Zileuton (3 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, EXTENDED RELEASE.
Routes of administration: ORAL.
Brand Names
- ZILEUTON
- ZYFLO
- ZYFLO CR
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 (see PRECAUTIONS, Hepatic).
Contraindications
ZYFLO tablets are contraindicated in patients with: Active liver disease or transaminase elevations greater than or equal to three times the upper limit of normal (≥3xULN) (see PRECAUTIONS, Hepatic). Hypersensitivity to zileuton or any of its inactive ingredients.
Adverse Reactions
Clinical Studies: A total of 5542 patients have been exposed to zileuton in clinical trials, 2252 of them for greater than 6 months and 742 for greater than 1 year. Adverse events most frequently occurring (frequency ≥3%) in ZYFLO-treated patients and at a frequency greater than placebo-treated patients are summarized in Table 2. Proportion of Patients Experiencing Adverse Events in Placebo-Controlled Studies in Asthma Less common adverse events occurring at a frequency of greater than 1% and more commonly in ZYFLO-treated patients included: arthralgia, chest pain, conjunctivitis, constipation, dizziness, fever, flatulence, hypertonia, insomnia, lymphadenopathy, malaise, neck pain/rigidity, nervousness, pruritus, somnolence, urinary tract infection, vaginitis, and vomiting. The frequency of discontinuation from the asthma clinical studies due to any adverse event was comparable between ZYFLO (9.7%) and placebo-treated (8.4%) groups. In placebo-controlled clinical trials, the frequency of ALT elevations ≥3xULN was 1.9% for ZYFLO-treated patients, compared with 0.2% for placebo-treated patients. In controlled and uncontrolled trials, one patient developed symptomatic hepatitis with jaundice, which resolved upon discontinuation of therapy. An additional 3 patients with transaminase elevations developed mild hyperbilirubinemia that was less than three times the upper limit of normal. There was no evidence of hypersensitivity or other alternative etiologies for these findings. ZYFLO is contraindicated in patients with active liver disease or transaminase elevations greater than or equal to 3xULN (see CONTRAINDICATIONS). It is recommended that hepatic transaminases be evaluated at initiation of and during therapy with ZYFLO (see PRECAUTIONS, Hepatic). Occurrences of low white blood cell count (≤2.8 x 109/L) were observed in 1.0% of 1,678 patients taking ZYFLO and 0.6% of 1,056 patients taking placebo in placebo-controlled studies. These findings were transient and the maj
Overdosage
Human experience of acute overdose with zileuton is limited. A patient in a clinical trial took between 6.6 and 9.0 grams of zileuton in a single dose. Vomiting was induced and the patient recovered without sequelae. Zileuton is not removed by dialysis. Should an overdose occur, the patient should be treated symptomatically and supportive measures instituted as required. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. A Certified Poison Control Center should be consulted for up-to-date information on management of overdose with ZYFLO. 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). No deaths occurred, but nephritis was reported in dogs at an oral dose of 1000 mg/kg (providing in excess of 12 times the systemic exposure [AUC] achieved at the maximum recommended human daily oral dose).