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Drug Dosage form Dosage Generic/Price Other Class/Mechanism of Action Indications
(FDA-approved)
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Montelukast

(Singulair®)
Montelukast
  • Chewable tablet: 4 and 5 mg
  • Tablet: 10mg
  • Granule: 4mg packet
Asthma
  • 1 - 5 years of age
    • 4mg once daily in the evening
  • 6 - 14 years of age
    • 5mg once daily in the evening
  • ≥ 15 years of age
    • 10mg once daily in the evening

Exercise-induced asthma
  • 6 - 14 years of age
    • 5mg at least 2 hours before exercise
  • ≥ 15 years old
    • 10mg at least 2 hours before exercise

Allergic rhinitis
  • 6 - 23 months
    • 4mg once daily in the evening
  • 2 - 5 years of age
    • 4mg once daily in the evening
  • 6 - 14 years of age
    • 5mg once daily in the evening
  • ≥ 15 years of age
    • 10mg once daily in the evening
Tablet
YES/$

Chewable Tablet
YES/$

Granule
YES/$$-$$$

Tablets
  • May take without regard to food

Granules
  • 4-mg oral granules can be administered either directly in the mouth, dissolved in 1 teaspoonful (5 mL) of cold or room temperature baby formula or breast milk, or mixed with a spoonful of cold or room temperature soft foods; based on stability studies, only applesauce, carrots, rice, or ice cream should be used
  • After opening the packet, the full dose (with or without mixing with baby formula, breast milk, or food) must be administered within 15 minutes
  • Leukotriene Receptor Antagonist (LTRA) - blocks leukotriene receptors and inhibits leukotriene-induced airway edema, smooth muscle contraction, and other inflammatory actions
  • Asthma - prevention and prophylaxis in patients 12 months of age and older
  • Exercise-induced asthma - in patients 6 years of age and older
  • Allergic rhinitis - seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 6 months of age and older
  • Montelukast does NOT treat acute bronchospasm
  • Headache - 18.4%, P - 18.1%
  • Influenza - 4.2%, P - 3.9%
  • Abdominal pain - 2.9%, P - 2.5%
  • Cough - 2.7%, P - 2.4%
  • Upset stomach - 2.1%, P - 1.1%
  • No clinically relevant drug interactions have been identified
  • Montelukast is a CYP2C8, CYP3A4, and CYP2C9 substrate (in vitro data)
  • Phenylketonuria - 4 and 5mg chewable tablets contain phenylalanine
  • Neuropsychiatric events - neuropsychiatric events including agitation, aggressive behavior, memory problems, depression, hallucinations, etc. have been reported in some patients
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) - in rare cases, montelukast has been associated with Churg-Strauss syndrome. It is unclear if there is a true causal relationship.
  • Liver disease - mild-moderate - no dose adjustment necessary; severe - has not been studied
  • Kidney disease - no dose adjustment necessary

Drug Dosage form Dosage Generic/Price Other Class/Mechanism of Action Indications
(FDA-approved)
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Zafirlukast

(Accolate®)
Zafirlukast tablet
  • 10mg
  • 20mg
Asthma
  • 5 - 11 years of age
    • 10mg twice a day
    • Take 1 hour before or 2 hours after a meal
  • ≥ 12 years of age and adults
    • 20mg twice a day
    • Take 1 hour before or 2 hours after a meal
YES/$$
  • Food decreases absorption
  • Leukotriene Receptor Antagonist (LTRA) - blocks leukotriene receptors and inhibits leukotriene-induced airway edema, smooth muscle contraction, and other inflammatory actions
  • Asthma - prevention and prophylaxis in patients 5 years of age and older
  • Zafirlukast does NOT treat acute bronchospasm
  • Headache - 12.9%, P - 11.7%
  • Infection - 3.5%, P - 3.4%
  • Nausea - 3.1%, P - 2.0%
  • Diarrhea - 2.8%, P - 2.1%
  • Generalized pain - 1.9%, P - 1.7%
  • CYP2C9 substrates - zafirlukast is a weak CYP2C9 inhibitor. It may increase levels of CYP2C9 substrates.
  • CYP2C9 inhibitors and inducers - zafirlukast is a CYP2C9 substrate. CYP2C9 inhibitors and inducers may affect zafirlukast levels.
  • Warfarin - zafirlukast may increase levels of warfarin and affect coagulation. Monitor INR closely when combining.
  • Erythromycin - may decrease zafirlukast levels
  • Theophylline - may decrease zafirlukast levels
  • Aspirin - aspirin may increase zafirlukast levels
  • CYP3A4 substrates - in vitro studies have shown zafirlukast to be a CYP3A4 inhibitor
  • Liver toxicity - Zafirlukast has been associated with liver toxicity. If signs of liver toxicity occur, zafirlukast should be stopped and a liver enzymes should be checked.
  • Neuropsychiatric events - neuropsychiatric events including insomnia and depression have been reported in some patients
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) - in rare cases, montelukast has been associated with Churg-Strauss syndrome. It is unclear if there is a true causal relationship.
  • Liver disease - DO NOT USE
  • Kidney disease - no dose adjustment necessary




Drug Dosage form Dosage Generic/Price Other Class/Mechanism of Action Indications
(FDA-approved)
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Zileuton

(Zyflo®)
(Zyflo CR®)
Zyflo® tablet
  • 600mg

Zyflo CR® extended-release tablet
  • 600mg
Zyflo®
  • 600mg four times a day
  • May take without regard to food
Zyflo CR®
  • Two 600mg tablets (1200mg) twice a day
  • Take within one hour after morning and evening meal
  • Food increases absorption
NO/$$$$ Other
  • Check serum ALT before treatment begins, once a month for the first 3 months, every 2-3 months for the remainder of the first year, and periodically thereafter.

Zyflo CR®
  • Food increases absorption. Take on full stomach
  • Do not crush, cut, or chew tablets
  • 5-lipoxygenase inhibitor - blocks leukotriene formation and inhibits leukotriene-induced airway edema, smooth muscle contraction, and other inflammatory actions
  • Asthma - prevention and prophylaxis in patients 12 years of age and older
  • Zafirlukast does NOT treat acute bronchospasm
  • Headache - 24.6%, P - 24%
  • Upset stomach - 8.2%, P - 2.9%
  • Pain (unspecified) - 7.8%, P - 5.3%
  • Nausea - 5.5%, P - 3.7%
  • Liver enzyme elevations (3XULN) - 4.6%, P - 1.1%
  • Abdominal pain - 4.6%, P - 2.4%
  • Asthenia - 3.8%, P - 2.4%
  • Muscle pain - 3.2%, P - 2.9%
  • CYP1A2 substrates - zileuton is a CYP1A2 moderate inhibitor. It may affect levels of CYP1A2 substrates.
  • CYP3A4 substrates - zileuton is a CYP3A4 weak inhibitor. It may affect levels of CYP3A4 substrates.
  • Theophylline - zileuton may increase theophylline levels. When adding zileuton to theophylline, the theophylline dose should be halved. Similarly, when adding theophylline to zileuton, use a lower dose of theophylline.
  • Propranolol - zileuton may increase propranolol levels. Use caution when combined.
  • Warfarin - zileuton may increase levels of warfarin and affect coagulation. Monitor INR closely when combining.
  • Liver toxicity - Zileuton has been associated with liver toxicity. Check serum ALT before treatment begins, once a month for the first 3 months, every 2-3 months for the remainder of the first year, and periodically thereafter.
  • Neuropsychiatric events - neuropsychiatric events including sleep disorders and behavior changes have been reported in some patients
  • Liver disease - DO NOT USE
  • Kidney disease - no dose adjustment necessary




Study Criteria Intervention Primary outcome Results

Montelukast + ICS
vs
LABA + ICS



BMJ
2003

PubMed abstract

Inclusion criteria:
  • Uncontrolled asthmatics aged 15 - 72 years
  • PFTs consistent with asthma
  • Regular ICS use

  • All participants were enrolled in a 4 week run-in period where they were given fluticasone 100mcg twice a day
Group 1 (747 patients) - Montelukast 10mg a day in addition to fluticasone for 48 weeks

Group 2 (743 patients) - Salmeterol 50mcg twice a day in addition to fluticasone for 48 weeks
  • Albuterol and prednisone were allowed as needed
  • Study was double-blinded with placebo alternative treatment in each arm
  • The primary end point was the percentage of patients with at least one asthma exacerbation, defined as worsening asthma requiring an unscheduled visit to a doctor, emergency department, or hospital or treatment with oral, intravenous, or intramuscular corticosteroids
Outcome
  • In Group 1, 20.1% of patients had at least one asthma exacerbation
  • In Group 2, 19.1% of patients had at least one asthma exacerbation
  • The difference between the groups was nonsignificant (1%, CI -3.1% to 5%)
  • Group 2 had a significantly greater increase in FEV₁ than Group 1 (p-value<0.001)

Study Criteria Intervention Primary outcome Results

CARE study



NEJM
2010

PubMed abstract
Inclusion criteria:
  • Children aged 6 - 17 years with mild-moderate asthma
  • An FEV₁ of at least 60% before bronchodilation, and an increase in the FEV₁ of at least 12% (bronchodilator reversibility)

  • All participants were enrolled in a 2 - 8 week run-in period where they were given fluticasone 100mcg twice a day
  • Patients who were still symptomatic during a 2 week period of the run-in phase were randomized to treatment
There were 3 treatment regimens and all patients received each regimen for 16 weeks in random order. A total of 165 patients were evaluated.
  • Treatment 1 - Fluticasone diskus 250 mcg twice daily for 16 weeks
  • Treatment 2 - Salmeterol 50mcg/fluticasone 100mcg (Advair diskus®) twice daily for 16 weeks
  • Treatment 3 - Fluticasone 100mcg twice daily + 5 - 10mg of montelukast (Singulair®) for 16 weeks

  • Albuterol and prednisone were allowed as needed
  • Study was double-blinded with placebo alternative treatment in each arm
  • The primary outcome was the differential response to each of the three step-up therapies on the basis of fixed threshold criteria for the following three asthma-control measures: the need for treatment with oral prednisone for acute asthma exacerbations, the number of asthma control days, and the FEV₁.
Outcome
  • Treatment 2 was more likely to be the best response when compared to Treatment 1 (p-value=0.002) and Treatment 3 (p-value=0.004)
  • There was no significant difference between Treatment 1 and Treatment 3
  • White race predicted a better response to LABA (Treatment 2)
  • Black patients were least likely to have a best response to LTRA (Treatment 3)



  • PRICING

    • $ = 0 - $50
    • $$ = $51 - $100
    • $$$ = $101 - $150
    • $$$$ = > $151

    • Pricing based on one month of therapy at standard dosing in an adult
    • Pricing based on survey of GoodRX.com®, HEB®, and Costco®, [accessed 2/2015]
    • Pricing may vary by region and availability



  • References:
  • 1 - Manufacturer's package insert