What Is Zyflo? Uses, Dosage, and What You Need to Know in 2026

Zyflo is a prescription asthma medication with a mechanism unlike any other drug on the market. If you've just been prescribed it, or are trying to understand why your doctor recommended it over other options, this guide gives you the essential facts about what Zyflo is, what it treats, how to take it, and what to watch for.

What Is Zyflo?

Zyflo is the brand name for zileuton, an orally active inhibitor of 5-lipoxygenase (5-LOX) — an enzyme involved in producing inflammatory molecules called leukotrienes. It was first approved by the FDA in January 1997 and is manufactured today by Chiesi USA, Inc.

Zyflo is the only 5-LOX inhibitor approved by the FDA. The drug blocks the production of all major leukotrienes (LTB4, LTC4, LTD4, and LTE4) from arachidonic acid — preventing them from causing the airway inflammation, bronchoconstriction, and mucus production that characterize asthma.

This distinguishes Zyflo from other leukotriene modifiers like montelukast (Singulair) and zafirlukast (Accolate), which block leukotriene receptors rather than preventing leukotriene synthesis.

What Is Zyflo Used For?

Zyflo is FDA-approved for:

Prophylaxis and chronic treatment of asthma in adults and children 12 years and older

Important: Zyflo is NOT for acute asthma attacks. It will not stop a sudden asthma episode. Always keep a rescue inhaler (such as albuterol) with you for acute symptoms.

Off-label uses for which zileuton is sometimes prescribed (based on evidence but not FDA-approved for these uses) include:

Aspirin-exacerbated respiratory disease (AERD / Samter's Triad)

Exercise-induced bronchoconstriction (when taken 1 hour before exercise)

Atopic dermatitis and other conditions involving leukotriene pathways (investigational)

Zyflo vs. Zyflo CR: What's the Difference?

There are two formulations of zileuton available:

Zyflo (immediate-release): 600 mg tablet taken 4 times daily (every 6 hours), with or without food. Tablets may be split in half if needed to swallow.

Zyflo CR (extended-release): 600 mg extended-release tablet. Take 2 tablets (1,200 mg) twice daily, within 1 hour after morning and evening meals. Do NOT crush, chew, or split Zyflo CR tablets — this destroys the extended-release mechanism.

Both formulations deliver a total daily dose of 2,400 mg. Zyflo CR is the more commonly prescribed formulation because twice-daily dosing improves adherence compared to four times daily.

Dosage Summary

Zyflo (IR): 600 mg × 4 daily = 2,400 mg/day. Can be taken with or without food; IR tablets may be taken with meals and at bedtime.

Zyflo CR (ER): 2 × 600 mg tablets (1,200 mg) twice daily = 2,400 mg/day. Must be taken within 1 hour after morning and evening meals.

Missed dose: Take the next dose at the scheduled time. Never double up.

Age restriction: Not approved for children under 12 due to potential liver risks.

Important Things to Know Before Starting Zyflo

Liver monitoring is required: Zyflo can cause liver enzyme elevations. Your doctor will order liver function tests before you start and every 2-3 months for the first year.

No alcohol: Combining Zyflo with alcohol increases liver toxicity risk and CNS depression. Avoid alcohol completely during treatment.

Drug interactions: Zyflo significantly raises blood levels of theophylline, propranolol, and warfarin. Tell your doctor about all medications before starting.

Not a rescue medication: Zyflo works by preventing inflammation over time. It must be taken every day for maximum benefit. Keep a rescue inhaler for acute symptoms.

Results take time: You may not feel the full benefit of Zyflo for several days to a few weeks. Keep taking it even if your symptoms improve — that means it's working.

How to Find Zyflo at a Pharmacy

Because Zyflo is a niche medication, many pharmacies don't routinely stock it. If you're having trouble filling your prescription, medfinder contacts pharmacies near you to check which ones have it in stock. You provide your medication, dosage, and ZIP code — medfinder does the calling and texts you the results.

For a deeper look at the science behind Zyflo, see: How Does Zyflo Work? Mechanism of Action Explained