Montelukast Sodium
Generic: MONTELUKAST SODIUM
Basic Information
Manufacturer
PD-Rx Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
c69ab399-8ea6-4002-9271-b6a57c862b14
Indications & Usage
1 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.
Reserve use for patients who have an inadequate response or intolerance to alternative therapies ( 1.3 ).
Limitations of Use: Not indicated to treat an acute asthma attack ( 5.2 ).
1.1 Asthma 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.
Because the benefits of montelukast sodium may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see Warnings and Precautions ( 5.1 )] , reserve use for patients who have an inadequate response or intolerance to alternative therapies.
1.4 Limitations of Use Montelukast sodium is not indicated for the treatment of an acute asthma attack.
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.
Reserve use for patients who have an inadequate response or intolerance to alternative therapies ( 1.3 ).
Limitations of Use: Not indicated to treat an acute asthma attack ( 5.2 ).
1.1 Asthma 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.
Because the benefits of montelukast sodium may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see Warnings and Precautions ( 5.1 )] , reserve use for patients who have an inadequate response or intolerance to alternative therapies.
1.4 Limitations of Use Montelukast sodium is not indicated for the treatment of an acute asthma attack.
Adverse Reactions
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.
The following clinically significant adverse reactions are described elsewhere in the labeling: • Neuropsychiatric Events [see Warnings and Precautions ( 5.1 )] .
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 2,950 adult and adolescent patients 15 years of age and older in clinical trials.
In placebo-controlled clinical trials, the following adverse reactions 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 5: Adverse Reactions Occurring in ≥1% of Patients with an Incidence Greater than that in Patients Treated with Placebo * Number of patients tested (montelukast sodium and placebo, respectively): ALT and AST, 1,935, 1,170; pyuria, 1,924, 1,159.
Montelukast 10 mg/day (%) (n=1,955) Placebo (%) (n=1,180) Body As A Whole Pain, abdominal 2.9 2.5 Asthenia/fatigue 1.8 1.2 Fever 1.5 0.9 Trauma 1.0 0.8 Digestive System Disorders Dyspepsia 2.1 1.1 Pain, dental 1.7 1.0 Gastroenteritis, infectious 1.5 0.5 Nervous System/Psychiatric Headache 18.4 18.1 Dizziness 1.9 1.4 Respiratory System Disorders Influenza 4.2 3.9 Cough 2.7 2.4 Congestion, nasal 1.6 1.3 Skin/Skin Appendages Disorder Rash 1.6 1.2 Laboratory Adverse Reactions* ALT increased 2.1 2.0 AST increased 1.6 1.2 Pyuria 1.0 0.9 The frequency of less common adverse reactions 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 reaction 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 reactions 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 reactions was comparable between montelukast sodium and placebo.
With prolonged treatment, the adverse reaction 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 reactions 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 reactions 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 reactions 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 reactions 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 reaction 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 reactions 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 reactions 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 Postmarketing 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, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor [see Boxed Warning, Warnings and Precautions ( 5.1 )] 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 reactions 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 )]
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.
The following clinically significant adverse reactions are described elsewhere in the labeling: • Neuropsychiatric Events [see Warnings and Precautions ( 5.1 )] .
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 2,950 adult and adolescent patients 15 years of age and older in clinical trials.
In placebo-controlled clinical trials, the following adverse reactions 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 5: Adverse Reactions Occurring in ≥1% of Patients with an Incidence Greater than that in Patients Treated with Placebo * Number of patients tested (montelukast sodium and placebo, respectively): ALT and AST, 1,935, 1,170; pyuria, 1,924, 1,159.
Montelukast 10 mg/day (%) (n=1,955) Placebo (%) (n=1,180) Body As A Whole Pain, abdominal 2.9 2.5 Asthenia/fatigue 1.8 1.2 Fever 1.5 0.9 Trauma 1.0 0.8 Digestive System Disorders Dyspepsia 2.1 1.1 Pain, dental 1.7 1.0 Gastroenteritis, infectious 1.5 0.5 Nervous System/Psychiatric Headache 18.4 18.1 Dizziness 1.9 1.4 Respiratory System Disorders Influenza 4.2 3.9 Cough 2.7 2.4 Congestion, nasal 1.6 1.3 Skin/Skin Appendages Disorder Rash 1.6 1.2 Laboratory Adverse Reactions* ALT increased 2.1 2.0 AST increased 1.6 1.2 Pyuria 1.0 0.9 The frequency of less common adverse reactions 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 reaction 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 reactions 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 reactions was comparable between montelukast sodium and placebo.
With prolonged treatment, the adverse reaction 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 reactions 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 reactions 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 reactions 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 reactions 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 reaction 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 reactions 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 reactions 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 Postmarketing 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, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor [see Boxed Warning, Warnings and Precautions ( 5.1 )] 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 reactions 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 )]