|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(mon te LOO kast)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prophylaxis and chronic treatment of asthma; relief of symptoms of seasonal allergic rhinitis and perennial allergic rhinitis; prevention of exercise-induced bronchospasm
Use: Unlabeled
Acute asthma
Pregnancy Risk Factor
B
Pregnancy Considerations
Montelukast was not teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Based on limited data, structural defects have been reported in neonates exposed to montelukast in utero; however, a specific pattern and relationship to montelukast has not been established. Healthcare providers should report any prenatal exposures to the montelukast pregnancy registry at (800) 986-8999.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to montelukast or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Eosinophilia and vasculitis: In rare cases, patients 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. Healthcare providers should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between montelukast and these underlying conditions has not been established.
• Neuropsychiatric events: Postmarketing reports of behavioral changes (eg, agitation, aggression, depression, insomnia, tremor) have been noted in pediatric and adult patients. In a retrospective analysis performed by Merck, serious behavior-related events were rare (Philip G, 2009); assess patients for behavioral changes. Patients should be instructed to notify prescriber if behavioral changes occur.
Concurrent drug therapy issues:
• Corticosteroids: Appropriate clinical monitoring and caution are recommended when systemic corticosteroid reduction is considered in patients receiving montelukast.
Dosage form specific issues:
• Chewable tablet: Contains phenylalanine.
Other warnings/precautions:
• Aspirin-sensitive asthmatics: Montelukast will not interrupt bronchoconstrictor response to aspirin or other NSAIDs. Patients with known aspirin sensitivity should continue to avoid these agents.
• Reversal of bronchospasm: Not FDA approved for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Some clinicians, however, support its use as adjunctive therapy (Camargo, 2003; Cylly, 2003; Ferreira, 2001; Harmancik 2006). Appropriate rescue medication should be available.
Adverse Reactions
Note: Percentages and adverse events as reported in adults
1% to 10%:
Central nervous system: Headache (18%), dizziness (2%), fatigue (2%), fever (2%)
Dermatologic: Rash (2%)
Gastrointestinal: Dyspepsia (2%), dental pain (2%), gastroenteritis (2%)
Hepatic: AST increased (2%), ALT increased (≥1%)
Neuromuscular & skeletal: Weakness (2%)
Respiratory: Cough (≥1%), nasal congestion (2%), epistaxis (≥1%), sinusitis (≥1%), upper respiratory infection (≥1%)
Postmarketing and/or case reports: Aggression, agitation, anaphylaxis, angioedema, anxiety, arthralgia, behavior/mood changes, bleeding tendency, bruising, Churg-Strauss syndrome, depression, diarrhea, disorientation, dream abnormalities, drowsiness, edema, eosinophilia (systemic), erythema multiforme, erythema nodosum, hallucinations, hepatic eosinophilic infiltration, hepatitis (mixed pattern, hepatocellular, and cholestatic), hostility, hypersensitivity, hypoesthesia, insomnia, irritability, muscle cramps, myalgia, nausea, palpitations, pancreatitis, paresthesia, pruritus, restlessness, seizures, somnambulism, suicidal thinking/behavior (suicidality), suicide, thrombocytopenia, tremor, urticaria, vasculitis, vomiting
Metabolism/Transport Effects
Substrate of CYP2C9 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (weak), CYP2C9 (weak)
Drug Interactions
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Mifepristone: May increase the serum concentration of CYP2C9 Substrates. Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Risk D: Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: St John's wort may decrease montelukast levels.
Storage
Store at room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Granules: Store in original package; use within 15 minutes of opening packet.
Mechanism of Action
Selective leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Cysteinyl leukotrienes are also released from the nasal mucosa following allergen exposure leading to symptoms associated with allergic rhinitis.
Pharmacodynamics/Kinetics
Duration: >24 hours
Absorption: Rapid
Distribution: Vd: 8-11 L
Protein binding, plasma: >99%
Metabolism: Extensively hepatic via CYP3A4 and 2C9
Bioavailability: Tablet: 10 mg: Mean: 64%; 5 mg: 63% to 73%
Half-life elimination, plasma: Mean: 2.7-5.5 hours
Time to peak, serum: Tablet: 10 mg: 3-4 hours; 5 mg: 2-2.5 hours; 4 mg: 2 hours
Excretion: Feces (86%); urine (<0.2%)
Dosage
Oral:
Children:
6-23 months: Perennial allergic rhinitis: 4 mg (oral granules) once daily
12-23 months: Asthma: 4 mg (oral granules) once daily, taken in the evening
2-5 years: Asthma, seasonal or perennial allergic rhinitis: 4 mg (chewable tablet or oral granules) once daily
6-14 years: Asthma, seasonal or perennial allergic rhinitis: 5 mg (chewable tablet) once daily
Children ≥15 years and Adults:
Asthma, seasonal or perennial allergic rhinitis: 10 mg once daily
Asthma, acute (unlabeled use): 10 mg as a single dose administered with first-line therapy (Camargo, 2003; Cylly, 2003)
Bronchoconstriction, exercise-induced (prevention): 10 mg at least 2 hours prior to exercise; additional doses should not be administered within 24 hours. Daily administration to prevent exercise-induced bronchoconstriction has not been evaluated.
Dosing adjustment in renal impairment: No adjustment necessary
Dosing adjustment in hepatic impairment: Mild-to-moderate: No adjustment necessary. Patients with severe hepatic disease were not studied.
Administration: Oral
When treating asthma, administer dose in the evening. Patients with allergic rhinitis may individualize administration time (morning or evening). Patients with both asthma and allergic rhinitis should take their dose in the evening. Granules may be administered directly in the mouth or mixed with a spoonful of applesauce, carrots, rice, ice cream, baby formula, or breast milk; do not add to any other liquids or foods. Administer within 15 minutes of opening packet. May administer without regard to meals.
Monitoring Parameters
Mood or behavior changes, including suicidal thinking/behavior
Dietary Considerations
Some products may contain phenylalanine.
Patient Education
Do not stop other asthma medication unless advised by prescriber. Chewable tablet contains phenylalanine. Granules may be administered directly in the mouth or mixed with applesauce, carrots, rice, ice cream, baby formula, or breast milk (do not add to any other liquids); administer within 15 minutes of opening packet. You may experience mild headache, fatigue, or dizziness. Report skin rash or itching, abdominal pain or persistent GI upset, unusual cough or congestion, behavior and mood changes including depression and suicide ideation, feeling of numbness in arms or legs, flu-like illness, or worsening of asthmatic condition.
Geriatric Considerations
The pharmacokinetic profile in the elderly is similar to younger adults except the half-life is slightly longer in the elderly. Despite this difference, no adjustment in dose is necessary in the elderly. Elimination is mostly fecal and bile with insignificant amounts from renal elimination, which is an advantage for the elderly.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Dental pain.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause agitation, aggression, anxiousness, depression, dizziness, dream abnormalities, drowsiness, hallucinations, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide)
Mental Health: Effects on Psychiatric Treatment
Barbiturates may decrease the effects of montelukast; CYP3A4 substrate; nefazodone may increase effects
Nursing: Physical Assessment/Monitoring
Not for use in acute asthma attacks, including status asthmaticus. Monitor mental and mood status. Be alert to signs of depression, hallucinations, irritability, agitation, and suicide ideation.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Granules, oral:
Singulair®: 4 mg/packet (30s)
Tablet, oral:
Singulair®: 10 mg [contains lactose 89.3 mg/tablet]
Tablet, chewable, oral:
Singulair®: 4 mg [contains phenylalanine 0.67 mg/tablet; cherry flavor]
Singulair®: 5 mg [contains phenylalanine 0.84 mg/tablet; cherry flavor]
Pricing: U.S. (www.drugstore.com)
Chewable (Singulair)
4 mg (30): $166.91
5 mg (30): $166.99
Pack (Singulair)
4 mg (30): $169.05
Tablets (Singulair)
10 mg (30): $167.99
References
Bakhireva LN, Jones KL, Schatz M, et al, “Organization of Teratology Information Specialists Collaborative Research Group. Safety of Leukotriene Receptor Antagonists in Pregnancy,” J Allergy Clin Immunol, 2007, 119(3):618-25.
Camargo CA Jr, Smithline HA, Malice MP, et al, “A Randomized Controlled Trial of Intravenous Montelukast in Acute Asthma,” Am J Respir Crit Care Med, 2003, 167(4):528-33.
Cylly A, Kara A, Ozdemir T, et al, “Effects of Oral Montelukast on Airway Function in Acute Asthma,” Respir Med, 2003, 97(5):533-6.
Ferreira MB, Santos AS, Pregal AL, et al, “Leukotriene Receptor Antagonists (Montelukast) in the Treatment of Asthma Crisis: Preliminary Results of a Double-Blind Placebo Controlled Randomized Study,” Allerg Immunol (Paris), 2001, 33(8):315-8.
Harmanci K, Bakirtas A, Turktas I, et al, “Oral Montelukast Treatment of Preschool-Aged Children With Acute Asthma,” Ann Allergy Asthma Immunol, 2006, 96(5):731-5.
National Asthma Education and Prevention Program (NAEPP), “Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma,” Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 08-4051, prepublication 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
Philip G, Hustad CM, Malice MP, et al, “Analysis of Behavior-Related Adverse Experiences in Clinical Trials of Montelukast,” J Allergy Clin Immunol, 2009, 124(4):699-706.
Philip G, Hustad C, Noonan G, et al, “Reports Of Suicidality In Clinical Trials Of Montelukast,” J Allergy Clin Immunol, 2009, 124(4):691-6.
Sarkar M, Koren G, Kalra S, et al, “Montelukast Use During Pregnancy: A Multicentre, Prospective, Comparative Study of Infant Outcomes,” Eur J Clin Pharmacol 2009, 65(12);1259-64.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
|
