Should Zyflo (zileuton) be taken on an empty stomach?

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Should Zyflo (Zileuton) Be Taken on an Empty Stomach?

No, Zyflo (zileuton) should be taken within one hour after morning and evening meals to ensure optimal absorption and effectiveness. 1

Rationale for Taking Zileuton with Food

Zileuton is a 5-lipoxygenase inhibitor used for the chronic treatment of asthma. The FDA-approved drug label specifically instructs that:

  • Zileuton extended-release tablets should be taken within one hour after morning and evening meals 1
  • The medication should not be cut, chewed, or crushed 1

Unlike some medications where food decreases bioavailability, zileuton's effectiveness depends on proper administration with meals to ensure consistent therapeutic levels.

Clinical Implications of Food Intake

Taking zileuton with food is not merely a convenience recommendation but a critical factor for therapeutic efficacy:

  • The medication is not a bronchodilator and should not be used to treat acute asthma episodes 1
  • Consistent blood levels are essential for its preventive mechanism of action in blocking leukotriene production
  • Proper administration helps minimize variability in drug absorption

Monitoring and Safety Considerations

When taking zileuton, patients should be aware of important monitoring requirements:

  • Liver enzyme monitoring is required before initiating therapy and monthly for the first 3 months, with periodic monitoring thereafter 2
  • Approximately 4.4% of patients may experience elevations in ALT levels to ≥3 times the upper limit of normal 2
  • The majority of liver enzyme elevations (64.2%) occur within the first 3 months of treatment 2
  • Discontinuation is recommended if ALT levels exceed 5 times the upper limit of normal 2

Administration Guidelines

For optimal therapeutic benefit:

  • Standard dosing of zileuton immediate-release is 600 mg four times daily 2
  • Extended-release formulation is dosed as two 600 mg tablets twice daily 1, 3
  • Always take with meals (within one hour after eating)
  • Maintain regular dosing schedule for consistent blood levels

Alternative Options

If administration with food presents challenges for the patient, consider that:

  • Montelukast (Singulair) is recommended as an alternative for patients older than one year, with once-daily dosing 2
  • Zafirlukast (Accolate) is an option for patients seven years and older, with twice-daily dosing 2
  • Unlike zileuton, zafirlukast should be taken at least 1 hour before or 2 hours after meals, as administration with meals decreases bioavailability 4

Key Takeaway

Taking zileuton with food is not optional but essential for proper treatment. Patients should be instructed to take zileuton within one hour after meals to ensure optimal absorption and therapeutic effect.

References

Guideline

Asthma Management with Leukotriene Modifiers

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Efficacy of zileuton controlled-release tablets administered twice daily in the treatment of moderate persistent asthma: a 3-month randomized controlled study.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2007

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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