Pharmacology

Binds to cysteinyl leukotriene type 1 (CysLT1) receptor in the upper and lower airways to prevent leukotriene-mediated effects associated with asthma and allergic rhinitis.

Pharmacokinetics

Absorption

Rapidly absorbed. Tmaxis 3 to 4 h and bioavailability is 64% for the 10 mg oral tablet in the fasted state. Tmaxis 2 to 2.5 h and bioavailability is 73% (63% if taken with food) for the 5 mg chewable tablet. Tmaxis 2 h for the 4 mg chewable tablet taken without food. The 4 mg granule formulation is bioequivalent to the 4 mg chewable tablet when administered in the fasted state. Administration of granules with a high-fat meal does not affect AUC, but prolongs Tmaxto 6.4 h and decreases Cmaxby 35%.

Distribution

Protein binding is more than 99%. Vd is 8 to 11 L.

Metabolism

Extensively metabolized; plasma concentrations of metabolites are undetectable at steady state. CYP-450 3A4 and 2C9 are involved in metabolism.

Elimination

Plasma Cl averages 45 mL/min and mean plasma half-life is 2.7 to 5.5 h; 86% is recovered in feces and less than 0.2% in urine.

Special Populations

Renal Function Impairment

Pharmacokinetics were not evaluated in patients with renal impairment.

Hepatic Function Impairment

AUC increased 41% and half-life was prolonged to 7.4 h in patients with mild to moderate hepatic impairment and cirrhosis. Patients with severe hepatic impairment or hepatitis have not been evaluated.

Elderly

Plasma half-life is slightly longer.

Children

In children 6 to 23 mo of age, the systemic exposure to montelukast is higher than in adults.

Gender

Pharmacokinetics are similar in male and female patients.

Race

Differences have not been studied.

Indications and Usage

Prophylaxis and long-term treatment of asthma in patients 12 mo and older; relief of symptoms of seasonal allergic rhinitis in patients 2 y and older; relief of symptoms of perennial allergic rhinitis in patients 6 mo and older; prevention of exercise-induced bronchoconstriction (EIB) in patients 6 y and older.

Unlabeled Uses

Atopic dermatitis, chronic urticaria.

Contraindications

Hypersensitivity to any component of the product.

Dosage and Administration

AsthmaAdults and adolescents 15 y and olderPO 10 mg daily in the evening.

Children 6 to 14 y of agePO 5 mg daily in the evening (chewable tablet).

Children 2 to 5 y of agePO 4 mg daily in the evening (chewable tablet or granules).

Children 12 to 23 mo of agePO 4 mg daily in the evening (granules).

Exercise-induced bronchoconstrictionAdults and adolescents 15 y and olderPO 10 mg at least 2 h prior to exercise. An additional dose should not be taken within 24 h of the previous dose.

Children 6 to 14 y of agePO 5 mg at least 2 h prior to exercise (chewable tablet). An additional dose should not be taken within 24 h of the previous dose.

Perennial Allergic RhinitisAdults and adolescents 15 y and olderPO 10 mg daily.

Children 6 to 14 y of agePO 5 mg once daily (chewable tablet).

Children 2 to 5 y of agePO 4 mg daily (chewable tablet or granules).

Children 6 to 23 mo of agePO 4 mg daily (granules).

Seasonal Allergic RhinitisAdults and adolescents 15 y and olderPO 10 mg daily.

Children 6 to 14 y of agePO 5 mg daily (chewable tablet).

Children 2 to 5 y of agePO 4 mg daily (chewable tablet or granules).

General Advice

Provide patients with appropriate rescue medication.

Patients taking a daily dose for a particular indication, including chronic asthma, should not take an additional dose to prevent EIB.

Patients with both asthma and allergic rhinitis should take only 1 tablet daily in the evening.

May be taken with or without food.

Oral granules

Do not open a packet containing granules until ready for use; the full dose must be administered within 15 min of opening the packet.

Granules can be administered directly in the mouth, dissolved in 5 mL of cold or room temperature baby formula or breast milk, or mixed with a spoonful of cold or room temperature soft foods (applesauce, carrots, rice, or ice cream only). If mixing with baby formula, breast milk, or food, do not prepare it ahead of time or store for future use. Discard any unused portion.

Do not dissolve granules in any liquid other than baby formula or breast milk for administration; however, liquids can be taken subsequent to administration.

Uses for Montelukast Sodium

Asthma

Prevention and long-term symptomatic management of asthma.131404345515354555657585960

HYPERLINK "http://www.drugs.com/monograph/montelukast-sodium.html" \l "r69" 6970105109110119Efficacy for this indication demonstrated when the drug was administered in the evening.13145In patients with mild persistent asthma, low-dose orally inhaled corticosteroids considered first-line agents for long-term control.214445477080

HYPERLINK "http://www.drugs.com/monograph/montelukast-sodium.html" \l "r86" 8692105110119Alternative agents, including certain leukotriene modifiers (i.e., montelukast, zafirlukast), may be used447080868788919899105110119but are less effective than inhaled corticosteroids and are not preferred as initial therapy.110119121Slideshow: What is Asthma? Causes, Symptoms, and Treatment

In patients with moderate persistent asthma, low-dose inhaled corticosteroids with a long-acting inhaled 2-agonist bronchodilator (e.g., salmeterol, formoterol) or monotherapy with medium-dose inhaled corticosteroids preferred.110119However, the National Asthma Education and Prevention Program (NAEPP) recommends that beneficial effects of long-acting inhaled 2-agonists be weighed carefully against increased risk of severe asthma exacerbations and asthma-related deaths associated with daily use of such agents.119Alternative agents, including certain leukotriene modifiers (i.e., montelukast, zafirlukast), can be added to a low dosage of inhaled corticosteroid for treatment of moderate persistent asthma, but these options are less effective.110119Considerations favoring combination with orally inhaled corticosteroids include intolerance to long-acting 2-adrenergic agonists, marked preference for oral therapy, and demonstration of superior responsiveness to these leukotriene modifiers.119In adults and children 5 years of age with severe persistent asthma, NAEPP and the Global Initiative for Asthma (GINA) state that maintenance therapy with inhaled corticosteroids at medium to high dosages and adjunctive therapy with a long-acting inhaled 2-agonist is preferred.110119Alternatives to a long-acting inhaled 2-agonist in such patients receiving medium-dose inhaled corticosteroids include certain leukotriene modifiers (i.e., montelukast, zafirlukast), but these agents are generally not preferred.110119In infants and children 4 years of age, NAEPP states that an inhaled corticosteroid at medium or high dosages and adjunctive therapy with either a long-acting inhaled 2-agonist or montelukast is the only preferred treatment.119Maintenance therapy with montelukast may be considered in patients who are unable or unwilling to comply with therapy using inhaled corticosteroids (e.g., young children).119Notrecommended for relief of acute bronchospasm; however, may continue therapy during acute asthma exacerbations.153(See Acute Asthma under Cautions.)

Exercise-induced Bronchospasm

Prevention of exercise-induced bronchospasm.148495052Leukotriene modifiers not included as first-line agents or as alternative agents to orally inhaled 2-adrenergic agonists in current guidelines;227092110119addition of montelukast may provide additional measure of control in patients currently maintained on long-term controller therapy.8898

HYPERLINK "http://www.drugs.com/monograph/montelukast-sodium.html" \l "r99" 99Manufacturer states that patients who experience exacerbations of asthma after exercise should have a short-acting orally inhaled 2-adrenergic agonist available for rescue.198Not established that daily administration of montelukast for chronic treatment of asthma prevents acute episodes of exercise-induced bronchospasm.1Allergic Rhinitis

Symptomatic management of seasonal or perennial allergic rhinitis.18793111Efficacy for this indication demonstrated when the drug was administered in the morning or evening.1Urticaria

Has been used successfully in patients with chronic idiopathic urticaria; beneficial when added to existing therapy.83Montelukast Sodium Dosage and Administration

Administration

Oral Administration

Administer at regular intervals (once daily) without regard to meals.13145Administer in the evening in patients with asthma with or without coexisting allergic rhinitis.13145May individualize time of administration in patients with allergic rhinitis; administer at the same time each day.1125Administer 2 hours before exercise in patients with exercise-induced bronchospasm; do not take an additional dose within 24 hours of previous dose.1125Oral GranulesGenerally used in children 12 months to 5 years of age.1Do not open packet until ready to use; administer full dose within 15 minutes of opening packet and without regard to meals.1125Administer directly in the mouth alone or mix with a teaspoonful (5 mL) of cold or room temperature baby formula, breast milk, or soft food (i.e., applesauce, carrots, rice, ice cream).1Granules are not intended to be dissolved in liquid other than baby formula or breast milk prior to administration; however, liquids can be taken after administration of the granules.1125(See Stability.)

Do not store granules mixed with food for future use; discard any unused portion.1125Dosage

Available as montelukast sodium; dosage expressed in terms of montelukast.1Pediatric PatientsAsthma With or Without Allergic Rhinitis

Oral

Children 1223 months: 4 mg once daily as oral granules.1Children 25 years of age: 4 mg once daily as chewable tablets or oral granules.1109Children 614 years of age: 5 mg once daily as chewable tablets.1Adolescents 15 years of age: 10 mg once daily as film-coated tablets.145Additional dosage not needed for treatment of allergic rhinitis in patients already receiving chronic therapy for asthma.1Exercise-induced BronchospasmPrevention

OralChildren 614 years of age: 5 mg daily has been used for prevention of exercise-induced bronchospasm.1484950527778Adolescents 15 years of age: 10 mg once daily as film-coated tablets.1484950527778Seasonal Allergic Rhinitis With or Without AsthmaOral

Children 25 years of age: 4 mg once daily as chewable tablets or oral granules.1Children 614 years of age: 5 mg once daily as chewable tablets.1Adolescents 15 years of age: 10 mg once daily as film-coated tablets.1Perennial Allergic Rhinitis With or Without AsthmaOral

Infants 623 months of age: 4 mg once daily as oral granules.1Children 25 years of age: 4 mg once daily as chewable tablets or oral granules.1Children 614 years of age: 5 mg once daily as chewable tablets.1Adolescents 15 years of age: 10 mg once daily as film-coated tablets.1AdultsAsthma With or Without Allergic Rhinitis

Oral

10 mg once daily as film-coated tablets.1Additional dosage not needed for treatment of allergic rhinitis in patients already receiving chronic therapy for asthma.1Exercise-induced BronchospasmPrevention

Oral10 mg as film-coated tablets.1484950527778Seasonal Allergic Rhinitis With or Without AsthmaOral

10 mg once daily as film-coated tablets.1Perennial Allergic Rhinitis With or Without AsthmaOral

10 mg once daily as film-coated tablets.1UrticariaOral

520 mg daily.83Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment.1Not evaluated in patients with severe hepatic impairment or hepatitis.1Renal ImpairmentNo dosage adjustment required.1