Critical Therapeutics Inc's Zyflo (zileuton tablets)

APRIL 01, 2006
Carolyn Soo, PharmD, and Phung Hoach

Asthma is a chronic respiratory disease caused by inflammation and narrowing of the airways. In 2002, approximately 30 million people had been diagnosed with asthma in their lifetime.1 Although asthma affects more males during childhood years, it is predominantly diagnosed in females after age 40.1

Typical symptoms of asthma include wheezing, shortness of breath, and cough. The goals of treatment include improving respiratory function and quality of life, as well as reducing exacerbations, emergency visits, hospitalizations, and mortality. In September 2005, Critical Therapeutics Inc received FDA approval for Zyflo (zileuton tablets) as alternative therapy for the prevention and chronic treatment of asthma in patients 12 years of age and older.2


Zileuton is a specific 5-lipoxygenase inhibitor that leads to the inhibition of leukotriene formation.3 The enzyme 5-lipoxygenase is responsible for the activation of leukotriene synthesis from arachidonic acid. Leukotrienes are mediators for inflammatory conditions and are most often associated with asthma. They are responsible for bronchoconstriction, inflammation, edema, and mucus secretion.4-6

Clinical Trials

A multicenter, double-blind, parallelgroup, placebo-controlled trial evaluated the long-term efficacy and safety of zileuton. Approximately 400 patients with mild-to-moderate asthma were randomized to receive zileuton 400 mg qid, 600 mg qid, or placebo. Sustained improvement in lung function was seen over a 6-month period with zileuton. The results demonstrated significantly greater increases in patients' forced expiratory volume in 1 second (FEV1) from baseline in both zileuton groups (P<.05) except at day 64. The zileuton 600-mg qid group demonstrated decreases in corticosteroid rescues and in daytime and nocturnal symptoms, as well as improvement in morning peak expiratory flow rate (P <.05).5

In a 12-month, parallel-group, multicenter, open-label study, investigators assessed the efficacy of zileuton in approximately 3000 patients with a history of chronic asthma. The patients were randomized to receive either zileuton 600 mg qid plus usual asthma care or usual asthma care alone. The findings demonstrated that patients treated with zileuton required fewer rescues with steroids (P<.001), as well as fewer hospitalizations and emergency care visits (P<.05). The patients also experienced significant improvement in their FEV1 (P<.048).6


The most common adverse reactions include abdominal pain, dyspepsia, nausea, and alanine transaminase (ALT) elevations.2 Because zileuton is metabolized via the cytochrome P-450 system, it should not be given to patients with active liver disease or to those who have ALT elevations 3 or more times the upper limit of normal.

Concurrent use of zileuton with ethanol may increase central nervous system depression. Zileuton is in pregnancy category C, and its excretion in breast milk is unknown.3


Zyflo appears to be safe and effective in reducing asthmatic exacerbations and improving respiratory function. Patients with long-term zileuton therapy should be monitored for ALT elevations. Zileuton is available in 600-mg tablets. The recommended daily adult dose is 600 mg qid for the treatment of chronic asthma.3

Dr. Soo is a senior research pharmacist with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Ms. Hoach is a sixth-year PharmD candidate from Northeastern University, currently on clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

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