(zye LOO ton)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Zyflo: 600 mg [scored]
Tablet Extended Release 12 Hour, Oral:
Zyflo CR: 600 mg
Brand Names: U.S.
- Zyflo CR
- 5-Lipoxygenase Inhibitor
Specific 5-lipoxygenase inhibitor which inhibits leukotriene formation. Leukotrienes augment neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction (which contribute to inflammation, edema, mucous secretion, and bronchoconstriction in the airway of the asthmatic.)
Hepatic and gastrointestinal; zileuton and N-dehydroxylated metabolite can be metabolized via CYP1A2, 2C9, and 3A4
Urine (~95% primarily as metabolites); feces (~2%)
Time to Peak
Immediate release: 1.7 hours
93%, primarily albumin
Use: Labeled Indications
Prophylaxis and chronic treatment of asthma
Hypersensitivity to zileuton or any component of the formulation; active liver disease or transaminase elevations ≥3 times ULN
Oral: Children ≥12 years and Adults:
Immediate release: 600 mg 4 times/day
Extended release: 1200 mg twice daily
Dosage adjustment in renal impairment: No dosage adjustment necessary.
Dosage adjustment in hepatic impairment: Contraindicated with hepatic impairment.
Immediate release: Administer without regard to meals.
Extended release: Do not crush, cut, or chew tablet; administer within 1 hour after morning and evening meals.
Immediate release: Take without regard to meals.
Extended release: Take with food.
Store tablets at 20°C to 25°C (68°F to 77°F). Protect from light.
Aminophylline: Zileuton may increase the serum concentration of Aminophylline. Management: Reduce aminophylline dose by 50% upon initiation of zileuton therapy. If aminophylline is added to existing zileuton therapy, use a lower starting dose. Monitor for increased theophylline serum concentrations and effects. Consider therapy modification
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination
Pimozide: Zileuton may increase the serum concentration of Pimozide. Avoid combination
Propranolol: Zileuton may increase the serum concentration of Propranolol. Monitor therapy
Theophylline: Zileuton may increase the serum concentration of Theophylline. Management: Reduce theophylline dose by 50% upon initiation of zileuton therapy. If theophylline is added to existing zileuton therapy, use a lower starting dose. Monitor for increased serum concentrations and effects of theophylline. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Warfarin: Zileuton may increase the serum concentration of Warfarin. Monitor therapy
>10%: Central nervous system: Headache (23% to 25%)
1% to 10%:
Cardiovascular: Chest pain
Central nervous system: Pain (8%), dizziness, fever, insomnia, malaise, nervousness, somnolence
Dermatologic: Pruritus, rash
Gastrointestinal: Dyspepsia (8%), diarrhea (5%), nausea (5% to 6%), abdominal pain (5%), constipation, flatulence, vomiting
Genitourinary: Urinary tract infection, vaginitis
Hematologic: Leukopenia (1% to 3%)
Hepatic: ALT increased (≥3 x ULN: 2% to 5%), hepatotoxicity
Neuromuscular & skeletal: Myalgia (7%), weakness (4%), arthralgia, hypertonia, neck pain/rigidity
Respiratory: Upper respiratory tract infection (9%), sinusitis (7%), pharyngolaryngeal pain (5%)
Miscellaneous: Hypersensitivity reactions, lymphadenopathy
<1% (Limited to important or life-threatening): Behavior/mood changes, hepatitis, hyperbilirubinemia, jaundice, liver failure, suicidality, suicide
Concerns related to adverse effects:
• Hepatotoxicity: There have been reports of hepatic adverse effects (elevated transaminase levels); serum ALT should be monitored. Females >65 years and patients with pre-existing elevated transaminases may be at greater risk. Discontinue therapy and follow transaminases until normal if patients develop clinical signs/symptoms of liver dysfunction or with transaminase levels >5 times ULN; use caution with history of liver disease and/or in those patients who consume substantial quantities of ethanol.
• Neuropsychiatric events: Postmarketing reports of behavioral changes and sleep disorders have been noted.
Concurrent drug therapy issues:
• Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.
• Elderly: Females >65 years of age may be at increased risk for ALT elevations. Pharmacokinetics were similar in older adults (≥65 years) compared to younger adults.
• Pediatric: Due to the risk of hepatotoxicity, the manufacturer does not recommend use of zileuton in children <12 years of age.
• Reversal of bronchospasm: Not indicated for the reversal of bronchospasm in acute asthma attacks, including status asthmaticus; therapy may be continued during acute asthma exacerbations.
Hepatic transaminases (prior to initiation and during therapy), specifically monitor serum ALT (prior to initiation, once-a-month for the first 3 months, every 2-3 months for the remainder of the first year, and periodically thereafter for patients receiving long-term therapy)
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. If a leukotriene modifier is needed during pregnancy, other agents are preferred (ACOG, 2008).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, dyspepsia, pyrosis, pharyngitis, rhinitis, rhinorrhea, or sternutation. Have patient report immediately to prescriber signs of depression (eg, depression, suicidal ideation, anxiety, emotional instability, illogical thinking), signs of hepatic impairment, angina, insomnia, or behavioral changes (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.