Drug & supplement interaction

Greater Celandine + 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 2 drug categories that Greater Celandine can interact with; the most serious is rated moderate. Research in vitro shows that chelidonine, a constituent of greater celandine, inhibits cytochrome P450 2D6 (CYP2D6) enzyme activity.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Greater Celandine and Acetaminophen, Butalbital, Codeine Phosphate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Greater Celandine interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine Phosphate falls into 2 of those categories, so it can interact with Greater Celandine in 2 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 2

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Greater Celandine interacts with.

Research in vitro shows that chelidonine, a constituent of greater celandine, inhibits cytochrome P450 2D6 (CYP2D6) enzyme activity. Theoretically, greater celandine might increase levels of drugs metabolized by CYP2D6.
Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and many 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 in your Phrenilin #3 is actually a prodrug. Your body has to convert it into morphine using a liver enzyme called CYP2D6 before it can ease your pain. Greater celandine may block that enzyme, at least based on early lab studies. So in theory, less of your codeine would turn into morphine, meaning weaker pain relief than you'd expect.

I'll be honest, this is mostly theoretical and comes from test-tube research, so it may not play out in real life. The bigger concern with greater celandine is its link to serious liver injury, which matters even more here since the acetaminophen in this medicine is also hard on the liver. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Cui T, Peng Y, Ji M, Zheng J. Mechanism-based inactivation of cytochrome P450 2D6 by chelidonine. J Biochem Mol Toxicol. 2019;33(2):e22251. PubMed
Moderate

HEPATOTOXIC DRUGS

2 of 2

Acetaminophen, Butalbital, Codeine Phosphate also falls under HEPATOTOXIC DRUGS.

There is some concern that greater celandine can adversely affect the liver. Greater celandine has been linked to many cases of hepatotoxicity. Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage. Some of these drugs include acarbose (Precose, Prandase), amiodarone (Cordarone), atorvastatin (Lipitor), azathioprine (Imuran), carbamazepine (Tegretol), cerivastatin (Baycol), diclofenac (Voltaren), felbamate (Felbatol), fenofibrate (TriCor), fluvastatin (Lescol), gemfibrozil (Lopid), isoniazid, itraconazole, (Sporanox), ketoconazole (Nizoral), leflunomide (Arava), lovastatin (Mevacor), methotrexate (Rheumatrex), nevirapine (Viramune), niacin, nitrofurantoin (Macrodantin), pioglitazone (Actos), pravastatin (Pravachol), pyrazinamide, rifampin (Rifadin), ritonavir (Norvir), rosiglitazone (Avandia), simvastatin (Zocor), tacrine (Cognex), tamoxifen, terbinafine (Lamisil), valproic acid, and zileuton (Zyflo).
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 main thing to know about pairing greater celandine with this combination product: it isn't about how your body breaks the medicine down. The concern is your liver. The acetaminophen piece of this pill is already processed by the liver, and taking too much (or layering it with other liver stressors) is a well-known cause of liver injury.

Greater celandine itself has been tied to cases of serious liver damage. So putting the two together theoretically stacks the risk. To be fair, this is based on scattered case reports, not strong studies, so it's a caution and not a sure thing. Still, with the liver, I'd rather be careful. Watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and please run this past your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Benninger J, Schneider HT, Schuppan D, et al. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterology 1999;117:1234-7. PubMed
  2. Stickel F, Poschl G, Seitz HK, et al. Acute hepatitis induced by Greater Celandine (Chelidonium majus). Scand J Gastroenterol 2003;38:565-8.
  3. Moro PA, Cassetti F, Giugliano G, et al. Hepatitis from greater celandine (Chelidonium majus L.): Review of literature and report of a new case. J Ethnopharmacol 2009;124:328-32. PubMed
  4. Stickel, F., Seitz, H. K., Hahn, E. G., and Schuppan, D. [Liver toxicity of drugs of plant origin]. Z.Gastroenterol. 2001;39(3):225-227.
  5. Hardeman, E., Van, Overbeke L., Ilegems, S., and Ferrante, M. Acute hepatitis induced by greater celandine (Chelidonium majus). Acta Gastroenterol.Belg. 2008;71(2):281-282.
  6. Gilca, M., Gaman, L., Panait, E., Stoian, I., and Atanasiu, V. Chelidonium majus--an integrative review: traditional knowledge versus modern findings. Forsch.Komplementmed. 2010;17(5):241-248. PubMed
  7. Teschke, R., Glass, X., and Schulze, J. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports. Regul.Toxicol.Pharmacol. 2011;61(3):282-291. PubMed
  8. Teschke, R., Glass, X., Schulze, J., and Eickhoff, A. Suspected Greater Celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe. Eur.J Gastroenterol.Hepatol. 2012;24(3):270-280. PubMed
  9. Teschke, R., Frenzel, C., Glass, X., Schulze, J., and Eickhoff, A. Greater Celandine hepatotoxicity: a clinical review. Ann.Hepatol. 2012;11(6):838-848. DOI

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

Greater Celandine Also Interacts With Other Medications

Greater Celandine has 624 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 624 No known interaction 2,206 (incl. Acetaminophen, Butalbital, Codeine Phosphate)
Taking anything else?

Check Another of Your Medications Against Greater Celandine

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Codeine Phosphate

This page covers Greater Celandine 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 Greater Celandine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 11 real supplement products containing Greater Celandine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Greater Celandine. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Codeine Phosphate too, on top of Greater Celandine — 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 Greater Celandine 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 Greater Celandine
Top half

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,636 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 Greater Celandine

What is Greater Celandine?

Greater Celandine
  • Digestive and gallbladder complaints
  • Stomach cramps and bloating
  • Topical use for warts and skin growths
  • Liver and gallbladder 'cleansing'
  • Mild pain relief

Greater celandine is a traditional herb most often promoted for digestive and gallbladder complaints, but solid human evidence for any use is lacking. More importantly, it has been linked to serious and sometimes severe liver injury, so most experts advise against taking it by mouth. If you are considering it, talk with your pharmacist or doctor first.

Read the full Greater Celandine monograph & all interactions
Keep checking

Other Drugs & Greater Celandine

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

0Major
624Moderate
0Minor
2,205No known interaction
624 Moderate 2,205 No interaction
Moderate

624 interactions

Showing 60 of 624 moderate interactions — see all 624 on the Greater Celandine page.

No interaction 2,205 drugs checked — show the list

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

Showing the 60 most looked-up of 2,205 medications checked with no known interaction — see the full Greater Celandine list.

See the full Greater Celandine 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
Greater Celandine 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 Greater Celandine and Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Greater Celandine 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 2 interactions listed for Greater Celandine and Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate belongs to more than one drug category, and Greater Celandine 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 Greater Celandine 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

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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.