Zileuton and Nebivolol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nebivolol
Zileuton
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
A significant increase in beta-adrenergic blockade
Interaction Deep Dive
Concurrent administration of zileuton and propranolol resulted in a significant increase in propranolol concentrations. There was an increase in beta-blockade and a decreased in heart rate associated with the coadministration of these two drugs. Although no formal drug-drug interaction studies have been conducted between zileuton and other beta-adrenergic blocking agents, zileuton is extensively metabolized by liver enzymes, and may interact with beta blockers that are hepatically cleared, as is nebivolol2. Also, zileuton is extensively protein bound, as is nebivolol. While interactions of zileuton and other highly protein bound drugs were minimal 3, an interaction by displacement of protein binding between zileuton and nebivolol has not been studied.
Why it happens (mechanism)
Competitive inhibition of hepatic metabolism and protein binding
Literature reports
1 report — tap to read
a) Sixteen healthy male volunteers received zileuton 600 mg every six hours for five days and a single dose of propranolol 80 mg. This resulted in a 42% decrease in propranolol clearance, 52% increase in the propranolol Cmax, 104% increase in the area under the curve (AUC), and a 25% increase in the elimination half-life. This corresponded with an increase in beta-blockade and decreased heart rate. It is reasonable to employ caution when administering zileuton with other hepatically cleared beta-adrenergic blocking agents, although studies have not been conducted 1.
Common questions
Can I take Zileuton and Nebivolol together?
A significant increase in beta-adrenergic blockade Always confirm with your pharmacist or prescriber before making any change.
How serious is the Zileuton and Nebivolol interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Zileuton or Nebivolol need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (3)
- Product Information: Zyflo(R) Filmtab, zileuton. Abbott Laboratories, North Chicago, IL, 1996. DailyMed
- Product Information: Zyflo(R) Filmtab, zileuton. Abbott Laboratories, North Chicago, IL, 1996. DailyMed
- Machinist JM, Kukulka MJ, & Bopp BA: In vitro plasma protein binding of zileuton and its N-dehydroxylated metabolite. Clin Pharmacokinet 1995; 29(suppl 2):34-41. PubMed
Keep reading about Nebivolol
Keep reading about Zileuton
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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