Comprehensive medication guide to Zyflo including estimated pricing, availability information, side effects, and how to find it in stock at your local pharmacy.
Estimated Insurance Pricing
$50–$100/month copay with Tier 3 commercial insurance coverage after approved prior authorization; Tier 4 specialty copays may reach $200–$400/month. Medicare Part D covers zileuton; some plans have copays around $320/month.
Estimated Cash Pricing
$2,800–$4,000 retail for a 30-day supply of Zyflo CR (120 tablets); as low as $260–$315 with GoodRx or SingleCare coupons — a savings of up to 91% off retail price.
Medfinder Findability Score
72/100
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Zyflo is the brand name for zileuton, an orally active inhibitor of 5-lipoxygenase (5-LOX) — the enzyme that produces inflammatory leukotrienes in the body. It was first approved by the FDA in January 1997 and is manufactured by Chiesi USA, Inc. Zyflo is available in two formulations: Zyflo (immediate-release, 600 mg taken 4 times daily) and Zyflo CR (extended-release, 2 × 600 mg taken twice daily).
Zyflo is FDA-approved for the prophylaxis and chronic treatment of asthma in adults and children aged 12 years and older. It is the only FDA-approved 5-lipoxygenase synthesis inhibitor in the United States, making it pharmacologically unique among leukotriene modifiers. The drug is most commonly prescribed by allergists and pulmonologists for patients with difficult-to-control asthma, aspirin-exacerbated respiratory disease (AERD), or those who have not responded adequately to other leukotriene modifiers.
Zyflo is not a rescue inhaler and will not stop an acute asthma attack. It must be taken regularly as a controller medication. Patients should always keep a fast-acting rescue bronchodilator (such as albuterol) available for acute symptoms.
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Leukotrienes are powerful inflammatory molecules that trigger the airway inflammation, bronchoconstriction, and mucus hypersecretion characteristic of asthma. They are produced from arachidonic acid through the 5-lipoxygenase (5-LOX) pathway. Zileuton directly inhibits the 5-LOX enzyme, blocking the first step of leukotriene synthesis and preventing the production of all four major leukotrienes: LTB4, LTC4, LTD4, and LTE4.
This upstream mechanism distinguishes Zyflo from leukotriene receptor antagonists (LTRAs) like montelukast (Singulair) and zafirlukast (Accolate), which block downstream receptors. By preventing leukotriene synthesis rather than just blocking their binding, Zyflo reduces levels of LTB4 (a neutrophil recruiter not blocked by LTRAs) in addition to the cysteinyl leukotrienes. This broader blockade is particularly relevant for patients with AERD, where leukotriene overproduction is a central disease mechanism.
Zileuton is metabolized by CYP1A2, 2C9, and 3A4 in the liver, and is itself a weak CYP1A2 inhibitor — which creates important drug interactions with theophylline, propranolol, and warfarin. Both enantiomers of the racemic zileuton molecule are pharmacologically active 5-LOX inhibitors.
600 mg — tablet (immediate-release)
Taken 4 times daily (total 2,400 mg/day). Can be split in half if needed to swallow. Take with or without food.
600 mg — tablet (extended-release, Zyflo CR)
Take 2 tablets (1,200 mg) twice daily within 1 hour after morning and evening meals. Total 2,400 mg/day. Do NOT crush, chew, or split.
Zyflo is not in an FDA-declared shortage as of 2026, but it can be genuinely difficult to find at local pharmacies. Because Zyflo is a niche medication with a high retail price ($2,800–$4,000 per 30-day supply) and relatively low prescribing volume, many pharmacies don't maintain regular stock. Patients may be told the drug needs to be specially ordered — a process that typically takes 1–3 business days.
Availability is generally better at large chain pharmacies (CVS, Walgreens, Costco, Walmart) and hospital-affiliated or specialty pharmacies in major metropolitan areas. Rural areas and smaller independent pharmacies are more likely to require special ordering. Insurance prior authorization requirements further complicate access for many patients.
To find Zyflo in stock near you without calling multiple pharmacies, use medfinder. medfinder calls pharmacies near your ZIP code to check which ones have Zyflo in stock and can fill your prescription today. You'll receive a text with the results — no hold music required.
Zyflo (zileuton) is not a controlled substance, so there are no DEA scheduling restrictions on who can prescribe it. Any licensed prescriber in the United States can write a Zyflo prescription, though due to its liver monitoring requirements and second-line position in asthma guidelines, it is most commonly prescribed by specialists.
Prescribers who commonly prescribe Zyflo include:
Allergists / Immunologists — most commonly, particularly for AERD and aspirin-sensitive asthma
Pulmonologists — for complex moderate-to-severe persistent asthma as add-on therapy
Primary Care Physicians (PCPs) — for patients with established asthma and documented prior treatment failures
Nurse Practitioners (NPs) and Physician Assistants (PAs) — in allergy, pulmonology, and primary care practices
Telehealth is a viable option for Zyflo prescriptions since it is not a controlled substance. Patients will need baseline liver function tests (LFTs) drawn at a local lab before their first prescription can be filled. Follow-up lab orders and monitoring can also be managed through telehealth. Platforms specializing in allergy and asthma care are best equipped to manage zileuton therapy.
No. Zyflo (zileuton) is not a DEA-scheduled controlled substance. It has no abuse potential and is not subject to any special DEA prescribing restrictions, limits on days supply, or requirements for in-person visits. Any licensed prescriber — including physicians, nurse practitioners, and physician assistants — can prescribe Zyflo without controlled substance registration or additional DEA authorization.
Because it is not a controlled substance, Zyflo can be prescribed via telehealth without any additional restrictions. Patients can also receive 90-day supply prescriptions through mail-order pharmacies. Refills can be authorized by phone or electronically without special documentation. The prescription can be transferred between pharmacies without restrictions specific to controlled substances.
The most common side effects reported in clinical trials of Zyflo CR (occurring in ≥5% of patients) include:
Sinusitis (6.5%)
Nausea (5%)
Pharyngolaryngeal pain (5%)
Headache, abdominal pain, and dizziness (>1%)
Serious side effects requiring medical attention include:
Hepatotoxicity (liver enzyme elevations): Occurs in approximately 2% of patients; regular LFT monitoring is required. Symptoms include jaundice, dark urine, right upper abdominal pain, and fatigue.
Neuropsychiatric events: Sleep disorders and behavioral/mood changes reported post-marketing. Can occur in patients without prior psychiatric history.
Severe allergic reactions: Rare but possible; seek emergency care for hives, throat swelling, or difficulty breathing.
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Montelukast (Singulair)
Leukotriene receptor antagonist; once daily; approved from 12 months; no liver monitoring required; widely available and affordable as generic ($10–$30/month). Less effective for AERD due to receptor (not synthesis) blockade.
Zafirlukast (Accolate)
Leukotriene receptor antagonist; twice daily on empty stomach; approved ages 5+; liver monitoring recommended. Closest alternative to Zyflo within the LTRA class but different mechanism.
Fluticasone inhaler (Flovent, Arnuity)
Inhaled corticosteroid (ICS); gold standard for persistent asthma; more effective than leukotriene modifiers for lung function improvement; does not block leukotriene pathway.
Budesonide/Formoterol (Symbicort)
ICS-LABA combination inhaler for moderate-to-severe asthma; twice daily; broader control when ICS alone is insufficient. LABAs must not be used without ICS.
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Theophylline
majorMajor interaction: zileuton reduces theophylline clearance by ~50%, doubling AUC. Reduce theophylline dose by approximately half; monitor plasma levels.
Propranolol
majorMajor interaction: zileuton increases propranolol AUC by ~104% and Cmax by ~52% via CYP1A2 inhibition. Reduce propranolol dose; monitor for bradycardia and hypotension.
Warfarin
moderateModerate interaction: zileuton increases effect of R-isomer of warfarin via CYP1A2 inhibition. Monitor PT/INR; adjust warfarin dose as needed.
Fezolinetant (Veozah)
majorContraindicated: zileuton significantly increases fezolinetant blood levels via CYP1A2 inhibition. These drugs cannot be used together.
Flibanserin (Addyi)
majorContraindicated: concurrent use can cause severe hypotension and syncope via CYP3A4 inhibition.
Alcohol
moderateSignificant risk: increases hepatotoxicity and CNS depression. Avoid alcohol entirely during Zyflo therapy.
Zyflo (zileuton) is a pharmacologically unique asthma medication that fills an important gap for patients with difficult-to-control asthma, aspirin-exacerbated respiratory disease, and those who have failed or partially responded to leukotriene receptor antagonists. Its 5-LOX inhibition mechanism provides broader leukotriene suppression than any other available oral agent, making it a valuable tool in the asthma management toolkit despite its niche positioning in clinical guidelines.
The two main practical challenges with Zyflo are its high retail cost and limited pharmacy availability. GoodRx and SingleCare coupons can dramatically reduce costs to $260–$315/month, and insurance coverage with prior authorization can bring copays down further. For patients who struggle to fill their prescription locally, specialty pharmacies, mail-order options, and early refilling strategies are all effective approaches.
If you're having trouble finding Zyflo at a pharmacy near you, medfinder can help. medfinder calls pharmacies near your ZIP code to check which ones have Zyflo in stock and can fill your prescription — no hold music, no wasted trips. Enter your medication, dosage, and location to get started.
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