Zileuton (Zyflo) is a specific 5-lipoxygenase inhibitor that inhibits leukotriene formation.

It is used to treat the following conditions:

• • Prophylaxis and chronic treatment of asthma in adults and children older than 12 years of age.

It should not be used to treat acute exacerbation of severe asthma.

Zileuton (Zyflo) dose in Adults

Zileuton (Zyflo) dose in the treatment of Asthma:

• Immediate-release zyflo:

  • 600 mg orally 4 times a day.

• Extended-release (Zyflo-CR):

  • 1,200 mg orally two times a day.

Zileuton (Zyflo) dose in Dose in Children

Zileuton (Zyflo) dose in the treatment of Asthma:

Note:

It is not routinely used to treat asthma and the current guidelines do not support its role in the management of asthma (GINA 2018).

• Children ≥12 years and Adolescents:

  • Immediate-release zileuton (Zyflo):

    • 600 mg orally 4 times a day
    • The maximum daily dose is 2,400 mg/day.

  • Extended-release (Zyflo-CR):

    • 1,200 mg orally two times a day.
    • The maximum daily dose is 2,400 mg/day.

Pregnancy Risk Factor: C

• Ziton exposure during pregnancy is not monitored and data on its use are limited.
• ACOG recommends using alternative medicines (like ciclesonide inhaler) to treat asthma during pregnancy.
• Uncontrolled asthma can lead to adverse pregnancy events. This may increase the risk of preterm birth, preeclampsia and perinatal mortality.

Use of zileuton during breastfeeding

• It is unknown if ziton can be excreted into breastmilk.
• Due to potential tumorigenicity of ziton in animal research, the manufacturer suggests that you weigh the benefits and risks for the mother and infant.

Zileuton (Zyflo) dose in Kidney disease:

• No dosage adjustment is necessary. 

Zileuton (Zyflo) dose in liver disease:

• It is contraindicated in patients with active liver disease or persistent transaminase elevations greater than 3 times the upper limit of normal.

Common Side Effects of Zileuton (Zyflo) Include:

• Central nervous system:

  • Headache

Less Common Side Effects of Zileuton (Zyflo) Include:

• Cardiovascular:

  • Chest pain

• Central nervous system:

  • Pain
  • Dizziness
  • Drowsiness
  • Hypertonia
  • Insomnia
  • Malaise
  • Nervousness

• Dermatologic:

  • Pruritus
  • Skin rash

• Gastrointestinal:

  • Dyspepsia
  • Nausea
  • Abdominal pain
  • Diarrhea
  • Constipation
  • Flatulence
  • Vomiting

• Genitourinary:

  • Urinary tract infection
  • Vaginitis

• Hematologic & oncologic:

  • Leukopenia
  • Lymphadenopathy

• Hepatic:

  • Increased serum ALT
  • Hepatotoxicity

• Hypersensitivity:

  • Hypersensitivity reaction

• Neuromuscular & skeletal:

  • Myalgia
  • Weakness
  • Arthralgia
  • Neck pain
  • Neck stiffness

• Ophthalmic:

  • Conjunctivitis

• Respiratory:

  • Upper respiratory tract infection
  • Sinusitis
  • Pharyngolaryngeal pain

• Miscellaneous:

  • Fever

Contraindication to Zileuton Include:

• Allergic reactions to ziton, or any component of this formulation.
• Transaminase elevations greater that 3 times the normal upper limit or active liver disease are not allowed.

Warnings and precautions

• Hepatotoxicity:

  • As liver-related adverse reactions have been reported with its use, monitor serum ALT.
  • Hepatotoxicity is more common in patients with liver dysfunction and those who are pregnant.
  • Patients with liver dysfunction or liver function abnormalities should stop treatment and continue to monitor their liver enzymes until they return to normal.

• Events in neuropsychiatrics:

  • It has been reported that it can cause sleep disorders and behavioral changes.

Zileuton: Drug Interaction

Monitor:

• Hepatic transaminases before initiating therapy and during treatment.
• Specifically, monitor serum ALT levels (before treatment initiation, once monthly for the first 3 months, then every 2 to 3 months for the remainder of the first year, and periodically thereafter)

How to administer Zileuton (Zyflo)?

Immediate-release tablets:

• Administer without regard to meals.

Extended-release:

• Do not crush, cut, or chew the tablet.
• Administer within one hour after morning and evening meals.

Mechanism of action of Zileuton (Zyflo):

• It inhibits the formation of leukotriene by being a 5-lipoxygenase specific inhibitor.
• Leukotrienes increase neutrophil migration and eosinophil migration, neutrophil and monocyte aggregateion, adhesion to leukocytes and increased capillarypermeability and smooth muscle contraction.
• All of these factors contribute to inflammation, bronchoconstriction and edema in the airways of asthmatics.

It works well93% of the protein is bound to proteins, most notably albumin. It is metabolized in both the liver and the gastrointestinal system.

It has a half-life elimination of approximatelyIt takes 3 hours for plasma to peak after administration of immediate-release tablets. The time it takes to reach maximum plasma levels is 1.7 hours.

Excretion can be viaUrine (95% primarily in metabolites and to a lesser degree via feces, (2%). 

International Brands of Zileuton (Zyflo):

• Zyflo
• Zyflo CR

Zileuton (Zyflo) Brands in Pakistan:

Zileuton (Zyflo) is not available in Pakistan.