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Indications and Dosage
Oral
Chronic asthma Adult: 600 mg 4 times daily (immediate-release); 1200 mg bid (controlled-release).
Child: ≥12 yr Same as adult dose. Elderly: No dosage adjustment needed. |
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Renal Impairment
No dosage adjustment needed.
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Hepatic Impairment
Contraindicated.
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Administration
normal release prep: May be taken with or without food. May be taken w/ meals & at bedtime.
extended-release tab: Should be taken with food. Take w/in 1 hr after meals. Swallow whole, do not chew/crush/cut. |
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Contraindications
Active liver disease or liver transaminase elevations ≥3 times the upper limit of normal (ULN). Treatment of acute asthma attacks including status asthmaticus.
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Special Precautions
Patient w/ history of liver disease or who consume substantial amount of alcohol. Mild hepatic impairment (serum ALT <3 times ULN). Pregnancy and lactation.
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Adverse Reactions
Headache, dizziness, pain including pharyngolaryngeal pain, GI disturbances, myalgia, arthralgia, sinusitis, conjunctivitis, fever, hypertonia, lymphadenopathy, malaise, neuropsychiatric events (e.g. sleep disorders, behaviour changes), UTI, vaginitis, hypersensitivity, urticaria, rash, leucopenia, jaundice, hyperbilirubinaemia and elevated liver enzymes.
Potentially Fatal: Severe hepatic injury. |
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Monitoring Parameters
Monitor hepatic transaminases specifically serum ALT prior to treatment, once a mth for the 1st 3 mth, every 2-3 mth for the remainder of the 1st yr, and periodically thereafter.
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Drug Interactions
Increases serum levels of propranolol, theophylline and warfarin (including increases in prothrombin time). May impair metabolism of CYP450-metabolised drugs (e.g. terfenadine).
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Food Interaction
Improved absorption when administered w/ food (controlled-release). Alcohol may increase CNS depression and risk of hepatotoxicity. St John's wort may decrease zileuton levels.
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Action
Description: Zileuton is a specific 5-lipoxygenase inhibitor that inhibits leukotriene formation. Leukotrienes induce biological effects e.g. augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, oedema, mucous secretion and bronchoconstriction in the airway of asthmatic patients.
Pharmacokinetics: Absorption: Well absorbed from the GI tract. Improved absorption when administered w/ food (controlled-release). Time to peak plasma concentration: Approx 2 hr (immediate-release). Distribution: Volume of distribution: 1.2 L/kg. Plasma protein binding: Approx 93% (mainly albumin). Metabolism: Hepatic metabolism via CYP1A2, CYP2C9 and CYP3A4 isoenzymes. Excretion: Via urine (approx 95% largely as glucuronide metabolites) and faeces (approx 2%). Elimination half-life: Approx 2.5 hr (immediate-release); approx 3 hr (controlled-release). |
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Storage
Store between 20-25°C. Protect from light.
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MIMS Class
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References
Anon. Zileuton. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/03/2014. Buckingham R (ed). Zileuton. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/03/2014. McEvoy GK, Snow EK, Miller J et al (eds). Zileuton. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 10/03/2014. Zyflo (Cornerstone Therapeutics Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 10/03/2014. Zyflo Tablets and Zyflo CR Extended-Release Tablets. U.S. FDA. https://www.fda.gov/. Accessed 10/03/2014.
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