ZILEUTON
Clinical safety rating: safe
Animal studies have demonstrated safety
Selective inhibitor of 5-lipoxygenase, blocking leukotriene synthesis
| Metabolism | Primarily hepatic via CYP1A2, CYP2C9, and CYP3A4; forms inactive metabolites |
| Excretion | Renal (94.2% as metabolites, <1% unchanged), fecal (2.2%), hepatic metabolism extensive via CYP1A2, CYP2C9, CYP3A4. Elimination primarily through urine. |
| Half-life | Terminal elimination half-life is 2.5 hours; clinical context: requires dosing four times daily due to short half-life; no accumulation with repeated dosing. |
| Protein binding | 93% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 1.2 L/kg; indicates extensive tissue distribution, including into bronchial tissue and inflammatory cells. |
| Bioavailability | Oral bioavailability is approximately 93% (tablet); food reduces rate but not extent of absorption (AUC unchanged). |
| Onset of Action | Oral: peak plasma concentrations at 1.7 hours post-dose; clinical effect on urinary leukotriene E4 within hours, maximal symptom relief may take days to weeks. |
| Duration of Action | Duration of action is 8 hours; dosing every 6 hours maintains therapeutic levels; clinical notes: consistent dosing required for sustained leukotriene inhibition. |
| Molecular Weight | 236.29 |
600 mg orally four times daily (total daily dose 2400 mg). Immediate-release tablets taken with or without food.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for renal impairment. Zileuton is hepatically metabolized and renal excretion is minimal. |
| Liver impairment | Contraindicated in patients with active liver disease or elevated transaminases (≥3 times ULN). In patients with Child-Pugh Class A or B, not recommended due to risk of hepatotoxicity. No specific dosing guidelines exist; avoid use. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy in children under 12 years have not been established. |
| Geriatric use | No specific dose adjustments recommended based on age alone. However, elderly patients may be more susceptible to hepatic adverse effects; monitor liver function tests closely. |
| 1st trimester | Contraindicated: risk of hepatotoxicity and limited human data. Use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | Contraindicated: risk of hepatotoxicity and limited human data. Use only if clearly needed and benefit outweighs risk. |
| 3rd trimester | Contraindicated: risk of hepatotoxicity and limited human data. Use only if clearly needed and benefit outweighs risk. |
Clinical note
Theophylline and warfarin levels may be increased Can cause hepatotoxicity and requires monitoring of liver enzymes.
| Placental transfer | Unknown; probable transfer due to low molecular weight and lipophilicity but no specific human data. |
| Breastfeeding | Not recommended due to potential hepatotoxicity and excretion into breast milk; limited data. Use alternative agents if possible. |
■ FDA Black Box Warning
None
| Common Effects | Headache |
| Serious Effects |
Active liver disease or hepatic impairment (e.g., elevated transaminases >3x ULN)Hypersensitivity to zileuton or any componentConcurrent use of other leukotriene receptor antagonists (not applicable, but note caution with hepatotoxic drugs)
| Precautions | Hepatotoxicity: monitor liver transaminases; discontinue if evidence of liver injury, Neuropsychiatric events: insomnia, agitation, depression |
| Food/Dietary | Take with food or milk to reduce gastrointestinal irritation. Avoid grapefruit juice? (Not well defined; generally no known interaction). Avoid excessive alcohol intake due to increased risk of hepatotoxicity. |
Loading safety data…
| Lactation Rating |
| L4 (Possibly Hazardous) |
| Teratogenic Risk | Pregnancy Category C. Animal studies show fetal toxicity at high doses. No adequate human studies. Risk cannot be ruled out; use only if benefit outweighs risk. No specific trimester risks defined due to limited data. |
| Fetal Monitoring | Monitor hepatic function (ALT/SGPT) monthly for first 3 months, then periodically. Observe for signs of hepatotoxicity. No specific fetal monitoring required beyond routine prenatal care. |
| Fertility Effects | No specific human data on fertility. In animal studies, no significant effects on fertility at clinically relevant doses. |
| Clinical Pearls | Zileuton is a 5-lipoxygenase inhibitor used for prophylaxis of chronic asthma; not for acute bronchospasm. Monitor hepatic function (ALT) at baseline, then monthly for first 3 months, then every 2-3 months for one year, then periodically. Inhibits CYP1A2, reducing clearance of theophylline, warfarin, and propranolol. Dizziness and dyspepsia are common; administer with food to reduce GI upset. May be used as add-on therapy if inhaled corticosteroids and long-acting beta-agonists are insufficient. |
| Patient Advice | Take exactly as prescribed, even if you feel well. · Not for use in acute asthma attacks; have rescue inhaler ready. · Take with food to decrease stomach upset. · Get periodic liver function tests as directed; report yellowing of skin/eyes, dark urine, fatigue. · Inform all healthcare providers you are taking zileuton. · Avoid alcohol to reduce risk of liver toxicity. · Report new or worsening symptoms, especially shortness of breath, to your doctor. |