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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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As a treatment for... Avg User Ratings [?]
Asthma -- Maintenance
6.0
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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 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.

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 older

PO 600 mg 4 times daily.

Adults and Children at least 12 yr of age and older

PO 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

Pimozide

Coadministration with zileuton is contraindicated.

Propranolol, theophylline, warfarin

Effects 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

Monitor

Monitor 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.



More Zileuton resources:

Cerner Multum zileuton

PDR Zileuton

MedFacts Zyflo CR Extended-Release Tablets

MedFacts Zileuton

Micromedex Zileuton - Includes detailed dosage instructions.

FDA Zyflo CR

FDA Zyflo

Zileuton Drug Interactions

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Asthma -- Maintenance

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