LEUKOTRIENE MODIFIERS

PRICING INFO


References:
ASTHMA STUDIES


Drug Dosage form Dosage Generic/Price Other Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Montelukast

Singulair®
Tablet
  • 10 mg

Chewable tablet
  • 4 mg
  • 5 mg

Granule
  • 4 mg 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. Montelukast does NOT treat acute bronchospasm.
  • 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
NOTE: P = % of patients on placebo who reported side effect

  • 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.
  • Kidney disease - no dose adjustment necessary
  • Liver disease
    • Mild-moderate: no dose adjustment necessary
    • Severe: has not been studied
Drug Dosage form Dosage Generic/Price Other Mechanism of Action FDA-approved Indications Side Effects Drug Interactions Precautions / Contraindications
Zafirlukast

Accolate®
Tablet
  • 10 mg
  • 20 mg
Asthma
  • 5 - 11 years of age
    • 10 mg twice a day
    • Take 1 hour before or 2 hours after a meal. Food decreases absorption.
  • ≥ 12 years of age and adults
    • 20 mg twice a day
    • Take 1 hour before or 2 hours after a meal. Food decreases absorption.
YES/$-$$
  • Take 1 hour before or 2 hours after a meal. 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.
NOTE: P = % of patients on placebo who reported side effect

  • 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, zafirlukast 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 Lab monitoring / Other Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Zileuton

Zyflo®
Zyflo CR®
Zyflo® tablet
Tablet
  • 600 mg

Zyflo CR®
extended-release tablet
  • 600 mg
Zyflo®
  • Asthma (≥ 12 years old and adults)
    • 600 mg four times a day
    • May take without regard to food

Zyflo CR®
  • Asthma (≥ 12 years old and adults)
    • Two 600 mg tablets (1200 mg) twice a day
    • Take within one hour after morning and evening meal. Food increases absorption.
Zyflo
NO/$$$$

Zyflo CR
YES/$$$$
Lab monitoring
  • 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.

Other

    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.
NOTE: P = % of patients on placebo who reported side effect

  • 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 disease - DO NOT USE
  • 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. In trials, 4.6% of zileuton-treated patients developed ALT elevations ≥ 3XULN compared to 1.1% of control patients. If symptoms of liver dysfunction (e.g. right upper quadrant pain, nausea, fatigue, lethargy, pruritus, jaundice, or “flu-like” symptoms) develop or if ALT levels greater than 5XULN occur, zileuton should be discontinued. In trials, ALT levels returned to <2XULN in an average of 32 days in patients who discontinued zileuton due to ALT elevations.
  • Neuropsychiatric events - neuropsychiatric events including sleep disorders and behavior changes have been reported in some patients
  • Kidney disease - no dose adjustment necessary