Milk Thistle - Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine Interaction
Herbal: Milk Thistle
Also Known As: Silybum marianum, Artichaut Sauvage, Blessed Milk Thistle, Cardo Lechoso, Cardui Mariae Fructus, Cardui Mariae Herba, Carduus Marianum, Chardon Argenté, Chardon de Marie, Chardon de Notre-Dame, Chardon Marbré, Chardon-Marie, Épine Blanche, Holy Thistle, Khar Maryam
Drug: Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine
Brand names:
Multi Symptom Cold Relief
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Apr 20, 2025
Interaction Details
Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.
Interaction Rating
Likelihood of Occurrence
UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
References
- Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3.
- Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-6.
- Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94.
- van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005;11:7800-6.
- Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007;85:966-78.
- Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7.
- Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15.
- Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6.
- Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178.
Interaction Details
Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine is classified as belonging to the following category: Glucuronidated Drugs
Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.
Interaction Rating
Likelihood of Occurrence
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
References
- Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3.
- Kim DH, Jin YH, Park JB, Kobashi K. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 1994;17:443-5.
- Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94.
Milk Thistle Overview
Milk thistle (Silybum marianum) is a plant belonging to the aster family (Asteraceae). It is native to the Mediterranean region and is widely cultivated in many parts of the world. The plant is known for its milk-white veins on the leaves, which gives it its name.
Milk thistle has a long history of use in traditional medicine, and is extremely popular as a dietary supplement, making it one of the most well-known plants in the world. It is purported to have liver-protectant effects and has been used to treat liver disorders such as hepatitis and cirrhosis. It has also been used to treat gallbladder problems and high cholesterol. While there are a number of compounds in milk thistle, one of the active constituents, silymarin, is thought to be responsible for many of its effects, and dietary supplements often report using a standardized amount (generally 70% to 80% silymarin in extracts).
Milk Thistle - More Interactions
Milk Thistle interacts with 927 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
| Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
| Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
| Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
| Unknown | No interactions have been reported or no interaction data is currently available. |
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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
Drug descriptions are provided by MedlinePlus.
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Dr. Brian Staiger, PharmD
In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!
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