Zileuton

Zileuton is an inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB 4 , LTC 4 , LTD 4 and LTE 4 ) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro and in vivo systems.

• Zileuton extended-release tablets are indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Zileuton extended-release tablets are not indicated for use in the reversal of bronchospasm in acute asthma attacks.ICD-10: J45.909

• The use of zileuton extended-release tablets are contraindicated in patients with: • Active liver disease or persistent hepatic function enzyme elevations greater than or equal to 3 times the upper limit of normal (≥3xULN) [see Warnings and Precautions ( 5 ), and Use in Specific Populations ( 8.7 ) ]. • A history of allergic reaction to zileuton or any of the ingredients of zileuton extended-release tablets (e.g., rash, eosinophilia, etc.).contraindicated

The recommended dosage of zileuton extended-release tablets for the treatment of patients with asthma is two 600 mg extended-release tablets twice daily, within one hour after morning and evening meals, for a total daily dose of 2400 mg. Tablets should not be chewed, cut or crushed. If a dose is missed, the patient should take the next dose at the scheduled time and not double the dose. Assess hepatic function enzymes prior to initiation of zileuton extended-release tablets and periodically during treatment [see Contraindications ( 4 ), Warnings and Precautions ( 5 ), and Use in Specific Populations ( 8.7 ) ]. Adults and children 12 years of age and older: The recommended dose of zileuton extended-release tablets is two 600 mg extended-release tablets twice daily, within one hour after morning and evening meals, for a total daily dose of 2400 mg. ( 2 ) Monitoring: Assess hepatic function enzymes prior to initiation of zileuton extended-release tablet and monitor periodically during treatment. ( 2 , 5.1 )

Hepatotoxicity: Elevations of one or more hepatic function enzymes and bilirubin may occur with zileuton extended-release tablets. Assess hepatic function enzymes prior to initiation of zileuton extended-release tablets, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and periodically thereafter. Use zileuton extended-release tablets with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. ( 5.1 ) Neuropsychiatric Events: Neuropsychiatric events, including sleep disorders and behavior changes, may occur with zileuton extended-release tablets. Instruct patients to be alert for neuropsychiatric events. Evaluate the risks and benefits of continuing treatment with zileuton extended-release tablets if such events occur. ( 5.2 ) 5.1 Hepatotoxicity Elevations of one or more hepatic function enzymes and bilirubin may occur during zileuton extended-release tablets therapy. These laboratory abnormalities may progress to clinically significant liver injury, remain unchanged, or resolve with continued treatment, usually within three weeks. The ALT (SGPT) test is considered the most sensitive indicator of liver injury for zileuton extended-release tablets. Assess hepatic function enzymes prior to initiation of, and during therapy with, zileuton extended-release tablets.

Hepatotoxicity: Elevations of one or more hepatic function enzymes and bilirubin may occur during zileuton extended-release tablets therapy [see Warnings and Precautions ( 5 ) ]. The most commonly occurring adverse reactions (≥5%) with zileuton extended-release tablets are sinusitis, nausea, and pharyngolaryngeal pain. Most common adverse reactions (≥5%) included: sinusitis, nausea, and pharyngolaryngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Annora Pharma Private Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Short-Term Clinical Studies Experience The safety data described below reflect exposure to zileuton extended-release tablets in 199 patients for 12 weeks duration. In a 12-week, randomized, double-blind, placebo-controlled trial in adults and adolescents 12 years of age and older with asthma, patients received zileuton extended-release tablets two 600 mg tablets (n=199) or placebo (n=198) twice daily by mouth. Eighty-three percent of patients were white, 48% were male, and the mean age was 34 years. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most commonly reported adverse reactions (occurring at a frequency of ≥5%) in zileuton extended-release tablets -treated patients and at a frequency greater than placebo-treated patients are reflected in Table 1. Table 1.

Information on specific populations is based on studies conducted with zileuton immediate-release tablets and is applicable to zileuton extended-release tablets. Hepatic Impairment: Zileuton extended-release tablets are contraindicated in patients with active liver disease and in patients with elevated hepatic function enzymes ≥3 times the upper limit of normal. ( 4 , 5 , 8.7 ) 8.1 Pregnancy Risk Summary There are no adequate human data on zileuton extended-release tablets use in pregnant women to inform a drug associated risk. In animal studies, oral administration of zileuton to pregnant rats and rabbits during organogenesis produced adverse developmental outcomes. Structural abnormalities (cleft palate) were observed in rabbits at a dose similar to the maximum recommended human daily oral dose (MRHD), and alterations to growth (reduced fetal body weight and increased skeletal variations) were observed in rats at maternal plasma exposures 20 times greater than at the MRHD [see Data]. In a pre- and post-natal development study, oral administration of zileuton to pregnant rats from organogenesis through weaning at maternal plasma exposures 20 times greater than the MRHD resulted in reduced pup survival and body weights.

Metabolism

Information on the pharmacokinetics of zileuton following the administration of zileuton immediate-release tablets is available in healthy subjects. The results of two clinical pharmacology studies using zileuton extended-release tablets are described below.

Human experience of acute overdose with zileuton is limited. A patient in a clinical study took between 6.6 and 9.0 grams of zileuton immediate-release tablets 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 zileuton extended-release tablets.

• Dec 9, 1996NDANDA020471Chiesi
• Mar 17, 2017ANDAANDA204929Rising
• Dec 16, 2019ANDAANDA212670Strides Pharma Intl
• Oct 11, 2022ANDAANDA215742Annora Pharma

1. 1Asthma7612%
2. 2Dyspnoea528.2%
3. 3Drug Ineffective487.5%
4. 4Nausea406.3%
5. 5Off Label Use386.0%
6. 6Pneumonia335.2%
7. 7Cough314.9%
8. 8Fatigue304.7%
9. 9Headache264.1%
10. 10Product Use In Unapproved Indication253.9%
11. 11Malaise233.6%
12. 12Wheezing233.6%
13. 13Anaphylactic Reaction223.5%
14. 14Pruritus223.5%
15. 15Sinusitis223.5%

The 10 most recently updated of 21 ClinicalTrials.gov registrations naming Zileuton as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers
  Completed · Phase 2 · Interventional · 63 enrolled · National Cancer Institute (NCI)
  NCT02348203updated 2022-06-02
• Comparision Efficacy of Carbamazepine & Oxcarbazepine in the Treatment of Trigeminal Neuralgia- a Randomised Clinical Trial
  Unknown · Phase 4 · Interventional · 132 enrolled · Postgraduate Institute of Dental Sciences Rohtak
  NCT04996199updated 2021-10-15
• Zileuton to Treat Adults With Chronic Obstructive Pulmonary Disease (The LEUKO Study)
  Terminated · Phase 3 · Interventional · 119 enrolled · University of Minnesota
  NCT00493974updated 2019-11-18
• Association Between Increased Oxidative Stress, Anti-Inflammatory Fatty Acid Formation, and Airway Infection in People With Asthma and Chronic Obstructive Pulmonary Disease
  Completed · Observational · 43 enrolled · Brigham and Women's Hospital
  NCT00595114updated 2016-10-19
• Evaluating the Safety of Zileuton (Zyflo®) in Combination With Dasatinib (Sprycel®) in Chronic Myelogenous Leukemia
  Terminated · Phase 1 · Interventional · 2 enrolled · University of Massachusetts, Worcester
  NCT02047149updated 2016-09-30
• Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer
  Completed · Phase 2 · Interventional · 140 enrolled · Alliance for Clinical Trials in Oncology
  NCT00070486updated 2016-06-30
• Zileuton for the Treatment of Idiopathic Pulmonary Fibrosis
  Completed · Phase 2 · Interventional · 44 enrolled · University of Michigan
  NCT00262405updated 2015-12-03
• Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in CML.
  Terminated · Phase 1 · Interventional · 2 enrolled · University of Massachusetts, Worcester
  NCT01130688updated 2015-05-27
• Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers
  Completed · Phase 1 · Phase 2 · Interventional · 84 enrolled · National Cancer Institute (NCI)
  NCT01021215updated 2015-04-02
• A Study Evaluating the Persistency of Response With or Without Xolair (Omalizumab) After Long-term Therapy
  Completed · Phase 4 · Interventional · 176 enrolled · Genentech, Inc.
  NCT01125748updated 2014-10-15

Frequently asked questions

How does Zileuton work?

Zileuton is an inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB 4 , LTC 4 , LTD 4 and LTE 4 ) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro and in vivo systems.

What is Zileuton used for?

According to FDA labeling, Zileuton carries indications including: Zileuton extended-release tablets are indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Zileuton extended-release tablets are not indicated for use in the reversal of bronchospasm in acute asthma attacks.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Zileuton?

Zileuton is classified as 5-Lipoxygenase Inhibitor, 5-Lipoxygenase Inhibitors, Bronchodilation, Decreased Capillary Permeability, Decreased Cellular Migration, Decreased Leukotriene Production.

What are the brand names for Zileuton?

Zileuton is marketed under brand names including Zyflo.

What are the contraindications for Zileuton?

Zileuton labeling lists contraindications including: The use of zileuton extended-release tablets are contraindicated in patients with: • Active liver disease or persistent hepatic function enzyme elevations greater than or equal to 3 times the upper limit of normal (≥3xULN) [see Warnings and Precautions ( 5 ), and Use in Specific Populations ( 8.7 ) ]. • A history of allergic reaction to zileuton or any of the ingredients of zileuton extended-release tablets (e.g., rash, eosinophilia, etc.).. Always consult the full prescribing information and a clinician.