Dosing and uses of Zyflo Filmtab, Zyflo (zileuton)
Adult dosage forms and strengths
tablet
- 600mg
tablet, extended release
- 600mg
Asthma
Extended release: 1200 mg PO twice daily, within 1 hour after morning and evening meals
Conventional: 600 mg PO four times daily
Monitor: LFTs
Contraindicated in hepatic dysfunction
Pediatric dosage forms and strengths
tablet
- 600mg
tablet, extended release
- 600mg
Asthma
<12 years
- Safety and efficacy not established
- The FDA has not required pediatric studies in patients <12 years old due to the risk of hepatotoxicity; not recommeded for children younger than 12 years
>12 years
- Extended Release: 1200 mg PO twice daily, within 1 hour after morning and evening meals
- Conventional: 600 mg PO four times daily
- Monitor: LFTs
- Contraindicated in hepatic dysfunction
Zyflo Filmtab, Zyflo (zileuton) adverse (side) effects
>10%
Headache (24.6%)
1-10%
Abdominal pain (5%)
ALT elevation ≥3 times ULN (1.9-5%)
Asthenia (3.8%)
Dyspepsia (8.2%)
Diarrhea (5%)
Generalized pain (7.8%)
Nausea (5.5%)
Leukopenia (1-3%)
Myalgia (7%)
Weakness (4%)
Sinusitis (7%)
Pharyngolaryngeal pain (5%)
< 1%
Hepatitis
Behavioral changes
Jaundice
Liver failure
Suicidality
Suicide
Warnings
Contraindications
Hypersensitivity
Liver disease, LFT's ≥3x ULn
Cautions
Not indicated for use in acute bronchospasm
History of liver disease, heavy alcohol use
Behavioral changes and sleep disorders reported
Not recommended for patients <12 years due to risk of hepatotoxicity
Pregnancy and lactation
Pregnancy category: C
Lactation: Not known if excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zyflo Filmtab, Zyflo (zileuton)
Mechanism of action
Inhibitor of 5-lipoxygenase, which inhibits formation of LTB4, LTC4, LTD4, & LTE4
Inhibition of leukotriene formation reduces eosinophil and neutrophil migration, neutrophil and monocyte aggregation, capillary permeability, and smooth muscle contraction
Pharmacokinetics
Half-Life: 2.5 hr
Onset: 2-5 hr
Peak Plasma Time: 1.7 hr
Protein Bound: 93%
Vd: 1.2 L/kg
Metabolites: O-glucuronide conjugate & N-dehydroxylated metabolite
Clearance: 7 mL/min/kg
Excretion: Urine (95%); feces (2%)
Enzymes inhibited: hepatic CYP1A2, CYP3A4, and CYP2C9
