MONTELUKAST SODIUM tablet, chewable

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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 is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older.             Montelukast sodium is indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older. 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. - 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 organogenesis at doses approximately 100 and 110 times, respe
Product summary:
Product: 71335-1326 NDC: 71335-1326-1 30 TABLET, CHEWABLE in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
71335-1326-1

MONTELUKAST SODIUM- montelukast sodium tablet, chewable

Bryant Ranch Prepack

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HIGHLIGHTS OF PRESCRIBING INFORMATION

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use MONTELUKAST SODIUM safely and

effectively. See full prescribing information for MONTELUKAST SODIUM.

MONTELUKAST sodium tablets, for oral use

MONTELUKAST sodium chewable tablets, for oral use and MONTELUKAST sodium oral granules, for oral use

Initial U.S. Approval: 1998

RECENT MAJOR CHANGES

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

INDICATIONS AND USAGE

Montelukast sodium 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).

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 packet of 4-mg oral granules.

6 to 23 months: one packet 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 packet (with or without mixing with food) ( 2.5).

DOSAGE FORMS AND STRENGTHS

Montelukast sodium Film-coated Tablets, 10 mg

Montelukast sodium Chewable Tablets, 4 mg and 5 mg

Montelukast sodium oral granules 4 mg ( 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 Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-

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

See 17 for PATIENT COUNSELING INFORMATION.

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

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

Montelukast sodium is 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 is indicated for prevention of exercise-induced bronchoconstriction (EIB)

in patients 6 years of age and older.

1.3 Allergic Rhinitis

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.

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 packet of 4-mg oral

granules.

For pediatric patients 12 to 23 months of age: one packet 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 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 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 packet 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 packet of 4-mg oral

granules.

For pediatric patients 6 to 23 months of age: one packet 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 packet should not be opened until ready to use. After

opening the packet, 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 tablets USP, 10 mg, are light brown colored, round, biconvex film coated

tablets debossed with "1081" on one side and "10 MG" on other side.

Montelukast Sodium Chewable Tablets USP, 4mg are pink colored, oval biconvex shaped, uncoated

tablets, debossed with '1079' on one side and '4 MG' on other side.

Montelukast Sodium Chewable Tablets USP, 5mg are pink colored, round shaped, uncoated tablets,

debossed with '1080' on one side and '5 MG' on other side.

Montelukast sodium oral granules USP 4 mg are white to off white granules with 500 mg net

weight, packed in a child-resistant foil packet.

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 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), 0.674 and 0.842 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,

o titis.

Adults and Adolescents 15 Years of Age and Older with Asthma

Montelukast sodium has been evaluated for safety in approximately 2,950 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

10 mg/day

(n=1,955)

Placebo

(n=1,180)

Body As A Whole

Pain, abdominal

Asthenia/fatigue

Fever

* Number of patients tested (montelukast sodium and placebo, respectively): ALT and AST,

1,935, 1,170; pyuria, 1,924, 1,159.

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 or 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 2,199 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 3,357 adult and adolescent patients 15 years

of age and older with perennial allergic rhinitis of whom 1,632 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 to 4% and 15 to 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 sodium 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

sodium. 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 sodium and

any potential adverse effects on the breastfed infant from montelukast sodium 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)

*The standard errors of the treatment group means in change in height are too small to be visible

on the plot

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 1,000 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 USP and

montelukast sodium oral granules USP, 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

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, which

is equivalent to 10 mg of montelukast, and the following inactive ingredients: croscarmellose sodium,

ferric oxide red, ferric oxide yellow, hydroxypropyl cellulose, hypromellose, lactose monohydrate,

magnesium stearate, microcrystalline cellulose 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: aspartame, cellulose microcrystalline, cherry flavor,

croscarmellose sodium, ferric oxide red, magnesium stearate, mannitol.

Each packet of Montelukast sodium oral granules USP 4 mg contains 4.16 mg Montelukast

sodium USP, which is equivalent to 4 mg of montelukast. The oral granule formulation contains the

following inactive ingredients: mannitol, hydroxypropyl cellulose, Tribasic sodium phosphate and

magnesium stearate.

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

by 35% and prolonged T

from 2.3 ± 1.0 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 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 (4,296 nghr/mL [range 1,200 to 7,153]) was 60% higher and the mean C

(667 ng/mL [range 201 to 1,058]) was 89% higher than those observed in adults (mean AUC 2,689

nghr/mL [range 1,521 to 4,595]) 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 (3,574 nghr/mL [range 2,229 to 5,408]) 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 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 1,576 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 (13.0%-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: FEV Mean Percent Change from Baseline

(U.S. Trial: Montelukast Sodium N=406; Placebo N=270)

(ANOVA Model)

1

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)

* p<0.00l, compared with placebo

Montelukast Sodium

Placebo

Endpoint

Baseline

Mean Change

from Baseline

Baseline

Mean Change

from Baseline

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 92.0% 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, 1,203 mcg/day), triamcinolone acetonide (mean dose, 2,004

mcg/day), flunisolide (mean dose, 1,971 mcg/day), fluticasone propionate (mean dose, 1,083 mcg/day),

or budesonide (mean dose, 1,192 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 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 FEV

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 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 FEV1 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 FEV1*

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 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

1

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 5,029 patients,

of whom 1,799 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

to 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 35.0 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 on Daytime Nasal Symptoms Score

in a Placebo- and Active-controlled

Trial in Patients with Seasonal Allergic Rhinitis(ANCOVA Model)

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

categorical scale.

The study was not designed for statistical comparison between Montelukast Sodium and the active control (loratadine).

Statistically different from placebo (p≤0.001).

Treatment Group (N)

Baseline

Mean Score

Mean Change from Baseline

Difference Between Treatment and Placebo (95% CI) Least-

Squares Mean

Montelukast 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 3,357 patients, of whom 1,632 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 1.0% 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 on Daytime Nasal Symptoms Score* in a

Placebo-controlled Trial in Patients with Perennial Allergic Rhinitis (ANCOVA Model)

*

* Average of individual scores of nasal congestion, rhinorrhea, sneezing as assessed by

patients on a 0 to 3 categorical scale.

Treatment Group (N)

Baseline

Mean Score

Mean

Change

from

Baseline

Difference Between

Treatment and

Placebo (95% CI)

Least-Squares Mean

Montelukast 10 mg

(1,000)

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 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: 71335-1326

NDC: 71335-1326-1 30 TABLET, CHEWABLE in a BOTTLE

17 PATIENT COUNSELING INFORMATION

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

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).

Manufactured by:

TORRENT PHARMACEUTICALS LTD., INDIA.

Manufactured For:

TORRENT PHARMA INC., Basking Ridge, NJ 07920.

8075204 Revised May 2019

Patient Information

Montelukast Sodium (MON-te-LOO-kast SO-dee-um) Tablets and

Montelukast Sodium (MON-te-LOO-kast SO-dee-um) Chewable Tablets

Montelukast Sodium (MON-te-LOO-kast SO-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.

2. 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.

3. Prevent exercise-induced asthma in people 6 years of age and older.

4. Help control the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the

nose). Montelukast sodium is 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 ofmontelukast 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 tablets, 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.

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 packet 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 oral granules 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 your or your child's condition is based on age:

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

2 to 5 years: one 4-mg chewable tablet or one packet 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 memory problems

or hostility obsessive-compulsive symptoms

attention problems restlessness

bad or vivid dreams sleep walking

depression suicidal thoughts and actions

disorientation (confusion) (including suicide)

feeling anxious tremor

hallucinations (seeing or hearing things trouble sleeping

that are not really there) uncontrolled muscle movements

irritability

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 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to

86°F) [see USP Controlled Room Temperature].

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 Torrent Pharma

Inc. at 1-800-912-9561.

What are the ingredients in montelukast sodium?

Active ingredient: montelukast sodium

Inactive ingredients:

4-mg oral granules : mannitol, hydroxypropyl cellulose, Tribasic Sodium phosphate and

magnesium stearate.

10-mg tablet : croscarmellose sodium, ferric oxide red, ferric oxide yellow, hydroxypropyl

cellulose, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and

titanium dioxide.

4-mg and 5-mg chewable tablets : aspartame, cellulose microcrystalline, cherry flavor,

croscarmellose sodium, ferric oxide red, magnesium stearate, mannitol.

People with Phenylketonuria: Montelukast sodium 4-mg chewable tablets contain 0.168 mg of

phenylalanine, and montelukast sodium 5-mg chewable tablets contain 0.210 mg of phenylalanine.

Manufactured by:

TORRENT PHARMACEUTICALS LTD., INDIA.

Manufactured for:

TORRENT PHARMA INC., Basking Ridge, NJ 07920.

8075205 Revised May 2019

MONTELUKAST SODIUM 5MG CHEW.

MONTELUKAST SODIUM

montelukast sodium tablet, chewable

Bryant Ranch Prepack

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:71335-1326 (NDC:136 6 8 -0 8 0 )

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

ASPARTAME (UNII: Z0 H242BBR1)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

CHERRY (UNII: BUC5I9 59 5W)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

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

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

MANNITO L (UNII: 3OWL53L36 A)

Product Characteristics

Color

pink (Pink)

S core

no sco re

S hap e

ROUND (Ro und)

S iz e

8 mm

Flavor

Imprint Code

10 8 0 ;5

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:71335-1326 -1

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

0 8 /0 3/20 12

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 9 0 9 8 4

0 8 /0 3/20 12

Labeler -

Bryant Ranch Prepack (171714327)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Bryant Ranch Prepack

171714327

REPACK(71335-1326 ) , RELABEL(71335-1326 )

Revised: 9/2019

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