Skip to Content
Looking to save on your medications?  Find out how 


Generic name: zileuton systemic

Brand names: Zyflo, Zyflo CR

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Zyflo: 600 mg [scored]

Tablet Extended Release 12 Hour, Oral:

Zyflo CR: 600 mg [DSC]

Generic: 600 mg


Mechanism of Action

Specific 5-lipoxygenase inhibitor which inhibits leukotriene formation. Leukotrienes augment neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction (which contribute to inflammation, edema, mucous secretion, and bronchoconstriction in the airway of the asthmatic).





1.2 L/kg


Hepatic and gastrointestinal; zileuton and N-dehydroxylated metabolite can be metabolized via CYP1A2, 2C9, and 3A4


Urine (~95% primarily as metabolites); feces (~2%)

Time to Peak

Immediate release: 1.7 hours

Half-Life Elimination

~3 hours

Protein Binding

93%, primarily albumin

Use in Specific Populations

Special Populations: Hepatic Function Impairment

The mean apparent plasma clearance of zileuton in subjects with hepatic impairment was approximately half the value of the healthy subjects. The percent binding of zileuton to plasma proteins after multiple dosing was significantly reduced in patients with moderate hepatic impairment.

Use: Labeled Indications

Asthma: Prophylaxis and chronic treatment of asthma in adults and children ≥12 years of age

Limitations of use: Not indicated for relief of acute bronchospasm


Hypersensitivity to zileuton or any component of the formulation; active liver disease or transaminase elevations ≥3 times ULN

Dosage and Administration

Dosing: Adult

Asthma: Oral:

Immediate release: 600 mg 4 times daily

Extended release: 1,200 mg twice daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Asthma: Note: Current guidelines do not describe a role for zileuton in the management of asthma (GINA 2018); not routinely used. Children ≥12 years and Adolescents:

Immediate release: Oral: 600 mg 4 times daily; maximum daily dose: 2,400 mg/day

Extended release: Oral: 1,200 mg twice daily; maximum daily dose: 2,400 mg/day


Immediate release: Administer without regard to meals.

Extended release: Do not crush, cut, or chew tablet; administer within 1 hour after morning and evening meals.

Dietary Considerations

Immediate release: Take without regard to meals.

Extended release: Take with food.


Store tablets at 20°C to 25°C (68°F to 77°F). Protect from light.

Zileuton Images

Drug Interactions

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Pimozide: Zileuton may increase the serum concentration of Pimozide. Avoid combination

Propranolol: Zileuton may increase the serum concentration of Propranolol. Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Warfarin: Zileuton may increase the serum concentration of Warfarin. Monitor therapy

Adverse Reactions

>10%: Central nervous system: Headache (23% to 25%)

1% to 10%:

Cardiovascular: Chest pain

Central nervous system: Pain (8%), dizziness, drowsiness, hypertonia, insomnia, malaise, nervousness

Dermatologic: Pruritus, skin rash

Gastrointestinal: Dyspepsia (8%), nausea (5% to 6%), abdominal pain (5%), diarrhea (5%), constipation, flatulence, vomiting

Genitourinary: Urinary tract infection, vaginitis

Hematologic & oncologic: Leukopenia (1% to 3%), lymphadenopathy

Hepatic: Increased serum ALT (≥3 x ULN: 2% to 5%), hepatotoxicity

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Myalgia (7%), weakness (4%), arthralgia, neck pain, neck stiffness

Ophthalmic: Conjunctivitis

Respiratory: Upper respiratory tract infection (9%), sinusitis (7%), pharyngolaryngeal pain (5%)

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Behavioral changes, hepatic failure, hepatitis, hyperbilirubinemia, jaundice, mood changes, sleep disorder, suicidal tendencies, urticaria


Concerns related to adverse effects:

  • Hepatotoxicity: There have been reports of hepatic adverse effects (elevated transaminase levels); serum ALT should be monitored. Females >65 years and patients with pre-existing elevated transaminases may be at greater risk. Discontinue therapy and follow transaminases until normal if patients develop clinical signs/symptoms of liver dysfunction or with transaminase levels >5 times ULN; use caution with history of liver disease and/or in those patients who consume substantial quantities of ethanol.
  • Neuropsychiatric events: Postmarketing reports of behavioral changes and sleep disorders have been noted.

Concurrent drug therapy issues:

  • Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

  • Elderly: Females >65 years of age may be at increased risk for ALT elevations. Pharmacokinetics were similar in older adults (≥65 years) compared to younger adults.
  • Pediatric: Due to the risk of hepatotoxicity, the manufacturer does not recommend use of zileuton in children <12 years of age.

Other warnings/precautions:

  • Reversal of bronchospasm: Not indicated for the reversal of bronchospasm in acute asthma attacks, including status asthmaticus; therapy may be continued during acute asthma exacerbations.

Monitoring Parameters

Hepatic transaminases (prior to initiation and during therapy), specifically monitor serum ALT (prior to initiation, once-a-month for the first 3 months, every 2 to 3 months for the remainder of the first year, and periodically thereafter for patients receiving long-term therapy)


Pregnancy Considerations

Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications (BTS 2016; GINA 2018). If a leukotriene modifier is needed during pregnancy, other agents are preferred (ACOG [Dombrowski] 2008).

Data collection to monitor pregnancy and infant outcomes following exposure to asthma medications in pregnancy is ongoing. Health care providers are encouraged to enroll females exposed to zileuton during pregnancy in the MothersToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (1-877-311-8972 or

Patient Education

  • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
  • Patient may experience headache, nausea, abdominal pain, heartburn, sore throat, stuffy nose, common cold symptoms, muscle pain, or diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), trouble sleeping, or behavioral changes (HCAHPS).
  • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Source: Wolters Kluwer Health. Last updated December 26, 2019.