Zyflo Shortage: What Providers and Prescribers Need to Know in 2026

If your patients are returning to clinic reporting they couldn't fill their Zyflo (zileuton) prescription, the issue likely isn't a manufacturer shortage — it's a structural access problem that has been building for years. This guide explains what's happening with Zyflo availability in 2026 and what you can do to help your patients navigate it.

Current Zyflo Supply Status in 2026

As of early 2026, neither Zyflo (zileuton immediate-release) nor Zyflo CR (extended-release) appears on the FDA's Drug Shortage Database. Chiesi USA, Inc. manufactures both formulations, and both are available through major pharmaceutical wholesalers. The supply chain is not disrupted.

However, 'nationally available' and 'accessible to your patient' are different things. Because zileuton has a narrow prescriber base and extremely high retail pricing, many community pharmacies have made the rational decision not to routinely stock it. This creates practical access barriers that your patients experience as shortages — even when the drug exists in the supply chain.

Why Pharmacy Stocking of Zileuton Is Unreliable

Community pharmacies make stocking decisions based on turnover rates. A medication with a retail price of $2,800-$4,000 per 30-day supply that moves only a few units per month creates significant inventory risk. Pharmacies also account for the administrative burden of managing prior authorizations for high-tier specialty drugs.

The net result: most chain and independent pharmacies outside major metro areas do not maintain standing Zyflo inventory. Patients may be told it needs to be ordered — a process that can take 1-3 business days — or referred elsewhere entirely.

Clinical Populations Most Affected

Understanding which patients are at highest risk of access failure helps prioritize proactive intervention:

AERD patients: Zileuton is pharmacologically distinct from LTRAs in its upstream mechanism of leukotriene synthesis inhibition. For patients with aspirin-exacerbated respiratory disease, this mechanistic difference is clinically meaningful. Survey data suggest 28% of AERD patients find zileuton 'extremely effective' versus 15% for montelukast, yet only 24% have ever been prescribed it.

LTRA non-responders: Patients who have failed or partially responded to montelukast may have already exhausted the receptor-antagonist pathway. Zileuton's distinct mechanism offers an alternative, and access failure leaves these patients with limited oral options.

Patients with exercise-induced bronchoconstriction: Zileuton has demonstrated efficacy in exercise-induced asthma when administered 1 hour before exercise, providing another clinical niche.

Pediatric and adolescent patients (12+): While approved from age 12, the four-times-daily immediate-release regimen often leads to adherence challenges. For adolescents, Zyflo CR's twice-daily schedule may improve compliance, but finding the ER formulation can be even more challenging than finding immediate-release.

Insurance Barriers Prescribers Should Anticipate

Zileuton's position as a non-first-line agent means most commercial plans will require prior authorization and/or step therapy before approval. Be prepared to document:

Failure or partial response to at least one inhaled corticosteroid at adequate dose

Failure or intolerance of montelukast (most plans require this)

A specific indication that positions zileuton favorably — AERD, aspirin-induced asthma, or documented inadequate response to LTRAs

Baseline LFTs and a monitoring plan, which demonstrates appropriate clinical management and supports formulary exception requests

Document the clinical rationale for zileuton specifically — not just 'asthma' — in your prior authorization letters. Medical necessity is more compelling when it explains why the receptor-blocking mechanism of montelukast is insufficient for this patient.

Monitoring Requirements: A Provider Checklist

Zileuton requires hepatic monitoring. The standard protocol includes:

Baseline hepatic transaminases (ALT, AST) before initiating therapy

Repeat LFTs every 2-3 months for the first year of therapy

Periodic monitoring annually thereafter

Discontinue if ALT elevations reach ≥3x upper limit of normal and are symptomatic, or ≥5x ULN regardless of symptoms

Counsel patients to avoid alcohol while on zileuton. The combination increases risk of both CNS depression and hepatotoxicity. This is especially important for patients on concomitant hepatotoxic agents.

Key Drug Interactions to Counsel On

As a weak CYP1A2 inhibitor, zileuton has three particularly important interactions:

Theophylline: Co-administration reduces theophylline clearance by ~50%, approximately doubling theophylline AUC. Reduce theophylline dose by approximately one-half and monitor plasma levels when initiating zileuton.

Propranolol: Zileuton increases propranolol AUC by approximately 104%. Monitor for bradycardia and hypotension; reduce propranolol dose as needed.

Warfarin: Zileuton affects metabolism of the R-isomer of warfarin via CYP1A2. Monitor PT/INR closely when initiating or stopping zileuton in patients on warfarin.

Fezolinetant and flibanserin: Contraindicated with zileuton. These interactions are particularly relevant as fezolinetant is increasingly used for menopausal symptoms in patients who may also have asthma.

What Providers Can Do to Improve Patient Access

Consider directing patients to medfinder, a service that contacts pharmacies near the patient to find which ones have zileuton in stock and can fill the prescription. This reduces the burden on both patients and clinical staff. Additional strategies include:

Establish a preferred pharmacy relationship — identify 1-2 local pharmacies that reliably stock Zyflo and send all your zileuton prescriptions there

Write 90-day supply prescriptions and route to mail-order pharmacy when clinically appropriate, reducing refill frequency and access risk

Counsel patients to begin refill process 7-10 days before their supply runs out

Inform patients that discount coupons (GoodRx, SingleCare) can reduce Zyflo CR costs to approximately $260-$315/month, often bypassing insurance delays entirely

See also our provider guide: How to Help Your Patients Find Zyflo in Stock