Clinical Information
Gen. Code and Des.
29803 zileuton ORAL TABLET 600 MG
Strength
600 mg
Dose Form
TABLET
Product Category
RX Pharmaceuticals
Fine Line Class
850085008510 All Rx Products
DEA Class
NC
OMP Family
AHFS Class
48102400 LEUKOTRIENE MODIFIERS
Active Ingredients
6297 zileuton 111406872
ZYFLO- zileuton tablet
Chiesi USA, Inc.
DESCRIPTION
Zileuton is an orally active inhibitor of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Zileuton has the chemical name (�)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
Zileuton has the molecular formula C11 H12 N2 O2 S and a molecular weight of 236.29. It is a racemic mixture (50:50) of R(+) and S(-) enantiomers. Zileuton is a practically odorless, white, crystalline powder that is soluble in methanol and ethanol, slightly soluble in acetonitrile, and practically insoluble in water and hexane. The melting point ranges from 144.2˚C to 145.2˚C. ZYFLO tablets for oral administration are supplied in one dosage strength containing 600 mg of zileuton.
Inactive Ingredients: crospovidone, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, propylene glycol, sodium starch glycolate, talc, and titanium dioxide.
CLINICAL PHARMACOLOGY
Mechanism of Action:
Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4 , LTC4 , LTD4 , and LTE4 ) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Sulfido-peptide leukotrienes (LTC4 , LTD4 , LTE4 , also known as the slow-releasing substances of anaphylaxis) and LTB4 , a chemoattractant for neutrophils and eosinophils, can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients.
Zileuton is an orally active inhibitor of ex vivo LTB4 formation in several species, including dogs, monkeys, rats, sheep, and rabbits. Zileuton inhibits arachidonic acid-induced ear edema in mice, neutrophil migration in mice in response to polyacrylamide gel, and eosinophil migration into the lungs of antigen-challenged sheep.
Zileuton inhibits leukotriene-dependent smooth muscle contractions in vitro in guinea pig and human airways. The compound inhibits leukotriene-dependent bronchospasm in antigen and arachidonic acid-challenged guinea pigs. In antigen-challenged sheep, zileuton inhibits late-phase bronchoconstriction and airway hyperreactivity. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.
INDICATIONS AND USAGE
ZYFLO is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.
DOSAGE AND ADMINISTRATION
The recommended dosage of ZYFLO for the symptomatic treatment of patients with asthma is one 600-mg tablet four times a day for a total daily dose of 2400 mg. For ease of administration, ZYFLO may be taken with meals and at bedtime. Hepatic transaminases should be evaluated prior to initiation of ZYFLO and periodically during treatment
