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Drugs reference index «Zileuton»


Pronunciation: (zye-LOO-ton)Class: Leukotriene formation inhibitor

Trade Names:Zyflo- Tablets 600 mg

Trade Names:Zyflo CR- Tablets, ER 600 mg


Attenuates bronchoconstriction by inhibiting leukotriene-dependent smooth muscle contractions.



Rapidly absorbed. T max is about 1.7 h. C max is about 4.98 mcg/mL. AUC is about 19.2 mcg•h/mL. The relative bioavailability of zileuton ER tablets compared with the immediate-release formulation is 0.39 and 0.57, respectively.

Food caused a 27% increase in zileuton immediate-release C max ; administer with or without food. Food increased the C max and the AUC of zileuton ER by 18% and 34%, respectively, and prolonged T max from 2.1 to 4.3 h.


Vd is about 1.2 L/kg. It is about 93% bound to plasma proteins, primarily albumin.


Two diastereomeric O-glucuronide conjugates (major metabolites) and an N-dehydroxylated metabolite have been identified. The N-dehydroxylated metabolite can be oxidatively metabolized by CYP-450 isoenzymes 1A2, 2C9, and 3A4.


Predominantly via metabolism with a mean terminal half-life of about 2.5 h (immediate-release). Oral Cl is about 7 mL/min/kg. It is 94.5% recovered in urine with 2.2% recovered in feces.

ER tablets

Mean terminal half-life is 3.2 h. Apparent oral Cl is 669 mL/min.

Special Populations

Renal Function Impairment

Dosage adjustments in patients with renal function impairment or undergoing hemodialysis are not necessary.

Hepatic Function Impairment

Contraindicated in patients with active liver disease. Because treatment with zileuton may result in increased hepatic transaminases, use zileuton with caution in patients who consume substantial quantities of alcohol or have a history of liver disease.


Pharmacokinetics were similar between younger adults and elderly patients.


No differences in pharmacokinetics were observed.

Indications and Usage

Prophylaxis and long—term treatment of asthma.


Active liver disease or resistant elevations in transaminases at least 3 times the ULN; history of allergic reactions to zileuton or any of its inactive ingredients.

Dosage and Administration

Adults and Children 12 yr of age and older ER tablets

PO Two 600 mg ER tablets twice daily within 1 h after morning and evening meals.

Immediate-release tablets

PO 600 mg 4 times daily.

General Advice

  • ER tablets
  • Do not chew, cut, or crush tablets.
  • Administer tablets within 1 h of morning and evening meals.


Store at 68° to 77°F. Protect from light.

Drug Interactions


Because zileuton treatment may result in increased hepatic function enzymes and liver injury, use with caution in patients who consume substantial quantities of alcohol.

Beta-adrenergic blocking agents (eg, propranolol)

Coadministration of zileuton may increase propranolol concentrations, increasing the pharmacologic effects and the risk of adverse reaction. Closely monitor the patient and adjust the dose of propranolol as needed. No drug interaction studies have been conducted with other beta-blocking agents; however, employ appropriate clinical monitoring when they are coadministered with zileuton.

CYP3A4 agents (eg, calcium channel blockers, cisapride, cyclosporine, ketoconazole)

No interaction studies have been conducted; however, because zileuton is metabolized by CYP3A4, an interaction cannot be ruled out. Use with caution and careful monitoring when these agents are coadministered with zileuton.

Food ER tablets

In studies involving healthy subjects, food increased zileuton plasma concentrations. Zileuton ER tablets should be taken within 1 h after morning and evening meals.


Coadministration with zileuton is contraindicated.


Coadministration of zileuton may elevate theophylline concentrations, increasing the pharmacologic effects and the risk of adverse reactions. Reduce the initial theophylline dose by 50% and monitor theophylline concentration. Adjust the theophylline dose as needed.


Coadministration may increase the PT time. Monitor coagulation parameters and adjust the warfarin dose as needed.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Headache (25%); asthenia (4%); dizziness, hypertonia, insomnia, malaise, nervousness, somnolence (more than 1%); behavioral changes, sleep disorder (postmarketing).


Pruritus (greater than 1%); rash, urticaria (postmarketing).


Pharyngolaryngeal pain (at least 5%); conjunctivitis (greater than 1%).


Dyspepsia (8%); nausea (6%); abdominal pain, diarrhea (5%); constipation, flatulence, vomiting (more than 1%).


UTI, vaginitis (more than 1%).


Low WBC (3%); lymphadenopathy (more than 1%).


Hepatic injury, including death; hyperbilirubinemia; symptomatic jaundice (postmarketing).

Lab Tests

Elevated ALT (3%).


Myalgia (7%); arthralgia, neck pain/rigidity (more than 1%).


Upper respiratory tract infection (9%); sinusitis (at least 5%).


Pain (8%); accidental injury (3%); chest pain, fever (more than 1%).



Monitor hepatic transaminases at initiation of and during therapy. Monitor serum ALT before therapy begins, once a month for the first 3 mo, every 2 to 3 mo for the remainder of the first year, and periodically thereafter.


Category C .




Safety and efficacy not established in children younger than 12 yr of age.

Acute asthma attacks

Not indicated for treatment of acute asthma attacks. Continue therapy during acute exacerbations of asthma.

CNS effects

Neuropsychiatric events have been reported, including sleep disorders and behavioral changes.


Transient decreases in WBC may occur.


Elevations in LFTs may occur. Use with caution in patients who consume substantial quantities of alcohol or who have history of liver disease.



Human experience in acute overdose is limited.

Patient Information

  • Advise patient to read the patient information leaflet before using product the first time and with each refill.
  • Inform patient that this medication is for long-term treatment of asthma.
  • Instruct patient to take the medication exactly as prescribed, even when symptom free.
  • Advise patient to take immediate-release tablets 4 times a day with each meal and at bedtime, and ER tablets twice a day 1 h before morning and evening meals.
  • Warn the patient that this is not a bronchodilator and not to use it for the treatment of acute asthma attacks. However, advise the patient to continue therapy during acute exacerbations of asthma.
  • Instruct the patient to continue to take other asthma medications as prescribed.
  • Advise patients that elevation of liver enzyme is the most serious adverse reaction and that they must have LFTs monitored periodically. Instruct patients to notify health care provider if experiencing any signs or symptoms of liver disease, including fatigue, flu-like symptoms, jaundice, lethargy, nausea, pruritus, or right upper quadrant pain.
  • Instruct patient to notify health care provider if the use of short-acting bronchodilators increases or if more than the maximum number of inhalations of short-acting bronchodilators is needed.
  • Instruct patient that if a dose is missed, to take the next dose at scheduled time and not to double the dose.
  • Advise patient to swallow ER tablet whole and not to chew, cut, or crush the tablets.
  • Inform patients to notify health care provider if neuropsychiatric events (eg, behavioral changes, sleep disorder) occur.

Copyright © 2009 Wolters Kluwer Health.

  • Zileuton Detailed Consumer Information (PDR)
  • Zileuton MedFacts Consumer Leaflet (Wolters Kluwer)
  • zileuton Concise Consumer Information (Cerner Multum)
  • zileuton Advanced Consumer (Micromedex) - Includes Dosage Information
  • Zyflo Prescribing Information (FDA)
  • Zyflo CR Prescribing Information (FDA)
  • Zyflo CR Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

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