Drug & supplement interaction

Ceylon Leadwort + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Acetaminophen, Butalbital, Codeine Phosphate 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 2D6 (CYP2D6) in vitro.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Ceylon Leadwort and Acetaminophen, Butalbital, Codeine Phosphate

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, Codeine Phosphate 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 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate 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. The codeine part of your Phrenilin tablet is actually a prodrug. Your body has to convert it using an enzyme called CYP2D6 into morphine, which is what actually relieves pain. Ceylon Leadwort contains plumbagin, which in lab studies appears to block that very enzyme.

So if that blocking happened in real people, you might convert less codeine into morphine, meaning weaker pain relief. It wouldn't change the acetaminophen or butalbital pieces. Honestly though, this is only based on test-tube research and hasn't been seen in humans, so I wouldn't lose sleep over it. Still, mention any supplement use to 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 1A2 (CYP1A2) SUBSTRATES

2 of 3

Acetaminophen, Butalbital, Codeine Phosphate 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

Here's the honest picture with this combo pill (acetaminophen, butalbital, and codeine). The flag on file is that plumbagin, a compound in Ceylon Leadwort, slowed down a liver enzyme called CYP1A2 in lab dishes. That's important to know, but it has never actually been reported in real people, and it's only test-tube data. On top of that, the three ingredients in this medication aren't mainly cleared by CYP1A2, so this particular enzyme issue isn't a great match for this drug.

That said, codeine is a sedating opioid and butalbital is a barbiturate, so stacking them with an herb of uncertain safety isn't something to wing on your own. If you're considering Ceylon Leadwort, please run it by your pharmacist or doctor first so they can look at your full list.

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

3 of 3

Acetaminophen, Butalbital, Codeine Phosphate 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 practical piece for your combination pill (Phrenilin #3 contains acetaminophen, butalbital, and codeine). The interaction on file focuses on acetaminophen. A compound in Ceylon Leadwort called plumbagin can slow down an enzyme called CYP2E1, and that enzyme handles a minor pathway of acetaminophen breakdown. In theory, blocking it could shift more acetaminophen toward that pathway, which is the route tied to liver stress, especially at higher doses.

I want to be honest with you: this is only seen in lab dish studies, not in real people, so the concern is theoretical and likely small with normal use. Still, since liver safety is the issue with acetaminophen, please run this combo past your pharmacist or doctor before pairing them, and never exceed your acetaminophen dose limit.

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, Codeine Phosphate 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, Codeine Phosphate)
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, Codeine Phosphate

This page covers Ceylon Leadwort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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 Gamma-hydroxybutyrate (ghb) (major).

Open the Acetaminophen, Butalbital, Codeine Phosphate 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, Codeine Phosphate 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, Codeine Phosphate 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, Codeine Phosphate
Steady interest

#1,700 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, Codeine Phosphate, 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, Codeine Phosphate supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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, Codeine Phosphate Together: Common Questions

Can you take Ceylon Leadwort with Acetaminophen, Butalbital, Codeine Phosphate?
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, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate 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, Codeine Phosphate 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, Codeine Phosphate and Ceylon Leadwort?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.