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| Product NDC Code | 70436-090 | ||||
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| Drug Name | Montelukast sodium |
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| Type | Generic | ||||
| Pharm Class | Leukotriene Receptor Antagonist [EPC], Leukotriene Receptor Antagonists [MoA] |
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| Active Ingredients |
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| Route | ORAL | ||||
| Dosage Form | TABLET, CHEWABLE | ||||
| RxCUI drug identifier | 242438, 311759 |
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| Application Number | ANDA205695 | ||||
| Labeler Name | Slate Run Pharmaceuticals, LLC. | ||||
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Overdosage of Montelukast Sodium
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE No specific information is available on the treatment of overdosage with montelukast sodium. 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. It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Neuropsychiatric Events [see Warnings and Precautions (5.1)] 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 Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Rev.: 06/2023 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. Pediatric Patients 6 to 14 Years of Age with Asthma Montelukast sodium has been evaluated for safety in 476 pediatric patients 6 to 14 years of age. Cumulatively, 289 pediatric patients were treated with montelukast sodium for at least 6 months, and 241 for one year or longer in clinical trials. The safety profile of montelukast sodium in the 8-week, double-blind, pediatric efficacy trial was generally similar to the adult safety profile. In pediatric patients 6 to 14 years of age receiving montelukast sodium, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo: pharyngitis, influenza, fever, sinusitis, nausea, diarrhea, dyspepsia, otitis, viral infection, and laryngitis. The frequency of less common adverse events was comparable between montelukast sodium and placebo. With prolonged treatment, the adverse experience profile did not significantly change. The safety profile of montelukast sodium, when administered as a single dose for prevention of EIB in pediatric patients 6 years of age and older, was consistent with the safety profile previously described for montelukast sodium. In studies evaluating growth rate, the safety profile in these pediatric patients was consistent with the safety profile previously described for montelukast sodium. In a 56-week, double-blind study evaluating growth rate in pediatric patients 6 to 8 years of age receiving montelukast sodium, the following events not previously observed with the use of montelukast sodium in this age group occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo: headache, rhinitis (infective), varicella, gastroenteritis, atopic dermatitis, acute bronchitis, tooth infection, skin infection, and myopia. Pediatric Patients 2 to 5 Years of Age with Asthma Montelukast sodium has been evaluated for safety in 573 pediatric patients 2 to 5 years of age in single- and multiple-dose studies. Cumulatively, 426 pediatric patients 2 to 5 years of age were treated with montelukast sodium for at least 3 months, 230 for 6 months or longer, and 63 patients for one year or longer in clinical trials. In pediatric patients 2 to 5 years of age receiving montelukast sodium, the following events occurred with a frequency ≥2% and more frequently than in pediatric patients who received placebo: fever, cough, abdominal pain, diarrhea, headache, rhinorrhea, sinusitis, otitis, influenza, rash, ear pain, gastroenteritis, eczema, urticaria, varicella, pneumonia, dermatitis, and conjunctivitis. Pediatric Patients 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. Pediatric Patients 2 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. 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) ].
Montelukast Sodium Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.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) ].
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The cysteinyl leukotrienes (LTC 4 , LTD 4 , LTE 4 ) 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 1 ) 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 1 receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or β-adrenergic receptor). Montelukast inhibits physiologic actions of LTD 4 at the CysLT 1 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 4 in asthmatics. Doses as low as 5 mg cause substantial blockage of LTD 4 -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. For the 5-mg chewable tablet, the mean C max 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 max 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 safety and effectiveness of Montelukast Sodium in patients with asthma were demonstrated in clinical trials in which the 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 comparative pharmacokinetics of montelukast when administered as two 5-mg chewable tablets versus one 10-mg film-coated tablet have not been evaluated. 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. Orally administered montelukast distributes into the brain in rats. 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%). 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. Special Populations Patients with Hepatic Impairment 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. Patients with 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 . Male and Female Patients The pharmacokinetics of montelukast are similar in males and females. Racial Groups Pharmacokinetic differences due to race have not been studied. Adolescents and Pediatric Patients: Pharmacokinetic studies evaluated the systemic exposure of 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. 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. 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 Interaction Studies 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, fexofenadine, Digoxin, and Warfarin In drug ineraction 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), digoxin, and warfarin. Montelukast at doses of ≥100t 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, did not change the pharmacokinetic profile or urinary excretion of immunoreactive digoxin; did not change the pharmacokinetic profile of warfarin (primarily a substrate of CYP2C9, 3A4 and 1A2) or influence the effect of a single 30-mg oral dose of warfarin on prothrombin time or the International Normalized Ratio (INR). Thyroid Hormones, Sedative Hypnotics, Non-Steroidal Anti-Inflammatory Agents, Benzodiazepines, and Decongestants Although additional specific interaction studies were not performed, montelukast sodium was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions. These medications included thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants. Cytochrome P450 (CYP) Enzyme Inducers Phenobarbital, which induces hepatic metabolism, decreased the area under the plasma concentration curve (AUC) of montelukast approximately 40% following a single 10-mg dose of montelukast. No dosage adjustment for montelukast sodium is recommended. It is reasonable to employ appropriate clinical monitoring when potent CYP enzyme inducers, such as phenobarbital or rifampin, are co-administered with montelukast sodium. Effect of Montelukast on Cytochrome P450 (CYP) Enzymes Montelukast is a potent inhibitor of CYP2C8 in vitro. However, data from a clinical drug-drug interaction study involving montelukast and rosiglitazone (a probe substrate representative of drugs primarily metabolized by CYP2C8) in 12 healthy individuals demonstrated that the pharmacokinetics of rosiglitazone are not altered when the drugs are coadministered, indicating that montelukast does not inhibit CYP2C8 in vivo . Therefore, montelukast is not anticipated to alter the metabolism of drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone, and repaglinide). Based on further in vitro results in human liver microsomes, therapeutic plasma concentrations of montelukast do not inhibit CYP 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6. Cytochrome P450 (CYP) Enzyme Inhibitors In vitro studies have shown that montelukast is a substrate of CYP 2C8, 2C9, and 3A4. Co-administration of montelukast with itraconazole, a strong CYP 3A4 inhibitor, resulted in no significant increase in the systemic exposure of montelukast. Data from a clinical drug-drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) demonstrated that gemfibrozil, at a therapeutic dose, increased the systemic exposure of montelukast by 4.4-fold. Co-administration of itraconazole, gemfibrozil, and montelukast did not further increase the systemic exposure of montelukast. Based on available clinical experience, no dosage adjustment of montelukast is required upon co-administration with gemfibrozil [see Overdosage (10) ] .
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS Montelukast Sodium Chewable Tablets are contraindicated in patients with hypersensitivity to any of its components. Hypersensitivity to any component of this product ( 4 ).
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Montelukast Sodium, the active ingredient in montelukast sodium chewable tablets, is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT 1 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 35 H 35 ClNNaO 3 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 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, cherry flavor, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, ferric oxide red, magnesium stearate, mannitol, microcrystalline cellulose, and sodium lauryl sulphate. Structure
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION Administration (by indications): Asthma : Once daily in the evening for patients 2 to 14 years of age ( 2.1 ). Acute prevention of EIB : One tablet at least 2 hours before exercise for patients 6 to 14 years of age ( 2.2 ). Seasonal allergic rhinitis : Once daily for patients 2 to 14 years of age ( 2.3 ). Perennial allergic rhinitis : Once daily for patients 2 to 14 years of age ( 2.3 ). Dosage (by age) : 6 to 14 years: one 5 mg chewable tablet ( 2 ). 2 to 5 years: one 4-mg chewable tablet ( 2 ). Patients with both asthma and allergic rhinitis should take only one dose daily in the evening ( 2.4 ). 2.1 Asthma For asthma, administer Montelukast sodium chewable tablets orally once daily in the evening, with or without food. There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The following doses are recommended: Table 1: Recommended Dosage in Asthma Age Dose Pediatric patients 6 to 14 years of age one 5-mg chewable tablet Pediatric patients 2 to 5 years of age one 4-mg chewable tablet Patients who miss a dose should take the next dose at their regular time and should not take 2 doses at the same time. 2.2 Exercise-Induced Bronchoconstriction (EIB) For prevention of EIB, administer a single dose of Montelukast Sodium chewable tablets orally at least 2 hours, before exercise. The following doses are recommended: Table 2: Recommended Dosage in Exercise-Induced Bronchoconstriction (EIB) Age Dose Pediatric patients 6 to 14 years of age * one 5-mg chewable tablet * Safety and effectiveness in patients younger than 6 years of age have not been established. An additional dose of Montelukast Sodium chewable tablets should not be taken within 24 hours of a previous dose. Patients already taking Montelukast Sodium chewable 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. Daily administration of Montelukast Sodium chewable tablets for the chronic treatment of asthma has not been established to prevent acute episodes of EIB. 2.3 Allergic Rhinitis For allergic rhinitis, administer Montelukast Sodium chewable tablets orally once daily without regard to time of food ingestion. Time of administration in patients with allergic rhinitis can be individualized to suit patient needs. The following doses for the treatment of symptoms of seasonal allergic rhinitis are recomended: Table 3: Recommended Dosage in Seasonal Allergic Rhinitis Age Dose Pediatric patients 6 to 14 years of age one 5 mg chewable tablet Pediatric patients 2 to 5 years of age* one 4 mg chewable tablet *Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established. The following doses for the treatment of symptoms of perennial allergic rhinitis are recommended: Table 4: Recommended Dosage in Perennial Allergic Rhinitis Age Dose Pediatric patients 6 to 14 years of age one 5 mg chewable tablet Pediatric patients 2 to 5 years of age one 4 mg chewable tablet 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 For patients with both asthma and allergic rhinitis, administer only one Montelukast Sodium chewable tablets 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.
| Pediatric patients 6 to 14 years of age | one 5-mg chewable tablet |
| Pediatric patients 2 to 5 years of age | one 4-mg chewable tablet |
| Pediatric patients 6 to 14 years of age * | one 5-mg chewable tablet |
| Pediatric patients 6 to 14 years of age | one 5 mg chewable tablet |
| Pediatric patients 2 to 5 years of age* | one 4 mg chewable tablet |
| Pediatric patients 6 to 14 years of age | one 5 mg chewable tablet |
| Pediatric patients 2 to 5 years of age | one 4 mg chewable tablet |
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS Montelukast Sodium 5-mg Chewable Tablets are pink, capsule-shaped tablets, debossed with “5” on one side and plain on the other. Montelukast Sodium 4-mg Chewable Tablets are pink, square-shaped tablets, debossed with “4” on one side and plain on the other. Montelukast Sodium 5-mg and 4-mg Chewable Tablets ( 3 ).
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE Montelukast sodium chewable tablets are leukotriene receptor antagonist indicated for: Prophylaxis and chronic treatment of asthma in patients 2 to 14 years of age( 1.1 ). Acute prevention of exercise-induced bronchoconstriction (EIB) in patients 6 to 14 years of age( 1.2 ). Relief of symptoms of allergic rhinitis (AR): seasonal allergic rhinitis (SAR) in patients 2 to 14 years of age, and perennial allergic rhinitis (PAR) in patients2 to 14 years of age. 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 chewable tablets are indicated for the prophylaxis and chronic treatment of asthma in patients 2 to 14 years of age. 1.2 Exercise-Induced Bronchoconstriction (EIB) Montelukast sodium chewable tablets indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 6 to 14 years of age. 1.3 Allergic Rhinitis Montelukast sodium chewable tablets are indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 to 14 years of age and perennial allergic rhinitis in patients 2 to 14 years of age . Because the benefits of Montelukast sodium chewable tablet 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 chewable tablets are not indicated for the treatment of an acute asthma attack.
Spl product data elements
Usually a list of ingredients in a drug product.Montelukast Sodium Montelukast Sodium CROSCARMELLOSE SODIUM MANNITOL CELLULOSE, MICROCRYSTALLINE SODIUM LAURYL SULFATE SILICON DIOXIDE ASPARTAME FERRIC OXIDE RED HYDROXYPROPYL CELLULOSE (70000 WAMW) MAGNESIUM STEARATE MONTELUKAST SODIUM MONTELUKAST square-shaped 4 Montelukast Sodium Montelukast Sodium MONTELUKAST SODIUM MONTELUKAST MANNITOL CELLULOSE, MICROCRYSTALLINE SODIUM LAURYL SULFATE SILICON DIOXIDE ASPARTAME FERRIC OXIDE RED CROSCARMELLOSE SODIUM HYDROXYPROPYL CELLULOSE (70000 WAMW) MAGNESIUM STEARATE capsule-shaped 5
Nonclinical toxicology
Information about toxicology in non-human subjects.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).
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.4 mg: 90s Bottle Label NDC 70436-090-06 Montelukast Sodium Chewable Tablets 4 mg* For Pediatric Patients 2-5 Years of Age Phenylketonurics: contains phenylalanine (a component of aspartame) 0.27 mg per 4 mg chewable tablet. Dispense the enclosed Medication Guide to each patient Rx only 90 Tablets 5 mg: 90s Bottle Label NDC 70436-091-06 Montelukast Sodium Chewable Tablets 5 mg* For Pediatric Patients 6-14 Years of Age Phenylketonurics: contains phenylalanine (a component of aspartame) 0.34 mg per 5 mg chewable tablet. Dispense the enclosed Medication Guide to each patient Rx only 90 Tablets 4mg 90s bottle label 5mg 90s bottle label
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.WARNING: SERIOUS NEUROPSYCHIATRIC EVENTS Serious neuropsychiatric (NP) events have been reported with the use of Montelukast Sodium. The types of events reported were highly variable, and included, but were not limited to, agitation, aggression, depression, sleep disturbances, suicidal thoughts and behavior (including suicide). The mechanisms underlying NP events associated with Montelukast Sodium use are currently not well understood [see Warnings and Precautions ( 5.1 )]. Because of the risk of NP events, the benefits of Montelukast Sodium may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies. Reserve use of Montelukast Sodium for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies [see Indications and Usage ( 1.3 )]. In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and risks before prescribing Montelukast Sodium. Discuss the benefits and risks of Montelukast Sodium with patients and caregivers when prescribing Montelukast Sodium. Advise patients and/or caregivers to be alert for changes in behavior or new NP symptoms when taking Montelukast Sodium. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts and/or behavior occur, advise patients to discontinue Montelukast Sodium and contact a healthcare provider immediately [see Warnings and Precautions ( 5.1 )]. Boxed Warning 04/2020 Indications and Usage ( 1.3 , 1.4 ) 02/2021 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 ) 02/2021 Warnings and Precautions ( 5.1 , 5.6 ) 02/2021
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Information not classified as belonging to one of the other fields. Approximately 40% of labeling with effective_time between June 2009 and August 2014 have information in this field.Distributed by: Slate Run Phamaceuticals, LLC Columbus, Ohio 43215 Rev. 06/2023
Montelukast Sodium: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION For the chewable tablets, advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide). • Advise patients about the potential risk for serious neuropsychiatric symptoms and behavioral changes with Montelukast Sodium use [ see Warnings and Precautions (5.1) ]. • Discuss the benefits and risks of Montelukast Sodium with patients when prescribing or continuing treatment with Montelukast Sodium [ see Warnings and Precautions (5.1) ]. • Advise patients to monitor for changes in behavior or neuropsychiatric symptoms in patients taking Montelukast Sodium [ see Warnings and Precautions (5.1) ]. • Instruct patients to discontinue Montelukast Sodium and contact a healthcare provider immediately if changes in behavior or thinking that are not typical for the patient occur, or if the patient develops suicidal ideation or suicidal behavior [ see Warnings and Precautions (5.1) ]. • Advise patients 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. • Advise patients 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 [ see Warnings and Precautions (5.2) ]. • Advise patients to seek medical attention 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. • Instruct patients to continue other anti-asthma medications as prescribed unless instructed by a physician. • Instruct patients with known aspirin sensitivity to continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking Montelukast Sodium [ see Warnings and Precautions (5.4) ]. • Inform phenylketonuric patients that the 4-mg and 5-mg chewable tablets contain phenylalanine (a component of aspartame) [ see Warnings and Precautions (5.6) ].
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Information about the patient medication guide that accompanies the drug product. Certain drugs must be dispensed with an accompanying medication guide. This field may contain information about when to consult the medication guide and the contents of the medication guide.MEDICATION GUIDE Montelukast Sodium (mon te loo kast soe dee um) Chewable Tablets What is the most important information I should know about Montelukast Sodium Chewable Tablets? Serious mental health problems have happened in people taking Montelukast Sodium Chewable Tablets or even after treatment has stopped. This can happen in people with or without a history of mental health problems. Stop taking Montelukast Sodium Chewable Tablets and tell your healthcare provider right away if you or your child have any unusual changes in behavior or thinking, including any of these symptoms: agitation, including aggressive behavior or hostility attention problems bad or vivid dreams depression disorientation (confusion) feeling anxious irritability hallucinations (seeing or hearing things that are not really there) memory problems obsessive-compulsive symptoms restlessness sleep walking stuttering suicidal thoughts and actions (including suicide) tremor trouble sleeping uncontrolled muscle movements What are Montelukast Sodium Chewable Tablets? Montelukast Sodium Chewable Tablets are a prescription medicine that blocks substances in the body called leukotrienes. This may help to improve symptoms of asthma and inflammation of the lining of the nose (allergic rhinitis). Montelukast Sodium Chewable Tablets does not contain a steroid. Montelukast sodium chewable tablets are used to: Prevent asthma attacks and for the long-term treatment of asthma in children ages 2 to 14 years. Do not take montelukast sodium chewables tablets if you need relief right away for a sudden asthma attack. If you have an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks. Prevent exercise-induced asthma in people 6 to 14 years of age. Help control the symptoms of allergic rhinitis such as sneezing, stuffy nose, runny nose, itching of the nose. Montelukast sodium chewable tablets are used to treat the following in people who have already taken other medicines that did not work well enough or in people who could not tolerate other medicines: outdoor allergies that happen part of the year (seasonal allergic rhinitis) in children ages 2 years to 14 years, and indoor allergies that happen all year (perennial allergic rhinitis) in children ages 2 to 14 years. Do not take Montelukast sodium chewable tablets if you are allergic to any of its ingredients. See the end of this Medication Guide for a complete list of the ingredients in Montelukast sodium chewable tablets. Before taking Montelukast Sodium chewable tablets, tell your healthcare provider about all your medical conditions, including if you: are allergic to aspirin. have phenylketonuria. Montelukast Sodium chewable tablets contain aspartame, a source of phenylalanine. have or have had mental health problems. are pregnant or plan to become pregnant. Talk to your healthcare provider if you are pregnant or plan to become pregnant, Montelukast Sodium chewable tablets may not be right for you. are breastfeeding or plan to breastfeed. 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 chewable tablets. Tell your healthcare provider about all the medicines you take, including prescription and over the counter medicines, vitamins, and herbal supplements. Some medicines may affect how montelukast sodium chewable tablets works, or montelukast sodium chewable tablets may affect how your other medicines work. How should I take montelukast sodium chewable tablets? For anyone who takes montelukast sodium chewable tablets: Take montelukast sodium chewable tablets exactly as prescribed by your healthcare provider. Your healthcare provider will tell you how much montelukast sodium chewable tablets to take, and when to take it . Stop taking montelukast sodium chewable tablets and tell your healthcare provider right away if you or your child have any unusual changes in behavior or thinking. You can take montelukast sodium chewable tablets with food or without food. If you or your child misses a dose of montelukast sodium chewable tablets, 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 chewable tablets, call your healthcare provide right away. For children 2 to 14 years of age with asthma: Take montelukast sodium chewable tablets 1 time each day, in the evening. Continue to take montelukast sodium chewable tablets 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. Always have your rescue inhaler medicine with you for asthma attacks. Continue to take your other asthma medicines as prescribed unless your healthcare provider tells you to change how you take these medicines. For people 6 to 14 years of age for the prevention of exercise-induced asthma: Take montelukast sodium chewable tablets at least 2 hours before exercise. Always have your rescue inhaler medicine with you for asthma attacks. If you take Montelukast Sodium chewable tablets 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 chewable tablets within 24 hours (1 day). For anyone 2 to 14 years of age with seasonal allergic rhinitis, or for anyone 2 to 14 years of age withperennial allergic rhinitis: Take Montelukast Sodium chewable tablets 1 time each day, at about the same time each day. What should I avoid while taking Montelukast Sodium chewable tablets? If you have asthma and aspirin makes your asthma symptoms worse, continue to avoid taking aspirin or other medicines called nonsteroidal anti-inflammatory drugs (NSAIDs) while taking montelukast sodium chewable tablets. What are the possible side effects of montelukast sodium chewable tablets? Montelukast sodium chewable tablets may cause serious side effects, including: See “What is the most important information I should know about Montelukast Sodium chewable tablets?” 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 chewable tablets. 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 of Montelukast Sodium chewable tablets include: upper respiratory infection fever headache sore throat cough stomach pain diarrhea earache or ear infection flu runny nose sinus infection These are not all the possible side effects of montelukast sodium chewable tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store montelukast sodium chewable tablets? Store montelukast sodium chewable tablets at room temperature between 59°F to 86°F (15°C to 30°C). Keep montelukast sodium chewable tablets in the package it comes in. Keep montelukast sodium chewable tablets in a dry place and keep it away from light. Keep montelukast sodium chewable tablets and all medicines out of reach of children. General Information about the safe and effective use of montelukast sodium chewable tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use montelukast sodium chewable tablets for a condition for which it was not prescribed. Do not give montelukast sodium chewable tablets to other people even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Montelukast Sodium chewable tablets that is written for health professionals. What are the ingredients in montelukast sodium chewable tablets? Active ingredient: Montelukast Sodium Inactive ingredients: 4 mg and 5 mg chewable tablets: aspartame, cherry flavor, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, ferric oxide red, magnesium stearate, mannitol, microcrystalline cellulose, and sodium lauryl sulphate. People with Phenylketonuria: montelukast sodium 4 mg chewable tablets contain 0.27 mg of phenylalanine, and montelukast sodium 5-mg chewable tablets contain 0.34 mg of phenylalanine. Distributed by: Slate Run Pharmaceuticals, LLC Columbus, Ohio 43215 Rev: 06/2023 This Medication Guide has been approved by the U.S. Food and Drug Administration
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Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES 14.1 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 1 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 1 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 1 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, 1203 mcg/day), triamcinolone acetonide (mean dose, 2004 mcg/day), flunisolide (mean dose, 1971 mcg/day), fluticasone propionate (mean dose, 1083 mcg/day), or budesonide (mean dose, 1192 mcg/day). Some of these inhaled corticosteroids were non-U.S.-approved formulations, and doses expressed may not be ex-actuator. The pre-study inhaled corticosteroid requirements were reduced by approximately 37% during a 5- to 7-week placebo run-in period designed to titrate patients toward their lowest effective inhaled corticosteroid dose. Treatment with montelukast sodium resulted in a further 47% reduction in mean inhaled corticosteroid dose compared with a mean reduction of 30% in the placebo group over the 12-week active treatment period (p≤0.05). It is not known whether the results of this study can be generalized to patients with asthma who require higher doses of inhaled corticosteroids or systemic corticosteroids. In another randomized, placebo-controlled, parallel-group trial (n=642) in a similar population of adult patients previously maintained, but not adequately controlled, on inhaled corticosteroids (beclomethasone 336 mcg/day), the addition of montelukast sodium to beclomethasone resulted in statistically significant improvements in FEV 1 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 1 , 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 (5.4) ]. 14.2 Exercise-Induced Bronchoconstriction (EIB) Exercise-Induced Bronchoconstriction (Pediatric Patients 6 to 14 years of age) The efficacy of montelukast sodium 5 mg chewable tablets, when given as a single dose 2 hours before exercise for the prevention of EIB, was investigated in one multinational, randomized, double-blind, placebo-controlled crossover study that included a total of 64 pediatric patients 6 to 14 years of age with EIB. Exercise challenge testing was conducted at 2 hours and 24 hours following administration of a single dose of study drug (montelukast sodium 5 mg or placebo). The primary endpoint was the mean maximum percent fall in FEV 1 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 ( TABLE1). 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 1: Mean Maximum Percent Fall in FEV1 Following Exercise Challenge in Pediatric Patients (N=64) ANOVA Model Time of exercise challenge following medication administration Mean Maximum percent fall in FEV1 Least squares-mean Treatment difference % for Montelukast Sodium versus Placebo (95% CI) * Montelukast Sodium Placebo 2 hours 15 20 -5 (-9, -1) 24 hours 13 17 -4 (-7, -1) *Least squares-mean 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 1 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 1 and mean time to recovery to within 5% of the pre-exercise FEV 1 . 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 1 after exercise (i.e., ≥20% decrease from pre-exercise baseline) in 52% of patients studied. In a separate crossover study in adults, a similar effect was observed after two once-daily 10 mg doses of montelukast sodium. In pediatric patients 6 to 14 years of age, using the 5 mg chewable tablet, a 2-day crossover study demonstrated effects similar to those observed in adults when exercise challenge was conducted at the end of the dosing interval (i.e., 20 to 24 hours after the preceding dose). 14.3 Allergic Rhinitis (Seasonal and Perennial) Seasonal Allergic Rhinitis The efficacy of montelukast sodium for the treatment of seasonal allergic rhinitis was investigated in 5 similarly designed, randomized, double-blind, parallel-group, placebo- and active-controlled (loratadine) trials conducted in North America. The 5 trials enrolled a total of 5029 patients, of whom 1799 were treated with montelukast sodium. Patients were 15 to 82 years of age with a history of seasonal allergic rhinitis, a positive skin test to at least one relevant seasonal allergen, and active symptoms of seasonal allergic rhinitis at study entry. The period of randomized treatment was 2 weeks in 4 trials and 4 weeks in one trial. The primary outcome variable was mean change from baseline in daytime nasal symptoms score (the average of individual scores of nasal congestion, rhinorrhea, nasal itching, sneezing) as assessed by patients on a 0-3 categorical scale. Four of the five trials showed a significant reduction in daytime nasal symptoms scores with montelukast sodium 10-mg tablets compared with placebo. The results of one trial are shown below. The median age in this trial was 35.0 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, loratadine, and placebo are shown in TABLE 2. The remaining three trials that demonstrated efficacy showed similar results. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening. Table2: Effects of Montelukast Sodium on Daytime Nasal Symptoms Score* in a Placebo- and Active-controlled Trial in Patients with Seasonal Allergic Rhinitis (ANCOVA Model) Treatment Group (N) Baseline Mean Score Mean Change from Baseline Difference Between Treatment and Placebo (95% CI) Least-Squares Mean Montelukast Sodium 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) * Average of individual scores of nasal congestion, rhinorrhea, nasal itching, sneezing as assessed by patients on a 0-3 categorical scale. † Statistically different from placebo (p≤0.001). ‡ The study was not designed for statistical comparison between Montelukast Sodium and the active control (loratadine). Perennial Allergic Rhinitis The efficacy of montelukast sodium tablets for the treatment of perennial allergic rhinitis was investigated in 2 randomized, double-blind, placebo-controlled studies conducted in North America and Europe. The two studies enrolled a total of 3357 patients, of whom 1632 received montelukast sodium 10-mg tablets. Patients 15 to 82 years of age with perennial allergic rhinitis as confirmed by history and a positive skin test to at least one relevant perennial allergen (dust mites, animal dander, and/or mold spores), who had active symptoms at the time of study entry, were enrolled. In the study in which efficacy was demonstrated, the median age was 35 years (range 15 to 81); 64.1% were females and 35.9% were males. The ethnic/racial distribution in this study was 83.2% Caucasian, 8.1% Black, 5.4% Hispanic, 2.3% Asian, and 1.0% 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 3); 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 3: Effects of Montelukast Sodium on Daytime Nasal Symptoms Score* in a Placebo-controlled Trial in Patients with Perennial Allergic Rhinitis (ANCOVA Model) Treatment Group (N) Baseline Mean Score Mean Change from Baseline Difference Between Treatment and Placebo (95% CI) Least-Squares Mean Montelukast Sodium 10 mg (1000) 2.09 -0.42 -0.08 † (-0.12, -0.04) Placebo (980) 2.10 -0.35 N.A. * Average of individual scores of nasal congestion, rhinorrhea, sneezing as assessed by patients on a 0-3 categorical scale. † Statistically different from placebo (p≤0.001). The other 6-week study evaluated montelukast sodium 10 mg (n=626), placebo (n=609), and an active-control (cetirizine 10 mg; n=120). The primary analysis compared the mean change from baseline in daytime nasal symptoms score for montelukast sodium vs. placebo over the first 4 weeks of treatment; the study was not designed for statistical comparison between montelukast sodium and the active-control. The primary outcome variable included nasal itching in addition to nasal congestion, rhinorrhea, and sneezing. The estimated difference between montelukast sodium and placebo was -0.04 with a 95% CI of (-0.09, 0.01). The estimated difference between the active-control and placebo was -0.10 with a 95% CI of (-0.19, -0.01).
| 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 | 15 | 20 | -5 (-9, -1) |
| 24 hours | 13 | 17 | -4 (-7, -1) |
| Treatment Group (N) | Baseline Mean Score | Mean Change from Baseline | Difference Between Treatment and Placebo (95% CI) Least-Squares Mean |
| Montelukast Sodium 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) |
| Treatment Group (N) | Baseline Mean Score | Mean Change from Baseline | Difference Between Treatment and Placebo (95% CI) Least-Squares Mean |
| Montelukast Sodium 10 mg (1000) | 2.09 | -0.42 | -0.08 † (-0.12, -0.04) |
| Placebo (980) | 2.10 | -0.35 | N.A. |
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.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.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.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 2 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 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 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) Figure 1: Change in Height (cm) from Randomization Visit by Scheduled Week (Treatment Group Mean ± Standard Error* of the Mean)
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary Available data from published prospective and retrospective cohort studies over decades with montelukast use in pregnant women have not established a drug-associated risk of major birth defects [see Data] . In animal reproduction studies, no adverse developmental effects were observed with oral administration of montelukast to pregnant rats and rabbits during organogenesis at doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based on AUCs [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly or moderately controlled asthma in pregnancy increases the maternal risk of perinatal adverse outcomes such as preeclampsia and infant prematurity, low birth weight, and small for gestational age. Data Human Data Published data from prospective and retrospective cohort studies have not identified an association with Montelukast 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).
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from published prospective and retrospective cohort studies over decades with montelukast use in pregnant women have not established a drug-associated risk of major birth defects [see Data] . In animal reproduction studies, no adverse developmental effects were observed with oral administration of montelukast to pregnant rats and rabbits during organogenesis at doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based on AUCs [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly or moderately controlled asthma in pregnancy increases the maternal risk of perinatal adverse outcomes such as preeclampsia and infant prematurity, low birth weight, and small for gestational age. Data Human Data Published data from prospective and retrospective cohort studies have not identified an association with Montelukast 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 2 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 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 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) Figure 1: Change in Height (cm) from Randomization Visit by Scheduled Week (Treatment Group Mean ± Standard Error* of the Mean) 8.5 Geriatric Use Of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetic profile and the oral bioavailability of a single 10-mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required. 8.6 Hepatic Impairment No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency [ see Clinical Pharmacology (12.3) ]. 8.7 Renal Impairment No dosage adjustment is recommended in patients with renal insufficiency [ see Clinical Pharmacology (12.3) ].
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING Montelukast Sodium 4 mg Chewable Tablets are pink, square-shaped tablets, debossed with “4” on one side and plain on the other. They are supplied as follows: Bottles of 90: NDC 70436-090-06 Montelukast Sodium 5 mg Chewable Tablets are pink, capsule-shaped tablets, debossed with “5” on one side and plain on the other. They are supplied as follows: Bottles of 90: NDC 70436-091-06 Storage Store montelukast sodium 4 mg chewable tablets and 5 mg chewable tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original package.
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: SERIOUS NEUROPSYCHIATRIC EVENTS Serious neuropsychiatric (NP) events have been reported with the use of montelukast sodium. The types of events reported were highly variable, and included, but were not limited to, agitation, aggression, depression, sleep disturbances, suicidal thoughts and behavior (including suicide). The mechanisms underlying NP events associated with montelukast sodium use are currently not well understood [see Warnings and Precautions (5.1)]. Because of the risk of NP events, the benefits of montelukast sodium may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies. Reserve use of Montelukast sodium for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies [see Indications and Usage (1.3)] . In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and risks before prescribing montelukast sodium. Discuss the benefits and risks of montelukast sodium with patients and caregivers when prescribing montelukast sodium. Advise patients and/or caregivers to be alert for changes in behavior or new NP symptoms when taking montelukast sodium. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts and/or behavior occur, advise patients to discontinue Montelukast sodium and contact a healthcare provider immediately [see Warnings and Precautions (5.1)]. WARNING: SERIOUS NEUROPSYCHIATRIC EVENTS See full prescribing information for complete boxed warning. Serious neuropsychiatric events have been reported in patients taking montelukast sodium （5.1） Discuss benefits and risks of montelukast sodium with patients and caregivers （5.1） Monitor for neuropsychiatric symptoms in patients taking montelukast sodium （5.1） Discontinue montelukast sodium immediately if neuropsychiatric symptoms occur （5.1） Because the benefits of montelukast sodium may not outweigh the potential risk of neuropsychiatric symptoms in patients with allergic rhinitis, reserve use for patients who have an inadequate response or intolerance to alternative therapies ( 1.3 , 5.1 ).
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API