Drug & supplement interaction

Feverfew + Zileuton

Zileuton brand names: Zyflo, Zyflo CR.

Moderate Interaction
The bottom line Moderate

Zileuton falls into 3 drug categories that Feverfew can interact with; the most serious is rated moderate. Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Feverfew and Zileuton

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Feverfew interacts with whole categories of medication. Zileuton falls into 3 of those categories, so it can interact with Feverfew in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Zileuton

Zileuton falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Feverfew interacts with.

Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.
Laboratory research shows that feverfew might inhibit CYP1A2. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the basic idea with these two. Your body relies on a liver enzyme called CYP1A2 to help clear zileuton. Feverfew, at least in lab dishes, looks like it can slow that enzyme down. If that were to happen in real life, zileuton could build up a bit higher than usual, which might bump up the chance of side effects like nausea, stomach upset, headache, or stress on the liver.

The important part to hear is that this is theoretical. It comes from test-tube research only and has never actually been reported in people, so I wouldn't lose sleep over it. Still, since zileuton already needs liver monitoring, it's worth mentioning feverfew to your pharmacist or doctor before you start it so they can keep an eye on things.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Zileuton also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, feverfew might increase levels of drugs metabolized by CYP2C9.
Laboratory research shows that feverfew might inhibit CYP2C9. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for Zileuton (Zyflo) and feverfew. Your body partly clears zileuton using a liver enzyme called CYP2C9. Lab studies hint that feverfew may slow that enzyme down. If that happened in real life, zileuton could build up a bit higher than usual, which might mean more of its typical side effects, like nausea, stomach upset, or headache, and potentially more strain on the liver (zileuton already requires periodic liver checks).

The important part: this is only seen in test-tube and lab research, not in actual people. So it's more of a theoretical caution than a proven problem. Still, since zileuton needs liver monitoring anyway, it's worth a quick chat with your pharmacist or doctor before adding feverfew.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Zileuton also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, feverfew might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that feverfew might inhibit CYP3A4. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for Zileuton (Zyflo): your body uses an enzyme called CYP3A4 to help clear this medicine. In lab tests, feverfew appears to slow that enzyme down a bit. If that happened in real life, more zileuton could linger in your system, which might mean a higher chance of its usual side effects, like headache, nausea, stomach upset, or changes in your liver enzymes (zileuton already requires liver monitoring).

I want to be honest about how soft this evidence is, though. This comes only from test-tube research, and it has never actually been reported in people taking the two together. So it's more of a theoretical caution than a proven problem. Before adding feverfew, just run it by your pharmacist or doctor, especially since zileuton already needs liver checks.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Sil'vestrov VP, Kinitin AV, and Chesnokova, IV. [Immunological and metabolic disorders and the means for their correction in patients with chronic bronchitis]. Ter.Arkh. 1991;63:7-11.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Feverfew Also Interacts With Other Medications

Feverfew has 928 moderate known drug interactions in our database — the Zileuton one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Feverfew

Covers the 2,830 medications we’ve checked against Feverfew. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Zileuton

This page covers Feverfew only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Zileuton page lists 213 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 163 moderate · 44 minor.

Open the Zileuton interaction page

One more smart check

Taking Feverfew as Part of a Dietary Supplement Product? Check It for Interactions

We hold 520 real supplement products containing Feverfew, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Feverfew. Your product may carry other ingredients that interact with Zileuton too, on top of Feverfew — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Feverfew and Zileuton Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Feverfew
Top 25%

#296 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Zileuton
Steady interest

#1,696 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Feverfew

What is Feverfew?

Feverfew
  • Migraine prevention
  • Headache
  • Fever (traditional)
  • Arthritis and joint pain
  • Menstrual discomfort

Feverfew is a daisy-family herb best known for migraine prevention, where some studies suggest it may modestly lower how often migraines occur, though the evidence is mixed. It is generally well tolerated for short-term use in most adults but should be avoided during pregnancy and breastfeeding and by people allergic to ragweed and related plants. Talk to your pharmacist or doctor before starting it.

Read the full Feverfew monograph & all interactions
Medication

About Zileuton

What Is Zileuton Used For?

Brand names: Zyflo, Zyflo CR

Zileuton is used for the ongoing prevention and treatment of asthma in adults and adolescents aged 12 and older. It is a maintenance medicine — meaning it is taken regularly to keep asthma under control, not to stop an asthma attack once it has started.

Zyflo (the tablet form) and zileuton extended-release tablets are both approved for this same purpose. Neither form should be used to treat a sudden asthma attack. However, both can be continued during a flare-up of asthma while you also use your rescue inhaler.

See full Zileuton drug information
Keep checking

Other Drugs & Feverfew

Browse every other medication we’ve checked against Feverfew — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
928Moderate
0Minor
1,901No known interaction
Moderate

928 interactions

Showing 60 of 928 moderate interactions — see all 928 on the Feverfew page.

No interaction 1,901 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Feverfew and Zileuton Together: Common Questions

Can you take Feverfew with Zileuton?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Feverfew and Zileuton?
Zileuton belongs to more than one drug category, and Feverfew interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Feverfew and Zileuton interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Zileuton and Feverfew?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.