Drug & supplement interaction

Ceylon Leadwort + Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 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 2D6 (CYP2D6) in vitro.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine, Codeine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Ceylon Leadwort interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 of those categories, so it can interact with Ceylon Leadwort in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 4

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Ceylon Leadwort interacts with.

Plumbagin, a constituent of Ceylon leadwort, has been shown to inhibit cytochrome P450 2D6 (CYP2D6) in vitro. So far, this interaction has not been reported in humans. Theoretically, Ceylon leadwort might increase the levels of drugs metabolized by CYP2D6. Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), fluoxetine (Prozac), ondansetron (Zofran), tramadol (Ultram), 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 wrinkle with this combo product: the codeine part is a prodrug. Your body needs an enzyme called CYP2D6 to turn codeine into morphine, which is what actually relieves pain. Ceylon Leadwort contains plumbagin, which in lab studies appears to block CYP2D6. If that happens in real life, less codeine would get converted to morphine, so you might get weaker pain relief from this medication.

I want to be honest about the evidence here: this is only seen in test-tube research, not in actual people, so it's theoretical. The other ingredients (acetaminophen, butalbital, caffeine) aren't the main concern with this pathway. Still, before pairing these, check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
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 1A2 (CYP1A2) SUBSTRATES

2 of 4

Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

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

This combination pill has a lot going on, but the piece that lines up with Ceylon Leadwort is the caffeine. Caffeine is cleared by an enzyme called CYP1A2, and a compound in Ceylon Leadwort (plumbagin) has been shown to slow that enzyme down in lab dishes. In theory, that could let caffeine linger longer, so you might notice more of the jittery side: a racing or pounding heart, restlessness, trouble sleeping, or an upset stomach.

Here is the honest part. This is only seen in test-tube research, never reported in real people, so I would not lose sleep over it. The codeine, butalbital, and acetaminophen pieces are handled by different pathways and are not the concern here. Still, since this product is potent on its own, please run any Ceylon Leadwort use past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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

3 of 4

Acetaminophen, Butalbital, Caffeine, Codeine 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

This combination pill has a few moving parts, and the part that matters here is the butalbital, a barbiturate that is partly handled by the CYP3A4 enzyme. In test-tube studies, the plumbagin in Ceylon Leadwort can slow that enzyme down. In theory, that could let butalbital build up a bit, which might mean more drowsiness, dizziness, slowed breathing, or a foggy, sedated feeling.

I want to be honest with you, though: this has only been seen in lab dishes, not in real people, so it's a theoretical concern rather than a proven one. Still, since this medicine already causes sedation and the codeine adds to that, I'd play it safe. Please check with your pharmacist or doctor before pairing them, especially if you take other sedating medicines.

Contact Dr. Brian directly if you have additional questions on this interaction
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

4 of 4

Acetaminophen, Butalbital, Caffeine, Codeine 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

The piece of this combo pill that matters here is the acetaminophen (the Tylenol part). Your liver uses several enzymes to break it down, and one of them, called CYP2E1, is the one Ceylon Leadwort's main compound (plumbagin) seems to block. That comes from lab and test-tube studies only, and it has never actually been seen in real people, so think of this as a theoretical concern rather than something proven.

In theory, slowing that enzyme could shift how acetaminophen is processed. Interestingly, CYP2E1 is the pathway that creates a harmful liver byproduct, so blocking it isn't simply about the drug building up. Either way, the practical takeaway is simple: don't exceed your acetaminophen dose, and check with your pharmacist or doctor before pairing these.

Contact Dr. Brian directly if you have additional questions on this interaction
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 1,096 moderate known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine, Codeine one above is among them. If you take anything else, check it against the full list below.

Moderate 1,096 No known interaction 1,734 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
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, Codeine

This page covers Ceylon Leadwort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine, Codeine page lists 305 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Ephedra (major).

By severity: 15 major · 245 moderate · 45 minor.

Open the Acetaminophen, Butalbital, Caffeine, Codeine 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, Codeine 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, Codeine 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

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine, Codeine
Top half

#991 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
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
1,096Moderate
0Minor
1,733No known interaction
1,096 Moderate 1,733 No interaction
Moderate

1,096 interactions

Showing 60 of 1,096 moderate interactions — see all 1,096 on the Ceylon Leadwort page.

No interaction 1,733 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 1,733 medications checked with no known interaction — see the full Ceylon Leadwort list.

See the full Ceylon Leadwort interactions page
See every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, ranked by severity
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

Keep exploring
Ceylon Leadwort monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Ceylon Leadwort with Acetaminophen, Butalbital, Caffeine, Codeine?
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 4 interactions listed for Ceylon Leadwort and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine 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, Codeine 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

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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.