Licorice - Methotrexate Sodium Interaction
Herbal: Licorice
Also Known As: Glycyrrhiza echinate, Alcacuz, Bois Doux, Can Cao, Deglycyrrhized Licorice, Gan Cao, Gan Zao, Glabra, Glycyrrhizic Acid, Glycyrrhizinic Acid, Kanzo, Lakritze, Liquiritiae Radix, Liquirizia, Mulathi, Mulethi, Orozuz, Subholz, Yashtimadhu, Yashti-Madhu
Drug: Methotrexate Sodium
Brand names:
Xatmep
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jun 15, 2025
Interaction Details
Methotrexate Sodium is classified as belonging to the following category: Methotrexate (Trexall, Others)
Theoretically, licorice might increase levels of methotrexate.
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin. This interaction has not yet been reported in humans.
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
- Abe K, Higurashi T, Takahashi M, et al. Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity. In Vivo 2021;35(4):2163-2169.
Licorice Overview
Licorice, also known as glycyrrhiza, is a plant native to parts of Europe, Asia, and the Mediterranean region. The root of the plant has been used for centuries in traditional medicine and is often consumed in the form of candy, tea, and supplements.
Licorice has a number of purported health benefits, including the ability to soothe sore throats, reduce inflammation, and improve digestive problems. It may also have antiviral and antibacterial properties.
Licorice naturally contains glycyrrhizin, or glycyrrhizic acid, which can have toxic effects if consumed in large amounts. However, licorice can be processed to remove glycyrrhizin, resulting in DGL (deglycyrrhizinated licorice). Many dietary supplements that contain deglycyrrhizinated licorice are often simply named 'DGL'.
Licorice - More Interactions
Licorice interacts with 1011 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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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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