Zileuton
Pronunciation: zye-LOO-ton.
- Generic name
- zileuton
- Drug class
- Leukotriene synthesis inhibitor (5-lipoxygenase inhibitor)
- Form
- Extended-release tablet (600 mg, Zyflo CR); immediate-release tablet (600 mg, Zyflo, historical formulation)
- Route
- Oral
- Legal status
- Prescription-only
Availability and supply rules vary by country
Trade names by country: United States
Australia: · Full directory
What zileuton is and how it works
Zileuton is an oral medicine that blocks the production of leukotrienes, inflammatory substances involved in asthma. It is used for the ongoing prevention and control of asthma symptoms -- it is not a rescue medicine and does not treat a sudden asthma attack. (1)
Zileuton's main real risk is liver injury, which is why regular blood tests to check liver function are a required part of treatment, especially in the first year. It does not carry the FDA's strongest ('boxed') warning, but the liver-monitoring requirement is a genuine, non-optional safety feature of this medicine.
Mechanism of action: how zileuton works
Zileuton is a selective and specific inhibitor of 5-lipoxygenase, the enzyme that catalyses the formation of leukotrienes from arachidonic acid; by inhibiting leukotriene synthesis, it reduces bronchoconstriction, mucus secretion, and inflammatory cell recruitment associated with asthma. (1)
What zileuton is used for
Prevention and long-term control of asthma
Used for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. It is taken regularly to help prevent symptoms and is not used to treat a sudden asthma attack. (1)
Before taking zileuton
Do not take / not appropriate for
- Do not take zileuton if you have active liver disease or persistently elevated liver enzyme tests (3 times the upper limit of normal or higher). (United States) (1)
- Do not take zileuton if you have had an allergic reaction to it or any of its ingredients. (United States) (1)
- Zileuton is not appropriate for children under 12 years of age, because of the hepatotoxicity risk. (United States) (1)
Tell your clinician about
- Any history of liver problems or abnormal liver blood tests.
- Whether you take theophylline, warfarin, or propranolol -- zileuton changes how your body handles each of these and your dose or monitoring may need to change.
- All other medicines and supplements you take.
- Whether you are pregnant, plan to become pregnant, or are breastfeeding.
- Your age -- women 65 and older may have a higher chance of liver enzyme elevations, per the prescribing information.
How to take zileuton
- Take two 600 mg extended-release tablets twice daily, within one hour after your morning and evening meals (total daily dose 2400 mg).
- Swallow tablets whole -- do not chew, cut, or crush them.
- Zileuton is for ongoing prevention only -- it will not relieve a sudden asthma attack; keep your prescribed rescue inhaler available.
- You will need regular blood tests to check your liver function while taking this medicine -- do not skip these appointments.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (5)
Missed dose
Contact your pharmacist or clinician for guidance if you miss a dose. Do not double up or adjust your next dose on your own.
Overdose
Seek urgent medical attention or contact a poison control service if you think too much zileuton has been taken. (1)
Side effects
Side effects and their urgency vary; report severe, persistent, or concerning symptoms.
Sinusitis.
What to notice: Sinusitis.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Nausea.
What to notice: Nausea.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Pain in the throat or voice box area (pharyngolaryngeal pain).
What to notice: Pain in the throat or voice box area (pharyngolaryngeal pain).
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Other gastrointestinal upset.
What to notice: Other gastrointestinal upset.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Rash or hypersensitivity reactions.
What to notice: Rash or hypersensitivity reactions.
What to do: Discuss persistent or troublesome symptoms with the treating clinician or pharmacist. (1)
Serious warnings
Signs of liver injury (hepatotoxicity) — high caution (Warnings and Precautions level -- this medicine does not carry an FDA boxed warning)
Symptoms: Pain in the right upper part of the abdomen, nausea, unusual tiredness, lack of energy, itching, yellowing of the skin or eyes (jaundice), or flu-like symptoms.
Action: Contact your clinician promptly and have liver blood tests checked. Zileuton requires liver enzyme monitoring before starting, monthly for the first 3 months, every 2-3 months for the rest of the first year, and periodically after that. Treatment is stopped if liver enzymes rise to 5 times the upper limit of normal or if these symptoms occur. (1)
Signs of a serious allergic reaction — emergency
Symptoms: Swelling of the face, lips, tongue, or throat; difficulty breathing; widespread rash or hives.
Action: Seek emergency medical help immediately. (1)
Toxicity from theophylline, warfarin, or propranolol while also taking zileuton — high caution
Symptoms: For theophylline: nausea, vomiting, tremor, fast heartbeat, seizures. For warfarin: unusual bruising or bleeding. For propranolol: unusually slow heart rate, dizziness, or fainting.
Action: Tell your clinician about any of these medicines before starting zileuton -- dose adjustments and closer monitoring (theophylline levels, INR/prothrombin time) are needed. (1)
Interactions
- Theophylline: zileuton reduces theophylline clearance by about 50% and roughly doubles its blood level (AUC); the theophylline dose is typically reduced and levels monitored. (1)
- Warfarin: zileuton decreases R-warfarin clearance by about 15% and increases its blood level (AUC) by about 22%; prothrombin time/INR is monitored and the warfarin dose adjusted as needed. (1)
- Propranolol: zileuton decreases propranolol clearance by about 42%, increasing peak levels by about 52% and overall exposure by about 104%; monitored appropriately by the treating clinician. (1)
- No formal studies with CYP3A4 inhibitor medicines have been conducted; appropriate clinical monitoring is recommended if these are combined with zileuton. (1)
Pregnancy, breastfeeding, kidney/liver function, age
Pregnancy
Animal studies showed structural abnormalities (cleft palate in rabbits) and altered fetal growth (rats) at high exposures; discuss the balance of risks and benefits with your clinician if pregnant or planning pregnancy. (1) (2) (5)
Breastfeeding
It is not known whether zileuton passes into human breast milk; the developmental benefits of breastfeeding should be weighed against the potential risk, in discussion with your clinician. (1) (2) (5)
Children
Approved for children 12 years and older; not appropriate for children under 12 because of the hepatotoxicity risk (pediatric studies below age 12 have not been required for this reason). (1) (2) (5)
Elderly
Subgroup analysis suggests women 65 years and older may be at increased risk of ALT (liver enzyme) elevation; monitored accordingly. (1) (2) (5)
Hepatic_impairment
Contraindicated in active liver disease or persistent transaminase elevation of 3 times the upper limit of normal or more. (1) (2) (5)
Renal_impairment
Not specifically detailed in the sources reviewed; use with the same liver-monitoring precautions regardless of kidney function. (1) (2) (5)
Source_ids
Monitoring
Before starting
- Baseline serum ALT (liver enzyme test)
- Review of theophylline, warfarin, or propranolol use
- Assessment of current or past liver disease
During treatment
- Serum ALT monitored monthly for the first 3 months.
- Serum ALT monitored every 2 to 3 months for the remainder of the first year.
- Serum ALT monitored periodically thereafter for long-term therapy.
- Prompt liver enzyme testing if symptoms of liver dysfunction occur.
- Theophylline level monitoring, and INR/prothrombin time monitoring if taking warfarin.
Storage
Store at room temperature in the original packaging, away from moisture, and out of reach of children.
Study the drug class: Leukotriene receptor antagonists
Professional information
Clinician-facing context only, sourced from the current US FDA prescribing information for Zyflo CR; verify against the current full label before prescribing.
United States
Indication: Asthma prophylaxis and chronic treatment (extended-release, Zyflo CR)
Dose summary: Two 600 mg extended-release tablets twice daily, within one hour after morning and evening meals (total daily dose 2400 mg).
Renal context: Not specifically detailed in the sources reviewed. (1)
Hepatic guidance
Contraindicated in active liver disease or persistent transaminase elevation >=3x ULN; mandatory ALT monitoring schedule applies to all patients.
Overdose note
No specific antidote identified in the sources reviewed; manage with supportive care and contact poison control for guidance. (1)
Frequently asked questions
Does zileuton have a boxed warning?
No. Zileuton's current US FDA label does not carry a boxed warning. Its main serious risk is liver injury (hepatotoxicity), which is addressed through a required schedule of liver blood tests rather than the FDA's strongest warning category. (1)
Is zileuton available outside the United States?
It is confirmed FDA-approved and marketed in the United States. Direct searches of UK, EU, Canadian, Australian, and New Zealand regulator databases did not find a confirmed authorised zileuton product in any of these markets (for example, a live UK emc search returned no results, and a live TGA database search returned zero documents) -- this is reported honestly as 'unable to verify' rather than assumed either way. Check with a local pharmacist or prescriber for availability outside the US. (1) (2) (5)
Can zileuton be used for a sudden asthma attack?
No. Zileuton is a long-term preventive medicine, not a rescue treatment. Continue to use your prescribed rescue inhaler for sudden symptoms and follow your asthma action plan. (1)
What is the mechanism of action of zileuton?
Zileuton is a selective and specific inhibitor of 5-lipoxygenase, the enzyme that catalyses the formation of leukotrienes from arachidonic acid; by inhibiting leukotriene synthesis, it reduces bronchoconstriction, mucus secretion, and inflammatory cell recruitment associated with asthma. (1)
What is the generic name of Zileuton?
The generic name is zileuton. (1)
What class of drug is zileuton?
Zileuton is classed as: Leukotriene synthesis inhibitor (5-lipoxygenase inhibitor). (1)
References
- ZILEUTON extended-release tablets (Zyflo CR) -- full prescribing informationU.S. Food and Drug Administration / DailyMed (NIH), full prescribing information · United States · accessed 2026-07-30 · source 1
- UK emc search for 'zileuton' -- no resultselectronic medicines compendium (emc), United Kingdom · United Kingdom · accessed 2026-07-30 · source 2
- No EMA-authorised zileuton product identifiedEuropean Medicines Agency (EMA) and general web search · European Union · accessed 2026-07-30 · source 3
- No Health Canada Drug Product Database record identified for zileutonHealth Canada Drug Product Database and general web search · Canada · accessed 2026-07-30 · source 4
- TGA PICMI search for 'zileuton' -- 0 documents returnedTherapeutic Goods Administration (TGA), Australia -- PICMI repository · Australia · accessed 2026-07-30 · source 5
- No Medsafe data sheet or product record identified for zileutonMedsafe (New Zealand regulator) and general web search · New Zealand · accessed 2026-07-30 · source 6
Brand names by country
Single-ingredient zileuton names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.
Priority countries
United States
- ZYFLO600 mg · chiesi usa, inc.