Montelukast Sodium

1 INDICATIONS AND USAGE Montelukast sodium tablets are a leukotriene receptor antagonist indicated for: Prophylaxis and chronic treatment of asthma in patients 15 years of age and older ( 1.1 ). Acute prevention of exercise-induced bronchoconstriction (EIB) in patients 15 years of age and older ( 1.2 ). Relief of symptoms of allergic rhinitis (AR): seasonal allergic rhinitis (SAR) in patients 15 years of age and older, and perennial allergic rhinitis (PAR) in patients 15 years of age and older. Reserve use for patients who have an inadequate response or intolerance to alternative therapies ( 1.3 ). 1.1 Asthma Montelukast sodium tablet is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 15 years of age and older. 1.2 Exercise-Induced Bronchoconstriction (EIB) Montelukast sodium tablet is indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 15 years of age and older. 1.3 Allergic Rhinitis Montelukast sodium tablet is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 15 years of age and older and perennial allergic rhinitis in patients 15 years of age and older. Because the benefits of montelukast sodium tablets 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.

2 DOSAGE AND ADMINISTRATION Administration (by indications): Asthma ( 2.1 ): Once daily in the evening for patients 15 years and older. Acute prevention of EIB ( 2.2 ): 10 mg tablet at least 2 hours before exercise for patients 15 years of age and older. Seasonal allergic rhinitis ( 2.3 ): Once daily for patients 15 years and older. Perennial allergic rhinitis ( 2.3 ): Once daily for patients 15 years and older. Dosage (by age) ( 2 ): 15 years and older: one 10-mg tablet. Patients with both asthma and allergic rhinitis should take only one dose daily in the evening ( 2.4 ). 2.1 Asthma Montelukast sodium tablets should be taken once daily in the evening. The following doses are recommended:Montelukast sodium tablets 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 adults and adolescents 15 years of age and older: one 10-mg tablet. Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established. Patients who miss a dose should take the next dose at their regular time and should not take 2 doses at the same time. 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.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 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. An additional dose of montelukast should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium tablets 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 15 years of age have not been established. Daily administration of montelukast sodium tablets 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 tablets 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.For allergic rhinitis, montelukast sodium tablets 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: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 adults and adolescents 15 years of age and older: one 10-mg tablet. Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.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: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 adults and adolescents 15 years of age and older: one 10-mg tablet. Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established.Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established. Patients who miss a dose should take the next dose at their regular time and should not take 2 doses at the same time. 2.4 Asthma and Allergic Rhinitis Patients with both asthma and allergic rhinitis should take only one montelukast sodium tablet dose daily in the evening.Patients with both asthma and allergic rhinitis should take only one montelukast sodium tablet dose daily in the evening. Patients who miss a dose should take the next dose at their regular time and should not take 2 doses at the same time.

4 CONTRAINDICATIONS Hypersensitivity to any component of this product. Hypersensitivity to any component of this product ( 4 ).

Not available.

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 Accord Healthcare Inc, at 1-866-941-7875 or www.accordhealthcare.us or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the following description of clinical trials experience, adverse reactions are listed regardless of causality assessment. The most common adverse reactions (incidence ≥5% and greater than placebo; listed in descending order of frequency) in controlled clinical trials were: upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis. Adults and Adolescents 15 Years of Age and Older with Asthma Montelukast sodium has been evaluated for safety in approximately 2950 adult and adolescent patients 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with montelukast sodium occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo: Table 1: Adverse Experiences Occurring in ≥1% of Patients with an Incidence Greater than that in Patients Treated with Placebo Montelukast 10 mg/day (%) (n=1955) Placebo (%) (n=1180) Body As A Whole Pain, abdominal Asthenia/fatigue Fever Trauma 2.9 1.8 1.5 1.0 2.5 1.2 0.9 0.8 Digestive System Disorders Dyspepsia Pain, dental Gastroenteritis, infectious 2.1 1.7 1.5 1.1 1.0 0.5 Nervous System/Psychiatric Headache Dizziness 18.4 1.9 18.1 1.4 Respiratory System Disorders Influenza Cough Congestion, nasal 4.2 2.7 1.6 3.9 2.4 1.3 Skin/Skin Appendages Disorder Rash 1.6 1.2 Laboratory Adverse Experiences Number of patients tested (montelukast sodium and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924, 1159. ALT increased AST increased Pyuria 2.1 1.6 1.0 2.0 1.2 0.9 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. Adults and Adolescents 15 Years of Age and Older with Seasonal Allergic Rhinitis Montelukast sodium has been evaluated for safety in 2199 adult and adolescent patients 15 years of age and older in clinical trials. Montelukast sodium administered once daily in the morning or in the evening had a safety profile similar to that of placebo. In placebo-controlled clinical trials, the following event was reported with montelukast sodium with a frequency ≥1% and at an incidence greater than placebo: upper respiratory infection, 1.9% of patients receiving montelukast sodium vs. 1.5% of patients receiving placebo. In a 4-week, placebo-controlled clinical study, the safety profile was consistent with that observed in 2-week studies. The incidence of somnolence was similar to that of placebo in all studies. Adults and Adolescents 15 Years of Age and Older with Perennial Allergic Rhinitis Montelukast sodium has been evaluated for safety in 3357 adult and adolescent patients 15 years of age and older with perennial allergic rhinitis of whom 1632 received montelukast sodium in two, 6-week, clinical studies. Montelukast sodium administered once daily had a safety profile consistent with that observed in patients with seasonal allergic rhinitis and similar to that of placebo. In these two studies, the following events were reported with montelukast sodium with a frequency ≥1% and at an incidence greater than placebo: sinusitis, upper respiratory infection, sinus headache, cough, epistaxis, and increased ALT. The incidence of somnolence was similar to that of placebo. 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 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) ] .