Drug & supplement interaction

Ceylon Leadwort + Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, and others.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Butalbital, Caffeine falls into 3 drug categories that Ceylon Leadwort can interact with; the most serious is rated moderate. Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 1A2 (CYP1A2) in vitro.

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

Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine

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

Why Are There 3 Interactions?

Ceylon Leadwort interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine falls into 3 of those categories, so it can interact with Ceylon Leadwort 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 Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Ceylon Leadwort interacts with.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 1A2 (CYP1A2) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP1A2. Some substrates of CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), zileuton (Zyflo), zolmitriptan (Zomig), and others.
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 piece that matters for your headache combo: the caffeine in it is cleared by a liver enzyme called CYP1A2. In lab tests, plumbagin (a compound in Ceylon Leadwort) appears to slow that enzyme down. If that happened in people, caffeine could hang around longer than usual, so you might feel jittery, have a racing heartbeat, feel anxious, or have trouble sleeping. The acetaminophen and butalbital parts aren't really driven by this same pathway.

I want to be honest about the strength here: this is only test-tube evidence, with nothing reported in actual patients, so it's more theoretical than proven. Still, if you use a concentrated Ceylon Leadwort supplement, it's worth a quick chat with your pharmacist or doctor first.

References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Butalbital, Caffeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 3A4 (CYP3A4) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP3A4. Some drugs metabolized by CYP3A4 include lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and numerous others.
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 with this combo headache pill. One part of it, butalbital (a barbiturate), is partly cleared by a liver enzyme called CYP3A4. In lab dish studies, plumbagin from Ceylon Leadwort slowed that enzyme down. If that happened in your body, butalbital could build up a bit, which might leave you feeling more drowsy, foggy, dizzy, or sleepy than usual.

I want to be honest about the strength of this, though. It comes only from test-tube and animal work, and it has never been confirmed in real people. So I'm not alarmed here. Still, since butalbital already causes sedation, it's worth running Ceylon Leadwort past your pharmacist or doctor before combining them, especially if you'll be driving.

References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Butalbital, Caffeine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 2E1 (CYP2E1) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP2E1. Some drugs metabolized by CYP2E1 include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and anesthetics such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), methoxyflurane (Penthrane).
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 angle worth knowing with your headache medication (the acetaminophen, butalbital, and caffeine combo): one compound in Ceylon Leadwort, called plumbagin, has been shown in lab dish studies to slow down an enzyme named CYP2E1. That same enzyme helps process the acetaminophen part of your pill. In theory, if that pathway gets blocked, acetaminophen could hang around a bit longer in your system.

Now, I want to be honest about how shaky this is. It's only been seen in test tubes, never in actual people, so we really don't know if it matters in real life. Still, since acetaminophen at higher levels can stress the liver, it's worth mentioning to your pharmacist or doctor before pairing these, especially if you also drink alcohol or take other acetaminophen products.

References
  1. Chen A, Zhou X, Tang S, Liu M, Wang X. Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach. Sci Rep. 2016 Jun 22;6:28482. PubMed

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

Ceylon Leadwort Also Interacts With Other Medications

Ceylon Leadwort has 1,098 moderate known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine 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 Ceylon Leadwort

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine

This page covers Ceylon Leadwort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine page lists 252 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Grapefruit (major).

By severity: 11 major · 197 moderate · 44 minor.

From our pharmacist’s overview on the Acetaminophen, Butalbital, Caffeine page

“Alcohol is the interaction I would flag first for anyone taking acetaminophen, butalbital, and caffeine (Esgic, Fiogesic, and others). Drinking raises the risk of liver injury from the acetaminophen component, and 38 of the 252 supplement ingredients on file carry that same liver concern.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Butalbital, Caffeine interaction page

One more smart check

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

We hold 96 real supplement products containing Ceylon Leadwort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ceylon Leadwort. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Ceylon Leadwort — 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 Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine 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 Ceylon Leadwort
Top half

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine
Top 5%

#62 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 Ceylon Leadwort

What is Ceylon Leadwort?

  • Digestive complaints and poor appetite
  • Skin conditions and wounds (applied to the skin)
  • Joint pain and swelling
  • Traditional 'metabolism-boosting' tonics
  • Antimicrobial folk remedy

Ceylon Leadwort (Plumbago zeylanica) is a plant long used in Ayurvedic and other traditional medicine systems, mainly for digestion, skin problems, and pain. Solid human studies are lacking, and the plant contains plumbagin, a compound that can irritate skin and tissues and may be unsafe in larger amounts. Talk to a pharmacist or doctor before using it, and avoid it in pregnancy.

Read the full Ceylon Leadwort monograph & all interactions
Medication

About Acetaminophen, Butalbital, and Caffeine

What Is Acetaminophen, Butalbital, and Caffeine Used For?

Brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, Esgic, Fioricet

This combination product — available as capsules, tablets, and oral solution under various names including Fioricet — is used to relieve the symptoms of tension headaches (also called muscle contraction headaches).

All supported products, including Fioricet capsules and the oral solution, share this same indication. Because butalbital can be habit-forming, extended or repeated use is not recommended, and these products are not established as safe or effective for treating headaches that come back frequently over time.

See full Acetaminophen, Butalbital, and Caffeine drug information
Keep checking

Other Drugs & Ceylon Leadwort

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

0Major
1,098Moderate
0Minor
1,731No known interaction
Moderate

1,098 interactions

Showing 60 of 1,098 moderate interactions — see all 1,098 on the Ceylon Leadwort page.

No interaction 1,731 drugs checked — show the list

We also checked Ceylon Leadwort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,731 medications checked with no known interaction — see the full Ceylon Leadwort 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 Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine Together: Common Questions

Can you take Ceylon Leadwort with Acetaminophen, Butalbital, Caffeine?
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 Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine?
Acetaminophen, Butalbital, Caffeine belongs to more than one drug category, and Ceylon Leadwort 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 Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine 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 Acetaminophen, Butalbital, Caffeine and Ceylon Leadwort?

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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.