ZYFLO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYFLO (ZYFLO).
Zyflo (zileuton) is a specific inhibitor of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. This reduces the synthesis of leukotrienes (LTA4, LTB4, LTC4, LTD4, LTE4), which are potent bronchoconstrictors and pro-inflammatory mediators.
| Metabolism | Zileuton is extensively metabolized primarily via cytochrome P450 isoenzymes, including CYP1A2, CYP2C9, and CYP3A4. The major metabolites are inactive glucuronide conjugates. |
| Excretion | Renal (approximately 0.5% unchanged); biliary/fecal (approximately 75% as metabolites); the remainder is metabolized and eliminated via other routes. |
| Half-life | Terminal half-life is approximately 2.5 hours in healthy adults; clinical context: requires dosing 4 times daily due to short half-life. |
| Protein binding | Approximately 93% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% (well absorbed, but extensive first-pass metabolism). |
| Onset of Action | Oral: clinical improvement in asthma symptoms may be observed within 2 to 4 weeks; not indicated for acute bronchospasm. |
| Duration of Action | Duration is approximately 8-12 hours; requires t.i.d. or q.i.d. dosing to maintain therapeutic effect. |
600 mg orally four times daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Contraindicated in patients with active liver disease or transaminase elevations >3x ULN. For mild hepatic impairment (Child-Pugh A), no adjustment; moderate to severe (Child-Pugh B or C) not studied, use with caution. |
| Pediatric use | Approved for age >=12 years: 600 mg orally four times daily. For age <12 years, safety and efficacy not established. |
| Geriatric use | No specific dose adjustment, but monitor for hepatic effects due to age-related decline in liver function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYFLO (ZYFLO).
| Breastfeeding | It is not known whether zileuton is excreted in human milk. Caution should be exercised when administered to a nursing woman. |
| Teratogenic Risk | Pregnancy Category B. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. Zileuton should be used during pregnancy only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Active liver disease","Transaminase elevations ≥3 times the upper limit of normal","Hypersensitivity to zileuton or any component of the formulation"]
| Precautions | ["Hepatotoxicity: Elevations of liver enzymes have been reported; monitoring of hepatic function (ALT) is recommended before and during therapy. Zileuton should be discontinued if signs of liver injury occur.","Neuropsychiatric events: Cases of sleep disorders, behavior changes, and depression have been reported, especially in adolescents.","Not for reversal of acute bronchospasm or status asthmaticus.","May interfere with the metabolism of drugs metabolized by CYP1A2 (e.g., theophylline, warfarin, tacrine), requiring dose adjustment or monitoring."] |
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| Monitor liver function tests (ALT, AST) at baseline and periodically during therapy due to risk of hepatotoxicity. Monitor for signs of bronchospasm and asthma exacerbation. |
| Fertility Effects | In animal studies, no impairment of fertility was observed. There are no human data regarding effects on fertility. |