DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Active ingredient: Zileuton - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Anti-Inflammatory Agents, Non-Steroidal
  • Leukotriene Antagonists
  • Lipoxygenase Inhibitors

Dosage Forms

  • Tablet (600mg)

Brands / Synonyms

Leutrol; Zileuton [USAN:BAN:INN]; Zileutonum [INN-Latin]; Zyflo; Zyflo ; Zyflo CR


For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.


Zileuton is an asthma drug. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. 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. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.

Mechanism of Action

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. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it 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.


Rapidly and almost completely absorbed. The absolute bioavailability is unknown.


The oral minimum lethal doses in mice and rats were 500-4000 and 300-1000 mg/kg in various preparations, respectively (providing greater than 3 and 9 times the systemic exposure [AUC] achieved at the maximum recommended human daily oral dose, respectively).

Biotrnasformation / Drug Metabolism

Hepatic. Zileuton and its N-dehydroxylated metabolite are oxidatively metabolized by the cytochrome P450 isoenzymes 1A2, 2C9 and 3A4.


  • Active liver disease or transaminase elevations greater than or equal to three times the upper limit of normal (³3xULN) .
  • Hypersensitivity to zileuton or any of its inactive ingredients.

Drug Interactions

In a drug-interaction study in 16 healthy volunteers, co-administration of multiple doses of zileuton (800 mg every 12 hours) and theophylline (200 mg every 6 hours) for 5 days resulted in a significant decrease (approximately 50%) in steady-state clearance of theophylline, an approximate doubling of theophylline A.C. and an increase in theophylline Cmax (by 73%). The elimination half-life of theophylline was increased by 24%. Also, during co-administration, theophylline-related adverse events were observed more frequently than after theophylline alone. Upon initiation of ZYFLO in patients receiving theophylline, the theophylline dosage should be reduced by approximately one-half and plasma theophylline concentrations monitored. Similarly, when initiating therapy with theophylline in a patient receiving ZYFLO, the maintenance dose and/or dosing interval of theophylline should be adjusted accordingly and guided by serum theophylline determinations .

Concomitant administration of multiple doses of ZYFLO (600 mg every 6 hours) and warfarin (fixed daily dose obtained by titration in each subject) to 30 healthy male volunteers resulted in a 15% decrease in R-warfarin clearance and an increase in AUC of 22%. The pharmacokinetics of S-warfarin were not affected. These pharmacokinetic changes were accompanied by a clinically significant increase in prothrombin times. Monitoring of prothrombin time, or other suitable coagulation tests, with the appropriate dose titration of warfarin is recommended in patients receiving concomitant ZYFLO and warfarin therapy .

Co-administration of ZYFLO and propranolol results in a significant increase in propranolol concentrations. Administration of a single 80-mg dose of propranolol in 16 healthy male volunteers who received ZYFLO 600 mg every 6 hours for 5 days resulted in a 42% decrease in propranolol clearance. This resulted in an increase in propranolol Cmax, AUC, and elimination half-life by 52%, 104%, and 25%, respectively. There was an increase in ß-blockade and decrease in heart rate associated with the co-administration of these drugs. Patients on ZYFLO and propranolol should be closely monitored and the dose of propranolol reduced as necessary. No formal drug-drug interaction studies between ZYFLO and other beta-adrenergic blocking agents (i.e., ß-blockers) have been conducted. It is reasonable to employ appropriate clinical monitoring when these drugs are co-administered with ZYFLO.

In a drug interaction study in 16 healthy volunteers, co-administration of multiple doses of terfenadine (60 mg every 12 hours) and ZYFLO (600 mg every 6 hours) for 7 days resulted in a decrease in clearance of terfenadine by 22% leading to a statistically significant increase in mean AUC and Cmax of terfenadine of approximately 35%. This increase in terfenadine plasma concentration in the presence of ZYFLO was not associated with a significant prolongation of the QTc interval. Although there was no cardiac effect in this small number of healthy volunteers, given the high inter-individual pharmacokinetic variability of terfenadine, co-administration of ZYFLO and terfenadine is not recommended.

Drug-drug interaction studies conducted in healthy volunteers between ZYFLO and prednisone and ethinyl estradiol (oral contraceptive), drugs known to be metabolized by the P450 3A4 (CYP3A4) isoenzyme, have shown no significant interaction. However, no formal drug-drug interaction studies between ZYFLO and dihydropyridine, calcium channel blockers, cyclosporine, cisapride, and astemizole, also metabolized by CYP3A4, have been conducted. It is reasonable to employ appropriate clinical monitoring when these drugs are co-administered with ZYFLO.

Drug-drug interaction studies in healthy volunteers have been conducted with ZYFLO and digoxin, phenytoin, sulfasalazine, and naproxen. There was no significant interaction between ZYFLO and any of these drugs.

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017