Drug & supplement interaction

Greater Celandine + Codeine, Paracetamol

Codeine, Paracetamol brand name: Co-codamol.

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

Codeine, Paracetamol 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 Codeine, Paracetamol

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. Codeine, Paracetamol 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 Codeine, Paracetamol

Codeine, Paracetamol 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 co-codamol: the codeine part is actually a prodrug. Your body relies on an enzyme called CYP2D6 to turn codeine into morphine, which is what actually relieves your pain. Greater celandine contains a compound (chelidonine) that may block that very enzyme. If it does, less of your codeine gets converted to morphine, so you could end up with weaker pain relief than expected.

I'll be honest, this is based only on lab testing, not real patients, so it's theoretical. But there's a bigger reason I'd steer you away from greater celandine: it has been tied to serious liver injury, and the paracetamol in co-codamol is also hard on the liver. Please run this by 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

Codeine, Paracetamol 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 simple version. The paracetamol (acetaminophen) part of your co-codamol is processed by your liver, and in higher doses or over time it can stress the liver. Greater celandine has been tied to real cases of liver injury too. So the worry isn't a chemical tug-of-war between them, it's that you'd be asking your liver to handle two things that can each be hard on it, which could add up.

To be honest, this is based on scattered case reports, not strong studies, so the risk is uncertain rather than proven. Still, since greater celandine itself can harm the liver, I'd lean toward avoiding it, especially with anything containing paracetamol. Watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and please check with 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 Codeine, Paracetamol 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. Codeine, Paracetamol)
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 Codeine, Paracetamol

This page covers Greater Celandine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Codeine, Paracetamol 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).

By severity: 9 major · 191 moderate · 40 minor.

From our pharmacist’s overview on the Codeine, Paracetamol page

“Co-codamol pairs codeine, an opioid that slows breathing, with paracetamol, which can strain the liver, so I read its supplement list warily. Nine of the 240 ingredients on file carry a major rating, and most of those pile extra sedation onto the codeine.”

Reviewed by 2 · Jul 18, 2026

Open the Codeine, Paracetamol 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 Codeine, Paracetamol 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 Codeine, Paracetamol 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
Steady interest

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

29 days ago today
Medication Codeine, Paracetamol
Top half

#920 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 Codeine, Paracetamol, 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 Codeine, Paracetamol supplement interactions › Every supplement checked against Codeine, Paracetamol, 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 Codeine, Paracetamol Together: Common Questions

Can you take Greater Celandine with Codeine, Paracetamol?
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 Codeine, Paracetamol?
Codeine, Paracetamol 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 Codeine, Paracetamol 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 Codeine, Paracetamol and Greater Celandine?

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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.