Montelukast (Monograph)
Brand name: Singulair
Drug class: Leukotriene Modifiers
VA class: RE109
Chemical name: [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl cyclopropane acetic acid sodium
Molecular formula: C35H35ClNNaO3S
CAS number: 151767-02-1
Warning
-
Serious neuropsychiatric effects, including suicidal thoughts or behavior, reported in patients receiving montelukast.128 129 (See Neuropsychiatric Effects under Cautions.)
-
Discuss benefits and risks of treatment with patients and caregivers; monitor patients receiving montelukast for neuropsychiatric symptoms.128 129
-
Discontinue montelukast if neuropsychiatric symptoms occur and contact a clinician immediately.128 129
-
Benefits of montelukast treatment may not outweigh the risks of neuropsychiatric symptoms, especially for respiratory disease symptoms that may be mild and adequately treated with alternative therapies.128 129 Reserve use of the drug for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies.128 129 In patients with asthma or exercise-induced bronchospasm, consider the benefits and risks of treatment before prescribing montelukast.128 129
Introduction
Antiasthmatic agent; leukotriene modifier.1 2 3 4 5 6 7 8 9 10 11 12 13 14 30 31 44 45 53 54 71 105 Pharmacologically but not structurally related to zafirlukast.2 71
Uses for Montelukast
Asthma
Prevention and long-term symptomatic management of asthma.1 31 40 43 45 51 53 54 55 56 57 58 59 60 69 70 105 109 110 119 Efficacy for this indication demonstrated when the drug was administered in the evening.1 31 45
Because of the risk of neuropsychiatric effects, consider the benefits and risks of montelukast treatment before prescribing the drug for patients with asthma.128 129 (See Neuropsychiatric Effects under Cautions.)
In patients with mild persistent asthma, low-dose orally inhaled corticosteroids considered first-line agents for long-term control.21 44 45 47 70 80 86 92 105 110 119 Alternative agents, including certain leukotriene modifiers (i.e., montelukast, zafirlukast), may be used44 70 80 86 87 88 91 98 99 105 110 119 but are less effective than inhaled corticosteroids and are not preferred as initial therapy.110 119 121
In patients with moderate persistent asthma, low-dose inhaled corticosteroids with a long-acting inhaled β2-agonist bronchodilator (e.g., salmeterol, formoterol) or monotherapy with medium-dose inhaled corticosteroids preferred.110 119 However, the National Asthma Education and Prevention Program (NAEPP) recommends that beneficial effects of long-acting inhaled β2-agonists be weighed carefully against increased risk of severe asthma exacerbations and asthma-related deaths associated with daily use of such agents.119
Alternative 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.110 119 Considerations favoring combination with orally inhaled corticosteroids include intolerance to long-acting β2-adrenergic agonists, marked preference for oral therapy, and demonstration of superior responsiveness to these leukotriene modifiers.119
In 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 β2-agonist is preferred.110 119 Alternatives to a long-acting inhaled β2-agonist in such patients receiving medium-dose inhaled corticosteroids include certain leukotriene modifiers (i.e., montelukast, zafirlukast), but these agents are generally not preferred.110 119
In 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 β2-agonist or montelukast is the only preferred treatment.119
Maintenance therapy with montelukast may be considered in patients who are unable or unwilling to comply with therapy using inhaled corticosteroids (e.g., young children).119
Not recommended for relief of acute bronchospasm; however, may continue therapy during acute asthma exacerbations.1 53 (See Acute Asthma under Cautions.)
Exercise-induced Bronchospasm
Prevention of exercise-induced bronchospasm.1 48 49 50 52
Because of the risk of neuropsychiatric effects, consider the benefits and risks of montelukast treatment before prescribing the drug for patients with exercise-induced bronchospasm.128 129 (See Neuropsychiatric Effects under Cautions.)
Leukotriene modifiers not included as first-line agents or as alternative agents to orally inhaled β2-adrenergic agonists in current guidelines;22 70 92 110 119 addition of montelukast may provide additional measure of control in patients currently maintained on long-term controller therapy.88 98 99
Manufacturer states that patients who experience exacerbations of asthma after exercise should have a short-acting orally inhaled β2-adrenergic agonist available for rescue.1 98 Not established that daily administration of montelukast for chronic treatment of asthma prevents acute episodes of exercise-induced bronchospasm.1
Allergic Rhinitis
Symptomatic management of seasonal or perennial allergic rhinitis.1 87 93 111 Efficacy for this indication demonstrated when the drug was administered in the morning or evening.1
Because the benefits of montelukast treatment may not outweigh the risks of neuropsychiatric effects in patients with allergic rhinitis, reserve use of the drug for such patients who have an inadequate response or intolerance to alternative therapies.128 129 (See Neuropsychiatric Effects under Cautions.)
Urticaria
Has been used successfully in patients with chronic idiopathic urticaria† [off-label]; beneficial when added to existing therapy.83
Related/similar drugs
Breztri Aerosphere, Anoro Ellipta, prednisone, albuterol, hydroxyzine, fluticasone nasal, loratadine
Montelukast Dosage and Administration
Administration
Oral Administration
Administer at regular intervals (once daily) without regard to meals.1 31 45
Administer in the evening in patients with asthma with or without coexisting allergic rhinitis.1 31 45
May individualize time of administration in patients with allergic rhinitis; administer at the same time each day.1 125
Administer ≥2 hours before exercise in patients with exercise-induced bronchospasm; do not take an additional dose within 24 hours of previous dose.1 125
Oral Granules
Generally used in children 12 months to 5 years of age.1 Do not open packet until ready to use; administer full dose within 15 minutes of opening packet and without regard to meals.1 125
Administer 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).1 Granules 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.1 125 (See Stability.)
Do not store granules mixed with food for future use; discard any unused portion.1 125
Dosage
Available as montelukast sodium; dosage expressed in terms of montelukast.1
Pediatric Patients
Asthma With or Without Allergic Rhinitis
Oral
Children 12–23 months: 4 mg once daily as oral granules.1
Children 2–5 years of age: 4 mg once daily as chewable tablets or oral granules.1 109
Children 6–14 years of age: 5 mg once daily as chewable tablets.1
Adolescents ≥15 years of age: 10 mg once daily as film-coated tablets.1 45
Additional dosage not needed for treatment of allergic rhinitis in patients already receiving chronic therapy for asthma.1
Exercise-induced Bronchospasm
Prevention
OralChildren 6–14 years of age: 5 mg as a chewable tablet administered at least 2 hours before exercise.128
Adolescents ≥15 years of age: 10 mg as a film-coated tablet administered at least 2 hours before exercise.1 48 49 50 52 77 78
Not indicated in those already taking the drug for another indication.128
Seasonal Allergic Rhinitis With or Without Asthma
Oral
Children 2–5 years of age: 4 mg once daily as chewable tablets or oral granules.1
Children 6–14 years of age: 5 mg once daily as chewable tablets.1
Adolescents ≥15 years of age: 10 mg once daily as film-coated tablets.1
Perennial Allergic Rhinitis With or Without Asthma
Oral
Infants 6–23 months of age: 4 mg once daily as oral granules.1
Children 2–5 years of age: 4 mg once daily as chewable tablets or oral granules.1
Children 6–14 years of age: 5 mg once daily as chewable tablets.1
Adolescents ≥15 years of age: 10 mg once daily as film-coated tablets.1
Adults
Asthma With or Without Allergic Rhinitis
Oral
10 mg once daily as film-coated tablets.1
Additional dosage not needed for treatment of allergic rhinitis in patients already receiving chronic therapy for asthma.1
Exercise-induced Bronchospasm
Prevention
Oral10 mg as a film-coated tablet administered at least 2 hours before exercise.1 48 49 50 52 77 78
Not indicated in those already taking the drug for another indication.128
Seasonal Allergic Rhinitis With or Without Asthma
Oral
10 mg once daily as film-coated tablets.1
Perennial Allergic Rhinitis With or Without Asthma
Oral
10 mg once daily as film-coated tablets.1
Urticaria† [off-label]
Oral
5–20 mg daily.83
Special Populations
Hepatic Impairment
No dosage adjustment required in patients with mild to moderate hepatic impairment.1 Not evaluated in patients with severe hepatic impairment or hepatitis.1
Renal Impairment
No dosage adjustment required.1
Geriatric Patients
No dosage adjustment required.1
Cautions for Montelukast
Contraindications
-
Known hypersensitivity to montelukast or any ingredient in the formulation.1
Warnings/Precautions
Warnings
Neuropsychiatric Effects
Serious neuropsychiatric effects reported with montelukast during postmarketing experience.120 125 126 127 128 129 Such reports were highly variable and included 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 thoughts and behavior (including completed suicide), tic, and tremor in adults, adolescents, and pediatric patients with or without a previous history of psychiatric disorders.128 129 Neuropsychiatric effects occurred mostly during treatment, and resolved after the drug was discontinued; some of these effects developed or continued following discontinuance of the drug.128 129 A total of 82 cases of completed suicide associated with montelukast use identified; many of these cases reported development of concomitant neuropsychiatric symptoms prior to the event.129 Most reports did not contain sufficient information to determine the exact relationship between montelukast and these neuropsychiatric events.129 Following extensive review of postmarketing reports and analysis of available clinical data, FDA convened a panel of outside experts to reevaluate benefits and risks of montelukast and concluded that there was a need to strengthen existing warnings in the labeling for the drug, including restrictions for use in patients with allergic rhinitis.129 (See Allergic Rhinitis under Uses.)
Be alert to the potential for neuropsychiatric effects in patients receiving the drug.128 129 Prior to initiation of therapy, ask patients about history of psychiatric illness.129 Consider the risks and benefits of montelukast when deciding to prescribe therapy with the drug.128 129 Instruct patients to discontinue the drug and contact their clinician immediately if behavior or mood changes occur.128 129 If neuropsychiatric effects occur during treatment, provide patient monitoring and supportive care until symptoms resolve.128 Carefully evaluate the risks and benefits of reinitiating montelukast therapy in patients who develop such symptoms.128 129 (See Advice to Patients.)
Sensitivity Reactions
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, angioedema, pruritus, urticaria, and, rarely, hepatic eosinophilic infiltration, reported.1
Eosinophilia and Churg-Strauss Syndrome
Systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, reported rarely in patients receiving leukotriene modifiers;1 33 39 61 62 63 64 65 66 67 72 85 96 in almost all cases, these events were associated with reduction (tapered dosage) or withdrawal of oral or high-dose inhaled corticosteroid therapy.1 33 39 61 62 63 64 65 66 67 72 96
Be alert to the development of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy;1 31 39 72 96 causal relationship not established.1 31 33 39 61 62 63 64 65 66 67 72 96 Advise patients to report symptoms (i.e., feeling of pins and needles, numbness of extremities, flu-like symptoms, rash, sinusitis) immediately to their clinician.125
Other Warnings and Precautions
Acute Asthma
Do not use for the relief of acute bronchospasm (including status asthmaticus); montelukast can be continued during acute exacerbations of asthma, but it will not provide immediate symptomatic relief.1
Concomitant Corticosteroid Therapy
Do not abruptly substitute montelukast for oral or inhaled corticosteroids.1 Orally inhaled corticosteroid requirements may be reduced during montelukast therapy; undertake only gradual (e.g., at 2-week intervals) reduction of corticosteroid dosage.1 40 98 99
Exercise-induced Bronchospasm
Do not use as monotherapy for prevention of exercise-induced bronchospasm; patients who experience exacerbations of asthma after exercise should continue their usual regimen of inhaled β2-adrenergic agonist for prophylaxis and have a short-acting orally inhaled β2-adrenergic agonist available for rescue.1
Aspirin Sensitivity
Patients in whom asthma is precipitated by aspirin or other NSAIAs should continue to avoid aspirin and NSAIAs.1 81 Montelukast can improve airway function in asthmatic patients with aspirin sensitivity; however, the drug has not been shown to truncate the bronchoconstrictor response to aspirin or other NSAIAs.1
Phenylketonuria
Montelukast chewable tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 0.674 mg of phenylalanine per 4-mg chewable tablet or 0.842 mg of phenylalanine per 5-mg chewable tablet.1 125
Specific Populations
Pregnancy
Category B.1
Pregnancy registry at 1 800-986-8999. ACOG generally recommends use of leukotriene receptor antagonists (i.e., montelukast, zafirlukast) as alternatives to a long-acting β2-agonist in pregnant women with moderate persistent asthma who are inadequately controlled with low to medium dosages of an inhaled corticosteroid.107 (See Asthma under Uses.)
Lactation
Distributed into milk in rats; not known whether distributed into human milk.1 Use with caution.1
Pediatric Use
Safety and efficacy for treatment of asthma in infants <12 months of age not established.1 31 Safety and efficacy for prevention of exercise-induced bronchospasm in children <6 years of age not established.128 Safety demonstrated in infants and children 12 months to 5 years of age with asthma; efficacy extrapolated from demonstrated efficacy in children ≥6 years of age based on similar pharmacokinetic data (systemic exposure), the similarity of the disease course, pathophysiology, and effects of the drug among these populations.1 85 Efficacy also supported by exploratory efficacy assessments from pediatric safety studies.1 109
Safety and efficacy in infants <6 months of age with perennial allergic rhinitis not established.1 Safety and efficacy in infants <2 years of age with seasonal allergic rhinitis not established.1 Efficacy in children 2–14 years of age or 6 months to 14 years of age with seasonal or perennial allergic rhinitis, respectively, extrapolated from demonstrated efficacy in adolescents ≥15 years of age and the similarity of the disease course, pathophysiology, and effects of the drug among these populations.1 Safety in pediatric patients 2–14 years of age with allergic rhinitis supported by data from studies in children from this age group with asthma.1 Safety in infants 6–23 months of age with perennial allergic rhinitis supported by data from studies in infants with asthma and by pharmacokinetic data comparing systemic exposure in such pediatric patients with that in adults.1
No effect of long-term therapy (56 weeks) on growth rate in pediatric patients (6–8 years of age) with mild asthma.1 112
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults; however, increased sensitivity in some older patients cannot be ruled out.1
Hepatic Impairment
Exposure to montelukast may be increased.1 (See Special Populations under Pharmacokinetics and see Special Populations under Dosage and Administration.)
Common Adverse Effects
Headache, influenza, abdominal pain, cough.1 125
Drug Interactions
Metabolized by CYP3A4 and CYP2C9.1 12
Does not inhibit CYP3A4, 2C9, 1A2, 2A6, 2C19, or 2D6.1 Inhibits CYP2C8 in vitro; 1 does not inhibit CYP2C8 in vivo.1 113
Drugs Affecting Hepatic Microsomal Enzymes
CYP3A4 or CYP2C9 inducers: Potential pharmacokinetic interaction (decreased plasma concentrations of montelukast).1
CYP3A4 or CYP2C9 inhibitors: Potential pharmacokinetic interaction (increased plasma concentrations of montelukast).1
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Benzodiazepines |
No increase in adverse effects noted1 |
|
Contraceptives, oral (fixed combination of ethinyl estradiol-norethindrone) |
||
Corticosteroids (prednisone, prednisolone) |
No clinically important effects on corticosteroid pharmacokinetics1 |
|
Decongestants |
No increase in adverse effects noted1 |
|
Digoxin |
||
NSAIAs |
No increase in adverse effects noted1 |
|
Paclitaxel |
||
Phenobarbital |
Montelukast dosage adjustment not recommended;1 monitor for alterations in clinical response and/or adverse effects1 |
|
Repaglinide |
||
Rifampin |
Potential for decreased montelukast concentrations1 |
Monitor for alterations in clinical response and/or adverse effects1 |
Rosiglitazone |
No effect anticipated on rosiglitazone pharmacokinetics1 113 |
|
Sedative-hypnotics |
No increase in adverse effects noted1 |
|
Terfenadine (no longer commercially available in US) |
No alteration in terfenadine pharmacokinetics; no effect on QTc interval1 103 |
|
Theophylline |
No clinically important effects on theophylline pharmacokinetics at usual montelukast dosage1 76 Decreased plasma concentrations, AUC, and half-life of theophylline at higher than recommended montelukast dosages76 |
|
Thyroid hormones |
No increase in adverse effects noted1 |
|
Warfarin |
No clinically important effects on warfarin pharmacokinetics; no alteration in PT or INR1 73 |
Montelukast Pharmacokinetics
Absorption
Bioavailability
Rapidly absorbed from the GI tract; peak plasma concentrations attained within 3–4, 2–2.5, or 2 hours following oral administration in the fasted state of a single 10-mg film-coated tablet (in adults), 5-mg chewable tablet (in adults), or 4-mg chewable tablet (in children 2–5 years of age), respectively.1 13 14 37 53
Oral bioavailability of the 10-mg tablet in adults is 58–66%; bioavailability of the 5-mg chewable tablet in fasting adults is 73%.1
Plasma concentration profile following oral administration of montelukast 10 mg in adolescents ≥15 years of age is similar to that in young adults.1
Plasma concentration profile following oral administration of 4- or 5-mg chewable tablet in children 2–5 or 6–14 years of age, respectively, is similar to the profile in adults receiving 10-mg film-coated tablet.1 37 101
Systemic exposure and variability of plasma concentrations with 4-mg granule formulation in infants 6–11 months of age are greater than the exposure and variability with the 10-mg film-coated tablet in adults.1 Systemic exposure with 4-mg granule formulation in infants 12–23 months of age is less variable than that with the same formulation in younger children but is still greater than that with the 10-mg film-coated tablet in adults.1
4-mg oral granule formulation and 4-mg chewable tablet are bioequivalent (fasting adults).1
Bioequivalence of the 10-mg film-coated tablet versus two 5-mg chewable tablets not evaluated.1
Onset
Improvement in asthma symptoms and/or lung function test results and decreased use of β-agonist bronchodilators are evident after the first dose.1 31 45
Duration
Therapeutic effects persist for at least 24 hours.1 31 45
Food
10-mg tablets: Food does not affect absorption.1
5-mg chewable tablet: Food decreases extent of absorption.1 Bioavailability is 63% when administered with a standard meal in the morning.1
4-mg oral granule formulation: High-fat meal decreases rate of absorption and peak plasma concentration; no effect on AUC.1 Applesauce does not appear to have a clinically important effect on the pharmacokinetics of montelukast granules.1
Special Populations
In patients with mild to moderate hepatic impairment, AUC increased 41%.1
Distribution
Extent
Crosses the placenta in animals (rats, rabbits); not known whether montelukast crosses the placenta in humans.1
Distributed into milk in rats; not known whether distributed into human milk.1
Plasma Protein Binding
99%.1
Elimination
Metabolism
Extensively metabolized in the GI tract and/or liver.1 12 20 Several pathways have been identified, including acyl glucuronidation and oxidation catalyzed by CYP3A4 and CYP2C9.1 12 20
Elimination Route
Excreted principally in feces (about 86%) via bile as unchanged drug and metabolites.1 12 20
Half-life
Children 6–14 years of age: 3.4–4.2 hours.37
Adults 19–48 years of age: 2.7–5.5 hours.1 13 14 37 51
Special Populations
In patients with mild to moderate hepatic impairment, elimination half-life prolonged (7.4 hours).1 13 51 Pharmacokinetics not evaluated in patients with severe hepatic impairment or hepatitis.1
In geriatric adults 65–73 years of age, elimination half-life prolonged (6.6 hours).1 13 51
Stability
Storage
Oral
Granules
25°C (may be exposed to 15–30°C).1 125 Protect from moisture and light.1 125
Do not store opened packets or granules mixed with food, baby formula, or breast milk for future use.1 125 Administer contents within 15 minutes of opening packet.1 125
Tablets, Chewable or Film-coated
25°C (may be exposed to 15–30°C).1 125 Protect from moisture and light.1 125
Compatibility
Oral
Granules
Granules may be mixed with cold or room temperature soft food; based on stability studies, only applesauce, carrots, rice, or ice cream should be used.1 125
Actions
-
Selective, competitive leukotriene-receptor antagonist.1 2 3 4 5 6 7 8 9 10 11 12 13 14 30 31 44 45 51 53 54 55 56 57 58 105
-
Binds selectively and with high affinity to a group of cysteinyl leukotriene receptors (CysLT1) in airway smooth muscle 1 2 4 5 6 7 8 9 10 11 12 13 14 30 45 51 and competitively inhibits the action of LTD4 (a cysteinyl leukotriene) at these receptors.1 2 4 5 6 7 8 9 10 11 12 13 14 30 51 58 100
-
Modification of leukotriene activity may be used to reduce symptoms of asthma,1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 30 44 45 47 58 since cysteinyl leukotrienes are especially important in the pathogenesis of asthma, causing increased mucus secretion and vascular permeability, airway edema, bronchoconstriction, and altered cellular activity associated with the inflammatory process.1 2 4 5 23 24 30 53 57 58
-
Inhibits bronchoconstriction induced by exposure to known precipitating factors (e.g., allergens, cold and/or dry air, exercise);80 89 inhibits both the acute bronchoconstrictor response and the delayed inflammatory response to inhaled antigen.1 30 41 44 47 51 55
-
May be used to reduce symptoms associated with allergic rhinitis, since cysteinyl leukotrienes are released from the nasal mucosa after allergen exposure during the early- and late-phase reactions and are associated with symptoms of allergic rhinitis.1
-
Has essentially no affinity for prostanoid, cholinergic or β-adrenergic receptors.1 30
Advice to Patients
-
Importance of patient and/or caregiver reading the manufacturer's patient information (Medication Guide) prior to initiation of therapy and with each prescription refill.128 129
-
Importance of advising patients and their caregivers about the potential risk for serious neuropsychiatric symptoms and behavioral changes associated with use of montelukast.128 129
-
Importance of discussing the benefits and risks of montelukast therapy with patients when deciding to prescribe or continue therapy with the drug.128 129
-
Importance of advising patients receiving montelukast to monitor for changes in behavior or neuropsychiatric symptoms.128 129
-
Importance of informing patients to discontinue montelukast and contact a clinician immediately if changes in behavior, new neuropsychiatric symptoms, or suicidal thoughts or behavior occur.128 129
-
Importance of taking montelukast exactly as prescribed and not exceeding recommended frequency of use.125
-
Importance of taking montelukast at regular intervals, when asymptomatic as well as during periods of worsening asthma.1 125
-
Importance of taking montelukast at least 2 hours prior to exercise for prevention of exercise-induced bronchospasm.125
-
Importance of advising patients who are receiving montelukast for chronic asthma or allergic rhinitis not to use an additional dose for the prevention of exercise-induced bronchospasm.125
-
Importance of contacting clinician promptly if asthma is not well controlled; seek medical attention if short-acting, inhaled β2-adrenergic bronchodilators are needed more often than usual or if the maximum number of inhalations for a 24-hour period are exceeded.1 125
-
Importance of not using montelukast for the relief of acute bronchospasm.1 125 Patients should be provided with and instructed in the use of a short-acting, inhaled β2-adrenergic bronchodilator as supplemental therapy for acute asthma symptoms.1 125
-
Importance of not discontinuing or reducing the dosage of other antiasthmatic agents unless instructed to do so by the clinician.1
-
In patients with known aspirin sensitivity, importance of continuing to avoid aspirin and NSAIAs.1 81 125
-
Importance of informing patients with phenylketonuria that the 4- and 5-mg chewable tablets of montelukast contain phenylalanine (a component of aspartame).128
-
Importance of informing clinicians immediately if symptoms of Churg-Strauss syndrome (e.g., feeling of pins and needles or numbness of extremities, flu-like symptoms, rash, sinusitis) occur.125
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 125
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., allergies).1 125
-
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Granules |
4 mg (of montelukast) per packet |
Singulair |
Merck |
Tablets, chewable |
4 mg (of montelukast) |
Singulair |
Merck |
|
5 mg (of montelukast) |
Singulair |
Merck |
||
Tablets, film-coated |
10 mg (of montelukast) |
Singulair |
Merck |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions December 21, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Merck & Co. Singulair (montelukast sodium) tablets, chewable tablets, and oral granules prescribing information. Whitehouse Station, NJ; 2009 Aug.
2. Hay DWP. Pharmacology of leukotriene receptor antagonists: more than inhibitors of bronchoconstriction. Chest. 1997; 111(Suppl):35-45S.
3. Thibert R, Mach H, Clas SD et al. Characterization of the self-association properties of a leukotriene D4 receptor antagonist, MK-0476. Int J Pharm. 1996; 134:59-70.
4. Drazen JM. Pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the management of asthma. Pharmacotherapy. 1997; 17:22-30S. http://www.ncbi.nlm.nih.gov/pubmed/9017763?dopt=AbstractPlus
5. Rachelefsky G. Childhood asthma and allergic rhinitis: the role of leukotrienes. J Pediatr. 1997; 131:348-55. http://www.ncbi.nlm.nih.gov/pubmed/9329408?dopt=AbstractPlus
6. Reiss TF, Sorkness CA, Stricker W et al. Effects of montelukast (MK-0476), a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax. 1997; 52:45-8. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1758407&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9039239?dopt=AbstractPlus
7. Reiss TF, Hill JB, Harman E et al. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax. 1997; 52:1030-5. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1758468&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9516894?dopt=AbstractPlus
8. De Lepeleire I, Reiss TF, Rochette F et al. Montelukast causes prolonged, potent leukotriene D4-receptor antagonism in the airways of patients with asthma. Clin Pharmacol Ther. 1997; 61:83-92. http://www.ncbi.nlm.nih.gov/pubmed/9024176?dopt=AbstractPlus
9. Reiss TF, Altman LC, Chervinsky P et al. Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma. J Allergy Clin Immunol. 1996; 98:528-34. http://www.ncbi.nlm.nih.gov/pubmed/8828530?dopt=AbstractPlus
10. Bronsky EA, Kemp JP, Zhang J et al. Dose-related protection of exercise bronchoconstriction by montelukast, a cysteinyl leukotriene-receptor antagonist, at the end of a once-daily dosing interval. Clin Pharmacol Ther. 1997; 62:556-61. http://www.ncbi.nlm.nih.gov/pubmed/9390112?dopt=AbstractPlus
11. Schoors DF, De Smet M, Reiss T et al. Single dose pharmacokinetics, safety and tolerability of MK-0476, a new leukotriene D4-receptor antagonist, in healthy volunteers. Br J Clin Pharmacol. 1995; 40:277-80. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1365110&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8527292?dopt=AbstractPlus
12. Balani SK, Xu X, Pratha V et al. Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene1 receptor antagonist, in human plasma and bile. Drug Metab Dispos. 1997; 25:1282-7. http://www.ncbi.nlm.nih.gov/pubmed/9351905?dopt=AbstractPlus
13. Zhao JJ, Rogers JD, Holland SD et al. Pharmacokinetics and bioavailability of montelukast sodium (MK-0476) in healthy young and elderly volunteers. Biopharm Drug Dispos. 1997; 18:769-77. http://www.ncbi.nlm.nih.gov/pubmed/9429741?dopt=AbstractPlus
14. Cheng H, Leff JA, Amin R et al. Pharmacokinetics, bioavailability, and safety of montelukast sodium (MK-0476) in healthy males and females. Pharm Res. 1996; 13:445-8. http://www.ncbi.nlm.nih.gov/pubmed/8692739?dopt=AbstractPlus
15. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400-2. http://www.ncbi.nlm.nih.gov/pubmed/2861297?dopt=AbstractPlus
16. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26,28-30.
17. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201]. Fed Regist. 1983; 48:54993-5.
18. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 FR Part 172]. Fed Regist. 1983; 48:31376-82.
19. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther. 1982; 24:1-2. http://www.ncbi.nlm.nih.gov/pubmed/7054648?dopt=AbstractPlus
20. Chiba M, Xu X, Nishime JA et al. Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metab Dispos. 1997; 25:1022-31. http://www.ncbi.nlm.nih.gov/pubmed/9311616?dopt=AbstractPlus
21. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. Bethesda, MD: National Institutes of Health. 1997 Feb.
22. Reviewers’ comments (personal observations) on zafirlukast.
23. Wenzel SE. Arachidonic acid metabolites: mediators of inflammation in asthma. Pharmacotherapy. 1997; 17:3-12S.
24. Larsen JS, Jackson SK. Antileukotriene therapy for asthma. Am J Health-Syst Pharm. 1996; 53:2821-30. http://www.ncbi.nlm.nih.gov/pubmed/8957342?dopt=AbstractPlus
25. Arm JP, O’Hickey SP, Hawksworth RJ et al. Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine. Am Rev Respir Dis. 1990; 142:1112-8. http://www.ncbi.nlm.nih.gov/pubmed/2173457?dopt=AbstractPlus
26. Davidson AB, Lee TH, Scanlon PD et al. Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects. Am Rev Respir Dis. 1987; 135:333-7. http://www.ncbi.nlm.nih.gov/pubmed/3028218?dopt=AbstractPlus
27. Bisgaard H, Groth S, Madsen F. Bronchial hyperreactivity to leukotriene D4 and histamine in exogenous asthma. BMJ. 1985; 290:1468-71. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1415696&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/3922535?dopt=AbstractPlus
28. Smith LJ, Greenberger PA, Patterson R et al. The effect of inhaled leukotriene D4 in humans. Am Rev Respir Dis. 1985; 131:368-72. http://www.ncbi.nlm.nih.gov/pubmed/3883862?dopt=AbstractPlus
29. Dworski R, Fitzgerald GA, Oates JA et al. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med. 1994; 149:953-9. http://www.ncbi.nlm.nih.gov/pubmed/8143061?dopt=AbstractPlus
30. Jones TR, Labelle M, Belley M et al. Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol. 1995; 73:191-201. http://www.ncbi.nlm.nih.gov/pubmed/7621356?dopt=AbstractPlus
31. Knorr B, Matz J, Bernstein JA et al, for the Pediatric Montelukast Study Group. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. JAMA. 1998; 279:1181-6 http://www.ncbi.nlm.nih.gov/pubmed/9555757?dopt=AbstractPlus
32. Spector SL, Smith LJ, Glass M and the Accolate Asthma Trialists Group. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. Am J Respir Crit Care Med. 1994; 150:618-23. http://www.ncbi.nlm.nih.gov/pubmed/8087328?dopt=AbstractPlus
33. Zeneca Pharmaceuticals. Accolate (zafirlukast) tablets prescribing information (dated 1997 Jul). In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998:3148-9.
34. Abbott Laboratories. Zyflo Filmtab (zileuton) tablets prescribing information. North Chicago, IL; 1996 Dec.
35. Israel E, Cohn J, Dube L et al et al. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma: a randomized controlled trial. JAMA. 1996; 275:931-6. http://www.ncbi.nlm.nih.gov/pubmed/8598621?dopt=AbstractPlus
36. Liu MC, Dube LM, Lancaster J et al. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. J Allergy Clin Immunol. 1996; 98:859-71. http://www.ncbi.nlm.nih.gov/pubmed/8939149?dopt=AbstractPlus
37. Knorr B, Larson P, Hguyen HH et al. Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults. J Clin Pharmacol. 1999; 39:786-93. http://www.ncbi.nlm.nih.gov/pubmed/10434229?dopt=AbstractPlus
39. Wechsler ME, Garpestad E, Flier SR et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA. 1998; 279:455-7. http://www.ncbi.nlm.nih.gov/pubmed/9466639?dopt=AbstractPlus
40. Lofdahl CG, Reiss TF, Leff JA et al. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ. 1999; 319:87-90. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=28156&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/10398629?dopt=AbstractPlus
41. Diamant Z, Grootendorst DC, Veselic-Charvat M et al. The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clin Exp Allergy. 1999, 29:42-51.
42. Leff JA, Pizzichini E, Efthimiadis A et al. Effect of montelukast (MK-0476) on airway eosinophilic inflammation in mildly uncontrolled asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 1997; 155:A977. http://www.ncbi.nlm.nih.gov/pubmed/9154849?dopt=AbstractPlus
43. Reiss TF, Chervinsky P, Noonan M et al. MK-0476, an LTD-4 receptor antagonist, exhibits a dose related improvement in the once daily treatment of patients with chronic asthma. Eur Respir J. 1995; 19(Suppl):289S.
44. Horwitz RJ, McGill KA, Busse WW. The role of leukotriene modifiers in the treatment of asthma. Am J Respir Crit Care Med. 1998; 157:1363-71. http://www.ncbi.nlm.nih.gov/pubmed/9603110?dopt=AbstractPlus
45. Reiss TF, Chervinsky P, Dockhorn RJ et al et al. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Arch Intern Med. 1998; 158:1213-20. http://www.ncbi.nlm.nih.gov/pubmed/9625400?dopt=AbstractPlus
46. Kuna P, Malmstrom K, Dahlen SE et al. Montelukast (MK-0476), a cysLT1 receptor antagonist, improves asthma control in aspirin-intolerant asthmatic patients. Am J Respir Crit Care Med. 1997; 155:A975. http://www.ncbi.nlm.nih.gov/pubmed/9196086?dopt=AbstractPlus
47. O’Byrne PM, Israel E, Drazen JM. Antileukotrienes in the treatment of asthma. Ann Intern Med. 1997; 127:472-80. http://www.ncbi.nlm.nih.gov/pubmed/9313005?dopt=AbstractPlus
48. Leff JA, Bronsky EA, Kemp J et al. Montelukast (MK-0476) inhibits exercise-induced bronchoconstriction (EIB) over 12-weeks without causing tolerance. Am J Respir Crit Care Med. 1997; 155:A977.
49. Leff JA, Busse WW, Pearlman D et al. Montelukast, a leukotriene receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998; 338:147-52. http://www.ncbi.nlm.nih.gov/pubmed/9428815?dopt=AbstractPlus
50. Hansen-Flaschen J, Schotland H. New treatments for for exercise-induced asthma. N Engl J Med. 1998; 338:192-3. http://www.ncbi.nlm.nih.gov/pubmed/9428823?dopt=AbstractPlus
51. Markham A, Faulds D. Montelukast. Drugs. 1998; 56:251-6. http://www.ncbi.nlm.nih.gov/pubmed/9711449?dopt=AbstractPlus
52. Kemp JP, Dockhorn RJ, Shapiro GG et al. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr. 1998:133:424-8.
53. Anon. Montelukast for persistent asthma. Med Lett Drugs Ther. 1998; 40:71-3. http://www.ncbi.nlm.nih.gov/pubmed/9698701?dopt=AbstractPlus
54. Anon. Drugs for asthma. Med Lett Drugs Ther. 2000: 42:19-24.
55. Sampson A, Holgate S. Leukotriene modifiers in the treatment of asthma: look promising across the board of asthma severity. BMJ. 1998; 316:1257-8. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1113026&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9554892?dopt=AbstractPlus
56. Smith LJ. A risk-benefit assessment of antileukotrienes in asthma. Drug Saf. 1998; 19:205-18. http://www.ncbi.nlm.nih.gov/pubmed/9747667?dopt=AbstractPlus
57. Wenzel SE. Antileukotriene drugs in the management of asthma. JAMA. 1998; 280:2068-9. http://www.ncbi.nlm.nih.gov/pubmed/9875862?dopt=AbstractPlus
58. Drazen JM, Israel E, O’Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med. 1999; 340:197-206. http://www.ncbi.nlm.nih.gov/pubmed/9895400?dopt=AbstractPlus
59. Noonan MJ, Chervinsky P, Brandon M et al. Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Eur Respir J. 1998; 11:1232-9. http://www.ncbi.nlm.nih.gov/pubmed/9657560?dopt=AbstractPlus
60. Altman LC, Munk Z, Seltzer J et al et al. A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. J Allergy Clin Immunol. 1998; 102:50-6. http://www.ncbi.nlm.nih.gov/pubmed/9679847?dopt=AbstractPlus
61. Churg J, Churg A. Zafirlukast and Churg-Strauss syndrome. JAMA. 1998; 279:1949-50. http://www.ncbi.nlm.nih.gov/pubmed/9643850?dopt=AbstractPlus
62. Wechsler ME, Drazen JM. Zafirlukast and Churg-Strauss syndrome. JAMA. 1998; 279:1950. http://www.ncbi.nlm.nih.gov/pubmed/9643851?dopt=AbstractPlus
63. Churg A, Churg J. Steroids and Churg-Strauss syndrome. Lancet. 1998; 352:32-4. http://www.ncbi.nlm.nih.gov/pubmed/9800746?dopt=AbstractPlus
64. Knoell DL, Lucas J, Allen JN. Churg-Strauss syndrome associated with zafirlukast. Chest. 1998; 114:332-4. http://www.ncbi.nlm.nih.gov/pubmed/9674492?dopt=AbstractPlus
65. Wechsler ME, Garpestad E, Flier SR et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteriod withdrawal in patients with asthma receiving zafirlukast. JAMA. 1998; 279:455-7. http://www.ncbi.nlm.nih.gov/pubmed/9466639?dopt=AbstractPlus
66. Katz RS, Papernik M. Zafirlukast and Churg-Strauss syndrome. JAMA. 1998; 279:1949. http://www.ncbi.nlm.nih.gov/pubmed/9643848?dopt=AbstractPlus
67. Honsinger RW. Zafirlukast and Churg-Strauss syndrome. JAMA. 1998; 279:1949. http://www.ncbi.nlm.nih.gov/pubmed/9643849?dopt=AbstractPlus
68. In KH, Asano K, Beier D et al. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest. 1997; 99:1130-7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=507922&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9062372?dopt=AbstractPlus
69. Malmstrom K, Rodriguez-Gomez G, Guerra J et al et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Ann Intern Med. 1999; 130:487-95. http://www.ncbi.nlm.nih.gov/pubmed/10075616?dopt=AbstractPlus
70. Smith LJ. Newer asthma therapies. Ann Intern Med. 1999; 130:531-2. http://www.ncbi.nlm.nih.gov/pubmed/10075622?dopt=AbstractPlus
71. Bernstein PR. Chemistry and structure-activity relationships of leukotriene receptor antagonists. Am J Resp Crit Care Med. 1998; 157:5220-6.
72. Wechsler ME, Pauwels R, Drazen JM. Leukotriene modifiers and Churg-Strauss syndrome: adverse effect or response to corticosteroid withdrawal? Drug Saf. 1999; 21:241-51.
73. Von Hecken A, Depré M, Verbesselt R et al. Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol. 1999; 39:495-500. http://www.ncbi.nlm.nih.gov/pubmed/10234597?dopt=AbstractPlus
74. Depré M, Van Hecken A, Verbesselt R et al. Effect of multiple doses of montelukast, a CysLT1 receptor antagonist, on digoxin pharmacokinetics in healthy volunteers. J Clin Pharmacol. 1999; 39:941-4. http://www.ncbi.nlm.nih.gov/pubmed/10471986?dopt=AbstractPlus
75. Geller M, Melo LR, Coutinho SV. Successful outcome of montelukast overdosage in an asthmatic child. Ann Allergy Asthma Immunol. 2000 84:370. Letter.
76. Malmstrom K, Schwartz J, Reiss TF et al. Effect of montelukast on single-dose theophylline pharmacokinetics. Am J Ther. 1998; 5:189-95. http://www.ncbi.nlm.nih.gov/pubmed/10099058?dopt=AbstractPlus
77. Edelman JM, Turpin JA, Bronsky EA et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction: a randomized, double-blind trial. Ann Intern Med. 2000; 132:97-104. http://www.ncbi.nlm.nih.gov/pubmed/10644288?dopt=AbstractPlus
78. Villaran C, O’Neill SJ, Helbling A et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. J Allergy Clin Immunol. 1999; 104:547-53. http://www.ncbi.nlm.nih.gov/pubmed/10482826?dopt=AbstractPlus
79. Laviolette M, Malmstrom K, Lu S et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Am J Respir Crit Care Med. 1999; 160:1862-8. http://www.ncbi.nlm.nih.gov/pubmed/10588598?dopt=AbstractPlus
80. Jarvis B, Markham A. Montelukast: a review of its therapeutic potential in persistent asthma. Drugs. 2000; 59:891-928. http://www.ncbi.nlm.nih.gov/pubmed/10804041?dopt=AbstractPlus
81. Enrique E, García-Ortega P, Gaig P et al. Failure of montelukast to prevent anaphylaxis to diclofenac. Allergy. 1999; 54:526-33. http://www.ncbi.nlm.nih.gov/pubmed/10380788?dopt=AbstractPlus
82. Dockhorn RJ, Baumgartner RA, Leff JA et al. Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients. Thorax. 2000; 55:260-5. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1745728&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/10722763?dopt=AbstractPlus
83. Bensch G, Borish L. Leukotriene modifiers in chronic urticaria. Ann Allergy Asthma Immunol. 1999; 83:348. http://www.ncbi.nlm.nih.gov/pubmed/10541429?dopt=AbstractPlus
84. Neustrom MR, Friesen C. Treatment of eosinophilic gastroenteritis with montelukast. J Asthma Clin Immunol. 1999; 104(2 Part 1):506.
85. Tuggey JM, Hosker HSR. Churg-Strauss syndrome associated with montelukast therapy. Thorax. 2000; 55:805-6. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1745850&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/10950903?dopt=AbstractPlus
86. Kemp JP. Comprehensive asthma management: guidelines for clinicians. J Asthma. 1998; 35:601-20. http://www.ncbi.nlm.nih.gov/pubmed/9860081?dopt=AbstractPlus
87. Lipworth BJ. The emerging role of leukotriene antagonists in asthma therapy. Chest. 1999; 115:313-4. http://www.ncbi.nlm.nih.gov/pubmed/10027422?dopt=AbstractPlus
88. Blake KV. Montelukast: data from clinical trials in the management of asthma. Ann Pharmacother. 1999; 33:1299-314. http://www.ncbi.nlm.nih.gov/pubmed/10630831?dopt=AbstractPlus
89. Diamant Z, Grootendorst DC, Veselic-Charvat M et al. The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clin Exp Allergy. 1999; 29:42-51. http://www.ncbi.nlm.nih.gov/pubmed/10051701?dopt=AbstractPlus
90. Meltzer EO, Malmstrom K, Lu S et al. Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial. J Allergy Clin Immunol. 2000; 105:917-22. http://www.ncbi.nlm.nih.gov/pubmed/10808172?dopt=AbstractPlus
91. Malmstrom K, Meltzer E, Prenner B et al. Effects of montelukast (a leukotriene receptor antagonist), lorataine, montelukast + lorataine and placebo in seasonal allergic rhinitis and conjunctivitis. J Allergy Clin Immunol. 1998; 101(Part 2):S97.
92. Kemp JP. Guidelines update: where do the new therapies fit in the management of asthma? Drugs. 2000; 59(Suppl 1):23-8.
93. Meltzer EO. Role for cysteinyl leukotriene receptor antagonist therapy in asthma and their potential role in allergic rhinitis based on the concept of “one linked airway disease”. Ann Allergy Asthma Immunol. 2000; 84:176-85. http://www.ncbi.nlm.nih.gov/pubmed/10719774?dopt=AbstractPlus
94. Masi AT, Hunder GG, Lie JT et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990; 33:1094-1100. http://www.ncbi.nlm.nih.gov/pubmed/2202307?dopt=AbstractPlus
95. Martin RM, Wilton LV, Mann RD. Prevalence of Churg-Strauss syndrome, vasculitis, eosinophilia and associated conditions: retrospective analysis of 58 prescription-event monitoring cohort studies. Pharmacoepidemiol Drug Saf. 1999; 8:179-89. http://www.ncbi.nlm.nih.gov/pubmed/15073927?dopt=AbstractPlus
96. Stirling RG, Chung KF. Leukotriene antagonists and Churg-Strauss syndrome: the smoking gun. Thorax. 1999; 54:865-6. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1745369&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/10491447?dopt=AbstractPlus
97. Churg A, Brallas M, Cronin SR et al. Formes frustes of Churg-Strauss syndrome. Chest. 1995; 108:320-3. http://www.ncbi.nlm.nih.gov/pubmed/7634860?dopt=AbstractPlus
98. Manufacturers’ comments: Merck, Whitehouse station, NJ: Personal communication.
99. Reviewer’s comments (personal observations).
100. Lynch KR, O’Neill GP, Liu Q et al. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature. 1999; 399:789-93. http://www.ncbi.nlm.nih.gov/pubmed/10391245?dopt=AbstractPlus
101. Knorr B, Nguyen H, Villaran C et al. Selection of a montelukast dose in 2- to 5-year-olds by a comparison of pediatric and adult single-dose population pharmacokinetic (PK) profiles. Clin Pharmacol Ther. 1998; 63:191.
102. Holland S, Shahane A, Rogers JD et al. Metabolism of montelukast (M) is increased by multiple doses of phenobarbital (P). Clin Pharmacol Ther. 1998; 63:231.
103. Holland S, Gertz B, DeSmet M et al. Montelukast (Mon) has no effect on terfenadine (T) pharmacokinetics (PK) or QTc. Clin Pharmacol Ther. 1998; 63:232.
104. Schwartz J, Larson P, Ebel D et al. Lack of impact of a leukotriene (LT) D4 receptor antagonist, montelukast (M), on ehinyl estradiol (EE) and norethindrone (NET) serum concentrations. Clin Pharmacol Ther. 1997; 61:162.
105. Jarvis B, Markam A. Montelukast: a review of its therapeutic potential in persistent asthma. Drugs. 2000; 59:891-928. http://www.ncbi.nlm.nih.gov/pubmed/10804041?dopt=AbstractPlus
106. Heise CE, O’Dowd BF, Figueroa DJ et al. Characterization of the human cysteinyl leukotriene 2 (CysLT2) receptor. J Biol Chem. 2000; 275:30531-6. http://www.ncbi.nlm.nih.gov/pubmed/10851239?dopt=AbstractPlus
107. American College of Obstetricians and Gynecologists. (ACOG) Practice bulletin No. 90. Asthma in pregnancy. Obstet Gynecol. 2008; 111:457-64. http://www.ncbi.nlm.nih.gov/pubmed/18238988?dopt=AbstractPlus
109. Knorr B, Franchi LM, Bisgaard H et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics. 2001; 108:E48. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4383837&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/11533366?dopt=AbstractPlus
110. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention. Bethesda, MD: National Institutes of Health. 2009 Dec. Accessed 2010 Sep 23. http://www.ginasthma.com
111. Philip G, Malmstrom K, Hampel FC et al. Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring. Clin Exp Allergy. 2002; 32:1020-8. http://www.ncbi.nlm.nih.gov/pubmed/12100048?dopt=AbstractPlus
112. Becker AB, Kuznetsova O, Vermeulen J et al. Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study. Ann Allergy Asthma Immunol. 2006; 96:800-7. http://www.ncbi.nlm.nih.gov/pubmed/16802767?dopt=AbstractPlus
113. Kajosaari LI, Niemi M, Backman JT et al. Telithromycin, but not montelukast, increases the plasma concentrations and effects of cytochrome P450 3A4 and 2C8 substrate repaglinide. Clin Pharmacol Ther. 2006; 79:231-42. http://www.ncbi.nlm.nih.gov/pubmed/16513447?dopt=AbstractPlus
119. National Asthma Education and Prevention Program. Expert panel report III: guidelines for the diagnosis and management of asthma. 2007 Jul. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available from website. Accessed Jul 27, 2008. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
120. Food and Drug Administration, Center for Drug Evaluation and Research. Early communication about an ongoing safety review of montelukast (Singular). 2008 Mar 27. Available from FDA website. Accessed 2008 Oct 7. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm070618.htm
121. British Thoracic Society/Scottish Intercollegiate Guidelines Network. Guidelines on the management of asthma: a national clinical guideline. London, Eng; British Thoracic Society. 2008 May. Available from website. Accessed Dec 5, 2008. http://www.brit-thoracic.org.UK/portals/0/clinical%20information/asthma/guidelines/asthma_final2008.pdf
125. Merck. Singulair (montelukast sodium) tablets, chewable tablets, and oral granules patient information. Whitehouse Station, NJ; 2009 Aug.
126. Food and Drug Administration. Update of safety review. Follow-up to the March 27, 2008 communication about the ongoing safety review of montelukast (Singulair). 2009 Jan 13. Available from FDA website. Accessed 2009 Oct 13. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079523.htm
127. Food and Drug Administration. Updated information on leukotriene inhibitors: montelukast (marketed as Singulair), zafirlukast (marketed as Accolate), and zileuton (marketed as Zyflo and Zyflo CR). 2009 Aug 28. Available from FDA website. Accessed 2009 Oct 13. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165489.htm
128. Merck & Co. Singulair (montelukast sodium) tablets, chewable tablets, and oral granules prescribing information. Whitehouse Station, NJ; 2020 Apr.
129. Food and Drug Administration. FDA requires Boxed Warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. 2020 Mar 4. Available from FDA website. Accessed 2020 Aug 6. https://www.fda.gov/media/135840/download
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