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Medically reviewed by Last updated on Jun 18, 2020.


(zye LOO ton)

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

Brand Names: U.S.

  • Zyflo
  • Zyflo CR [DSC]

Pharmacologic Category

  • 5-Lipoxygenase Inhibitor


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

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

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: Swallow tablet whole; do not crush, cut, or chew; administer within 1 hour after morning and evening meals.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR tablet formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

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.

Drug Interactions

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. 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. 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

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>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, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes).

Agents other than zileuton may be preferred for the treatment of asthma during pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2020).

Data collection to monitor pregnancy and infant outcomes associated with asthma and the medications used to treat asthma in pregnancy is ongoing. Health care providers are encouraged to enroll exposed pregnant females in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (1-877-311-8972 or Patients may also enroll themselves.

Patient Education

What is this drug used for?

• It is used to treat or prevent asthma.

• Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Nausea

• Abdominal pain

• Heartburn

• Sore throat

• Stuffy nose

• Common cold symptoms

• Muscle pain

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Trouble sleeping

• Behavioral changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.