly or moderately controlled asthma in pregnancy increases the maternal risk of perinatal adverse

outcomes such as preeclampsia and infant prematurity, low birth weight, and small for gestational age.

Data

Human Data

Published data from prospective and retrospective cohort studies have not identified an association with

montelukast use during pregnancy and major birth defects. Available studies have methodologic

limitations, including small sample size, in some cases retrospective data collection, and inconsistent

comparator groups.

Animal Data

In embryo-fetal development studies, montelukast administered to pregnant rats and rabbits during

organogenesis (gestation days 6 to 17 in rats and 6 to 18 in rabbits) did not cause any adverse

developmental effects at maternal oral doses up to 400 and 300 mg/kg/day in rats and rabbits,

respectively (approximately 100 and 110 times the AUC in humans at the MRHDOD, respectively).

8.2 Lactation

Risk Summary

A published clinical lactation study reports the presence of montelukast in human milk. Data available on

the effects of the drug on infants, either directly [see Use in Specific Populations (8.4)] or through breast

milk, do not suggest a significant risk of adverse events from exposure to montelukast. The effects of

the drug on milk production are unknown. The developmental and health benefits of breastfeeding

should be considered along with the mother’s clinical need for montelukast and any potential adverse

effects on the breastfed infant from montelukast or from the underlying maternal condition.

8.4 Pediatric Use

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.

Growth Rate in Pediatric Patients

A 56-week, multi-center, double-blind, randomized, active- and placebo-controlled parallel group study

was conducted to assess the effect of montelukast sodium on growth rate in 360 patients with mild

asthma, aged 6 to 8 years. Treatment groups included montelukast sodium 5 mg once daily, placebo, and

beclomethasone dipropionate administered as 168 mcg twice daily with a spacer device. For each

subject, a growth rate was defined as the slope of a linear regression line fit to the height measurements

over 56 weeks. The primary comparison was the difference in growth rates between montelukast

sodium and placebo groups. Growth rates, expressed as least-squares (LS) mean (95% CI) in cm/year,

for the montelukast sodium, placebo, and beclomethasone treatment groups were 5.67 (5.46, 5.88), 5.64

(5.42, 5.86), and 4.86 (4.64, 5.08), respectively. The differences in growth rates, expressed as least-

squares (LS) mean (95% CI) in cm/year, for montelukast sodium minus placebo, beclomethasone minus

placebo, and montelukast sodium minus beclomethasone treatment groups were 0.03 (-0.26, 0.31), -0.78

(-1.06, -0.49); and 0.81 (0.53, 1.09), respectively. Growth rate (expressed as mean change in height

over time) for each treatment group is shown in FIGURE 1.

Figure 1: Change in Height (cm) from Randomization Visit by Scheduled Week (Treatment

Group Mean ± Standard Error* of the Mean)

8.5 Geriatric Use

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.

8.6 Hepatic Insufficiency

No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency [see Clinical

Pharmacology (12.3)].

8.7 Renal Insufficiency

No dosage adjustment is recommended in patients with renal insufficiency [see Clinical Pharmacology

(12.3)].

10 OVERDOSAGE

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.

11 DESCRIPTION

Montelukast sodium USP, the active ingredient in montelukast sodium tablets, chewable tablets and oral

granules, is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl

leukotriene CysLT 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 C

H ClNNaO S, 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 USP, which is

equivalent to 10 mg of montelukast, and the following inactive ingredients: microcrystalline cellulose,

lactose monohydrate, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. The

film coating consists of: hydroxypropyl methylcellulose, hydroxypropyl cellulose, titanium

dioxide, ferric oxide red and ferric oxide yellow.

Each 4-mg and 5-mg chewable montelukast sodium tablet contains 4.2 and 5.2 mg montelukast sodium

USP, respectively, which are equivalent to 4 and 5 mg of montelukast, respectively. Both chewable

tablets contain the following inactive ingredients: mannitol, microcrystalline cellulose, hydroxypropyl

cellulose, ferric oxide red, croscarmellose sodium, cherry flavor, aspartame, and magnesium stearate.

Each sachet of montelukast sodium 4-mg oral granules contains 4.2 mg montelukast sodium USP, which

is equivalent to 4 mg of montelukast. The oral granule formulation contains the following inactive

ingredients: mannitol, hydroxypropyl cellulose, and magnesium stearate.

Montelukast sodium oral granules meets USP Dissolution Test 4.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The cysteinyl leukotrienes (LTC , LTD , LTE ) 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 (CysLT ) 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 CysLT

receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid,

cholinergic, or β-adrenergic receptor). Montelukast inhibits physiologic actions of LTD at the

CysLT receptor without any agonist activity.

12.2 Pharmacodynamics

Montelukast causes inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to

inhibit bronchoconstriction due to inhaled LTD in asthmatics. Doses as low as 5 mg cause substantial

blockage of LTD -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)].

12.3 Pharmacokinetics

Absorption

Montelukast 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

) is achieved in 3 to

4 hours (T

). The mean oral bioavailability is 64%. The oral bioavailability and C

are not

influenced by a standard meal in the morning.

For the 5-mg chewable tablet, the mean C

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

is achieved 2 hours after administration in pediatric

patients 2 to 5 years of age in the fasted state.

The 4-mg oral granule formulation is bioequivalent to the 4-mg chewable tablet when administered to

adults in the fasted state. The co-administration of the oral granule formulation with applesauce did not

have a clinically significant effect on the pharmacokinetics of montelukast. A high fat meal in the

morning did not affect the AUC of montelukast oral granules; however, the meal decreased C

35% and prolonged T

from 2.3 ± 1 hours to 6.4 ± 2.9 hours.

The safety and efficacy of montelukast sodium 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 montelukast sodium 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

safety and efficacy of montelukast sodium in patients with seasonal allergic rhinitis were demonstrated

in clinical trials in which the 10-mg film-coated tablet was administered in the morning or evening

without regard to the time of food ingestion.

The comparative pharmacokinetics of montelukast when administered as two 5-mg chewable tablets

versus one 10-mg film-coated tablet have not been evaluated.

Distribution

Montelukast is more than 99% bound to plasma proteins. The steady state volume of distribution of

montelukast averages 8 to 11 liters. Studies in rats with radiolabeled montelukast indicate minimal

distribution across the blood-brain barrier. In addition, concentrations of radiolabeled material at 24

hours postdose were minimal in all other tissues.

Metabolism

Montelukast is extensively metabolized. In studies with therapeutic doses, plasma concentrations of

metabolites of montelukast are undetectable at steady state in adults and pediatric patients.

In vitro studies using human liver microsomes indicate that CYP3A4, 2C8, and 2C9 are involved in the

metabolism of montelukast. At clinically relevant concentrations, 2C8 appears to play a major role in the

metabolism of montelukast.

Elimination

The plasma clearance of montelukast 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 montelukast oral bioavailability, this indicates that

montelukast and its metabolites are excreted almost exclusively via the bile.

In several studies, the mean plasma half-life of montelukast ranged from 2.7 to 5.5 hours in healthy

young adults. The pharmacokinetics of montelukast are nearly linear for oral doses up to 50 mg. During

once-daily dosing with 10-mg montelukast, there is little accumulation of the parent drug in plasma

(14%).

Special Populations

Hepatic Insufficiency: Patients with mild-to-moderate hepatic insufficiency and clinical evidence of

cirrhosis had evidence of decreased metabolism of montelukast resulting in 41% (90% CI=7%, 85%)

higher mean montelukast AUC following a single 10-mg dose. The elimination of montelukast 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

montelukast sodium in patients with more severe hepatic impairment or with hepatitis have not been

evaluated.

Renal Insufficiency: Since montelukast and its metabolites are not excreted in the urine, the

pharmacokinetics of montelukast were not evaluated in patients with renal insufficiency. No dosage

adjustment is recommended in these patients.

Gender: The pharmacokinetics of montelukast are similar in males and females.

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

Adolescents and Pediatric Patients: Pharmacokinetic studies evaluated the systemic exposure of the 4-mg

oral granule formulation in pediatric patients 6 to 23 months of age, the 4-mg chewable tablets in

pediatric patients 2 to 5 years of age, the 5-mg chewable tablets in pediatric patients 6 to 14 years of

age, and the 10-mg film-coated tablets in young adults and adolescents ≥15 years of age.

The plasma concentration profile of montelukast following administration of the 10-mg film-coated

tablet is similar in adolescents ≥15 years of age and young adults. The 10-mg film-coated tablet is

recommended for use in patients ≥15 years of age.

The mean systemic exposure of the 4-mg chewable tablet in pediatric patients 2 to 5 years of age and

the 5-mg chewable tablets in pediatric patients 6 to 14 years of age is similar to the mean systemic

exposure of the 10-mg film-coated tablet in adults. The 5-mg chewable tablet should be used in

pediatric patients 6 to 14 years of age and the 4-mg chewable tablet should be used in pediatric patients

2 to 5 years of age.

In children 6 to 11 months of age, the systemic exposure to montelukast and the variability of plasma

montelukast concentrations were higher than those observed in adults. Based on population analyses, the

mean AUC (4296 nghr/mL [range 1200 to 7153]) was 60% higher and the mean C

(667 ng/mL

[range 201 to 1058]) was 89% higher than those observed in adults (mean AUC 2689 nghr/mL [range

1521 to 4595]) and mean C

(353 ng/mL [range 180 to 548]). The systemic exposure in children 12 to

23 months of age was less variable, but was still higher than that observed in adults. The mean AUC

(3574 nghr/mL [range 2229 to 5408]) was 33% higher and the mean C

(562 ng/mL [range 296 to

814]) was 60% higher than those observed in adults. Safety and tolerability of montelukast in a single-

dose pharmacokinetic study in 26 children 6 to 23 months of age were similar to that of patients two

years and above [see Adverse Reactions (6.1)]. The 4-mg oral granule formulation should be used for

pediatric patients 12 to 23 months of age for the treatment of asthma, or for pediatric patients 6 to 23

months of age for the treatment of perennial allergic rhinitis. Since the 4-mg oral granule formulation is

bioequivalent to the 4-mg chewable tablet, it can also be used as an alternative formulation to the 4-mg

chewable tablet in pediatric patients 2 to 5 years of age.

Drug-Drug Interactions

Theophylline, Prednisone, and Prednisolone: Montelukast sodium has been administered with other

therapies routinely used in the prophylaxis and chronic treatment of asthma with no apparent increase in

adverse reactions. In drug-interaction studies, the recommended clinical dose of montelukast did not

have clinically important effects on the pharmacokinetics of the following drugs: theophylline,

prednisone, and prednisolone.

Montelukast at a dose of 10 mg once daily dosed to pharmacokinetic steady state, did not cause

clinically significant changes in the kinetics of a single intravenous dose of theophylline [predominantly

a cytochrome P450 (CYP) 1A2 substrate]. Montelukast at doses of ≥100 mg daily dosed to

pharmacokinetic steady state, did not cause any clinically significant change in plasma profiles of

prednisone or prednisolone following administration of either oral prednisone or intravenous

prednisolone.

Oral Contraceptives, Terfenadine, Digoxin, and Warfarin: In drug interaction studies, the recommended

clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the

following drugs: oral contraceptives (norethindrone 1 mg/ethinyl estradiol 35 mcg), terfenadine,

digoxin, and warfarin. Montelukast at doses of ≥100 mg daily dosed to pharmacokinetic steady state did

not significantly alter the plasma concentrations of either component of an oral contraceptive containing

norethindrone 1 mg/ethinyl estradiol 35 mcg. Montelukast at a dose of 10 mg once daily dosed to

pharmacokinetic steady state did not change the plasma concentration profile of terfenadine (a substrate

of CYP3A4) or fexofenadine, the carboxylated metabolite, and did not prolong the QTc interval

following co-administration with terfenadine 60 mg twice daily; did not change the pharmacokinetic

profile or urinary excretion of immunoreactive digoxin; did not change the pharmacokinetic profile of

warfarin (primarily a substrate of CYP2C9, 3A4 and 1A2) or influence the effect of a single 30-mg oral

dose of warfarin on prothrombin time or the International Normalized Ratio (INR).

Thyroid Hormones, Sedative Hypnotics, Non-Steroidal Anti-Inflammatory Agents, Benzodiazepines, and

Decongestants: Although additional specific interaction studies were not performed, montelukast sodium

was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without

evidence of clinical adverse interactions. These medications included thyroid hormones, sedative

hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants.

Cytochrome P450 (CYP) Enzyme Inducers: Phenobarbital, which induces hepatic metabolism, decreased

the area under the plasma concentration curve (AUC) of montelukast approximately 40% following a

single 10-mg dose of montelukast. No dosage adjustment for montelukast sodium is recommended. It is

reasonable to employ appropriate clinical monitoring when potent CYP enzyme inducers, such as

phenobarbital or rifampin, are co-administered with montelukast sodium.

Effect of Montelukast on Cytochrome P450 (CYP) Enzymes: Montelukast is a potent inhibitor of

CYP2C8 in vitro. However, data from a clinical drug-drug interaction study involving montelukast and

rosiglitazone (a probe substrate representative of drugs primarily metabolized by CYP2C8) in 12

healthy individuals demonstrated that the pharmacokinetics of rosiglitazone are not altered when the

drugs are coadministered, indicating that montelukast does not inhibit CYP2C8 in vivo. Therefore,

montelukast is not anticipated to alter the metabolism of drugs metabolized by this enzyme (e.g.,

paclitaxel, rosiglitazone, and repaglinide). Based on further in vitro results in human liver microsomes,

therapeutic plasma concentrations of montelukast do not inhibit CYP 3A4, 2C9, 1A2, 2A6, 2C19, or

2D6.

Cytochrome P450 (CYP) Enzyme Inhibitors: In vitro studies have shown that montelukast is a substrate of

CYP 2C8, 2C9, and 3A4. Co-administration of montelukast with itraconazole, a strong CYP 3A4

inhibitor, resulted in no significant increase in the systemic exposure of montelukast. Data from a

clinical drug-drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP

2C8 and 2C9) demonstrated that gemfibrozil, at a therapeutic dose, increased the systemic exposure of

montelukast by 4.4-fold. Co-administration of itraconazole, gemfibrozil, and montelukast did not further

increase the systemic exposure of montelukast. Based on available clinical experience, no dosage

adjustment of montelukast is required upon co-administration with gemfibrozil [see Overdosage (10)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

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).

14 CLINICAL STUDIES

14.1 Asthma

Adults and Adolescents 15 Years of Age and Older with Asthma

Clinical trials in adults and adolescents 15 years of age and older demonstrated there is no additional

clinical benefit to montelukast doses above 10 mg once daily.

The efficacy of montelukast sodium for the chronic treatment of asthma in adults and adolescents 15

years of age and older was demonstrated in two (U.S. and Multinational) similarly designed, randomized,

12-week, double-blind, placebo-controlled trials in 1576 patients (795 treated with montelukast sodium,

530 treated with placebo, and 251 treated with active control). The median age was 33 years (range 15 to

85); 56.8% were females and 43.2% were males. The ethnic/racial distribution in these studies was

71.6% Caucasian, 17.7% Hispanic, 7.2% other origins and 3.5% Black. Patients had mild or moderate

asthma and were non-smokers who required approximately 5 puffs of inhaled β-agonist per day on an

"as-needed" basis. The patients had a mean baseline percent of predicted forced expiratory volume in 1

second (FEV ) of 66% (approximate range, 40 to 90%). The co-primary endpoints in these trials were

FEV and daytime asthma symptoms. In both studies after 12 weeks, a random subset of patients

receiving montelukast sodium was switched to placebo for an additional 3 weeks of double-blind

treatment to evaluate for possible rebound effects.

The results of the U.S. trial on the primary endpoint, morning FEV , expressed as mean percent change

from baseline averaged over the 12-week treatment period, are shown in FIGURE 2. Compared with

placebo, treatment with one montelukast sodium 10-mg tablet daily in the evening resulted in a

statistically significant increase in FEV percent change from baseline (13%-change in the group

treated with montelukast sodium vs. 4.2%-change in the placebo group, p<0.001); the change from

baseline in FEV for montelukast sodium was 0.32 liters compared with 0.10 liters for placebo,

corresponding to a between-group difference of 0.22 liters (p<0.001, 95% CI 0.17 liters, 0.27 liters).

The results of the Multinational trial on FEV were similar.

Figure 2: FEV1 Mean Percent Change from Baseline

(U.S. Trial: Montelukast sodium tablets N=406; Placebo N=270) (ANOVA Model)

The effect of montelukast sodium on other primary and secondary endpoints, represented by the

Multinational study is shown in TABLE 2. Results on these endpoints were similar in the US study.

Table 2: Effect of Montelukast sodium on Primary and Secondary Endpoints in a Multinational Placebo-controlled Trial

(ANOVA Model)

Endpoint

Montelukast Sodium

Placebo

N

Bas eline

Mean Change from

Bas eline

N

Bas eline

Mean Change from

Bas eline

*p<0.001, compared with placebo

Daytime Asthma Symptoms

(0 to 6 scale)

2.35

-0.49

2.40

-0.26

β-agonist (puffs per day)

5.35

-1.65

5.78

-0.42

AM PEFR (L/min)

339.57

25.03

335.24

1.83

PM PEFR (L/min)

355.23

20.13

354.02

-0.49

Nocturnal Awakenings

(#/week)

5.46

-2.03

5.57

-0.78

Both studies evaluated the effect of montelukast sodium on secondary outcomes, including asthma attack

(utilization of health-care resources such as an unscheduled visit to a doctor's office, emergency room,

or hospital; or treatment with oral, intravenous, or intramuscular corticosteroid), and use of oral

corticosteroids for asthma rescue. In the Multinational study, significantly fewer patients (15.6% of

patients) on montelukast sodium experienced asthma attacks compared with patients on placebo (27.3%,

p< 0.001). In the US study, 7.8% of patients on montelukast sodium and 10.3% of patients on placebo

experienced asthma attacks, but the difference between the two treatment groups was not significant

(p=0.334). In the Multinational study, significantly fewer patients (14.8% of patients) on montelukast

sodium were prescribed oral corticosteroids for asthma rescue compared with patients on placebo

(25.7%, p < 0.001). In the US study, 6.9% of patients on montelukast sodium and 9.9% of patients on

placebo were prescribed oral corticosteroids for asthma rescue, but the difference between the two

treatment groups was not significant (p=0.196).

Onset of Action and Maintenance of Effects

In each placebo-controlled trial in adults, the treatment effect of montelukast sodium, measured by daily

diary card parameters, including symptom scores, "as-needed" β-agonist use, and PEFR measurements,

was achieved after the first dose and was maintained throughout the dosing interval (24 hours). No

significant change in treatment effect was observed during continuous once-daily evening administration

in non-placebo-controlled extension trials for up to one year. Withdrawal of montelukast sodium in

asthmatic patients after 12 weeks of continuous use did not cause rebound worsening of asthma.

Pediatric Patients 6 to 14 Years of Age with Asthma

The efficacy of montelukast sodium in pediatric patients 6 to 14 years of age was demonstrated in one

8-week, double-blind, placebo-controlled trial in 336 patients (201 treated with montelukast sodium and

135 treated with placebo) using an inhaled β-agonist on an "as-needed" basis. The patients had a mean

baseline percent predicted FEV of 72% (approximate range, 45 to 90%) and a mean daily inhaled β-

agonist requirement of 3.4 puffs of albuterol. Approximately 36% of the patients were on inhaled

corticosteroids. The median age was 11 years (range 6 to 15); 35.4% were females and 64.6% were

males. The ethnic/racial distribution in this study was 80.1% Caucasian, 12.8% Black, 4.5% Hispanic,

and 2.7% other origins.

Compared with placebo, treatment with one 5-mg montelukast sodium chewable tablet daily resulted in a

significant improvement in mean morning FEV percent change from baseline (8.7% in the group treated

with montelukast sodium vs. 4.2% change from baseline in the placebo group, p<0.001). There was a

significant decrease in the mean percentage change in daily "as-needed" inhaled β-agonist use (11.7%

decrease from baseline in the group treated with montelukast sodium vs. 8.2% increase from baseline in

the placebo group, p<0.05). This effect represents a mean decrease from baseline of 0.56 and 0.23

puffs per day for the montelukast and placebo groups, respectively. Subgroup analyses indicated that

younger pediatric patients aged 6 to 11 had efficacy results comparable to those of the older pediatric

patients aged 12 to 14.

Similar to the adult studies, no significant change in the treatment effect was observed during continuous

once-daily administration in one open-label extension trial without a concurrent placebo group for up to

6 months.

Pediatric Patients 2 to 5 Years of Age with Asthma

The efficacy of montelukast sodium for the chronic treatment of asthma in pediatric patients 2 to 5 years

of age was explored in a 12-week, placebo-controlled safety and tolerability study in 689 patients, 461

of whom were treated with montelukast sodium. The median age was 4 years (range 2 to 6); 41.5% were

females and 58.5% were males. The ethnic/racial distribution in this study was 56.5% Caucasian, 20.9%

Hispanic, 14.4% other origins, and 8.3% Black.

While the primary objective was to determine the safety and tolerability of montelukast sodium in this

age group, the study included exploratory efficacy evaluations, including daytime and overnight asthma

symptom scores, β-agonist use, oral corticosteroid rescue, and the physician's global evaluation. The

findings of these exploratory efficacy evaluations, along with pharmacokinetics and extrapolation of

efficacy data from older patients, support the overall conclusion that montelukast sodium is efficacious

in the maintenance treatment of asthma in patients 2 to 5 years of age.

Effects in Patients on Concomitant Inhaled Corticosteroids

Separate trials in adults evaluated the ability of montelukast sodium to add to the clinical effect of

inhaled corticosteroids and to allow inhaled corticosteroid tapering when used concomitantly.

One randomized, placebo-controlled, parallel-group trial (n=226) enrolled adults with stable asthma

with a mean FEV of approximately 84% of predicted who were previously maintained on various

inhaled corticosteroids (delivered by metered-dose aerosol or dry powder inhalers). The median age

was 41.5 years (range 16 to 70); 52.2% were females and 47.8% were males. The ethnic/racial

distribution in this study was 92% Caucasian, 3.5% Black, 2.2% Hispanic, and 2.2% Asian. The types of

inhaled corticosteroids and their mean baseline requirements included beclomethasone dipropionate

(mean dose, 1203 mcg/day), triamcinolone acetonide (mean dose, 2004 mcg/day), flunisolide (mean

dose, 1971 mcg/day), fluticasone propionate (mean dose, 1083 mcg/day), or budesonide (mean dose,

1192 mcg/day). Some of these inhaled corticosteroids were non-U.S.-approved formulations, and doses

expressed may not be ex-actuator. The pre-study inhaled corticosteroid requirements were reduced by

approximately 37% during a 5- to 7-week placebo run-in period designed to titrate patients toward their

lowest effective inhaled corticosteroid dose. Treatment with montelukast sodium resulted in a further

47% reduction in mean inhaled corticosteroid dose compared with a mean reduction of 30% in the

placebo group over the 12-week active treatment period (p≤0.05). It is not known whether the results of

this study can be generalized to patients with asthma who require higher doses of inhaled

corticosteroids or systemic corticosteroids.

In another randomized, placebo-controlled, parallel-group trial (n=642) in a similar population of adult

patients previously maintained, but not adequately controlled, on inhaled corticosteroids

(beclomethasone 336 mcg/day), the addition of montelukast sodium to beclomethasone resulted in

statistically significant improvements in FEV compared with those patients who were continued on

beclomethasone alone or those patients who were withdrawn from beclomethasone and treated with

montelukast or placebo alone over the last 10 weeks of the 16-week, blinded treatment period. Patients

who were randomized to treatment arms containing beclomethasone had statistically significantly better

asthma control than those patients randomized to montelukast sodium alone or placebo alone as indicated

by FEV , daytime asthma symptoms, PEFR, nocturnal awakenings due to asthma, and "as-needed" β-

agonist requirements.

In adult patients with asthma with documented aspirin sensitivity, nearly all of whom were receiving

concomitant inhaled and/or oral corticosteroids, a 4-week, randomized, parallel-group trial (n=80)

demonstrated that montelukast sodium, compared with placebo, resulted in significant improvement in

parameters of asthma control. The magnitude of effect of montelukast sodium in aspirin-sensitive

patients was similar to the effect observed in the general population of asthma patients studied. The

patients was similar to the effect observed in the general population of asthma patients studied. The

effect of montelukast sodium on the bronchoconstrictor response to aspirin or other non-steroidal anti-

inflammatory drugs in aspirin-sensitive asthmatic patients has not been evaluated [see Warnings and

Precautions (5.3)].

14.2 Exercise-Induced Bronchoconstriction (EIB)

Exercise-Induced Bronchoconstriction (Adults, Adolescents, and Pediatric Patients 6 years of

age and older)

The efficacy of montelukast sodium, 10 mg, when given as a single dose 2 hours before exercise for

the prevention of EIB was investigated in three (U.S. and Multinational), randomized, double-blind,

placebo-controlled crossover studies that included a total of 160 adult and adolescent patients 15 years

of age and older with EIB. Exercise challenge testing was conducted at 2 hours, 8.5 or 12 hours, and 24

hours following administration of a single dose of study drug (montelukast sodium 10 mg or placebo).

The primary endpoint was the mean maximum percent fall in FEV following the 2 hours post-dose

exercise challenge in all three studies (Study A, Study B, and Study C). In Study A, a single dose of

montelukast sodium 10 mg demonstrated a statistically significant protective benefit against EIB when

taken 2 hours prior to exercise. Some patients were protected from EIB at 8.5 and 24 hours after

administration; however, some patients were not. The results for the mean maximum percent fall at each

timepoint in Study A are shown in TABLE 3 and are representative of the results from the other two

studies.

Table 3: Mean Maximum Percent Fall in FEV1 Following Exercise Challenge in Study A (N=47)

ANOVA Model

*Least squares-mean

Time of exercise challenge

following medication

administration

Mean Maximum percent fall in FEV

Treatment difference % for

Montelukast Sodium versus

Placebo (95% CI)

Montelukast Sodium

Placebo

2 hours

-9 (-12, -5)

8.5 hours

-5 (-9, -2)

24 hours

-4 (-7, -1)

The efficacy of montelukast sodium 5-mg chewable tablets, when given as a single dose 2 hours before

exercise for the prevention of EIB, was investigated in one multinational, randomized, double-blind,

placebo-controlled crossover study that included a total of 64 pediatric patients 6 to 14 years of age

with EIB. Exercise challenge testing was conducted at 2 hours and 24 hours following administration of

a single dose of study drug (montelukast sodium 5 mg or placebo). The primary endpoint was the mean

maximum percent fall in FEV following the 2 hours post-dose exercise challenge. A single dose of

montelukast sodium 5 mg demonstrated a statistically significant protective benefit against EIB when

taken 2 hours prior to exercise (TABLE 4). Similar results were shown at 24 hours post-dose (a

secondary endpoint). Some patients were protected from EIB at 24 hours after administration; however,

some patients were not. No timepoints were assessed between 2 and 24 hours post-dose.

Table 4: Mean Maximum Percent Fall in FEV Following Exercise Challenge in Pediatric Patients

(N=64) ANOVA Model

*Least squares-mean

Time of exercise challenge

following medication

administration

Mean Maximum percent fall in FEV *

Treatment difference % for

Montelukast Sodium versus

Placebo (95% CI)*

Montelukast Sodium

Placebo

2 hours

-5 (-9, -1)

24 hours

-4 (-7, -1)

The efficacy of montelukast sodium for prevention of EIB in patients below 6 years of age has not been

established.

Daily administration of montelukast sodium for the chronic treatment of asthma has not been established

to prevent acute episodes of EIB.

In a 12-week, randomized, double-blind, parallel group study of 110 adult and adolescent asthmatics 15

years of age and older, with a mean baseline FEV percent of predicted of 83% and with documented

exercise-induced exacerbation of asthma, treatment with montelukast sodium, 10 mg, once daily in the

evening, resulted in a statistically significant reduction in mean maximal percent fall in FEV and mean

time to recovery to within 5% of the pre-exercise FEV . Exercise challenge was conducted at the end

1

of the dosing interval (i.e., 20 to 24 hours after the preceding dose). This effect was maintained

throughout the 12-week treatment period indicating that tolerance did not occur. Montelukast sodium did

not, however, prevent clinically significant deterioration in maximal percent fall in FEV after exercise

(i.e., ≥20% decrease from pre-exercise baseline) in 52% of patients studied. In a separate crossover

study in adults, a similar effect was observed after two once-daily 10-mg doses of montelukast sodium.

In pediatric patients 6 to 14 years of age, using the 5-mg chewable tablet, a 2-day crossover study

demonstrated effects similar to those observed in adults when exercise challenge was conducted at the

end of the dosing interval (i.e., 20 to 24 hours after the preceding dose).

14.3 Allergic Rhinitis (Seasonal and Perennial)

Seasonal Allergic Rhinitis

The efficacy of montelukast sodium tablets for the treatment of seasonal allergic rhinitis was

investigated in 5 similarly designed, randomized, double-blind, parallel-group, placebo- and active-

controlled (loratadine) trials conducted in North America. The 5 trials enrolled a total of 5029 patients,

of whom 1799 were treated with montelukast sodium tablets. Patients were 15 to 82 years of age with a

history of seasonal allergic rhinitis, a positive skin test to at least one relevant seasonal allergen, and

active symptoms of seasonal allergic rhinitis at study entry.

The period of randomized treatment was 2 weeks in 4 trials and 4 weeks in one trial. The primary

outcome variable was mean change from baseline in daytime nasal symptoms score (the average of

individual scores of nasal congestion, rhinorrhea, nasal itching, sneezing) as assessed by patients on a

0-3 categorical scale.

Four of the five trials showed a significant reduction in daytime nasal symptoms scores with

montelukast sodium 10-mg tablets compared with placebo. The results of one trial are shown below.

The median age in this trial was 35 years (range 15 to 81); 65.4% were females and 34.6% were males.

The ethnic/racial distribution in this study was 83.1% Caucasian, 6.4% other origins, 5.8% Black, and

4.8% Hispanic. The mean changes from baseline in daytime nasal symptoms score in the treatment

groups that received montelukast sodium tablets, loratadine, and placebo are shown in TABLE 5. The

remaining three trials that demonstrated efficacy showed similar results.

Table 5: Effects of Montelukast sodium tablets on Daytime Nasal Symptoms Score* in a Placebo- and Active-

controlled Trial in Patients with Seasonal Allergic Rhinitis (ANCOVA Model)

Treatment Group (N)

Baseline Mean

Score

Mean Change from

Bas eline

Difference Between Treatment and

Placebo (95% CI) Least-Squares

Mean

*Average of individual scores of nasal congestion, rhinorrhea, nasal itching, sneezing as assessed by patients on a 0-3

categorical scale.

†Statistically different from placebo (p≤0.001).

‡The study was not designed for statistical comparison between montelukast sodium and the active control (loratadine).

Montelukast Sodium Tablets

10 mg (344)

2.09

-0.39

-0.13 (-0.21, -0.06)

Placebo

(351)

2.10

-0.26

N.A.

Active Control

(Loratadine 10 mg)

(599)

2.06

-0.46

-0.24 (-0.31, -0.17)

Perennial Allergic Rhinitis

The efficacy of montelukast sodium tablets for the treatment of perennial allergic rhinitis was

investigated in 2 randomized, double-blind, placebo-controlled studies conducted in North America and

Europe. The two studies enrolled a total of 3357 patients, of whom 1632 received montelukast sodium

10-mg tablets. Patients 15 to 82 years of age with perennial allergic rhinitis as confirmed by history and

a positive skin test to at least one relevant perennial allergen (dust mites, animal dander, and/or mold

spores), who had active symptoms at the time of study entry, were enrolled.

In the study in which efficacy was demonstrated, the median age was 35 years (range 15 to 81); 64.1%

were females and 35.9% were males. The ethnic/racial distribution in this study was 83.2% Caucasian,

8.1% Black, 5.4% Hispanic, 2.3% Asian, and 1% other origins. Montelukast sodium 10-mg tablets once

daily was shown to significantly reduce symptoms of perennial allergic rhinitis over a 6-week treatment

period (TABLE 6); in this study the primary outcome variable was mean change from baseline in

daytime nasal symptoms score (the average of individual scores of nasal congestion, rhinorrhea, and

sneezing).

Table 6: Effects of Montelukast sodium tablets on Daytime Nasal Symptoms Score in a Placebo-controlled Trial in

Patients with Perennial Allergic Rhinitis (ANCOVA Model)

Treatment Group (N)

Baseline Mean

Score

Mean Change from

Bas eline

Difference Between Treatment and Placebo

(95% CI) Least-Squares Mean

Average of individual scores of nasal congestion, rhinorrhea, sneezing as assessed by patients on a 0-3 categorical scale.

Statistically different from placebo (p≤0.001).

Montelukast Sodium

Tablets 10 mg (1000)

2.09

-0.42

-0.08 (-0.12,-0.04)

Placebo (980)

2.10

-0.35

N.A.

The other 6-week study evaluated montelukast sodium 10 mg (n=626), placebo (n=609), and an active-

control (cetirizine 10 mg; n=120). The primary analysis compared the mean change from baseline in

daytime nasal symptoms score for montelukast sodium vs. placebo over the first 4 weeks of treatment;

the study was not designed for statistical comparison between montelukast sodium and the active-

control. The primary outcome variable included nasal itching in addition to nasal congestion, rhinorrhea,

and sneezing. The estimated difference between montelukast sodium and placebo was -0.04 with a 95%

CI of (-0.09, 0.01). The estimated difference between the active-control and placebo was -0.10 with a

95% CI of (-0.19, -0.01).

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 63629-8235

NDC: 63629-8235-1 30 TABLET, CHEWABLE in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Information for Patients

Patients should be advised to take montelukast sodium daily as prescribed, even when they are

asymptomatic, as well as during periods of worsening asthma, and to contact their physicians if their

asthma is not well controlled.

Patients should be advised that oral montelukast sodium is not for the treatment of acute asthma

attacks. They should have appropriate short-acting inhaled β-agonist medication available to treat

asthma exacerbations. Patients who have exacerbations of asthma after exercise should be instructed

to have available for rescue a short-acting inhaled β-agonist. Daily administration of montelukast

sodium for the chronic treatment of asthma has not been established to prevent acute episodes of

EIB.

Patients should be advised that, while using montelukast sodium, medical attention should be sought

if short-acting inhaled bronchodilators are needed more often than usual, or if more than the

maximum number of inhalations of short-acting bronchodilator treatment prescribed for a 24-hour

period are needed.

Patients receiving montelukast sodium should be instructed not to decrease the dose or stop taking

any other anti-asthma medications unless instructed by a physician.

Patients should be instructed to notify their physician if neuropsychiatric events occur while using

montelukast sodium.

Patients with known aspirin sensitivity should be advised to continue avoidance of aspirin or non-

steroidal anti-inflammatory agents while taking montelukast sodium.

Phenylketonuric patients should be informed that the 4-mg and 5-mg chewable tablets contain

phenylalanine (a component of aspartame).

Marketed by:

Ajanta Pharma USA Inc.

Bridgewater, NJ 08807.

Made in India.

Revised: 01/2019

Patient Information

Montelukast Sodium (mon te loo' kast soe' dee um) Tablets, USP

Montelukast Sodium (mon te loo' kast soe' dee um) Chewable Tablets, USP

*

Montelukast Sodium (mon te loo' kast soe' dee um) Oral Granules, USP

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 tablets, chewable tablets or oral granules are used to treat:

outdoor allergies that happen part of the year (seasonal allergic rhinitis) in adults and children

ages 2 years and older, and

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 phenylketonuria. Montelukast sodium chewable tablets contain aspartame, a source of

phenylalanine

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. See the information below in the

section "How should I give montelukast sodium oral granules to my child?" for information about

what foods and liquids can be taken with montelukast sodium oral granules.

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 tablets or chewable tablets 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.

How should I give montelukast sodium oral granules to my child?

Give montelukast sodium oral granules to your child exactly as instructed by your healthcare provider.

Do not open the sachet until ready to use.

Montelukast sodium 4-mg oral granules can be given:

right in the mouth; or

dissolved in 1 teaspoonful (5 mL) of cold or room temperature baby formula or breast milk; or

mixed with 1 spoonful of one of the following soft foods at cold or room temperature: applesauce,

mashed carrots, rice, or ice cream.

Give the child all of the mixture right away, within 15 minutes.

Do not store any leftover montelukast sodium mixture (oral granules mixed with food, baby

formula, or breast milk) for use at a later time. Throw away any unused portion.

Do not mix montelukast sodium oral granules with any liquid drink other than baby formula or

breast milk. Your child may drink other liquids after swallowing the mixture.

What is the dose of montelukast sodium?

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

6 to 23 months: one sachet of 4-mg oral granules.

2 to 5 years: one 4-mg chewable tablet or one sachet of 4-mg oral granules.

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

obsessive-compulsive symptoms

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

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

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 tablets, chewable tablets or oral granules for a condition for

which it was not prescribed. Do not give montelukast sodium tablets, chewable tablets or oral granules

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.

What are the ingredients in montelukast sodium?

Active ingredient: montelukast sodium

Inactive ingredients:

4-mg oral granules: mannitol, hydroxypropyl cellulose, and magnesium stearate.

4-mg and 5-mg chewable tablets: mannitol, microcrystalline cellulose, hydroxypropyl

cellulose, ferric oxide red, croscarmellose sodium, cherry flavor, aspartame, and magnesium

stearate.

People with Phenylketonuria: Montelukast sodium 4-mg chewable tablets contain 0.449 mg of

phenylalanine, and montelukast sodium 5-mg chewable tablets contain 0.561 mg of phenylalanine.

10-mg tablet: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium,

hydroxypropyl cellulose, and magnesium stearate. The film coating contains: hydroxypropyl

methylcellulose, hydroxypropyl cellulose, titanium dioxide, ferric oxide red, and ferric oxide

yellow.

Marketed by:

Ajanta Pharma USA Inc.

Bridgewater, NJ 08807.

Made in India.

Revised: 01/2019

MONTELUKAST SODIUM 5MG CHEW.

MONTELUKAST SODIUM

montelukast tablet, chewable

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 36 29 -8 235(NDC:27241-0 17)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

MO NTELUKAST SO DIUM (UNII: U1O3J18 SFL) (MONTELUKAST - UNII:MHM278 SD3E)

MONTELUKAST

5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

MANNITO L (UNII: 3OWL53L36 A)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

HYDRO XYPRO PYL CELLULO SE ( 16 0 0 0 0 0 WAMW) (UNII: RFW2ET6 71P)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

ASPARTAME (UNII: Z0 H242BBR1)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Bryant Ranch Prepack

Product Characteristics

Color

PINK

S core

no sco re

S hap e

ROUND (circular)

S iz e

9 mm

Flavor

CHERRY

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 36 29 -8 235-1

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 9 /0 6 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 3328

0 8 /13/20 15

Labeler -

Bryant Ranch Prepack (171714327)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Bryant Ranch Prepack

171714327

REPACK(6 36 29 -8 235) , RELABEL(6 36 29 -8 235)

Revised: 9/2019

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