respiratory:drugs:zileuton []

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====== Zileuton ======

===== Classification =====
  * 5-Lipoxygenase (5-LO) Inhibitor
  * Leukotriene synthesis inhibitor

Parent class:
  * [[respiratory:drug_classes:leukotriene_modifiers|Leukotriene Modifiers]]

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===== Mechanism of Action =====

Zileuton inhibits the 5-lipoxygenase enzyme.

Normal pathway:

  Arachidonic acid
      ↓ (5-lipoxygenase)
  Leukotrienes (LTA4 → LTC4, LTD4, LTE4)

Zileuton:

  * Blocks leukotriene synthesis at the source
  * Reduces ALL leukotrienes (not just receptor activation)

Effects:

  * ↓ Bronchoconstriction
  * ↓ Airway inflammation
  * ↓ Mucus production
  * ↓ Eosinophilic activity

Unlike montelukast and zafirlukast, zileuton blocks production rather than receptor binding.

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===== Pharmacokinetics =====

  * Oral administration
  * Immediate-release: four times daily
  * Extended-release: twice daily
  * Hepatic metabolism (CYP1A2, CYP2C9, CYP3A4)
  * Eliminated via liver

Requires liver function monitoring.

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===== Indications =====

  * [[respiratory:clinical:asthma|Asthma]] (maintenance therapy)

Not used for:
  * Acute asthma exacerbations

Less commonly used due to liver toxicity risk.

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===== Dosing (Adult) =====

  * Immediate-release: 600 mg PO four times daily
  * Extended-release: 1200 mg PO twice daily

Monitor liver function tests before initiation and periodically during therapy.

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===== Adverse Effects =====

Common:
  * Headache
  * Dyspepsia
  * Nausea

Serious:
  * Hepatotoxicity
  * Elevated liver enzymes

Black box warning for liver injury.

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===== Drug Interactions =====

Inhibits CYP enzymes:

  * ↑ Theophylline levels
  * ↑ Warfarin levels
  * ↑ Propranolol levels

Monitor INR and drug levels when applicable.

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===== Clinical Role =====

Compared to receptor blockers:

  * Broader leukotriene suppression
  * More drug interactions
  * Requires liver monitoring
  * More frequent dosing

Because of safety concerns and complexity, it is rarely first choice.

May be considered in:

  * Aspirin-exacerbated respiratory disease
  * Select refractory asthma cases

See:
  * [[respiratory:clinical:asthma|Asthma Management]]

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===== Comparison Within Class =====

^ Drug ^ Mechanism ^ Major Risk ^
| [[respiratory:drugs:montelukast|Montelukast]] | CysLT1 receptor blocker | Neuropsychiatric effects |
| [[respiratory:drugs:zafirlukast|Zafirlukast]] | CysLT1 receptor blocker | Hepatotoxicity (rare) |
| [[respiratory:drugs:zileuton|Zileuton]] | 5-LO inhibitor | Hepatotoxicity (monitor LFTs) |

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===== Clinical Pearls =====

  * Only leukotriene drug that blocks synthesis.
  * Requires liver monitoring.
  * Significant CYP drug interactions.
  * Not commonly used in current practice.
  * Not a rescue medication.
  * More mechanistically comprehensive but less convenient.

----

===== Related Pages =====

  * [[respiratory:drug_classes:leukotriene_modifiers|Leukotriene Modifiers]]
  * [[respiratory:drugs:montelukast|Montelukast]]
  * [[endocrine:drug_classes:corticosteroids|Corticosteroids]]
  * [[allergy:histamine|Histamine & Antihistamines]]