Zyflo Cr (zileuton)

Zileuton, a leukotriene synthesis inhibitor, is an antiasthmatic agent.

Zileuton, a leukotriene synthesis inhibitor, is an antiasthmatic agent. The drug differs chemically and pharmacologically from other antiasthmatic agents (e.g., corticosteroids, mast-cell stabilizers, beta-adrenergic agonist bronchodilators, theophylline), including other currently available drugs that modify leukotriene activity (e.g., zafirlukast). Current evidence indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes.

Leukotriene B4 (LTB4), a potent chemotactic mediator, and the cysteinyl leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4). Leukotrienes are associated with numerous biologic effects, including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability and edema, and smooth muscle contraction.

The involvement of leukotrienes in asthma is supported by evidence of increased concentrations of leukotrienes in biologic fluids (e.g., urine, bronchoalveolar lavage fluid, nasal fluid, plasma) of some asthmatic patients following allergen challenge, episodes of asthma, and in patients with aspirin-induced asthma.

Zileuton exerts beneficial effects in patients with asthma by inhibiting 5-lipoxygenase, the first dedicated enzyme active in the conversion of arachidonic acid to leukotrienes. Zileuton does not appreciably inhibit either the acute bronchoconstrictor response (immediate/early asthmatic response (IAR, EAR)) or the delayed inflammatory response (late asthmatic response (LAR)) to inhaled antigen and irritants, but the drug does inhibit bronchoconstriction occurring after administration of aspirin to aspirin-sensitive asthmatic patients. Commercially available zileuton is a racemic mixture (50:50) of the r+ and s- enantiomers, both of which have been shown in vitro to be pharmacologically active inhibitors of 5-lipoxygenase.

Because of the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of 5-lipoxygenase action may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control. Leukotriene modifiers (e.g., zileuton, zafirlukast) have actions consistent with those of anti-inflammatory agents in that an expert panel of the National Asthma Education and Prevention Program has defined anti-inflammatory agents as those that reduce the markers of airway inflammation (e.g., eosinophils, mast cells, activated lymphocytes, macrophages, cytokines) in airway tissue or airway secretions and thereby reduce the intensity of airway hyperresponsiveness. However, the precise anti-inflammatory actions responsible for therapeutic effects of drugs in asthma (e.g., symptom reduction, improvement in expiratory flow, reduction in airway hyperresponsiveness, prevention of exacerbations, prevention of airway wall remodeling) remain to be fully elucidated.

Zileuton does not appear to produce appreciable bronchodilation in healthy individuals.

SumMon(R) (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the labeling be consulted for detailed information on the usual cautions, precautions, and contraindications.

USES: Zileuton is used to control and prevent symptoms (such as wheezing and shortness of breath) caused by asthma. Controlling symptoms of asthma helps you maintain your normal activities and cuts down on time lost from work or school. This medication must be used regularly to be effective.

It does not work right away and should not be used to relieve sudden asthma attacks. If an asthma attack occurs, use your quick-relief inhaler (such as albuterol, salbutamol) as prescribed. This drug is not recommended for use in children younger than 12 years due to possible risk of liver problems.

Generic name: zileuton
Pronunciation: (zye-LOO-ton)

The following indications are listed for Zyflo Cr:

• Maintenance Therapy For Asthma

Also known as: Therapy To Achieve Long-Term Asthma Control.

No ICD codes are available for this drug.