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Indications and Dosage
Oral
Chronic asthma Adult: For prophylaxis and long-term treatment: As conventional tab: 600 mg 4 times daily. As extended-release tab: 1,200 mg bid.
Child: ≥12 years Same as adult dose. |
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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 elevated liver transaminases of ≥3 times the upper limit of normal (ULN).
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Special Precautions
Patient with a history of liver disease; those who consume substantial alcohol quantities. Not indicated to reverse bronchospasm in acute asthma attacks, including status asthmaticus; however, zileuton treatment may be continued during acute asthma exacerbations. Mild hepatic impairment (serum ALT <3 times the ULN). Children and elderly. Pregnancy and lactation.
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Adverse Reactions
Significant: Hepatotoxicity (particularly increased transaminase levels); neuropsychiatric events (e.g. changes in behaviour, sleep disorders).
Gastrointestinal disorders: Nausea, dyspepsia, diarrhoea, vomiting, abdominal pain, constipation, flatulence. General disorders and administration site conditions: Malaise, asthenia, pain, chest pain. Immune system disorders: Hypersensitivity reactions. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, weakness, neck pain or stiffness. Nervous system disorders: Headache, dizziness, drowsiness, hypertonia. Psychiatric disorders: Insomnia, nervousness. Respiratory, thoracic and mediastinal disorders: URTI, sinusitis, pharyngolaryngeal pain. Skin and subcutaneous tissue disorders: Rash, pruritus. Potentially Fatal: Severe hepatic injury, including symptomatic jaundice, hyperbilirubinaemia, and elevated ALT levels >8 times the ULN. |
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Monitoring Parameters
Monitor LFTs at baseline and during therapy (particularly obtain serum ALT before treatment initiation, once monthly for the 1st 3 months, every 2-3 months for the remainder of the 1st year, then regularly thereafter in patients receiving chronic treatment). Assess for signs and symptoms of hepatotoxicity and neuropsychiatric events.
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Drug Interactions
Significantly increased serum concentrations of theophylline and propranolol. May result in a significantly increased prothrombin time with warfarin.
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Action
Description:
Mechanism of Action: Zileuton is a specific 5-lipoxygenase inhibitor that blocks the formation of potent leukotrienes (LTB4, LTC4, LTD4, LTE4). Leukotrienes induce several biological effects in the body, including the augmentation of neutrophil and eosinophil migration, aggregation of neutrophils and monocytes, adhesion of leucocytes, increased permeability of capillaries, and contraction of smooth muscles. These effects contribute to inflammation, oedema, mucous secretion, and airway bronchoconstriction in asthmatic patients. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Increased absorption with food (extended-release tab). Time to peak plasma concentration: 1.7 hours (conventional tab). Distribution: Volume of distribution: 1.2 L/kg. Plasma protein binding: 93%, mainly to albumin. Metabolism: Extensively metabolised in the liver by CYP1A2, CYP2C9 and CYP3A4 isoenzymes. Excretion: Via urine (approx 95% mainly as metabolites); faeces (approx 2%). Elimination half-life: Approx 3 hours. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 60490, Zileuton. https://pubchem.ncbi.nlm.nih.gov/compound/Zileuton. Accessed Mar. 22, 2024. |
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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. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/03/2024. Anon. Zileuton. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/03/2024. Buckingham R (ed). Zileuton. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2024. Zileuton Tablet, Extended Release (Rising Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/03/2024. Zileuton. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 08/03/2024. Zyflo CR Extended-release Tablets (Chiesi USA, Inc.). U.S. FDA. https://www.fda.gov. Accessed 08/03/2024. Zyflo Tablet (Chiesi USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/03/2024.
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