Zileuton
Pronouncation: (ZYE-LOO-ton)Class: Leukotriene formation inhibitor
Trade Names:
Zyflo
- Tablets 600 mg
Trade Names:
Zyflo CR
- Tablets, extended-release 600 mg
Pharmacology
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Attenuates bronchoconstriction by inhibiting leukotriene-dependent smooth muscle contractions.
Pharmacokinetics
Absorption
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. Food caused a 27% increase in C max ; administer with or without food.
The relative bioavailability of zileuton extended-release (ER) tablets compared with the immediate-release (IR) formulation is 0.39 and 0.57, respectively.
Food increases the C max and the AUC of zileuton ER by 18 and 34%, respectively, and prolonged T max from 2.1 to 4.3 hours.
Distribution
Vd is about 1.2 L/kg. It is about 93% bound to plasma proteins, primarily albumin.
Metabolism
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.
Elimination
Predominantly via metabolism with a mean t ½ of about 2.5 h. 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 t ½ is 3.2 h. Apparent oral Cl is 669 mL/min.
Special Populations
Renal Function ImpairmentDosage adjustments in patients with renal function impairment or undergoing hemodialysis are not necessary.
Hepatic Function ImpairmentContraindicated 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.
Indications and Usage
Prophylaxis and chronic treatment of asthma.
Contraindications
Active liver disease; elevations in transaminases at least 3 times the ULN.
Dosage and Administration
Adults and children 12 yr of age and olderPO 600 mg 4 times daily.
Adults and Children at least 12 yr of age and olderPO ER tablets: Two 600 mg ER tablets twice daily, within 1 h after morning and evening meals.
General Advice
- Do not chew, cut, or crush ER tablets.
- Administer ER tablets with food.
Storage/Stability
Store at room temperature (68° to 77°F). Protect from light.
Drug Interactions
PimozideCoadministration with zileuton is contraindicated.
Propranolol, theophylline, warfarinEffects of these agents may be increased.
Laboratory Test Interactions
None well documented.
Adverse Reactions
CNS
Headache (25%); dizziness, hypertonia, insomnia, malaise, nervousness, somnolence (more than 1%).
Dermatologic
Pruritus (greater than 1%); rash, urticaria (postmarketing).
EENT
Pharyngolaryngeal pain (5%); conjunctivitis (greater than 1%).
GI
Dyspepsia (8%); nausea (6%); constipation, flatulence, vomiting (more than 1%); diarrhea, upper abdominal pain (at least 1%).
Genitourinary
UTI, vaginitis (more than 1%).
Hematologic-Lymphatic
Low WBC (3%); lymphadenopathy (more than 1%).
Hepatic
Hepatic injury including death, hyperbilirubinemia, symptomatic jaundice (postmarketing).
Lab Tests
Elevated ALT (2%).
Musculoskeletal
Arthralgia, neck pain/rigidity (more than 1%).
Pulmonary
Sinusitis (7%).
Respiratory
Asthma (4%).
Miscellaneous
Pain (8%); abdominal pain (5%); accidental injury (3%); chest pain, fever (more than 1%).
Precautions
MonitorMonitor hepatic transaminases at initiation of and during therapy. |
Pregnancy
Category C .
Lactation
Undetermined.
Children
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.
Hematologic
Transient decreases in WBCs may occur.
Hepatotoxicity
Elevations in LFTs may occur. Use with caution in patients who consume substantial quantities of alcohol or who have history of liver disease.
Overdosage
Symptoms
Human experience in acute overdose is limited.
Patient Information
- 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 medication 4 times/day with each meal and at bedtime.
- Warn the patient that this is not a bronchodilator and should not be used 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 elevations of liver enzyme is the most serious adverse reaction and that they must have LFTs 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 max number of inhalations of short-acting bronchodilators are needed.
- Advise patient to read the patient information leaflet before using product the first time and with each refill.
- Instruct patient that if a dose of the ER tablet is missed, the next dose should be taken 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.
- Advise patient to take ER tablet within 1 h after morning and evening meals.
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More Zileuton resources:
Zyflo CR Extended-Release Tablets
Zileuton - Includes detailed dosage instructions.
